CN118225732A - Apparatus, system and method for sample testing - Google Patents
Apparatus, system and method for sample testing Download PDFInfo
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- CN118225732A CN118225732A CN202311664309.6A CN202311664309A CN118225732A CN 118225732 A CN118225732 A CN 118225732A CN 202311664309 A CN202311664309 A CN 202311664309A CN 118225732 A CN118225732 A CN 118225732A
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Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/41—Refractivity; Phase-affecting properties, e.g. optical path length
- G01N21/45—Refractivity; Phase-affecting properties, e.g. optical path length using interferometric methods; using Schlieren methods
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/41—Refractivity; Phase-affecting properties, e.g. optical path length
- G01N21/4133—Refractometers, e.g. differential
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
- G01N2021/0106—General arrangement of respective parts
- G01N2021/0112—Apparatus in one mechanical, optical or electronic block
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/41—Refractivity; Phase-affecting properties, e.g. optical path length
- G01N2021/4173—Phase distribution
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/41—Refractivity; Phase-affecting properties, e.g. optical path length
- G01N21/45—Refractivity; Phase-affecting properties, e.g. optical path length using interferometric methods; using Schlieren methods
- G01N2021/458—Refractivity; Phase-affecting properties, e.g. optical path length using interferometric methods; using Schlieren methods using interferential sensor, e.g. sensor fibre, possibly on optical waveguide
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Investigating Or Analysing Materials By Optical Means (AREA)
Abstract
Methods, apparatus, and systems associated with sample testing devices are provided. The sample testing device includes a waveguide. The method for manufacturing the waveguide device includes: forming a thermal silicon dioxide layer on a silicon wafer; forming a stress reducing pattern on the thermal silicon dioxide layer, wherein the stress reducing pattern includes a plurality of polygonal pattern units; and forming a silicon nitride film on the stress reducing pattern. The present invention also provides a parallel flow multichannel pathogen sensing system, comprising: a multichannel peristaltic pump including a plurality of pump flow channel tubes through which a buffer solution flows; a sample valve array comprising a plurality of sample valves, wherein each of the plurality of sample valves comprises a buffer solution injection port for receiving a buffer solution and a sensing channel connection port connected to a sensing channel input port on the waveguide fluidic assembly; and a waveguide fluidic assembly including a parallel flow microfluidic cover defining a plurality of sensing channel input ports.
Description
Cross Reference to Related Applications
The present application claims priority and benefit from U.S. provisional patent application No. 63/476,350 filed on 12 months 20 of 2022, the contents of which are incorporated by reference in their entirety.
The present application is also a continuation of the application in part of U.S. patent application Ser. No. 18/326,778, filed 5/31 at 2023. U.S. patent application Ser. No. 18/326,778 claims priority and benefit from U.S. provisional patent application Ser. No. 63/366,128, filed on 6/9 of 2022, the contents of which are incorporated by reference in their entirety. U.S. patent application Ser. No. 18/326,778 is also a continuation of the application from part of U.S. patent application Ser. No. 18/156,221, filed on 1 month 18 of 2023, the contents of which are incorporated by reference in their entirety. U.S. patent application Ser. No. 18/156,221 claims priority and benefit from U.S. provisional patent application Ser. No. 63/316,257, filed 3/2022, the contents of which are incorporated by reference in their entirety. The section of U.S. patent application Ser. No. 18/156,221, or U.S. patent application Ser. No. 17/936,764 filed on 9/29 of 2022, the contents of which are incorporated by reference in their entirety. U.S. patent application Ser. No. 17/936,764 claims priority and benefit from U.S. provisional patent application Ser. No. 63/262,076, filed on 4/10/2021, the contents of which are incorporated by reference in their entirety. U.S. patent application Ser. No. 17/936,764 also claims priority and benefit from U.S. provisional patent application Ser. No. 63/263,481 filed on day 11 and 3 of 2021, the contents of which are incorporated by reference in their entirety. U.S. patent application Ser. No. 17/936,764, the contents of which are incorporated by reference in their entirety, is also a continuation of the application in part of U.S. patent application Ser. No. 17/302,536, filed 5 at 2021. U.S. patent application Ser. No. 17/302,536 claims the priority and benefit of U.S. patent application Ser. No. 63/021,416 (filed 5/7/2020), U.S. patent application Ser. No. 63/198,609 (filed 10/29/2020), and U.S. patent application Ser. No. 63/154,476 (filed 26/2021), which are incorporated herein by reference in their entireties. U.S. patent application Ser. No. 18/156,221 is also a continuation of the section of U.S. patent application Ser. No. 17/302,536 filed 5/2021, the contents of which are incorporated by reference in their entirety. U.S. patent application Ser. No. 17/302,536 claims the priority and benefit of U.S. patent application Ser. No. 63/021,416 (filed 5/7/2020), U.S. patent application Ser. No. 63/198,609 (filed 10/29/2020), and U.S. patent application Ser. No. 63/154,476 (filed 26/2021), which are incorporated herein by reference in their entireties. The section of U.S. patent application Ser. No. 18/326,778, or U.S. patent application Ser. No. 17/936,764 filed on 9/29 of 2022, the contents of which are incorporated by reference in their entirety. U.S. patent application Ser. No. 17/936,764 claims priority and benefit from U.S. provisional patent application Ser. No. 63/262,076, filed on 4/10/2021, the contents of which are incorporated by reference in their entirety. U.S. patent application Ser. No. 17/936,764 also claims priority and benefit from U.S. provisional patent application Ser. No. 63/263,481 filed on day 11 and 3 of 2021, the contents of which are incorporated by reference in their entirety. U.S. patent application Ser. No. 17/936,764, the contents of which are incorporated by reference in their entirety, is also a continuation of the application in part of U.S. patent application Ser. No. 17/302,536, filed 5 at 2021. U.S. patent application Ser. No. 17/302,536 claims the priority and benefit of U.S. patent application Ser. No. 63/021,416 (filed 5/7/2020), U.S. patent application Ser. No. 63/198,609 (filed 10/29/2020), and U.S. patent application Ser. No. 63/154,476 (filed 26/2021), which are incorporated herein by reference in their entireties. U.S. patent application Ser. No. 18/326,778 is also a continuation of the section of U.S. patent application Ser. No. 17/302,536 filed 5 at 2021, the contents of which are incorporated by reference in their entirety. U.S. patent application Ser. No. 17/302,536 claims the priority and benefit of U.S. patent application Ser. No. 63/021,416 (filed 5/7/2020), U.S. patent application Ser. No. 63/198,609 (filed 10/29/2020), and U.S. patent application Ser. No. 63/154,476 (filed 26/2021), which are incorporated herein by reference in their entireties.
The present application is also a continuation of the application in part of U.S. patent application Ser. No. 18/156,221, filed 1/18 of 2023. U.S. patent application Ser. No. 18/156,221 claims priority and benefit from U.S. provisional patent application Ser. No. 63/316,257, filed 3/2022, the contents of which are incorporated by reference in their entirety. The section of U.S. patent application Ser. No. 18/156,221, or U.S. patent application Ser. No. 17/936,764 filed on 9/29 of 2022, the contents of which are incorporated by reference in their entirety. U.S. patent application Ser. No. 17/936,764 claims priority and benefit from U.S. provisional patent application Ser. No. 63/262,076, filed on 4/10/2021, the contents of which are incorporated by reference in their entirety. U.S. patent application Ser. No. 17/936,764 also claims priority and benefit from U.S. provisional patent application Ser. No. 63/263,481 filed on day 11 and 3 of 2021, the contents of which are incorporated by reference in their entirety. U.S. patent application Ser. No. 17/936,764, the contents of which are incorporated by reference in their entirety, is also a continuation of the application in part of U.S. patent application Ser. No. 17/302,536, filed 5 at 2021. U.S. patent application Ser. No. 17/302,536 claims the priority and benefit of U.S. patent application Ser. No. 63/021,416 (filed 5/7/2020), U.S. patent application Ser. No. 63/198,609 (filed 10/29/2020), and U.S. patent application Ser. No. 63/154,476 (filed 26/2021), which are incorporated herein by reference in their entireties. U.S. patent application Ser. No. 18/156,221 is also a continuation of the section of U.S. patent application Ser. No. 17/302,536 filed 5/2021, the contents of which are incorporated by reference in their entirety. U.S. patent application Ser. No. 17/302,536 claims the priority and benefit of U.S. patent application Ser. No. 63/021,416 (filed 5/7/2020), U.S. patent application Ser. No. 63/198,609 (filed 10/29/2020), and U.S. patent application Ser. No. 63/154,476 (filed 26/2021), which are incorporated herein by reference in their entireties.
The present application is also part of the continued application of U.S. patent application Ser. No. 17/936,764, filed on 9/29 of 2022. U.S. patent application Ser. No. 17/936,764 claims priority and benefit from U.S. provisional patent application Ser. No. 63/262,076, filed on 4/10/2021, the contents of which are incorporated by reference in their entirety. U.S. patent application Ser. No. 17/936,764 also claims priority and benefit from U.S. provisional patent application Ser. No. 63/263,481 filed on day 11 and 3 of 2021, the contents of which are incorporated by reference in their entirety. U.S. patent application Ser. No. 17/936,764, the contents of which are incorporated by reference in their entirety, is also a continuation of the application in part of U.S. patent application Ser. No. 17/302,536, filed 5 at 2021. U.S. patent application Ser. No. 17/302,536 claims the priority and benefit of U.S. patent application Ser. No. 63/021,416 (filed 5/7/2020), U.S. patent application Ser. No. 63/198,609 (filed 10/29/2020), and U.S. patent application Ser. No. 63/154,476 (filed 26/2021), the contents of which are incorporated herein by reference in their entirety.
The present application is also a continuation of the application in the section of U.S. patent application Ser. No. 17/302,536 filed 5/2021. U.S. patent application Ser. No. 17/302,536 claims the priority and benefit of U.S. patent application Ser. No. 63/021,416 (filed 5/7/2020), U.S. patent application Ser. No. 63/198,609 (filed 10/29/2020), and U.S. patent application Ser. No. 63/154,476 (filed 26/2021), the contents of which are incorporated herein by reference in their entirety.
Background
Existing methods, devices, and systems suffer from challenges and limitations. For example, the efficiency and/or accuracy of many devices may be affected by various factors such as structural limitations, ambient temperature, contamination, and the like.
Disclosure of Invention
According to various examples of the present disclosure, various exemplary methods, devices, and systems for sample testing are provided. In some embodiments, the exemplary methods, devices, and systems may utilize interferometry to detect the presence of viral indicators of viral and/or other protein content in a collected sample.
In some examples, the sample testing device may include a waveguide and integrated optical components. In some examples, the integrated optical component may be coupled to the waveguide. In some examples, the integrated optical component may include a collimator and a beam splitter.
In some examples, the beam splitter may include a first prism and a second prism. In some examples, the second prism may be attached to the first inclined surface of the first prism. In some examples, the first prism and the second prism form a cube shape.
In some examples, the beam splitter may include a polarizing beam splitter.
In some examples, a collimator may be attached to the second inclined surface of the first prism.
In some examples, the sample testing device may include a light source coupled to the integrated optical component. In some examples, the light source may be configured to emit a laser beam.
In some examples, the waveguide may include a waveguide layer and an interface layer having a sample opening. In some examples, the interface layer may be disposed on a top surface of the waveguide layer.
In some examples, the integrated optical component may be disposed on a top surface of the waveguide layer.
In some examples, the sample testing device may include a lens component positioned over the interface layer. In some examples, the lens component may at least partially overlap with the output opening of the interface layer in the output light direction.
In some examples, the sample testing device may include an imaging component disposed on a top surface of the lens component.
In some examples, the imaging component may be configured to detect an interference fringe pattern.
In some examples, a sample testing device may include a waveguide having a first surface and a lens array disposed on the first surface. In some examples, the lens array includes at least one optical lens.
In some examples, the lens array may include at least one microlens array. In some examples, a first shape of a first optical lens of the microlens array may be different from a second shape of a second optical lens of the microlens array. In some examples, the at least one optical lens may include at least one prismatic lens.
In some examples, the first surface curvature of the first optical lens may be different from the second surface curvature of the second optical lens in the waveguide light transmission direction.
In some examples, the sample testing device may include an integrated optical component coupled to the waveguide through a lens array.
In some examples, the sample testing device may include an imaging component coupled to the waveguide through a lens array.
In some examples, a sample testing device may include a waveguide having a sample opening on a first surface and an opening layer disposed on the first surface. In some examples, the opening layer may include a first opening that at least partially overlaps the sample opening.
In some examples, the sample testing device may further include a cover layer coupled to the waveguide via at least one sliding mechanism. In some examples, the cover layer may include a second opening.
In some examples, the cover layer may be positioned on top of the opening layer and movable between a first position and a second position.
In some examples, the second opening overlaps the first opening when the cover layer may be in the first position.
In some examples, the second opening does not overlap the first opening when the cover layer is in the second position.
In some examples, the sample testing device may include a waveguide having a top surface and a bottom surface, and a light source configured to couple light into the sample testing device via the bottom surface of the waveguide.
In some examples, the light source may be configured to emit a light beam through a top surface of the waveguide.
In some examples, the sample testing device may include a waveguide having a top surface and a bottom surface. In some examples, the top surface of the waveguide may be configured to be integrated with a user computing device.
In some examples, the thickness of the waveguide may be in the range of 5 millimeters to 7 millimeters.
In some examples, the user computing device component may be configured for common use by the sample testing device.
In some examples, the sample testing device may include a waveguide and an insulating layer disposed on at least one surface of the waveguide.
In some examples, the sample testing device may further include at least one sensor configured to control the temperature of the insulating layer.
In some examples, a sample testing device may include a waveguide and a thermally controlled waveguide enclosure enclosing the waveguide.
In some examples, the sample testing device may include a waveguide including at least: a substrate layer defining a bottom surface of the sample testing device; a waveguide layer deposited on the substrate layer, configured to laterally couple light from an input side of the waveguide to an output side of the waveguide; and an interface layer defining a top surface of the sample testing device.
In some examples, the substrate layer may include an integrated circuit.
In some examples, the waveguide layer may further include at least one reference channel and at least one sample channel.
In some examples, the at least one reference channel may be associated with a reference window in the interface layer and the at least one sample channel is associated with at least one sample window in the interface layer.
In some examples, a computer-implemented method is provided. The computer-implemented method may include: receiving first interference fringe data for an unidentified sample medium, the first interference fringe data associated with a first wavelength; receiving second interference fringe data for the unidentified sample medium, the second interference fringe data associated with a second wavelength; deriving refractive index profile data based on the first interference fringe data associated with the first wavelength and the second interference fringe data associated with the second wavelength; and determining sample identity data based on the refractive index profile data.
In some examples, the computer-implemented method further comprises: triggering the light source to generate (i) first projected light at a first wavelength, wherein the first projected light represents a first interference fringe pattern, and (ii) second projected light at a second wavelength, wherein the second projected light represents a second interference fringe pattern, wherein receiving the first interference fringe data comprises capturing the first interference fringe data representing the first interference fringe pattern associated with the first wavelength using the imaging component, and wherein receiving the second interference fringe data comprises capturing the second interference fringe data representing the second interference fringe pattern associated with the second wavelength using the imaging component.
In some examples, the computer-implemented method further comprises: triggering a first light source to generate first projection light with a first wavelength, wherein the first projection light represents a first interference fringe pattern; and triggering a second light source to generate a second projected light of the first wavelength, wherein the second projected light represents a second interference fringe pattern, wherein receiving the first interference fringe data comprises capturing, using the imaging component, first interference fringe data representing the first interference fringe pattern associated with the first wavelength, and wherein receiving the second interference fringe data comprises capturing, using the imaging component, second interference fringe data representing the second interference fringe pattern associated with the second wavelength.
In some examples, determining sample identity data based on the refractive index profile data includes: a refractive index database of sample identity data is queried based on refractive index profile data, wherein the sample identity data corresponds to a stored refractive index profile in the refractive index database that best matches the refractive index profile data.
In some examples, the computer-implemented method further comprises: an operating temperature associated with the unidentified sample medium is determined, wherein the refractive index database is queried to determine sample identity data based at least on the refractive index profile data and the operating temperature.
In some examples, the refractive index database may be configured to store a plurality of known refractive index profile data associated with a plurality of identified samples associated with a plurality of known sample identity data.
In some examples, the refractive index database is further configured to store a plurality of known refractive index profile data associated with the plurality of temperature data.
In some examples, a computer-implemented method is provided. The computer-implemented method may include: triggering a light source calibration event associated with the light source; capturing reference interference fringe data representing a reference interference fringe pattern in the sample environment, the reference interference pattern projected via a reference channel of the waveguide; comparing the reference fringe data with stored calibration interferometer data to determine a refractive index offset between the reference fringe data and the stored calibration interferometer data; and tuning the light source based on the refractive index offset.
In some examples, tuning the light source based on the refractive index offset includes adjusting a voltage level applied to the light source to adjust a wavelength of light associated with the light source.
In some examples, tuning the light source based on the refractive index offset includes adjusting a current level applied to the light source to adjust a wavelength of light associated with the light source.
In some examples, the computer-implemented method further comprises: and adjusting the temperature control, wherein the adjusting the temperature control sets the sample environment to a tuned operating temperature, and wherein the tuned operating temperature is within a threshold range of the desired operating temperature.
In some examples, the computer-implemented method further comprises: initiating a calibration setup event associated with the light source; capturing calibrated reference fringe data representing a calibrated fringe pattern in a calibrated environment, the calibrated fringe pattern projected via a reference channel of the waveguide; and storing the calibrated reference fringe data in a local memory as stored calibrated fringe data.
In some examples, the calibrated environment includes an environment having a known operating temperature.
In some examples, a computer-implemented method is provided. The computer-implemented method includes: receiving sample interference fringe data for an unidentified sample medium, the sample interference fringe data associated with a determinable wavelength; providing at least sample interference fringe data to the trained sample recognition model; and receiving sample identity data associated with the sample interference fringe data from the trained sample identification model.
In some examples, receiving sample interference fringe data for an unidentified sample medium includes: triggering the light source to generate projected light of a determinable wavelength, wherein the projected light is associated with the sample interference fringe pattern; sample interference fringe data representing a sample interference fringe pattern is captured using an imaging component.
In some examples, the sample identity data includes a sample identity tag.
In some examples, the sample identity data includes a plurality of confidence scores associated with a plurality of sample identity tags.
In some examples, the trained sample recognition model includes a trained deep learning model or a trained statistical model.
In some examples, the computer-implemented method further comprises: determining an operating temperature associated with the sample environment; and providing operating temperature and sample interference fringe data to the trained sample identification model, wherein sample identity data is received in response to the operating temperature and sample interference fringe data. In some examples, the computer-implemented method further comprises: collecting a plurality of interference fringe data, the plurality of interference fringe data associated with a plurality of known sample identity tags; storing each of the plurality of interference fringe data having the plurality of known sample identity tags in a training database; and training the trained sample recognition model from the training database.
In some examples, the sample testing device may include: a substrate; a waveguide disposed on the substrate; and a lens array disposed on the substrate. In some embodiments, the lens array may be configured to direct light to an input edge of the waveguide.
In some embodiments, the lens array may comprise a Compound Parabolic Concentrator (CPC) lens array.
In some embodiments, the lens array may comprise a micro CPC lens array.
In some embodiments, the lens array may comprise an asymmetric CPC lens array.
In some embodiments, the lens array may comprise an asymmetric micro CPC lens array.
In some embodiments, the waveguide may include at least one reference channel and at least one sample channel.
In some embodiments, the lens array may be configured to direct light to a first input edge of the at least one reference channel and to a second input edge of the at least one sample channel.
In some embodiments, the sample testing device may comprise: an integrated optical component coupled to the lens array, wherein the integrated optical component may include a collimator and a beam splitter.
In some embodiments, the waveguide may comprise: a plurality of optical channels within the waveguide, wherein each optical channel of the plurality of optical channels defines an optical path; and an input edge comprising a plurality of input openings, wherein each input opening of the plurality of input openings corresponds to one optical channel of the plurality of optical channels.
In some embodiments, the input edge may be configured to receive light.
In some embodiments, each of the plurality of input openings may be configured to receive light.
In some embodiments, each optical channel of the plurality of optical channels may be configured to direct light from a corresponding input opening through the corresponding optical channel.
In some embodiments, each optical channel of the plurality of optical channels may include a curved portion and a straight portion.
In some embodiments, methods for fabricating waveguides are provided. The method may include: attaching an intermediate layer to the substrate layer; attaching a waveguide layer on the intermediate layer; and etching the first edge of the intermediate layer, the first edge of the waveguide layer, the second edge of the intermediate layer, and the second edge of the waveguide layer.
In some implementations, the first edge of the waveguide layer can include an input opening, wherein the second edge of the waveguide layer can include an output opening.
In some embodiments, the first edge of the waveguide layer may include a recessed optical edge.
In some embodiments, the second edge of the waveguide layer may include a recessed optical edge.
In some embodiments, the method may include coupling a light source to a first edge of the waveguide layer.
In some embodiments, a method for manufacturing may include: creating a waveguide with on-chip fluid; and attaching a cover glass component to the waveguide with the on-chip fluid.
In some embodiments, producing a waveguide with on-chip fluid may include: generating a waveguide layer; generating an on-chip fluid layer; and attaching the on-chip fluid layer to the top surface of the waveguide layer.
In some embodiments, attaching the cover glass component may include: creating an adhesive layer; attaching an adhesive layer on a top surface of the waveguide with the on-chip fluid; and attaching a cover glass layer on the top surface of the adhesive layer.
In some embodiments, the sample testing device may comprise: a waveguide holder component, wherein the first surface of the waveguide holder comprises at least one alignment feature; and a waveguide comprising at least one etched edge, wherein the at least one etched edge is in contact with the at least one alignment feature of the waveguide holder member in an alignment arrangement.
In some embodiments, the at least one alignment feature may comprise at least one protrusion on the first surface of the waveguide holder member, wherein the at least one etched edge is in contact with the at least one protrusion when in the alignment arrangement.
In some embodiments, the waveguide retainer member may comprise: a retainer cover member; and a fluid shim element secured to the holder cover element, wherein the fluid shim element is positioned between the holder cover element and the waveguide.
In some embodiments, the retainer cover element may include a plurality of input openings on a top surface of the retainer cover element, wherein the fluid shim element may include a plurality of inlets protruding from the top surface of the fluid shim element.
In some embodiments, the sample testing device further comprises a thermal pad member disposed on the bottom surface of the waveguide.
In some embodiments, a method is provided. The method may comprise applying an antibody solution through a sample channel of a sample testing device; and injecting a sample medium through the sample channel.
In some embodiments, the method may comprise, prior to injecting the sample medium: after an incubation period following the application of the antibody solution, a buffer solution is applied through the sample channel.
In some embodiments, after injection of the sample medium, the method may comprise: a cleaning solution is applied through the sample channel.
In some embodiments, a computer-implemented method is provided. The method may include: receiving first interference fringe data for an unidentified sample medium; calculating at least one statistical metric based on the first interference fringe data; comparing the at least one statistical metric to one or more statistical metrics associated with one or more identified media; and determining sample identity data based on the at least one statistical metric and the one or more statistical metrics.
In some embodiments, the at least one statistical metric may include one or more of the following: the sum associated with the first fringe data, the mean associated with the first fringe data, the standard deviation associated with the first fringe data, the skewness associated with the first fringe data (skewness), or the Kurtosis value associated with the first fringe data.
In some embodiments, the computer-implemented method may include: receiving second interference fringe data for the identified reference medium; calculating a plurality of statistical measures based on the second interference fringe data; and storing the plurality of statistical measures in a database.
In some embodiments, comparing the at least one statistical metric to the one or more statistical metrics may include: it is determined whether a difference between the at least one statistical measure and the one or more statistical measures meets a threshold.
In some embodiments, the computer-implemented method may include: in response to determining that the difference between the at least one statistical metric and the one or more statistical metrics satisfies a threshold, sample identity data is determined based on the identity data of the identified reference medium associated with the one or more statistical metrics.
In some embodiments, the sample testing device may comprise: an analyzer device comprising a slot base and at least one optical window; and a sensor cartridge secured to the slot base, wherein the at least one optical window is aligned with one of an input window of the sensor cartridge or an output window of the sensor cartridge. In some embodiments, the sensor cartridge includes a substrate layer and a waveguide as described herein.
In some embodiments, the sensor cartridge may comprise: a substrate layer; a waveguide disposed on a top surface of the substrate layer; and a cladding layer disposed on the top surface of the waveguide.
In some embodiments, the waveguide may include at least one opening on a top surface of the waveguide.
In some embodiments, the cover layer may include at least one opening.
In some embodiments, the cover layer may be slidably attached to the waveguide.
In some embodiments, the sample testing device may comprise: a waveguide; and a sampler member disposed on the top surface of the waveguide, wherein the sampler member may include an anode element.
In some embodiments, the top surface of the waveguide may include a ground grid layer.
In some embodiments, the ground mesh layer may comprise a metallic material.
In some embodiments, the ground mesh layer may be connected to ground.
In some embodiments, the waveguide may include a cladding window layer disposed below the ground grid layer.
In some embodiments, the waveguide may include a light shielding layer disposed below the cladding window layer.
In some embodiments, the waveguide may include a planar layer disposed below the light shielding layer.
In some embodiments, the waveguide may include a waveguide core layer disposed below the planar layer.
In some embodiments, the waveguide may include a cladding layer disposed below the waveguide core layer.
In some embodiments, the waveguide may include a substrate layer disposed below the cladding layer.
In some embodiments, a sample testing device may include a housing component including at least one airflow opening element; and a base component including a blower element corresponding to the at least one airflow opening element, wherein the blower element is configured to direct air to the waveguide.
In some embodiments, the waveguide may be disposed on an inner surface of the base member.
In some embodiments, the sample testing device may comprise: an aerosol sampler member disposed on an inner surface of the base member and connecting the blower element with the waveguide.
In some embodiments, the base component may include a power plug element.
In some embodiments, the sample testing device comprises: a pump; a first valve connected to the pump and the first flow passage; and a buffer circuit connected to the first valve and the second valve.
In some embodiments, the first valve and the second valve are 2-configuration 6-port valves. In some embodiments, the pump is connected to the fifth port of the first valve. In some embodiments, the first flow channel is connected to a sixth port of the first valve.
In some embodiments, the fifth port of the first valve is connected to the sixth port of the first valve when the first valve is in the first configuration. In some embodiments, the pump is configured to provide the buffer solution to the first flow channel through the first valve when the first valve is in the first configuration.
In some embodiments, the fifth port of the first valve is connected to the fourth port of the first valve when the first valve is in the second configuration. In some embodiments, the fourth port of the first valve is connected to the first port of the first valve through a first sample loop.
In some embodiments, the first sample loop comprises a first fluid. In some embodiments, the pump is configured to inject the first fluid into the first flow channel when the first valve is in the second configuration.
In some embodiments, the second valve is connected to the second flow channel. In some embodiments, the second valve comprises a second sample loop. In some embodiments, the second sample loop comprises a second fluid. In some embodiments, the pump is configured to inject a first test liquid into the first flow channel and simultaneously inject a second test liquid into the second flow channel.
In some embodiments, the sample testing device further comprises: a processor configured to align the laser source with the waveguide by moving the laser source or an optical element refracting or reflecting therefrom in a vertical dimension until a change in back reflected power from the surface is detected, wherein a characteristic reflectivity of the dielectric embedded with the waveguide is used as a signal indicating when the laser is incident on the film; and moving the laser source or an optical element refracted or reflected therefrom in a horizontal dimension in a direction indicated by the pattern of light diffracted to either side of the target area from a grating formed in the waveguide for coupling into the main function waveguide, the position or spatial frequency of the grating being different on one side of the target than the other. In some embodiments, a method for aligning a laser source with a waveguide includes: aiming a laser beam emitted by a laser source at a waveguide mount; and moving the laser source upward in a vertical dimension until at least one grating coupler spot formed by the laser beam reflected from the grating coupler in the waveguide is detected via the imaging component.
In some embodiments, the waveguide is disposed on a top surface of the waveguide mount. In some embodiments, a fluid cap is disposed on the top surface of the waveguide.
In some embodiments, the reflectivity of the waveguide mount is higher than the reflectivity of the waveguide.
In some embodiments, the waveguide includes an optical channel and a plurality of alignment channels. In some embodiments, each alignment channel of the plurality of alignment channels includes at least one grating coupler.
In some embodiments, the method for aligning a laser source with a waveguide further comprises: the laser source is caused to move in a horizontal dimension based at least in part on the spatial frequency associated with the at least one grating coupler spot.
In some embodiments, a method for aligning a laser source with a waveguide includes: aiming a laser beam emitted by a laser source at a waveguide mount; and moving the laser source upward in the vertical dimension until the back reflected signal power from the laser beam detected by the photodiode meets a threshold.
In some embodiments, the waveguide is configured to receive a sample medium comprising a non-viral indicator of a biological component (biological content) and a viral indicator of the biological component. In some embodiments, the sample testing device further comprises: a processor configured to determine whether the concentration level of the non-viral indicator of the biological component meets a threshold. In some embodiments, a method comprises: detecting a concentration level of a non-viral indicator of a biological component; and determining whether the concentration level of the non-viral indicator of the biological component meets a threshold.
In some embodiments, in response to determining that the concentration level of the non-viral indicator of the biological component meets a threshold, the method further comprises detecting the concentration level of the viral indicator of the biological component.
In some embodiments, in response to determining that the concentration level of the non-viral indicator of the biological component does not meet the threshold, the method further comprises transmitting a warning signal.
In some embodiments, a method comprises: detecting a concentration level of a non-viral indicator of the biological component, detecting a concentration level of a viral indicator of the biological component, and calculating a comparative concentration level of a viral indicator of the biological component.
In some embodiments, the sample testing device comprises: a waveguide platform; an aiming control mount disposed on a top surface of the waveguide platform; and a waveguide base disposed on a top surface of the waveguide platform.
In some embodiments, the waveguide base comprises a waveguide. In some embodiments, the aiming control mount includes a laser source. In some embodiments, the aiming control mount is configured to align the laser source with an input end of the waveguide.
In some embodiments, the aiming control base includes at least one electromagnetic actuator configured to control at least one of pitch or roll of the aiming control base.
In some embodiments, the aiming control mount includes a scanning element.
In some embodiments, a waveguide cassette includes a waveguide, a flow channel plate disposed on a top surface of the waveguide, a cassette body disposed on a top surface of the flow channel plate, a fluid cap disposed on a top surface of the cassette body, and a cassette cover disposed on a top surface of the fluid cap.
In some embodiments, the cartridge body includes a plurality of ports disposed on a bottom surface of the cartridge body, wherein each of the plurality of ports is connected to at least one flow channel defined by a flow channel plate.
In some embodiments, the cartridge body includes a buffer reservoir, a reference port, a sample port, and a drain chamber.
In some embodiments, the system includes an evaporator unit and a condenser unit. In some embodiments, the evaporator unit includes an evaporator coil connected to the compressor and to a condenser coil of the condenser unit. In some embodiments, the evaporator unit includes a condensate tray positioned below the evaporator coil and configured to receive the condensed liquid. In some embodiments, the condenser unit comprises a sample collection device connected to the condensate tray.
In some embodiments, the evaporator coil includes one or more hydrophobic layers.
In some embodiments, the sample collection device stores a buffer solution.
According to various examples of the present disclosure, a method for manufacturing a waveguide device is provided. In some embodiments, the method comprises: forming a thermal silicon dioxide layer on a silicon wafer; forming a stress reducing pattern on the thermal silicon dioxide layer, wherein the stress reducing pattern comprises a plurality of polygonal pattern units; and forming a silicon nitride film on the stress reducing pattern.
In some embodiments, when forming the thermal silicon dioxide layer, the method further comprises thermally oxidizing the silicon wafer.
In some embodiments, when forming the stress-reducing pattern on the thermal silicon dioxide layer, the method further comprises: the thermal silicon dioxide layer is etched according to the stress reduction pattern.
In some implementations, the etch depth associated with the stress reduction pattern is based at least in part on a film depth associated with the silicon nitride film.
In some embodiments, after forming the silicon nitride film on the stress-reducing pattern, the method further comprises: forming a single mode region on the silicon nitride film; and forming at least one waveguide rib in an analysis window portion of the silicon nitride film.
In some embodiments, the distance between the pattern edge of the stress reduction pattern and the analysis window edge of the analysis window portion is at least 250 microns.
In some embodiments, when forming the silicon nitride film, the method further comprises: the silicon nitride film is fabricated based at least in part on a Low Pressure Chemical Vapor Deposition (LPCVD) process.
According to various embodiments of the present disclosure, a parallel flow multichannel pathogen sensing system is provided. In some embodiments, a parallel flow multichannel pathogen sensing system includes: a multichannel peristaltic pump including a plurality of pump flow channel tubes through which the buffer solution flows; a sample valve array comprising a plurality of sample valves, wherein each of the plurality of sample valves comprises a buffer solution injection port for receiving a buffer solution and a sensing channel connection port connected to a sensing channel input port on the waveguide fluidic assembly; and a waveguide fluidic assembly including a parallel flow microfluidic cover defining a plurality of sensing channel input ports.
In some embodiments, a multichannel peristaltic pump includes: a pump frame; and a plurality of pump wheels fixed to the pump frame, wherein a plurality of pump pipes are provided on the plurality of pump wheels.
In some embodiments, the parallel flow multichannel pathogen sensing system further comprises: a multi-channel flow sensor array comprising a plurality of flow sensor input ports and a plurality of flow sensor output ports, wherein a plurality of pump tubes are connected to the plurality of flow sensor input ports.
In some embodiments, a waveguide fluidic component comprises: a thermal control sensor base; a multichannel waveguide sensor disposed on top of the thermal control sensor base, wherein a parallel flow microfluidic cover is disposed on top of the multichannel waveguide sensor.
In some embodiments, a waveguide fluidic component comprises: at least one of a heater component, a cooler component, or a dual function heater-cooler component.
In some embodiments, a waveguide fluidic component comprises: a spacer secured to a bottom surface of the parallel flow microfluidic cover, wherein the spacer is aligned with the multichannel waveguide sensor.
In some embodiments, the parallel flow multichannel pathogen sensing system further comprises: a fiber array comprising a plurality of array fibers, wherein the plurality of array fibers are aligned with an optical input of a multi-channel waveguide sensor.
In some embodiments, the parallel flow multichannel pathogen sensing system further comprises: a tunable laser diode emitting laser light; and a fiber coupler that receives the laser light and provides the laser light to the fiber array via a coupler input fiber.
According to various embodiments of the present disclosure, a dual flow viral particle filtration device is provided. In some embodiments, a dual flow viral particle filtration device comprises: a filter base defining a circular flow channel; a pass-through filter ring disposed over the circular flow channel; and a blocking filter ring disposed on the circular flow channel and positioned within the pass-through filter ring.
In some embodiments, the dual-flow viral particle filtration apparatus further comprises: a filter cover disposed on top of the filter base and covering the circular flow channels.
In some embodiments, the filter cover defines a flow input opening and a flow output opening.
In some embodiments, the flow input opening is positioned within the pass-through filter ring and within the barrier filter ring. In some embodiments, the flow output opening is positioned between the pass-through filter ring and the barrier filter ring.
In some embodiments, the sample solution flows into the circular flow channel through the flow input opening and out of the circular flow channel through the flow output opening.
In some embodiments, the barrier filter ring includes a barrier filter membrane that prevents particles in the sample solution associated with a diameter greater than a barrier filter threshold from flowing through the barrier filter ring.
In some embodiments, the blocking filter threshold is 130 nanometers.
In some embodiments, the pass-through filter ring includes a pass-through filter membrane that prevents particles in the sample solution associated with a diameter greater than a pass-through filter threshold from flowing through the pass-through filter ring.
In some embodiments, the pass filter threshold is 70 nanometers.
According to various embodiments of the present disclosure, a sample testing method is provided. In some embodiments, the sample testing method comprises: coating a plurality of sample channels with antibodies associated with one or more antibody types; inputting one or more sample solutions into the plurality of sample channels; and receiving a plurality of sample detection signals corresponding to the plurality of sample channels.
In some embodiments, the one or more sample solutions consist of a sample solution. In some embodiments, the one or more antibody types include a plurality of antibody types. In some embodiments, the sample testing method further comprises: a determination is made as to whether the sample solution is associated with one or more of a plurality of sample types corresponding to the plurality of antibody types based at least in part on the plurality of sample detection signals.
In some embodiments, the one or more sample solutions comprise a plurality of sample solutions. In some embodiments, the one or more antibody types consist of antibody types. In some embodiments, the sample testing method further comprises: based at least in part on the plurality of sample detection signals, it is determined whether any of the plurality of sample solutions are associated with a sample type corresponding to the antibody type.
In some embodiments, the one or more sample solutions comprise n sample solutions. In some embodiments, the one or more antibody types include n antibody types. In some embodiments, the sample testing method further comprises: determining whether any of the n sample solutions are associated with one or more sample types corresponding to any of the n antibody types based at least in part on the plurality of sample detection signals.
In some embodiments, the one or more sample solutions comprise n sample solutions. In some embodiments, the one or more antibody types include 2n antibody types. In some embodiments, the sample testing method further comprises: determining whether any of the n sample solutions are associated with one or more sample types corresponding to any of the 2n antibody types based at least in part on the plurality of sample detection signals.
In some embodiments, the one or more sample solutions comprise 2n sample solutions. In some embodiments, the one or more antibody types include n antibody types. In some embodiments, the sample testing method further comprises: determining whether any of the 2n sample solutions is associated with one or more sample types corresponding to any of the n antibody types based at least in part on the plurality of sample detection signals.
In some embodiments, the one or more sample solutions comprise 2n sample solutions. In some embodiments, the one or more antibody types include 2n antibody types. In some embodiments, the sample testing method further comprises: determining whether any of the 2n sample solutions is associated with one or more sample types corresponding to any of the 2n antibody types based at least in part on the plurality of sample detection signals.
According to various embodiments of the present disclosure, a precision shim is provided. In some embodiments, the precision shim comprises: a plurality of alignment ribs on an outer surface of the precision shim; and a plurality of channel cover portions located between the plurality of alignment ribs.
In some embodiments, the plurality of alignment ribs are positioned based on a plurality of alignment grooves on the parallel flow microfluidic cover.
In some embodiments, the plurality of channel cover portions define a plurality of chevron patterns on an inner surface of the precision shim.
In some embodiments, the inner surface of the precision shim is opposite the outer surface of the precision shim.
In some embodiments, each of the plurality of channel cover portions defines a flow channel input opening and a flow channel output opening.
According to various embodiments of the present disclosure, a flow rate compensator is provided. In some embodiments, the flow rate compensator comprises: a fluid housing defining a solution reservoir; a membrane covering the solution reservoir; and at least one actuator disposed on an outer surface of the membrane and electrically coupled to the flow controller.
In some embodiments, the solution reservoir defines a reservoir input opening. In some embodiments, the input fluid conduit is connected to the reservoir input opening.
In some embodiments, the flow rate compensator comprises: an input fluid fitting secured to the fluid housing. In some embodiments, the input fluid conduit is positioned within the input fluid fitting.
In some embodiments, the solution reservoir defines a reservoir output opening. In some embodiments, the output fluid conduit is connected to the reservoir output opening.
In some embodiments, the flow rate compensator further comprises: an output fluid fitting secured to the fluid housing. In some embodiments, the output fluid conduit is positioned within the output fluid fitting.
In some embodiments, the output fluid conduit is connected to a flow meter. In some embodiments, a flow meter is coupled to the flow controller and transmits a flow rate signal to the flow controller.
In some embodiments, the flow controller is configured to: determining at least one flow rate adjustment signal based on the flow rate signal; and transmitting the at least one flow rate adjustment signal to the at least one actuator.
In some embodiments, the at least one actuator is configured to: at least one deformation of the membrane is caused based at least in part on the at least one flow rate adjustment signal.
According to various embodiments of the present disclosure, an edge optical coupling waveguide device is provided. In some embodiments, the edge light coupling waveguide device includes a top light pipe; and a bottom light pipe positioned below the top light pipe, wherein a top light pipe length associated with the top light pipe is shorter than a bottom light pipe length associated with the bottom light pipe.
In some embodiments, the bottom surface of the bottom light pipe mates with the top surface of the silicon nitride waveguide.
In some embodiments, the top light pipe includes two curved side surfaces.
In some embodiments, the bottom light pipe includes two curved side surfaces.
The foregoing exemplary summary, as well as other exemplary objects and/or advantages of the present disclosure, and the manner in which the same are accomplished, is further explained in the following detailed description and the accompanying drawings thereof.
Drawings
The description of the illustrative examples may be read in connection with the accompanying drawings. It will be appreciated that for simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn to scale, unless otherwise indicated. For example, the dimensions of some of the elements or components may be exaggerated relative to other elements unless indicated otherwise. Examples of the teachings of the present disclosure are illustrated and described with respect to the figures presented herein, wherein:
FIG. 1 illustrates an exemplary block diagram of an exemplary sample testing device according to various examples of the present disclosure;
FIG. 2 illustrates an exemplary sample testing device including an exemplary waveguide according to various examples of the present disclosure;
FIG. 3 illustrates an exemplary diagram showing exemplary variations of evanescent waves according to various examples of the present disclosure;
FIG. 4 illustrates an exemplary perspective view of an exemplary sample testing device according to various examples of the present disclosure;
FIG. 5 illustrates an exemplary side cross-sectional view of the exemplary sample testing device of FIG. 4, according to various examples of the present disclosure;
FIG. 6 illustrates an exemplary perspective view of an exemplary sample testing device according to various examples of the present disclosure;
FIG. 7 illustrates an exemplary side cross-sectional view of the exemplary sample testing device of FIG. 6 in accordance with various examples of the present disclosure;
FIG. 8 illustrates an exemplary diagram of an exemplary lens array according to various examples of the present disclosure;
FIG. 9 illustrates an exemplary diagram of an exemplary lens array according to various examples of the present disclosure;
FIG. 10 illustrates an exemplary perspective view of an exemplary sample testing device according to various examples of the present disclosure;
FIG. 11 illustrates an exemplary side cross-sectional view of the exemplary sample testing device of FIG. 10 in accordance with various examples of the present disclosure;
FIG. 12 illustrates an exemplary perspective view of an exemplary sample testing device according to various examples of the present disclosure;
FIG. 13 illustrates an exemplary side cross-sectional view of the exemplary sample testing device of FIG. 12, according to various examples of the present disclosure;
FIG. 14 illustrates an exemplary perspective view of an exemplary sample testing device according to various examples of the present disclosure;
FIG. 15 illustrates an exemplary side cross-sectional view of an exemplary sample testing device according to various examples of the present disclosure;
FIG. 16A illustrates an exemplary perspective view of an exemplary mobile point-of-care component according to various examples of the present disclosure;
FIG. 16B illustrates an exemplary top view of the exemplary mobile point-of-care component of FIG. 16A in accordance with various examples of the present disclosure;
FIG. 16C illustrates an exemplary side cross-sectional view of the exemplary mobile point-of-care component of FIG. 16A in accordance with various examples of the present disclosure;
FIG. 17 illustrates an exemplary perspective view of an exemplary thermally controlled waveguide enclosure according to various examples of the present disclosure;
FIG. 18 illustrates an exemplary side cross-sectional view of an exemplary thermally controlled waveguide housing according to various examples of the present disclosure;
FIG. 19 illustrates an exemplary perspective view of an exemplary waveguide according to various examples of the present disclosure;
FIG. 20A illustrates an exemplary side cross-sectional view of an exemplary waveguide according to various examples of the present disclosure;
FIG. 20B illustrates an exemplary side cross-sectional view of an exemplary waveguide according to various examples of the present disclosure;
FIG. 21 illustrates an exemplary perspective view of an exemplary waveguide according to various examples of the present disclosure;
FIG. 22 illustrates an exemplary top view of an exemplary waveguide according to various examples of the present disclosure;
FIG. 23 illustrates an exemplary side view of an exemplary waveguide according to various examples of the present disclosure;
FIG. 24 illustrates an exemplary method for providing an exemplary waveguide according to various examples of the present disclosure;
FIG. 25 illustrates an exemplary view of a portion of an exemplary sample testing device according to various examples of the present disclosure;
FIG. 26 illustrates an exemplary view of a portion of an exemplary sample testing device according to various examples of the present disclosure;
FIG. 27 illustrates an exemplary view of a portion of an exemplary sample testing device according to various examples of the present disclosure;
FIG. 28A illustrates an exemplary view of an exemplary sample testing device according to various examples of the present disclosure;
FIG. 28B illustrates an exemplary view of an exemplary sample testing device according to various examples of the present disclosure;
FIG. 29 illustrates an exemplary view of an exemplary sample testing device according to various examples of the present disclosure;
FIG. 30 illustrates a portion of an exemplary waveguide according to various examples of the present disclosure;
FIG. 31 illustrates a portion of an exemplary waveguide according to various examples of the present disclosure;
FIG. 32 illustrates a portion of an exemplary waveguide according to various examples of the present disclosure;
FIG. 33A illustrates a portion of an exemplary waveguide according to various examples of the present disclosure;
FIG. 33B illustrates a portion of an exemplary waveguide according to various examples of the present disclosure;
FIG. 34 illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 35A illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 35B illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 36 illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 37 illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 38 illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 39A illustrates an exemplary waveguide retainer component according to various examples of the present disclosure;
FIG. 39B illustrates an exemplary waveguide retainer component according to various examples of the present disclosure;
FIG. 39C illustrates an exemplary waveguide retainer component according to various examples of the present disclosure;
FIG. 40A illustrates an exemplary waveguide according to various examples of the present disclosure;
FIG. 40B illustrates an exemplary waveguide according to various examples of the present disclosure;
FIG. 40C illustrates an exemplary waveguide according to various examples of the present disclosure;
FIG. 41A illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 41B illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 42A illustrates an exemplary waveguide according to various examples of the present disclosure;
FIG. 42B illustrates an exemplary waveguide according to various examples of the present disclosure;
FIG. 42C illustrates an exemplary waveguide according to various examples of the present disclosure;
FIG. 42D illustrates an exemplary waveguide according to various examples of the present disclosure;
FIG. 43 illustrates an exemplary graphical visualization according to various examples of the present disclosure;
FIG. 44 illustrates an exemplary graphical visualization according to various examples of the present disclosure;
FIG. 45 illustrates an example block diagram of an example apparatus for sensing and/or processing in accordance with various examples of this disclosure;
FIG. 46 illustrates an example block diagram of an example apparatus for sensing and/or processing in accordance with various examples of this disclosure;
FIG. 47 illustrates an exemplary flowchart showing exemplary operations according to various examples of the present disclosure;
FIG. 48 illustrates an exemplary flowchart showing exemplary operations according to various examples of the present disclosure;
FIG. 49 illustrates an exemplary flowchart showing exemplary operations according to various examples of the present disclosure;
FIG. 50 illustrates an exemplary flowchart showing exemplary operations according to various examples of the present disclosure;
FIG. 51 illustrates an exemplary flowchart showing exemplary operations according to various examples of the present disclosure;
FIG. 52 illustrates an exemplary flowchart showing exemplary operations according to various examples of the present disclosure;
FIG. 53 illustrates an exemplary flowchart showing exemplary operations according to various examples of the present disclosure;
FIG. 54 illustrates an exemplary flowchart showing exemplary operations according to various examples of the present disclosure;
FIG. 55 illustrates an exemplary infrastructure according to various examples of the present disclosure;
FIG. 56 illustrates an exemplary flow chart according to various examples of the present disclosure;
FIG. 57 illustrates an exemplary flow chart according to various examples of the present disclosure;
FIG. 58 illustrates an exemplary flow chart according to various examples of the present disclosure;
FIG. 59 illustrates an exemplary exploded view of an exemplary sensor cartridge according to various examples of the present disclosure;
FIG. 60A illustrates an exemplary view of an exemplary sensor cartridge according to various examples of the present disclosure;
FIG. 60B illustrates an exemplary view of an exemplary sensor cartridge according to various examples of the present disclosure;
FIG. 61A illustrates an exemplary view of an exemplary sensor cartridge according to various examples of the present disclosure;
FIG. 61B illustrates an exemplary view of an exemplary sensor cartridge according to various examples of the present disclosure;
FIG. 62 illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 63A illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 63B illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 63C illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 64A illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 64B illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 64C illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 65A illustrates a portion of an exemplary sample testing device according to various examples of the present disclosure;
FIG. 65B illustrates a portion of an exemplary sample testing device according to various examples of the present disclosure;
FIG. 66A illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 66B illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 66C illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 66D illustrates an exemplary sample testing device according to various examples of the present disclosure;
FIG. 67A illustrates exemplary components associated with an exemplary sample testing device according to various examples of the present disclosure;
FIG. 67B illustrates exemplary components associated with an exemplary sample testing device according to various examples of the present disclosure;
FIG. 68 illustrates an exemplary diagram showing an exemplary sample testing device according to various examples of the present disclosure;
FIG. 69A illustrates an exemplary perspective view associated with an exemplary sample testing device according to various examples of the present disclosure;
FIG. 69B illustrates an exemplary exploded view associated with an exemplary sample testing device according to various examples of the present disclosure;
FIG. 70A illustrates an exemplary perspective view of exemplary components associated with an exemplary sample testing device according to various examples of the present disclosure;
FIG. 70B illustrates an exemplary top view of exemplary components associated with an exemplary sample testing device according to various examples of the present disclosure;
FIG. 70C illustrates an example side view of example components associated with an example sample testing device according to various examples of this disclosure;
FIG. 70D illustrates an example side view of example components associated with an example sample testing device according to various examples of this disclosure;
FIG. 71 illustrates an exemplary graph showing exemplary raw response signals from an exemplary sample testing device according to various examples of the present disclosure;
FIG. 72 illustrates an exemplary graph showing exemplary normalized response signals from an exemplary sample testing device according to various examples of the present disclosure;
FIG. 73A illustrates an exemplary cross-sectional side view associated with at least a portion of an exemplary sample testing device and an exemplary laser alignment device according to various examples of the present disclosure;
FIG. 73B illustrates an exemplary cross-sectional side view associated with at least a portion of an exemplary sample testing device and an exemplary laser alignment device according to various examples of the present disclosure;
FIG. 73C illustrates an exemplary cross-sectional side view associated with at least a portion of an exemplary sample testing device and an exemplary laser alignment device according to various examples of the present disclosure;
FIG. 74 illustrates an exemplary top view associated with at least a portion of an exemplary sample testing device according to various examples of the present disclosure;
FIG. 75A illustrates an exemplary top view associated with at least a portion of an exemplary sample testing device and an exemplary laser alignment device according to various examples of the present disclosure;
FIG. 75B illustrates an exemplary top view associated with at least a portion of an exemplary sample testing device and an exemplary laser alignment device according to various examples of the present disclosure;
FIG. 76A illustrates an exemplary cross-sectional side view associated with at least a portion of an exemplary sample testing device and an exemplary laser alignment device according to various examples of the present disclosure;
FIG. 76B illustrates an exemplary cross-sectional side view associated with at least a portion of an exemplary sample testing device and an exemplary laser alignment device according to various examples of the present disclosure;
FIG. 76C illustrates an exemplary cross-sectional side view associated with at least a portion of an exemplary sample testing device and an exemplary laser alignment device according to various examples of the present disclosure;
FIG. 77 illustrates an exemplary graph showing exemplary signals from an exemplary laser alignment device according to various examples of the present disclosure;
FIG. 78 illustrates an exemplary top view associated with at least a portion of an exemplary sample testing device according to various examples of the present disclosure;
FIG. 79A illustrates an exemplary top view associated with at least a portion of an exemplary sample testing device and an exemplary laser alignment device according to various examples of the present disclosure;
FIG. 79B illustrates an exemplary top view associated with at least a portion of an exemplary sample testing device and an exemplary laser alignment device according to various examples of the present disclosure;
FIG. 80 illustrates an exemplary diagram showing exemplary flow channels and exemplary non-viral indicators of biological components and exemplary viral indicators of biological components according to various examples of the present disclosure;
FIG. 81 illustrates an exemplary diagram showing an exemplary method according to various examples of the present disclosure;
FIG. 82 illustrates an exemplary diagram showing an exemplary method according to various examples of the present disclosure;
FIG. 83A illustrates an exemplary perspective view of a sample testing device according to various examples of the present disclosure;
FIG. 83B illustrates another exemplary perspective view of a sample testing device according to various examples of the present disclosure;
FIG. 83C illustrates an exemplary side view of a sample testing device according to various examples of the present disclosure;
FIG. 83D illustrates an exemplary top view of a sample testing device according to various examples of the present disclosure;
FIG. 83E illustrates an exemplary cross-sectional view of a sample testing device according to various examples of the present disclosure;
fig. 84A illustrates an exemplary perspective view of an aiming control base in accordance with various examples of the present disclosure;
Fig. 84B illustrates another exemplary perspective view of an aiming control base in accordance with various examples of the present disclosure;
Fig. 84C illustrates an exemplary side view of an aiming control base according to various examples of the present disclosure;
Fig. 84D illustrates an exemplary top view of an aiming control base according to various examples of the present disclosure;
FIG. 85A illustrates an exemplary perspective view of a scanning element according to various examples of the present disclosure;
FIG. 85B illustrates another exemplary exploded view of a scanning element according to various examples of the present disclosure;
FIG. 85C illustrates another exemplary exploded view of a scanning element according to various examples of the present disclosure;
FIG. 85D illustrates an exemplary side view of a scanning element according to various examples of the present disclosure;
FIG. 85E illustrates an exemplary perspective view of a resonant bending component according to various examples of the present disclosure;
Fig. 86A illustrates an exemplary perspective view of a waveguide box according to various examples of the present disclosure;
Fig. 86B illustrates an exemplary perspective view of a waveguide box according to various examples of the present disclosure;
fig. 86C illustrates an exemplary exploded view of a waveguide enclosure according to various examples of the present disclosure;
fig. 86D illustrates an exemplary top view of a waveguide box according to various examples of the present disclosure;
fig. 86E illustrates an exemplary side view of a waveguide box according to various examples of the present disclosure;
Fig. 86F illustrates an exemplary bottom view of a waveguide box according to various examples of the present disclosure;
FIG. 87A illustrates an exemplary perspective view of a waveguide according to various examples of the present disclosure;
FIG. 87B illustrates an exemplary top view of a waveguide according to various examples of the present disclosure;
FIG. 87C illustrates an exemplary side view of a waveguide according to various examples of the present disclosure;
FIG. 88A illustrates an exemplary perspective view of a flow channel plate according to various examples of the present disclosure;
FIG. 88B illustrates an exemplary top view of a flow channel plate according to various examples of the present disclosure;
FIG. 88C illustrates an exemplary cross-sectional view of a flow channel plate according to various examples of the present disclosure;
fig. 88D illustrates an exemplary side view of a flow channel plate according to various examples of the present disclosure;
Fig. 89A illustrates an exemplary perspective view of a cartridge body according to various examples of the present disclosure;
Fig. 89B illustrates an exemplary perspective view of a cartridge body 8900 according to various examples of the present disclosure;
Fig. 89C illustrates an exemplary top view of a cartridge body according to various examples of the present disclosure;
fig. 89D illustrates an exemplary bottom view of a cartridge body according to various examples of the present disclosure;
fig. 89E illustrates an exemplary side view of a cartridge body according to various examples of the present disclosure;
FIG. 90A illustrates an exemplary perspective view of a fluid cap according to various examples of the present disclosure;
FIG. 90B illustrates an exemplary perspective view of a fluid cap according to various examples of the present disclosure;
FIG. 90C illustrates an exemplary top view of a fluid cap according to various examples of the present disclosure;
FIG. 90D illustrates an exemplary side view of a fluid cap according to various examples of the present disclosure;
FIG. 90E illustrates an exemplary bottom view of a fluid cap according to various examples of the present disclosure;
FIG. 91A illustrates an exemplary perspective view of an exhaust filter according to various examples of the present disclosure;
FIG. 91B illustrates an exemplary side view of an exhaust filter according to various examples of the present disclosure;
FIG. 91C illustrates an exemplary bottom view of an exhaust filter according to various examples of the present disclosure;
fig. 92A illustrates an exemplary perspective view of a lid according to various examples of the present disclosure;
Fig. 92B illustrates an exemplary top view of a lid according to various examples of the present disclosure;
FIG. 92C illustrates an exemplary side view of a lid according to various examples of the present disclosure;
FIG. 93A illustrates an example block diagram of an example system in accordance with various examples of this disclosure;
FIG. 93B illustrates an example block diagram of an example system in accordance with various examples of this disclosure;
94A, 94B, 94C, 94D and 94E illustrate an exemplary sample testing device 9400 according to various embodiments of the present disclosure;
95A, 95B, 95C, 95D, 95E, 95F, 95G, 95H, 95I and 95J illustrate exemplary sample testing devices according to various embodiments of the present disclosure;
96A, 96B, and 96C illustrate exemplary multiport valves according to various embodiments of the present disclosure;
FIGS. 97A and 97B illustrate an exemplary sample testing device according to various embodiments of the present disclosure;
FIGS. 98A, 98B, and 98C illustrate an exemplary multi-port valve according to various embodiments of the present disclosure;
99A and 99B illustrate an exemplary valve according to various embodiments of the present disclosure;
FIGS. 100A, 100B, and 100C illustrate an exemplary method for manufacturing a sample testing device according to various embodiments of the present disclosure;
FIG. 101 illustrates an exemplary sample testing device according to various embodiments of the present disclosure;
fig. 102A, 102B, 102C, 102D, and 102E illustrate exemplary waveguides according to various embodiments of the present disclosure;
Fig. 103A, 103B, 103C, and 103D illustrate exemplary waveguides;
FIGS. 104A, 104B, and 104C illustrate an exemplary sample testing device according to various embodiments of the present disclosure;
105A, 105B, 105C, 105D illustrate an exemplary light source coupler according to various embodiments of the present disclosure;
FIGS. 106A and 106B illustrate an exemplary fiber holder according to various embodiments of the present disclosure;
FIG. 107 illustrates an exemplary wave plate according to various embodiments of the present disclosure;
FIG. 108 illustrates an exemplary light source coupler according to various embodiments of the present disclosure;
FIGS. 109A, 109B, and 109C illustrate an exemplary microlens array according to various embodiments of the present disclosure;
FIG. 110 illustrates an exemplary method according to various embodiments of the present disclosure;
FIG. 111 illustrates an exemplary method according to various embodiments of the present disclosure;
FIGS. 112A and 112B provide exemplary diagrams of exemplary waveguides according to various embodiments of the present disclosure;
FIGS. 113A and 113B provide exemplary graphs illustrating exemplary signal amplitudes from channels in an exemplary waveguide according to various embodiments of the present disclosure;
FIGS. 114A and 114B provide exemplary graphs illustrating exemplary signal amplitudes from channels in an exemplary waveguide according to various embodiments of the present disclosure;
FIGS. 115A, 115B, and 115C provide exemplary graphs illustrating exemplary signal amplitudes from channels in an exemplary waveguide according to various embodiments of the present disclosure;
FIG. 116 provides an exemplary graph illustrating exemplary signal amplitudes from channels in an exemplary waveguide according to various embodiments of the present disclosure;
FIG. 117 provides an exemplary graph illustrating exemplary signal amplitudes from channels in an exemplary waveguide according to various embodiments of the present disclosure;
FIG. 118 provides an exemplary graph illustrating exemplary signal amplitudes from channels in an exemplary waveguide according to various embodiments of the present disclosure;
FIG. 119 provides an exemplary graph illustrating exemplary signal amplitudes from channels in an exemplary waveguide according to various embodiments of the present disclosure;
FIG. 120 provides an exemplary graph illustrating exemplary signal amplitudes from channels in an exemplary waveguide according to various embodiments of the present disclosure;
FIG. 121 provides an exemplary graph illustrating exemplary signal amplitudes from channels in an exemplary waveguide according to various embodiments of the present disclosure;
FIG. 122 illustrates an exemplary method according to various embodiments of the present disclosure;
FIG. 123 illustrates an exemplary method according to various embodiments of the present disclosure;
124A, 124B and 124C illustrate exemplary views of exemplary sample testing devices according to various embodiments of the present disclosure;
FIGS. 125A and 125B illustrate exemplary views of exemplary imager baffle components in accordance with various embodiments of the disclosure;
126A, 126B and 126C illustrate exemplary views of exemplary imager baffle components in accordance with various embodiments of the disclosure;
FIG. 127 illustrates an exemplary sample testing device according to various embodiments of the present disclosure;
FIG. 128 illustrates an exemplary system according to various embodiments of the present disclosure;
FIG. 129 illustrates an exemplary controller according to various embodiments of the present disclosure;
FIG. 130 illustrates an exemplary method according to various embodiments of the present disclosure;
FIG. 131 illustrates an exemplary graph according to various embodiments of the present disclosure;
FIG. 132 illustrates an exemplary method according to various embodiments of the present disclosure;
FIGS. 133A, 133B, and 133C illustrate exemplary methods according to various embodiments of the present disclosure;
FIG. 134A illustrates an exemplary sample testing device according to various embodiments of the present disclosure;
FIG. 134B illustrates an exemplary sample testing device according to various embodiments of the present disclosure;
FIG. 135A illustrates an exemplary side view of an exemplary sample testing device having an exemplary wavelength adjustment device according to various embodiments of the present disclosure;
FIG. 135B illustrates an exemplary cross-sectional view of an exemplary wavelength tuning device in accordance with various embodiments of the present disclosure;
FIG. 136 illustrates an exemplary block diagram of exemplary components associated with a wavelength adjustment device and an imaging device according to various embodiments of the present disclosure;
FIGS. 137A and 137B illustrate an exemplary method of operating a wavelength-tuning device in a continuous wavelength scanning mode according to some embodiments of the present disclosure;
FIG. 138 illustrates an exemplary method of operating a wavelength tuning device in a direct wavelength setting mode in accordance with various embodiments of the present disclosure;
FIG. 139 illustrates an exemplary graph showing data correlation between voltage value data and wavelength value data of an example voltage correlation data object in accordance with various embodiments of the present disclosure;
FIG. 140 illustrates an exemplary method of determining a sample type of a sample in a sample mixture according to various embodiments of the present disclosure;
FIG. 141 illustrates an exemplary block diagram showing exemplary components of a sample type determination device according to various embodiments of the present disclosure;
FIGS. 142A and 142B illustrate an exemplary method of determining a sample type associated with a sample according to various embodiments of the present disclosure;
FIG. 143A illustrates an exemplary perspective view of an exemplary waveguide according to various embodiments of the present disclosure;
FIG. 143B illustrates an exemplary enlarged view of at least a portion of an exemplary waveguide according to various embodiments of the present disclosure;
fig. 144A illustrates an exemplary exploded view of an exemplary waveguide enclosure according to various embodiments of the present disclosure;
Fig. 144B illustrates another exemplary exploded view of an exemplary waveguide enclosure according to various embodiments of the present disclosure;
fig. 144C illustrates an exemplary top view of an exemplary waveguide box according to various embodiments of the present disclosure;
fig. 144D illustrates an exemplary side view of an exemplary waveguide box according to various embodiments of the present disclosure;
fig. 144E illustrates an exemplary bottom view of an exemplary waveguide box according to various embodiments of the present disclosure;
fig. 144F illustrates an exemplary perspective view of an exemplary waveguide box according to various embodiments of the present disclosure;
fig. 144G illustrates an exemplary left side view of an exemplary waveguide box according to various embodiments of the present disclosure;
fig. 145A illustrates an exemplary top view of an exemplary cartridge body according to various embodiments of the present disclosure;
fig. 145B illustrates an exemplary bottom view of an exemplary cartridge body according to various embodiments of the present disclosure;
Fig. 145C illustrates an exemplary cross-sectional view of an exemplary cartridge body according to various embodiments of the present disclosure;
fig. 145D illustrates an exemplary perspective view of an exemplary cartridge body according to various embodiments of the present disclosure;
fig. 145E illustrates an exemplary perspective view of an exemplary cartridge body according to various embodiments of the present disclosure;
Fig. 145F illustrates an exemplary left side view of an exemplary cartridge body according to various embodiments of the present disclosure;
FIG. 146A illustrates an exemplary perspective view of an exemplary sample testing device according to various embodiments of the present disclosure;
FIG. 146B illustrates an exemplary enlarged view of at least a portion of an exemplary sample testing device according to various embodiments of the present disclosure;
FIG. 146C illustrates an exemplary side view of an exemplary sample testing device according to various embodiments of the present disclosure;
FIG. 146D illustrates another exemplary enlarged view of at least a portion of an exemplary sample testing device according to various embodiments of the present disclosure;
Fig. 147A illustrates an exemplary perspective view of an exemplary field lens (FIELD LENS) according to various embodiments of the present disclosure;
FIG. 147B illustrates an exemplary side view of an exemplary field lens according to various embodiments of the present disclosure;
FIG. 148 provides an exemplary schematic diagram illustrating an exemplary waveguide according to various embodiments of the present disclosure;
FIG. 149 provides an exemplary schematic diagram illustrating exemplary signal amplitudes from channels in an exemplary waveguide according to various embodiments of the present disclosure;
FIG. 150 provides another exemplary graph illustrating exemplary signal amplitudes from channels in an exemplary waveguide according to various embodiments of the present disclosure;
FIG. 151 provides yet another exemplary graph illustrating exemplary signal amplitudes from channels in an exemplary waveguide according to various embodiments of the present disclosure;
FIG. 152 illustrates an exemplary method according to various embodiments of the present disclosure;
FIG. 153 is an exemplary diagram illustrating exemplary interferometry sensing data modeled as an exemplary sine wave according to some embodiments of the present disclosure;
FIG. 154 is an exemplary diagram illustrating an exemplary interferometric sensing dataset in accordance with some embodiments of the present disclosure;
FIG. 155 is an exemplary diagram illustrating an exemplary interferometric sensing dataset in accordance with some embodiments of the present disclosure;
FIG. 156 is an exemplary diagram illustrating an exemplary interferometric sensing dataset in accordance with some embodiments of the present disclosure;
FIG. 157 illustrates an exemplary method according to some embodiments of the present disclosure;
FIG. 158 provides an exemplary diagram of an exemplary interferometry sensing dataset and an exemplary linearized interferometry sensing dataset according to some embodiments of the present disclosure;
Fig. 159A, 159B, and 159C illustrate exemplary fluid caps;
FIGS. 160A, 160B, and 160C illustrate exemplary fluid caps according to some embodiments of the present disclosure;
161A, 161B, and 161C illustrate flow rates associated with an exemplary fluid cap according to some embodiments of the present disclosure; and
Fig. 162A, 162B, 162C, 162D, 162E, and 162F illustrate exemplary components associated with an exemplary sample testing device according to some embodiments of the present disclosure.
FIG. 163 illustrates an exemplary waveguide;
FIG. 164 illustrates an exemplary waveguide fabricated in accordance with some embodiments of the present disclosure;
FIG. 165 illustrates an exemplary portion of an exemplary waveguide fabricated in accordance with some embodiments of the present disclosure;
Fig. 166A, 166B, 166C illustrate an exemplary method according to some embodiments of the present disclosure;
FIG. 167 illustrates an exemplary parallel flow multichannel pathogen sensing system according to some embodiments of the disclosure;
Fig. 168 illustrates an exemplary cross-sectional view of an exemplary multichannel peristaltic pump according to some embodiments of the present disclosure;
fig. 169A and 169B illustrate exemplary views associated with an exemplary multichannel peristaltic pump according to some embodiments of the present disclosure;
FIGS. 170A and 170B illustrate exemplary cross-sectional views associated with an exemplary multichannel peristaltic pump in accordance with some embodiments of the present disclosure;
FIG. 171A illustrates an exemplary view of an exemplary sample injection valve array according to some embodiments of the present disclosure;
FIG. 171B illustrates an exemplary exploded view of an exemplary sample injection valve array, according to some embodiments of the present disclosure;
FIG. 172A illustrates an exemplary block diagram of an exemplary sample valve array according to some embodiments of the present disclosure;
FIG. 172B illustrates an exemplary block diagram of an exemplary sample valve array according to some embodiments of the present disclosure;
FIG. 173A illustrates an exemplary exploded view of an exemplary waveguide fluid assembly according to some embodiments of the present disclosure;
fig. 173B illustrates an exemplary top view of an exemplary waveguide fluidic assembly according to some embodiments of the present disclosure;
Fig. 173C illustrates an exemplary perspective view of an exemplary waveguide fluidic assembly according to some embodiments of the present disclosure;
FIG. 174 illustrates an exemplary top view of an exemplary shim and an exemplary waveguide according to some embodiments of the present disclosure;
Fig. 175A illustrates an exemplary perspective view of an exemplary waveguide according to some embodiments of the present disclosure;
Fig. 175B illustrates an example top view of an example waveguide according to some embodiments of the present disclosure;
FIG. 176A illustrates an exemplary perspective view of an exemplary dual-flow viral particle filtration device according to some embodiments of the present disclosure;
FIG. 176B illustrates an exemplary exploded view of an exemplary dual-flow viral particle filtration device according to some embodiments of the present disclosure;
FIG. 176C illustrates an exemplary top view of at least an exemplary portion of an exemplary dual-flow viral particle filtration device according to some embodiments of the present disclosure;
FIG. 177 illustrates an exemplary top view of at least an exemplary portion of an exemplary dual-flow viral particle filtration device according to some embodiments of the present disclosure;
FIG. 178A illustrates an exemplary exploded view of at least an exemplary portion of an exemplary parallel flow multi-channel pathogen sensing system according to some embodiments of the present disclosure;
FIG. 178B illustrates an exemplary exploded view of at least an exemplary portion of an exemplary parallel flow multi-channel pathogen sensing system according to some embodiments of the present disclosure;
FIG. 179A illustrates an exemplary exploded view of an exemplary fluid cap and an exemplary multi-channel waveguide sensor, according to some embodiments of the present disclosure;
FIG. 179B illustrates an exemplary perspective view of an exemplary fluid cap and an exemplary multi-channel waveguide sensor, according to some embodiments of the present disclosure;
FIG. 180A illustrates an exemplary top view of an exemplary fluid cap and an exemplary multi-channel waveguide sensor, according to some embodiments of the present disclosure;
FIG. 180B illustrates an exemplary bottom view of an exemplary multi-channel waveguide sensor according to some embodiments of the present disclosure;
FIG. 181A illustrates an exemplary perspective view of an exemplary shim;
FIG. 181B illustrates an exemplary top view of an exemplary shim;
FIG. 181C illustrates an exemplary cross-sectional view of an exemplary shim;
FIG. 182A illustrates an exemplary perspective view of an exemplary precision shim according to some embodiments of the present disclosure;
FIG. 182B illustrates an exemplary top view of an exemplary precision shim according to some embodiments of the present disclosure;
FIG. 182C illustrates an exemplary cross-sectional view of an exemplary precision shim according to some embodiments of the present disclosure;
FIG. 183A illustrates an exemplary top perspective view of an exemplary precision shim according to some embodiments of the present disclosure;
FIG. 183B illustrates an exemplary bottom perspective view of an exemplary precision shim according to some embodiments of the present disclosure;
FIG. 183C illustrates an exemplary top view of an exemplary precision shim according to some embodiments of the present disclosure;
FIG. 183D illustrates an exemplary cross-sectional view of an exemplary precision shim according to some embodiments of the present disclosure;
FIG. 183E illustrates an exemplary bottom view of an exemplary precision shim according to some embodiments of the present disclosure;
FIG. 183F illustrates an exemplary enlarged view of at least a portion of an exemplary precision shim according to various embodiments of the present disclosure;
FIG. 183G illustrates an exemplary cross-sectional view of at least a portion of an exemplary precision shim according to some embodiments of the present disclosure;
FIG. 184A illustrates an exemplary perspective view of a parallel flow microfluidic cover and an exemplary thermal control sensor base in accordance with some embodiments of the present disclosure;
FIG. 184B illustrates an exemplary exploded view of a parallel flow microfluidic cover and an exemplary thermal control sensor base, according to some embodiments of the present disclosure;
FIG. 185A illustrates an exemplary perspective view of an exemplary flow rate compensator according to some embodiments of the present disclosure;
FIG. 185B illustrates an exemplary cross-sectional view of an exemplary flow rate compensator according to some embodiments of the present disclosure;
FIG. 185C illustrates another exemplary perspective view of an exemplary flow rate compensator according to some embodiments of the present disclosure;
FIG. 185D illustrates an exemplary bottom view of an exemplary flow rate compensator according to some embodiments of the present disclosure;
FIG. 186A illustrates an exemplary cross-sectional view of an exemplary flow rate compensator according to some embodiments of the present disclosure;
FIG. 186B illustrates an exemplary cross-sectional view of an exemplary flow rate compensator according to some embodiments of the present disclosure;
FIG. 186C illustrates an exemplary cross-sectional view of an exemplary flow rate compensator according to some embodiments of the present disclosure;
FIG. 187 illustrates an exemplary block diagram illustrating an exemplary flow rate compensation system, according to some embodiments of the present disclosure;
FIG. 188A illustrates an exemplary flow rate graph showing an exemplary flow rate at the beginning of injection of an exemplary solution without implementing an exemplary flow rate compensator, in accordance with some embodiments of the present disclosure;
FIG. 188B illustrates an exemplary flow rate graph showing exemplary flow rates of an exemplary solution when the flow of the sample solution is stable without implementing an exemplary flow rate compensator, according to some embodiments of the present disclosure;
FIG. 189A shows an exemplary flow rate graph illustrating an exemplary flow rate at the beginning of injection of an exemplary solution by an exemplary peristaltic pump having a compressed ripple filter;
FIG. 189B shows an exemplary flow rate graph illustrating an exemplary flow rate when injection of an exemplary solution through an exemplary peristaltic pump having a compressed ripple filter is stabilized;
FIG. 190A illustrates an exemplary flow rate graph showing exemplary flow rates when injection of an exemplary solution is initiated by an exemplary peristaltic pump having an exemplary flow rate compensator, in accordance with some embodiments of the present disclosure;
FIG. 190B illustrates an exemplary flow rate graph showing an exemplary flow rate when injection of an exemplary solution through an exemplary peristaltic pump having an exemplary flow rate compensator according to some embodiments of the present disclosure is stabilized;
FIG. 191A illustrates an exemplary exploded view of an exemplary edge optical coupling waveguide device according to some embodiments of the present disclosure;
FIG. 191B illustrates an exemplary perspective view of an exemplary edge optical coupling waveguide device according to some embodiments of the present disclosure;
FIG. 191C illustrates an exemplary perspective view of an exemplary edge optical coupling waveguide device according to some embodiments of the present disclosure;
FIG. 191D illustrates an exemplary perspective view of at least an exemplary portion of an exemplary edge optical coupling waveguide device, according to some embodiments of the present disclosure;
FIG. 191E illustrates an exemplary perspective view of at least an exemplary portion of an exemplary edge optical coupling waveguide device, according to some embodiments of the present disclosure;
FIG. 192A illustrates an exemplary top view associated with an exemplary top light pipe of an exemplary edge light coupling waveguide device, according to some embodiments of the present disclosure;
FIG. 192B illustrates an exemplary side view of an exemplary top light pipe of an exemplary edge optical coupling waveguide device, according to some embodiments of the present disclosure;
FIG. 192C illustrates an exemplary perspective view of an exemplary top light pipe of an exemplary edge optical coupling waveguide device, according to some embodiments of the present disclosure;
FIG. 193A illustrates an exemplary top view associated with an exemplary bottom light pipe of an exemplary edge light coupling waveguide device, according to some embodiments of the present disclosure;
FIG. 193B illustrates an exemplary side view of an exemplary bottom light pipe of an exemplary edge optical coupling waveguide device according to some embodiments of the present disclosure;
FIG. 193C illustrates an exemplary bottom view of an exemplary bottom light pipe of an exemplary edge optical coupling waveguide device according to some embodiments of the present disclosure;
FIG. 193D illustrates an exemplary perspective view of an exemplary bottom light pipe of an exemplary edge optical coupling waveguide device, according to some embodiments of the present disclosure;
FIG. 194A illustrates an exemplary side view of an exemplary silicon nitride waveguide of an exemplary edge light coupling waveguide device according to some embodiments of the present disclosure;
FIG. 194B illustrates an exemplary portion of an exemplary silicon nitride waveguide of an exemplary edge optical coupling waveguide device according to some embodiments of the present disclosure;
FIG. 194C illustrates an exemplary perspective view of an exemplary silicon nitride waveguide of an exemplary edge optical coupling waveguide device according to some embodiments of the present disclosure;
Fig. 195A illustrates an example side view of an example edge optical coupling waveguide device according to some embodiments of this disclosure;
fig. 195B illustrates an example side view of an example edge optical coupling waveguide device according to some embodiments of this disclosure;
Fig. 195C illustrates an exemplary top view of an exemplary edge optical coupling waveguide device according to some embodiments of the present disclosure;
Fig. 195D illustrates an exemplary cross-sectional view of an edge optical coupling waveguide device according to some embodiments of the present disclosure;
FIG. 195E illustrates an exemplary cross-sectional view of an exemplary portion of an exemplary edge optical coupling waveguide device, according to some embodiments of the present disclosure; and
Fig. 195F illustrates an example cross-sectional view of an example portion of an example edge optical coupling waveguide device, according to some embodiments of the present disclosure.
Detailed Description
Some examples of the present disclosure will be described more fully hereinafter with reference to the accompanying drawings, in which some, but not all examples of the disclosure are shown. Indeed, these disclosures may be embodied in many different forms and should not be construed as limited to the examples set forth herein; rather, these examples are provided so that this disclosure will satisfy applicable legal requirements. Like numbers refer to like elements throughout.
The phrases "in one example," "according to one example," "in some examples," and the like generally mean that a particular feature, structure, or characteristic following the phrase may be included in at least one example of the present disclosure, and may be included in more than one example of the present disclosure (importantly, such phrases do not necessarily refer to the same example).
If the specification states a component or feature "may", "might", "could", etc.) "should", "will", "preferably", "possible", "usual", "will", "be" and "be" or "" optionally, "" for example, "" as an example, "" in some examples, "" often, "or" possibly "(or other such language) is included or has the property, the particular component or feature need not be included or provided with this feature. Such components or features may optionally be included in some examples, or may be excluded.
The word "example" or "exemplary" is used herein to mean "serving as an example, instance, or illustration. Any implementation described herein as "exemplary" is not necessarily to be construed as preferred or advantageous over other implementations.
The terms "electrically coupled," "in communication with," "in electronic communication with," or "connected to" in this disclosure refer to two or more elements or components connected by wired and/or wireless means such that signals, voltages/currents, data, and/or information may be transmitted to and/or received from the elements or components.
Interferometry refers to mechanisms and/or techniques that can cause one or more waves, beams, signals, etc. (including but not limited to optical beams, electromagnetic waves, acoustic waves, etc.) to overlap, superimpose, and/or interfere with each other. Interferometry may provide a basis for various methods, devices, and systems for sensing (including, but not limited to, detecting, measuring, and/or identifying) objects, substances, organisms, chemical and/or biological solutions, and the like.
In accordance with examples of the present disclosure, various methods, devices, and systems for sensing (including, but not limited to, detecting, measuring, and/or identifying) objects, substances, organisms, chemical and/or biological solutions, compounds, and the like may be based on interferometry. For example, an "interferometry-based sample testing device" or "sample testing device" may be an instrument that may output one or more measurements based on interference, superposition, and/or superposition of two or more waves, beams, signals, etc., that may, for example, emit energy (including, but not limited to, optical beams, electromagnetic waves, acoustic waves, etc.).
In some examples, interferometry-based sample testing devices may compare, contrast, and/or distinguish the location or surface structure of two or more objects, substances, organisms, chemical and/or biological solutions, compounds, and the like. Referring now to FIG. 1, an exemplary block diagram illustrating an exemplary sample testing device 100 is shown. In some examples, exemplary sample testing device 100 may be an interferometry-based sample testing device, such as, but not limited to, an amplitude interferometer.
In the example shown in fig. 1, sample testing device 100 may include a light source 101, a beam splitter 103, a reference surface component 105, a sample surface component 107, and/or an imaging component 109.
In some examples, the light source 101 may be configured to generate, emit light, and/or trigger the generation, and/or emission of light. Exemplary light sources 101 may include, but are not limited to, laser diodes (e.g., violet laser diodes, visible laser diodes, edge-emitting laser diodes, surface-emitting laser diodes, etc.). Additionally or alternatively, the light source 101 may include, but is not limited to, incandescent lamp-based light sources (such as, but not limited to, halogen lamps, nernst lamps), luminescent-based light sources (such as, but not limited to, fluorescent lamps), combustion-based light sources (such as, but not limited to, carbide lamps, acetylene gas lamps), arc-based light sources (such as, but not limited to, carbon arc lamps), gas discharge-based light sources (such as, but not limited to, xenon lamps, neon lamps), high intensity discharge-based light Sources (HIDs) (such as, but not limited to, mercury quartz iodination (HQI) lamps, metal halide lamps). Additionally or alternatively, the light source 101 may include one or more Light Emitting Diodes (LEDs). Additionally or alternatively, the light source 101 may comprise one or more other forms of natural and/or artificial light sources.
In some examples, the light source 101 may be configured to generate light having a spectral purity within a predetermined threshold. For example, the light source 101 may include a laser diode that may generate a single frequency laser beam. Additionally or alternatively, the light source 101 may be configured to generate light having a spectral purity difference. For example, the light source 101 may comprise a laser diode that may generate a wavelength tunable laser beam. In some examples, the light source 101 may be configured to generate light having a broad spectrum.
In the example shown in fig. 1, light generated, emitted, and/or triggered by light source 101 may travel through an optical path and reach beam splitter 103. In some examples, beam splitter 103 may include one or more optical elements that may be configured to divide, split, and/or split light into two or more branches, portions, and/or beams. For example, beam splitter 103 may comprise a flat plate beam splitter. The plate beam splitter may comprise a glass plate. One or more surfaces of the flat glass sheet may be coated with one or more chemical coatings. For example, the glass sheet may be coated with a chemical coating such that at least a portion of the light may be reflected from the glass sheet and at least another portion of the light may be transmitted through the glass sheet. In some examples, the plate beam splitter may be positioned at a 45 degree angle relative to the angle of the input light. In some examples, the plate beam splitter may be positioned at other angles.
Although the above description provides an example of the beam splitter 103, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary beam splitter 103 may include one or more additional and/or alternative elements. For example, beam splitter 103 may include a cube beam splitter element. In this example, the cube beam splitter element may comprise two right angle prisms attached to one another. For example, one lateral or inclined surface of one right angle prism may be attached to one lateral or inclined surface of another right angle prism. In some examples, the two right angle prisms may form a cube shape. Additionally or alternatively, the beam splitter 103 may include other elements.
Although the above description provides exemplary materials for beam splitter 103, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary beam splitter 103 may include one or more additional and/or alternative materials, such as, but not limited to, transparent plastic, fiber optic materials, and the like. Additionally or alternatively, the beam splitter 103 may comprise other materials.
In the example shown in fig. 1, the beam splitter 103 may split the light received from the light source 101 into at least two portions. For example, a first portion of the light that may be reflected from the beam splitter 103 may reach the reference surface component 105. A second portion of the light may be transmitted through the beam splitter 103 and reach the sample surface component 107.
In this disclosure, the term "surface component" refers to a physical structure that may be configured to allow at least a portion of a wave, beam, signal, etc. it receives to pass through and/or reflect at least a portion of a wave, beam, signal, etc. it receives. In some examples, the exemplary surface features may include one or more optical features, including one or more reflective optical features and/or one or more projection optical features. For example, exemplary surface features may include mirrors, retroreflectors, and the like. Additionally or alternatively, the surface features may include one or more lenses, filters, windows, optical planes, prisms, polarizers, beam splitters, wave plates, and the like.
In the example shown in fig. 1, an exemplary sample testing device may include two surface features: a reference surface part 105 and a sample surface part 107. In some examples, the reference surface component 105 and/or the sample surface component 107 may include one or more optical components, such as, but not limited to, those described above. As will be described in detail herein, the reference medium may be in contact with at least a portion of the surface of the reference surface component 105 and/or the sample medium may be in contact with at least a portion of the surface of the sample surface component 107.
In the example shown in fig. 1, the reference surface component 105 and the sample surface component 107 each reflect at least one beam of light back to the beam splitter 103. For example, the reference surface component 105 may reflect at least one beam of the first portion of light back toward the beam splitter 103. Sample surface component 107 may reflect at least one light beam of the second portion of light back toward beam splitter 103.
In some examples, the light beam reflected from the reference surface component 105 and the light beam reflected from the sample surface component 107 may be at least partially recombined and/or re-polymerized at the beam splitter 103.
For example, the reference surface component 105 and the sample surface component 107 may be arranged perpendicular to each other (such as the example shown in fig. 1). In such an example, the light beam reflected from the reference surface component 105 and the light beam reflected from the sample surface component 107 may be recombined by the beam splitter 103 into at least one light beam that may travel toward the imaging component 109. Additionally or alternatively, the beam splitter 103 may reflect at least some of the light beam from the reference surface component 105 and the light beam from the sample surface component 107 back to the light source 101.
In some examples, the recombination of the light beams may occur at a location different from the beam splitter 103. For example, beam splitter 103 may include one or more retroreflectors. In such an example, the beam splitter 103 can recombine light from the reference surface component 105 and the sample surface component 107 into two or more beams.
In some examples, the intensity of the observed recombined light beam varies according to the amplitude and phase difference between the light beam reflected from the reference surface component 105 and the light beam reflected from the sample surface component 107.
For example, as the light beams travel along different lengths and/or directions of the optical path, a phase difference between the light beam reflected from the reference surface component 105 and the light beam reflected from the sample surface component 107 may occur, which may be due to, for example, differences in form, texture, shape, tilt, and/or refractive index between the reference surface component 105 and/or the sample surface component 107. As further described herein, the refractive index may vary due to the presence of one or more objects, substances, organisms, chemical and/or biological solutions, compounds, etc., on, for example, the reference surface component 105 and/or the sample surface component 107.
In some examples, if the light beam reflected from the reference surface component 105 and the light beam reflected from the sample surface component 107 are exactly out of phase when they are recombined, the two light beams may cancel each other out and the resulting intensity may be 0. This is also known as "destructive interference".
In some examples, if the beam reflected from the reference surface component 105 and the beam reflected from the sample surface component 107 are equal in intensity and exactly in phase when they are recombined, the resulting intensity may be four times the intensity of either beam alone. This is also known as "constructive interference".
Additionally or alternatively, if the beam reflected from the reference surface component 105 and the beam reflected from the sample surface component 107 spatially extend, there may be variations in the surface area in the relative phases of the wavefronts comprising the two beams. For example, alternating regions of constructive and destructive interference may produce alternating bright and dark bands, thereby producing an interference fringe pattern. Exemplary details of the interference fringe pattern are further described and illustrated herein.
In the example shown in fig. 1, the example sample testing device 100 may include an imaging component 109 that may be configured to detect, measure, and/or identify interference fringe patterns. For example, the imaging component 109 can be positioned in the path of travel of the recombined beam from the beam splitter 103.
In this disclosure, the term "imaging component" refers to a device, instrument, and/or apparatus that may be configured to detect, measure, capture, and/or identify images and/or information associated with images. In some examples, the imaging component may include one or more imagers and/or image sensors (such as integrated 1D, 2D, or 3D image sensors). Various examples of image sensors may include, but are not limited to, contact Image Sensors (CIS), charge Coupled Devices (CCD) or Complementary Metal Oxide Semiconductor (CMOS) sensors, photodetectors, one or more optical components (e.g., one or more lenses, filters, mirrors, beam splitters, polarizers, etc.), auto-focusing circuitry, motion tracking circuitry, computer vision circuitry, image processing circuitry (e.g., one or more digital signal processors configured to process images to improve image quality, reduce image size, increase image transmission bit rate, etc.), a checker, a scanner, a camera, any other suitable imaging circuitry, or any combination thereof.
In the example shown in fig. 1, imaging component 109 can receive the recombined beam as it travels from beam splitter 103. In some examples, the imaging component 109 may be configured to generate imaging data associated with the received light beam. In some examples, the processing component may be electrically coupled to the imaging component 109 and may be configured to analyze the imaging data to determine, for example, but not limited to, a change in refractive index associated with the reference surface component 105 and/or the sample surface component 107, exemplary details of which are described herein.
Additionally or alternatively, based on imaging data generated by the imaging component 109, two-dimensional and/or three-dimensional topography images associated with the reference surface component 105 and/or the sample surface component 107 may be generated. For example, the imaging data may correspond to an interference fringe pattern received by the imaging component 109, exemplary details of which are described herein.
Additionally or alternatively, based on imaging data generated by imaging component 109, the processing component may determine a difference between the first optical path length (between sample surface component 107 and beam splitter 103) and the second optical path length (between reference surface component 105 and beam splitter 103). For example, as described above, when there is at least a partial phase difference between the light beam reflected from the reference surface part 105 and the light beam reflected from the sample surface part 107, an interference fringe pattern may occur. Phase differences may occur when light beams travel in different optical path lengths and/or directions, which may be due in part to differences in form, texture, shape, inclination, and/or refractive index between the reference surface component 105 and/or the sample surface component 107. Thus, by analyzing the interference fringe pattern, the processing section can determine the phase difference. Based on the phase difference, the processing component may determine a path length difference between the first optical path length and the second optical path length based on, for example, the following equation:
Wherein the method comprises the steps of Corresponding to the phase difference, L corresponds to the path length difference, n corresponds to the refractive index, and λ corresponds to the wavelength.
Although the above description provides examples of interferometry-based sample testing devices, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the example sample testing device may include one or more additional and/or alternative elements, and/or these elements may be arranged and/or positioned differently than those shown above.
In some examples, an exemplary sample testing device may include parallel surface features. For example, the reference surface component and the sample surface component may be positioned in a parallel arrangement to each other such that a light beam may be reflected between the reference surface component and the sample surface component. For example, a light beam may be reflected from the reference surface component to the sample surface component, and then the light beam may be reflected from the sample surface component to the reference surface component. In some examples, one or both of the sample surface component and the reference surface component may be coated with a reflective coating on one or both sides. In some examples, one or both of the reference surface component and the sample surface component may have a transmittance that targets one or more particular optical frequencies. For example, the sample surface feature may allow light within the optical frequency to pass through the sample surface feature and reach the imaging feature. Based on the interference fringe pattern associated with the light within the optical frequency, the sample testing device may detect, measure, and/or identify changes in form, texture, shape, inclination, and/or refractive index between the reference surface features and/or the sample surface features.
In some examples, the exemplary sample testing device may utilize counter-propagating light beams. For example, a light beam from a light source may be split by a beam splitter into two light beams, which may travel in opposite directions along a common optical path. In some examples, one or more surface features may be positioned such that two light beams form a closed loop. For example, an exemplary sample testing device may include three surface elements. The three surface elements and the beam splitter may each be positioned at a corner of the square shape such that the optical path of the light beam may form the square shape. In some examples, the sample testing device may provide different polarization states.
In some examples, the exemplary sample testing device may additionally or alternatively include one or more optical fibers in the beam splitter. In some examples, an exemplary sample testing device may include an optical fiber in the form of a fiber optic coupler. For example, an exemplary sample testing device may include a fiber optic polarization controller to control the polarization state of light as it travels through the fiber optic coupler. Additionally or alternatively, the sample testing device may comprise an optical fiber in the form of a polarization maintaining optical fiber.
In some examples, an exemplary sample testing device may include two or more separate beam splitters. For example, a first beam splitter may split a light beam into two or more portions, and a second beam splitter may combine the two or more portions of the light beam into a single light beam. In such examples, the sample testing device may generate two or more interference fringe patterns, and one of the beam splitters may direct the two or more interference fringe patterns to one or more imaging components. In some examples, the distance between the reference surface component and the beam splitter and the distance between the sample surface component and the beam splitter may be different. In some examples, the distance between the reference surface component and the beam splitter and the distance between the sample surface component and the beam splitter may be the same.
For example, the sample testing device may include a Mach-Zehnder interferometer. In such an example, the optical path lengths in the two arms of the Mach-Zehnder interferometer may be the same or may be different (e.g., with additional delay lines). In some examples, the distribution of optical power at the two outputs of the Mach-Zehnder interferometer may depend on the difference in optical arm length and wavelength (or optical frequency), which may be adjusted (e.g., by slightly changing the position of the sample surface component and/or the reference surface component).
In some examples, the sample testing device may include a Fabry-perot interferometer. In some examples, the sample testing device may include a Gires-Tournois interferometer. In some examples, the sample testing device may include a Michelson interferometer. In some examples, the sample testing device may include a Sagnac interferometer. In some examples, the sample testing device may include a Sagnac interferometer. Additionally or alternatively, the sample testing device may include other types and/or forms of interferometers.
Exemplary sample testing devices according to examples of the present disclosure may be implemented in one or more environments, use cases, applications, and/or purposes. As described above, the phase differenceThe relationship between the path length difference L, the refractive index n, and the wavelength λ can be summarized by the following formula:
In some examples, an exemplary sample testing device according to examples of the present disclosure may be implemented to measure optical system performance, surface roughness, and/or surface contact condition variations (e.g., wet surfaces). Additionally or alternatively, an exemplary sample testing device according to examples of the present disclosure may be implemented to measure deviations and/or flatness of an optical surface.
In some examples, an exemplary sample testing device according to examples of the present disclosure may be used to measure distance, positional changes, and/or displacement. In some examples, an exemplary sample testing device according to examples of the present disclosure may be implemented to calculate the rotation angle.
In some examples, an exemplary sample testing device according to examples of the present disclosure may be used to measure the wavelength of a light source and/or the wavelength component of a light source. For example, an exemplary sample testing device may be configured as a wavelength meter for measuring the wavelength of a laser beam. In some examples, an exemplary sample testing device according to examples of the present disclosure may be implemented to monitor changes in optical wavelength or frequency. Additionally or alternatively, an exemplary sample testing device according to examples of the present disclosure may be implemented to measure linewidths of lasers.
In some examples, an exemplary sample testing device according to examples of the present disclosure may be implemented to modulate the power or phase of a laser beam. In some examples, an exemplary sample testing device according to examples of the present disclosure may be implemented to measure dispersion of an optical component as an optical filter.
In some examples, an exemplary sample testing device according to examples of the present disclosure may be implemented to determine a change in refractive index of a surface component. Referring now to fig. 2, an exemplary diagram illustrating an exemplary sample testing device 200 is shown. In some examples, the example sample testing device 200 may be implemented to detect, measure, and/or identify refractive index variations and/or changes. In some examples, exemplary sample testing device 200 may be an interferometry-based sample testing device.
In the example shown in fig. 2, an exemplary sample testing device 200 may include a waveguide 202. As used herein, the terms "waveguide," "waveguide device," "waveguide component" are used interchangeably to refer to a physical structure that can guide waves, light beams, signals, etc. (including but not limited to optical beams, electromagnetic waves, acoustic waves, etc.). An exemplary structure of a waveguide is shown herein.
In some examples, waveguide 202 may include one or more layers. For example, waveguide 202 may include an interface layer 208, a waveguide layer 206, and a substrate layer 204.
In some examples, the interface layer 208 may include a material such as, but not limited to, glass, silicon oxide, a polymer, and the like. In some examples, interface layer 208 may be disposed on top of waveguide layer 206 by various means, including but not limited to mechanical means (e.g., fastening clips) and/or chemical means (such as using an adhesive material (e.g., glue)).
In some examples, waveguide layer 206 may include materials such as, but not limited to, silicon oxide, silicon nitride, polymers, glass, optical fibers, and/or the like that may guide guided waves, optical beams, signals, and the like as they propagate through waveguide layer 206. In some examples, the waveguide layer 206 may provide physical constraints for propagation such that minimal energy loss is achieved. In some examples, waveguide layer 206 may be disposed on top of substrate layer 204 by various means, including but not limited to mechanical means (e.g., fastening clips) and/or chemical means (such as using an adhesive material (e.g., glue)).
In some examples, the substrate layer 204 may provide mechanical support for the waveguide layer 206 and the interface layer 208. For example, the substrate layer 204 may include materials such as, but not limited to, glass, silicon oxide, and polymers.
In the example shown in fig. 2, light (e.g., light from a light source such as the light source shown above in connection with fig. 1) may be directed to, emitted through, and/or otherwise enter the waveguide 202.
In some examples, light may enter the waveguide 202 through a side surface of the waveguide 202. For example, as shown in fig. 2, light may enter the waveguide 202 through a side surface in the optical direction 210, and the optical path of the light may be arranged perpendicular to the side surface. In some examples, the light source may be coupled to a side surface of the waveguide 202 by one or more fastening mechanisms and/or attachment mechanisms, including, but not limited to, chemical means (e.g., an adhesive material such as glue), mechanical means (e.g., one or more mechanical fasteners or methods such as welding, snap-fitting, permanent and/or non-permanent fasteners), magnetic means (e.g., through the use of magnets), and/or suitable means.
Although the above description provides an example of the direction in which light may enter the waveguide 202, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, light may additionally or alternatively enter waveguide 202 at different surfaces and/or in different directions. For example, light may enter the waveguide 202 from a top surface of the waveguide 202. Additionally or alternatively, light may enter the waveguide 202 from a bottom surface of the waveguide 202. Additional details are described herein.
Referring back to fig. 2, the waveguide 202 may include a first waveguide portion 212.
In some examples, the first waveguide portion 212 may be configured to provide, support, and/or cause a single transverse mode of light as the light travels through the first waveguide portion 212. As used herein, the term "transverse mode," "transverse mode," or "vertical mode" refers to a pattern of waves, beams, and/or signals that may be in a plane or arrangement perpendicular to the direction of propagation of the waves, beams, and/or signals. For example, the pattern may be associated with an intensity pattern of optical radiation measured along a line formed by a plane perpendicular to the propagation direction of the light and/or a plane perpendicular to the first waveguide portion 212. In some examples, transverse modes may be classified as including, but not limited to, transverse Electromagnetic (TEM) mode, transverse Electric (TE) mode, and Transverse Magnetic (TM) mode. For example, in TEM mode, there is neither an electric nor a magnetic field in the direction of light propagation. In TE mode, there is no electric field in the direction of light propagation. In TM mode, there is no magnetic field in the direction of light propagation.
For example, as the laser light travels through a confined channel (such as, but not limited to, first waveguide portion 212), the laser light may form one or more modes. For example, the laser may form a peak pattern 0. In some examples, the laser may form a mode other than peak mode 0. In some examples, the size and thickness of the waveguide or waveguide portion may affect the number of modes of the laser as the laser propagates through the waveguide or waveguide portion.
In some examples, the first waveguide portion 212 may have a thickness less than an optical wavelength of light traveling through the first waveguide portion 212. In some examples, the first waveguide portion 212 may have a thickness of one-fourth of the wavelength. In some examples, the first waveguide portion 212 may have a thickness between 0.1 μm and 0.2 μm, which may limit light to only one single mode. In some examples, the thickness of the first waveguide portion 212 may be other values.
Although the above description provides exemplary characteristics of the first waveguide portion 212 associated with the transverse mode, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the first waveguide portion 212 may be configured to provide, support, and/or induce two or more lateral modes as light travels through the first waveguide portion 212. Additionally or alternatively, the first waveguide portion 212 may be configured to provide, support, and/or induce one or more longitudinal modes. As used herein, the term "longitudinal mode" or "horizontal mode" refers to a pattern of waves, beams, and/or signals that may be in a plane or arrangement parallel to the direction of propagation of the waves, beams, and/or signals. For example, the pattern may be associated with an intensity pattern of optical radiation measured along a line formed by a plane parallel to the propagation direction of the light and/or perpendicular to the plane of the first waveguide portion 212. In some examples, longitudinal modes may be classified into different types.
Referring back to fig. 2, the waveguide 202 may include a stepped portion 214 and/or a second waveguide portion 216. In some examples, the stepped portion 214 may correspond to a portion of the waveguide 202 having an increased thickness. For example, the thickness of the waveguide 202 may increase from the thickness of the first waveguide portion 212 to the thickness of the second waveguide portion 216.
In some examples, the thickness of the second waveguide portion 216 may be twice the thickness of the first waveguide portion 212. In some examples, the ratio between the thickness of the first waveguide portion 212 and the thickness of the second waveguide portion 216 may be other values.
In the example shown in fig. 2, the stepped portion 214 may include a vertical surface protruding from and disposed perpendicular to the top surface of the first waveguide portion 212. Note that the scope of the present disclosure is not limited to this example only. In some examples, the stepped portion 214 may include a curved surface. Additionally or alternatively, the stepped portion 214 may include other shapes and/or be in other forms.
As described above, the size and thickness of the waveguide or waveguide portion may affect the number of modes of the laser light as it propagates through the waveguide or waveguide portion. In some examples, due to the increased thickness (e.g., vertical asymmetry) from the first waveguide portion 212 to the second waveguide portion 216, the mode of the laser light traveling from the first waveguide portion 212 to the second waveguide portion 216 may change. For example, the first waveguide portion 212 may be configured to provide, support, and/or induce a single transverse mode of light as the light travels through the first waveguide portion 212, and the second waveguide portion 216 may be configured to provide, support, and/or induce two transverse modes of light as the light travels through the second waveguide portion 216.
In some examples, the thickness of the second waveguide portion 216 may be greater than the thickness of the first waveguide portion 212. Thus, the second waveguide portion 216 may allow for more than one single mode, as described above.
Although the above description provides an exemplary structure of the waveguide 202, it is noted that the scope of the present disclosure is not limited to the above description. For example, waveguide layer 206 may include a first waveguide sublayer and a second waveguide sublayer. The second waveguide sublayer may be disposed on the top surface of the first waveguide sublayer and the length of the second waveguide sublayer may be shorter than the length of the first waveguide sublayer. In such an example, the difference in length may increase stepped portion 214, which may increase the thickness of waveguide layer 206 from the thickness of the first waveguide sub-layer to the combined thickness of the first waveguide sub-layer and the second first waveguide sub-layer.
Although the above description provides an example of changing the mode from the single transverse mode to the two modes, it is noted that the scope of the present disclosure is not limited to the above description. For example, the number of modes associated with the first waveguide portion 212 may be more than one, and the number of modes associated with the second waveguide portion 216 may be any value that is greater or less than the number of modes associated with the first waveguide portion 212.
Continuing with the example above, the two modes of light beam may propagate through the second waveguide portion 216. For example, the light beam of the first mode may have a different speed than the light beam of the second mode. In some examples, the first mode of light beam and the second mode of light beam may interfere with each other (e.g., mode interference). In some examples, when the two modes of light beams leave the waveguide 202 in the optical direction 220, they may produce an interference fringe pattern similar to those described above in connection with fig. 1.
As described in connection with fig. 1, the variation of the interference fringe pattern may be caused by the variation of the phase difference of the light beams. Continuing with the above example, the change in the interference fringe pattern of the first mode light and the second mode light may be due to a change in the phase difference between the first mode light and the second mode light, which in turn may be due to a change in the optical path length between the first mode light and the second mode light.
In some examples, the optical path length change may be due to a change in a physical structure, parameter, and/or characteristic associated with the waveguide 202 (such as, but not limited to, a change in a refractive index associated with a surface of the waveguide 202).
For example, the refractive index associated with the surface of waveguide layer 206 exposed through sample opening 222 of interface layer 208 may vary due to, for example, but not limited to, a change in the evanescent wave. Referring now to fig. 3, an exemplary diagram illustrating such a variation is shown.
In the example shown in fig. 3, an exemplary sample testing device 300 may include a waveguide 301, similar to waveguide 202 described above in connection with fig. 2. For example, waveguide 202 may include a substrate layer 303, a waveguide layer 305, and an interface layer 307, similar to substrate layer 204, waveguide layer 206, and interface layer 208 described above in connection with fig. 2.
In some examples, the sample medium may be placed on the surface of the waveguide layer 305 exposed through the sample opening of the interface layer 307 and/or may be in contact with the surface of the waveguide layer 305. As used herein, the term "sample medium" refers to a subject, substance, organism, chemical and/or biological solution, molecule, or the like, that a sample testing device according to examples of the present disclosure may be configured to detect, measure, and/or identify. For example, the sample medium may include an analyte (e.g., in the form of a biochemical sample), and the sample testing device 300 may be configured to detect, measure, and/or identify whether the analyte includes a particular substance or organism.
In some examples, the sample medium may be placed on the surface of the waveguide layer 305 via physical and/or chemical attraction (such as, but not limited to, through the flow channels, gravity, surface tension, chemical bonding, etc., described herein). For example, the sample testing device 300 may be configured to detect the presence of one or more specific viruses (e.g., coronaviruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) in a sample medium. In some examples, sample testing device 300 may include antibodies attached to a surface of waveguide layer 305, and these antibodies may correspond to one or more particular viruses that sample testing device 300 is configured to detect. The chemical or biological reaction between the antibody and the virus may cause a change in the evanescent wave, which in turn may change the refractive index of the chemical in contact with the surface of waveguide layer 305 (e.g., without limitation, interface layer 307).
Continuing the SARS-CoV-2 example above, an antibody to SARS-CoV-2 (e.g., without limitation, a SARS-CoV polyclonal antibody) can be attached to the surface of waveguide layer 305 by physical and/or chemical attraction (such as, without limitation, gravity, surface tension, chemical bonding, etc.). When the sample medium is placed on the surface of the waveguide layer 305 through the opening of the interface layer 307, the antibody to SARS-CoV-2 can attract molecules of the SARS-CoV-2 virus (if present in the sample medium).
In the case where molecules of SARS-CoV-2 virus are present in the sample medium, antibodies to SARS-CoV-2 can pull the molecules towards the surface of waveguide layer 305. As described above, chemical and/or biological reactions between antibodies and viruses may cause a change in the evanescent wave, which in turn may change the refractive index of chemicals in contact with the surface of waveguide layer 305 (e.g., without limitation, interface layer 307).
In the absence of molecules of the SARS-CoV-2 virus in the sample medium, there may not be any chemical and/or biological reaction between the antibody and the virus, and thus the refractive index of the evanescent wave and chemicals proximate to the surface of waveguide layer 305 (e.g., without limitation, interface layer 307) may not change.
As described above, as light propagates through waveguide layer 305, a change in the refractive index of a chemical in contact with the surface of waveguide layer 305 (e.g., without limitation, interface layer 307) may result in a change in the optical path length of the light. Further, similar to those described above in connection with fig. 2, light exiting waveguide layer 305 may include two (or more) modes and may create an interference fringe pattern. Thus, a change in the interference fringe pattern may indicate a change in refractive index, which in turn may indicate the presence of an object, substance, organism, chemical and/or biological solution (e.g., SARS-CoV-2 virus) that the sample testing device 300 is configured to detect, measure and/or identify.
Some examples of the present disclosure may overcome various technical challenges. For example, an exemplary sample testing device may include integrated optical components. Referring now to fig. 4 and 5, exemplary views of an exemplary sample testing device 800 according to examples of the present disclosure are shown. In some examples, the exemplary sample testing device 800 may be an interferometry-based sample testing device.
In the example shown in fig. 4 and 5, the example sample testing device 800 may include a light source 820, a waveguide 802, and/or an integrated optical component 804.
Similar to the light source 101 described above in connection with fig. 1, the light source 820 of the sample testing device 800 may be configured to generate, emit light (including but not limited to a laser beam) and/or trigger the generation, and/or emission of light. Exemplary light sources 820 may include, but are not limited to, laser diodes (e.g., violet laser diodes, visible laser diodes, edge-emitting laser diodes, surface-emitting laser diodes, etc.). Additionally or alternatively, light source 820 may include, but is not limited to, incandescent lamp-based light sources (such as, but not limited to, halogen lamps, nernst lamps), luminescent-based light sources (such as, but not limited to, fluorescent lamps), combustion-based light sources (such as, but not limited to, carbide lamps, acetylene gas lamps), arc-based light sources (such as, but not limited to, carbon arc lamps), gas discharge-based light sources (such as, but not limited to, xenon lamps, neon lamps), high intensity discharge-based light Sources (HIDs) (such as, but not limited to, mercury quartz iodination (HQI) lamps, metal halide lamps). Additionally or alternatively, the light source 820 may include one or more Light Emitting Diodes (LEDs). Additionally or alternatively, the light source 820 may include one or more other forms of natural and/or artificial light sources.
Referring back to fig. 4 and 5, the light generated by the light source 820 may travel along an optical path and reach the integrated optical component 804. In some examples, the integrated optical component 804 may collimate, polarize, and/or couple light into the waveguide 802. For example, the integrated optical component 804 can be an integrated collimator, polarizer, and coupler.
Referring now to FIG. 5, an exemplary structure of an integrated optical component 804 is shown. In the example shown in fig. 5, the integrated optical component 804 may include a collimator 816 and a beam splitter 818.
In some examples, collimator 816 may include one or more optical components to redirect and/or adjust the direction of light it receives. For example, the optical components may include one or more optical collimating lenses and/or imaging lenses, such as, but not limited to, one or more lenses having a spherical surface, one or more lenses having a parabolic surface, and the like. For example, the optical component may comprise a silicon meniscus lens.
For example, the light beams received by collimator 816 may each travel along an optical direction that may not be parallel to the optical direction of another light beam or light. As the beam travels through collimator 816, collimator 816 may collimate the beam into a parallel or nearly parallel beam. Additionally or alternatively, collimator 816 may narrow the beam by making the direction of the beam more aligned in the normal direction and/or making the spatial cross-section of the beam smaller.
Referring back to fig. 4 and 5, the collimator 816 may be attached to the inclined surface of the beam splitter 818.
Similar to the beam splitter 103 described above in connection with fig. 1, the beam splitter 818 of the exemplary sample testing device 800 may include one or more optical elements that may be configured to divide, split, and/or split light into two or more branches, portions, and/or beams.
In the example shown in fig. 5, the beam splitter 818 may include a first prism 812 and a second prism 814. In some examples, each of the first prism 812 and the second prism 814 may be a right angle prism.
In some examples, second prism 814 may be attached to the first sloped surface of first prism 812 by various means, including, but not limited to, mechanical and/or chemical means. For example, an adhesive material (such as glue) may be applied on the first inclined surface of the first prism 812 such that the first prism 812 may be combined with the second prism 814. Additionally or alternatively, the second prism 814 may be bonded with the first prism 812.
In some examples, collimator 816 may be attached to the second sloped surface of first prism 812 by various means, including, but not limited to, mechanical and/or chemical means. For example, an adhesive material (such as glue) may be applied on the second inclined surface of the first prism 812 such that the collimator 816 may be combined with the first prism 812. Additionally or alternatively, the collimator 816 may be bonded with the first prism 812.
As described above, the collimator 816 may collimate the light beam into a parallel or approximately parallel light beam, which may then be received by the beam splitter 818. In some examples, the light received by the beam splitter 818 may be split into two or more portions as it travels through the inclined surface of the first prism 812. For example, the inclined surface of the first prism 812 may reflect a portion of the light and may allow another portion of the light to pass through. In some examples, the hypotenuse surface of the first prism 812 and/or the second prism 814 may include a chemical coating. In some examples, the first prism 812 and the second prism 814 may together form a cube shape.
In some examples, the beam splitter 818 may be a polarizing beam splitter. As used herein, a polarizing beam splitter may split light into one or more portions, and each portion may have a different polarization. In some examples, one (or, in some examples, two or more) light beams having a selected polarization may be transmitted into waveguide 802 by implementing a polarizing beam splitter. Thus, the beam splitter 818 can act as a polarizer.
In some examples, based on the acceptance efficiency of light directly entering the waveguide 802, the angles of the first prism 812 and the second prism 814 may be calculated to redirect the light into the waveguide. For example, the first prism 812 and the second prism 814 may each be disposed at a 45 degree angle to the waveguide 802, as shown in fig. 5. Additionally or alternatively, the angles of the first prism 812 and the second prism 814 may be arranged based on other values to increase the acceptance efficiency.
Although the above description provides an example of the beam splitter 818, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary beam splitter 818 can include one or more additional and/or alternative elements. For example, beam splitter 103 may include a flat plate beam splitter similar to those described above in connection with beam splitter 103 of fig. 1.
In some examples, the dimensions (e.g., width, length, and/or height) of the beam splitter 818 may be 5 millimeters. In some examples, the size of the beam splitter 818 may be other values.
Referring back to fig. 4 and 5, an integrated optical component 804 can be coupled to the waveguide 802. For example, the surface of the integrated optical component 804 may be attached to the surface of the waveguide 802 by various means, including but not limited to mechanical and/or chemical means. For example, an adhesive material (such as glue) may be applied on the surface of the waveguide 802 and/or on the surface of the integrated optical component 804 so that the waveguide 802 may be bonded with the integrated optical component 804. Additionally or alternatively, the waveguide 802 may be bonded with the integrated optical component 804.
In some examples, waveguide 802 may include one or more layers. For example, waveguide 802 may include an interface layer 806, a waveguide layer 808, and a substrate layer 810, similar to interface layer 208, waveguide layer 206, and substrate layer 204 described above in connection with fig. 2. For example, the interface layer 806 may be disposed on a top surface of the waveguide layer 808.
In some examples, the interface layer 208 may include an opening for receiving the waveguide 802. For example, the opening of the interface layer 208 may correspond to the shape of the integrated optical component 804. In some examples, the integrated optical component 804 may be securely positioned on the top surface of the waveguide layer 808 through the opening of the interface layer 208 such that the integrated optical component 804 may be in direct contact with the waveguide layer 808. In some examples, a layer (e.g., a coupler layer) may be implemented between the integrated optical component 804 and the waveguide layer 808.
In the example shown in fig. 4 and 5, the interface layer 806 may include a sample opening 822. Similar to those described above in connection with fig. 2, sample opening 822 may receive a sample medium. In some examples, the integrated optical component 804 may be disposed on and/or attached to a top surface of the interface layer 806, and input light may be provided to the waveguide layer 808 through the interface layer 806. In such an example, input light may be provided to the top surface of waveguide 802 (without passing through the side surfaces).
In some examples, interface layer 806 may include output openings 824. In some examples, the output opening 824 may allow light to exit the waveguide 802. Similar to those described in connection with fig. 2, the waveguide 802 may cause two modes of light to exit the waveguide 802, thereby creating an interference fringe pattern.
Referring back to fig. 4 and 5, the exemplary sample testing device 800 may include a lens component 826 disposed on a top surface of the interface layer 806. For example, the lens component 826 may at least partially overlap with the output opening 824 of the interface layer 806 such that light exiting the waveguide 802 may pass through the lens component 826.
In some examples, lens component 826 can include one or more optical imaging lenses, such as, but not limited to, one or more lenses having a spherical surface, one or more lenses having a parabolic surface, and the like. In some examples, the lens component 826 may redirect and/or adjust the direction of light exiting the waveguide 802 toward the imaging component 828. In some examples, imaging component 828 may be disposed on a top surface of lens component 826.
In some examples, the lens component 826 can be positioned at a distance from the output opening 824. For example, the lens component 826 can be securely supported by a support structure (e.g., a support layer) such that it is positioned on top of the output opening 824 and is not in contact with the output opening 824. In some examples, the lens component 826 may at least partially overlap with the output opening 824 of the interface layer 806 in the direction of the output light such that light output from the waveguide 802 may travel through the lens component 826.
In some examples, imaging component 828 may be positioned at a distance from lens component 826. For example, the imaging component 828 and/or the lens component 826 may each be securely supported by a support structure (e.g., a support layer) such that the imaging component 828 is positioned on top of the lens component 826 and is not in contact with the lens component 826. In some examples, the imaging component 828 may at least partially overlap the lens component 826 in the direction of the output light such that light output from the waveguide 802 may travel through the lens component 826 and reach the imaging component 828.
Similar to the imaging component 109 described above in connection with fig. 1, the imaging component 828 may be configured to detect interference fringe patterns. For example, the imaging component 109 can include one or more imagers and/or image sensors (such as integrated 1D, 2D, or 3D image sensors). Various examples of image sensors may include, but are not limited to, contact Image Sensors (CIS), charge Coupled Devices (CCD) or Complementary Metal Oxide Semiconductor (CMOS) sensors, photodetectors, one or more optical components (e.g., one or more lenses, filters, mirrors, beam splitters, polarizers, etc.), auto-focusing circuitry, motion tracking circuitry, computer vision circuitry, image processing circuitry (e.g., one or more digital signal processors configured to process images to improve image quality, reduce image size, increase image transmission bit rate, etc.), a checker, a scanner, a camera, any other suitable imaging circuitry, or any combination thereof.
In the example shown in fig. 4 and 5, the integrated optical component 804 may provide input light to the top surface of the waveguide 802, and after the light travels through the waveguide 802, the input light may exit from the top surface of the waveguide 802. By directing the optical path of the input light to the waveguide 802 and the output light from the waveguide via the opening of the interface layer 806 directly coupled to the surface of the waveguide layer 808 and/or in contact with the best-matching coupler layer therebetween, light efficiency and fringe calculation accuracy may be improved, which may improve the performance of the sample testing device 800 and reduce the size of the sample testing device 800.
In some examples, interferometry-based sample testing devices may use a coupler or grating mechanism to couple a light source and a waveguide. However, the use of a coupler or grating mechanism may adversely affect the optical efficiency of light traveling from the light source to the waveguide. In addition, implementing a coupler or grating mechanism to couple the light source to the waveguide may require additional manufacturing processes, increase the costs associated with manufacturing the sample testing device, and increase the size of the sample testing device.
Some examples of the present disclosure may overcome various technical challenges. For example, an exemplary sample testing device may include a lens array. Referring now to fig. 6 and 7, an exemplary sample testing device 900 is shown.
In the example shown in fig. 6 and 7, an exemplary sample testing device 900 may include a light source 901, a waveguide 905, and/or an integrated optical component 903, similar to the light source 820, waveguide 802, and integrated optical component 804 described above in connection with fig. 4 and 5.
For example, light source 901 may be configured to generate, emit light, and/or trigger the generation, and/or emission of light. The light may be received by an integrated optical component 903, which may direct the light to a waveguide 905. For example, the integrated optical component 903 may include at least one collimator and at least one beam splitter, similar to the integrated optical component 804 described above in connection with fig. 4 and 5.
Referring back to fig. 6 and 7, the waveguide 905 may cause two modes of light to exit the waveguide 905 and be received by the imaging component 907, similar to those described above in connection with fig. 4 and 5. For example, imaging component 907 may include a Complementary Metal Oxide Semiconductor (CMOS) sensor that may detect an interference fringe pattern of light exiting waveguide 905.
Similar to the sample testing device 800 described above in connection with fig. 4 and 5, the sample testing device 900 shown in fig. 6 and 7 may direct the optical path of input light to the waveguide 905 and direct light output from the waveguide through the top surface of the waveguide 905. In fig. 4 and 5, the light source 820 may emit light in an optical direction parallel to the top surface of the waveguide 802. In fig. 6 and 7, the light source 901 may emit light in an optical direction perpendicular to the top surface of the waveguide 905. The integrated optical component may direct input light to the waveguide through the top surface of the waveguide regardless of the direction of the light emitted by the light source.
In some examples, the integrated optical component 903 and/or the imaging component 907 may be coupled to the waveguide 905 by a coupler or grating mechanism. However, as described above, the coupler and grating mechanism may require additional manufacturing processes, increasing the costs associated with manufacturing the sample testing device, and increasing the size of the sample testing device. In some examples, the integrated optical component 903 and/or the imaging component 907 may be coupled to the waveguide 905 by a lens array. Referring now to fig. 8, an exemplary diagram illustrating an exemplary lens array is shown.
In the example shown in fig. 8, an exemplary sample testing device may include an exemplary integrated optical component 1004 coupled to a waveguide 1006 by an exemplary lens array 1008. In some examples, the lens array 1008 may direct light received from the integrated optical component 1004 to the waveguide 1006. In some examples, the integrated optical component 1004 may be the same as or similar to the integrated optical component 804 described above in connection with fig. 8. For example, the integrated optical component 1004 can include one or more collimators and/or polarizers.
In some examples, the lens array 1008 can include at least one microlens array. As used herein, the term "microlens" refers to a transmissive optical device (e.g., an optical lens) having a diameter that is less than a predetermined value. For example, an exemplary microlens may have a diameter of less than 1 millimeter (e.g., 10 microns). The small size of the microlenses may provide the technical benefit of improving optical quality.
As used herein, the term "microlens array" refers to a collection of microlenses that are arranged. For example, the set of microlenses arranged may form a one-dimensional or two-dimensional array pattern. Each microlens in the array pattern may be used to focus and concentrate light, so that light efficiency may be improved. Examples of the present disclosure may encompass various types of microlens arrays, the details of which are described herein.
In some examples, the microlens array may redirect and/or couple light into the waveguide 905 with optimal efficiency. Referring back to fig. 8, the exemplary lens array 1008 may include at least one optical lens. In some examples, each optical lens in lens array 1008 may have a shape similar to a prism shape. For example, each optical lens in the lens array 1008 may be a right angle prism lens. In such an example, each of the optical lenses may be arranged parallel to the other optical lens without overlap or gaps.
In some examples, lens array 1008 may include lenses having different shapes and/or pitches in two or more directions. For example, a first shape of a first optical lens of the microlens array may be different from a second shape of a second optical lens of the microlens array.
For example, the lenses in the lens array 1008 may have a prismatic surface shape along the direction of light transmitted through the waveguide 905, and the pitch of each lens may be determined based on, for example, the microlens height and the prism angle. For example, along another direction (e.g., a direction transverse to the direction of light transmitted through the waveguide 905), the surface of the lens array 1008 may be curved to concentrate light into the central region of the waveguide, which may improve collection efficiency. In this example, the spacing in the direction may be determined based on the height of the microlenses and the surface curvature associated with the lenses.
In some examples, the microlens array may have different arrangements along the waveguide light transmission direction to achieve light uniformity. In some examples, the first surface curvature of the first optical lens may be different from the second surface curvature of the second optical lens in the waveguide light transmission direction. For example, differences between the surface curvatures of the lenses in a microlens array can produce different lens powers. In some examples, the lens power difference may in turn change the light collection efficiency. For example, the light collection efficiency may be varied using different microlens surface curvatures. In some examples, uniform surface curvature microlenses may produce uniform light collection efficiency along, for example, the direction in which light is transmitted through the waveguide. In some examples, different microlens power arrangements may produce non-uniform light collection efficiency to compensate for light intensity variations due to, for example, energy loss along the waveguide. In some examples, different surface powers may produce different pitches for a uniform height microlens array.
Although the above description provides exemplary shapes and pitches of microlens arrays, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, an exemplary microlens array may include one or more shapes and/or pitches.
Although the above description provides an exemplary pattern of an exemplary microlens array, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the example microlens array may include one or more additional and/or alternative elements. For example, one or more optical lenses in the microlens array may be a shape other than a prism shape. Additionally or alternatively, one or more optical lenses in the microlens array may be placed in a hexagonal array.
In some examples, the lens array 1008 may be disposed on the first surface of the waveguide 1006 by a wafer process that utilizes direct etching or etching with post-thermoforming. For example, direct etching using a gray scale mask may produce microlenses having any surface shape, such as spherical lenses or microprisms. Additionally or alternatively, thermoforming may form a spherical lens. Additionally or alternatively, other fabrication processes and/or techniques may be implemented for the disposed lens array disposed on the surface of the waveguide 1006.
Although the above description provides examples of coupling mechanisms between the integrated optical component 1004 and the waveguide 1006, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, one or more additional and/or alternative elements may be implemented to provide a coupling mechanism. For example, a single microlens may be implemented to couple the integrated optical component 1004 with the waveguide 1006.
Referring now to fig. 9, an exemplary diagram illustrating an exemplary lens array is shown. In particular, the exemplary sample testing device may include an exemplary imaging component 1101 coupled to a waveguide 1105 through an exemplary lens array 1103. In some examples, the lens array 1103 may direct light received from the waveguide 1006 to the imaging component 1101.
Similar to the example lens array 1008 described above in connection with fig. 8, the example lens array 1103 may include at least one optical lens. In some examples, each optical lens in the lens array 1103 may have a shape similar to a prism shape. For example, each optical lens in the lens array 1103 may be a right angle prism lens. In such an example, each of the optical lenses may be arranged parallel to the other optical lens without overlap or gaps.
In some examples, a lens component (e.g., lens component 826 described above in connection with fig. 8) may be positioned between the lens array 1103 (e.g., microlens array) and the imaging component 1101.
Although the above description provides an exemplary pattern of an exemplary microlens array, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the example microlens array may include one or more additional and/or alternative elements. For example, one or more optical lenses in the microlens array may be a shape other than a prism shape. Additionally or alternatively, one or more optical lenses in the microlens array may be placed in a hexagonal array.
In some examples, the lens array 1103 may be disposed on the first surface of the waveguide 1105 by a wafer process that utilizes direct etching or etching with post-thermoforming. For example, direct etching using a gray scale mask may produce microlenses having any surface shape, such as spherical lenses or microprisms. Additionally or alternatively, thermoforming may form a spherical lens. Additionally or alternatively, other fabrication processes and/or techniques may be implemented for the disposed lens array disposed on the surface of the waveguide 1105.
Although the above description provides an example of a coupling mechanism between the exemplary imaging component 1101 and the waveguide 1105, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, one or more additional and/or alternative elements may be implemented to provide a coupling mechanism. For example, a single microlens may be implemented to couple the exemplary imaging component 1101 with the waveguide 1105.
In some examples, the sample opening of the interferometry-based sample testing device may be less than 0.1 millimeters. Thus, delivering sample media to the waveguide layer through the sample opening can be technically challenging.
Some examples of the present disclosure may overcome various technical challenges. For example, an exemplary sample testing device may include an open layer and/or a cover layer. Referring now to fig. 10 and 11, exemplary views of an exemplary sample testing device 1200 according to examples of the present disclosure are shown.
In the example shown in fig. 10 and 11, the example sample testing device 1200 may include a waveguide. In some examples, the waveguide may include one or more layers, such as a substrate layer 1202, a waveguide layer 1204, and an interface layer 1206, similar to interface layer 208, waveguide layer 206, and substrate layer 204 described above in connection with fig. 2.
In some examples, the waveguide may have a sample opening on the first surface. For example, as shown in fig. 10 and 11, the interface layer 1206 of the waveguide may include a sample opening 1216. Similar to sample opening 222 described above in connection with fig. 2, sample opening 1216 may be configured to receive a sample medium.
In some examples, the sample testing device 1200 may include an open layer disposed on a first surface of the waveguide. For example, as shown in fig. 10 and 11, an opening layer 1208 may be disposed on a top surface of the interface layer 1206 of the waveguide.
In some examples, the opening layer 1208 may include a first opening 1214. In some examples, the first opening 1214 may at least partially overlap the sample opening 1216 of the interface layer 1206. For example, as shown in fig. 11, the first opening 1214 of the opening layer 1208 may cover the sample opening 1216 of the interface layer 1206. In some examples, the diameter of the first opening 1214 of the opening layer 1208 may be greater than the diameter of the sample opening 1216 of the interface layer 1206.
In some examples, the opening layer 1208 may be formed as an additional oxide layer using a silicon wafer process. In some examples, the first opening 1214 may be etched.
In the example shown in fig. 10 and 11, the example sample testing device 1200 may include a cover layer 1210.
In some examples, the cover layer 1210 may be placed over the sample testing device in a packaging process using polymer molding, such as PMMA.
In some examples, the cover layer 1210 may be coupled to a waveguide of the sample testing device 1200. In some examples, the coupling between the cover layer 1210 and the waveguide may be implemented via at least one sliding mechanism. For example, the cross-section of the cover layer 1210 may be shaped similar to the letter "n". A sliding guard may be attached to the inner surface of each leg of the cover layer 1210 and a corresponding rail may be attached to one or more side surfaces of the waveguide (e.g., side surfaces of the interface layer 1206). Thus, the cover 1210 is slidable between a first position and a second position defined by the slide guard and the rail.
Although the above description provides an example of a sliding mechanism, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the example sliding mechanism may include one or more additional and/or alternative elements and/or structures. For example, the cover layer 1210 may include t-slot sliders disposed on a bottom surface of the cover layer 1210, and the interface layer 1206 may include corresponding t-slot tracks disposed on a top surface of the interface layer 1206.
In some examples, the sliding mechanism may be in contact with the substrate layer 1202 and/or the interface layer 1206 such that it may not be in contact with the waveguide layer 1204. In some examples, there will be no change in optical properties of the waveguide layer 1204 due to the addition of the sliding mechanism.
In some examples, the cover layer 1210 can include a second opening 1212. In some examples, the second opening 1212 of the cover layer 1210 may be circular in shape. In some examples, the second opening 1212 of the cover layer 1210 may be other shapes.
In some examples, the second opening 1212 may have a size (e.g., diameter or width) between 0.5 millimeters and 2.5 millimeters. In contrast, the size (e.g., diameter or width) of sample opening 1216 may be less than 0.1 millimeters. In some examples, the size of the second opening 1212 and/or the size of the sample opening 1216 may have other values.
As described above, the cover layer 1210 may be coupled to the waveguide of the sample testing device 1200 via at least one sliding mechanism. In such an example, the cover layer 1210 may be positioned on top of the opening layer 1208 and may be movable between a first position and a second position.
Fig. 10 and 11 illustrate an example of the cover layer 1210 in a first position. As shown, when the cover layer 1210 is in the first position, the second opening 1212 of the cover layer 1210 may overlap the first opening 1214 of the opening layer 1208.
Referring now to fig. 12 and 13, exemplary views of an exemplary sample testing device 1300 according to examples of the present disclosure are shown.
In the example shown in fig. 12 and 13, the example sample testing device 1300 may include a waveguide. In some examples, the waveguide may include one or more layers, such as a substrate layer 1301, a waveguide layer 1303, and an interface layer 1305, similar to the substrate layer 1202, the waveguide layer 1204, and the interface layer 1206 described above in connection with fig. 10 and 11.
In some examples, the waveguide may have a sample opening on the first surface. For example, as shown in fig. 12 and 13, the interface layer 1305 of the waveguide may include a sample opening 1315. Similar to sample opening 1216 described above in connection with fig. 10 and 11, sample opening 1315 may be configured to receive a sample medium.
In some examples, the sample testing device 1300 may include an open layer disposed on a first surface of the waveguide. For example, as shown in fig. 12 and 13, an opening layer 1307 may be provided on the top surface of the interface layer 1305 of the waveguide.
In some examples, the opening layer 1307 can include a first opening 1313. In some examples, the first opening 1313 may at least partially overlap with the sample opening 1315 of the interface layer 1305. For example, as shown in fig. 13, the first opening 1313 of the opening layer 1307 may cover the sample opening 1315 of the interface layer 1305. In some examples, the diameter of the first opening 1313 of the opening layer 1307 may be greater than the diameter of the sample opening 1315 of the interface layer 1305.
In the example shown in fig. 12 and 13, the example sample testing device 1300 may include a cover layer 1309, similar to the cover layer 1210 described above in connection with fig. 10 and 11.
In some examples, the cover layer 1309 can be coupled to a waveguide of the sample testing device 1300. In some examples, coupling between the cladding layer 1309 and the waveguide can be achieved via at least one sliding mechanism, similar to those described in connection with fig. 10 and 11, in connection with the cladding layer 1210.
In some examples, the cover layer 1309 can include a second opening 1311. In some examples, the second opening 1311 of the cover layer 1309 can comprise a circular shape. In some examples, the second opening 1311 of the overlay 1309 can comprise other shapes.
As described above, the cover layer 1309 may be coupled to the waveguide of the sample testing device 1300 via at least one sliding mechanism. In such an example, the cover layer 1309 can be positioned on top of the opening layer 1307 and can be movable between a first position and a second position.
Fig. 12 and 13 show examples of the cover layer 1309 in a second position. As shown, when the cover layer 1309 is in the second position, the second opening 1311 of the cover layer 1309 may not overlap the first opening 1313 of the opening layer 1307.
In some examples, additional latching or bolting features may be implemented to secure the overlay 1309 in the first or second position. For example, a slidable latch bar may be attached to a side surface of the cover layer 1309, and the waveguide may include a first recessed portion and a second recessed portion on the side surface of the waveguide. In some examples, the overlay 1309 can be secured in the first position when the first recessed portion receives the slidable latch bar. In some examples, the overlay 1309 can be secured in the second position when the second recessed portion receives the slidable latch bar.
While the above description provides examples of latching or bolting features, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the example latch or toggle feature may include one or more additional and/or alternative elements.
In some examples, interferometry-based sample testing devices (e.g., without limitation, dual mode waveguide interferometer-based sample testing devices) may require additional space for imaging components (including, for example, imaging components and lens components). However, the ability to reduce the size (e.g., without limitation, chip size) of the sample testing device may be limited. Thus, the sample testing device may require additional space for the output fringe imaging function.
Some examples of the present disclosure may overcome various technical challenges. For example, by introducing back side illumination and imaging, the output fringe area can be shared with the sampling area to reduce the size of the sample testing device/sensor chip. The cost of the sample testing device may be reduced and the product size may be reduced and/or the product cost may be reduced.
According to various examples of the present disclosure, a two-sided (e.g., without limitation, two-sided) waveguide sample testing apparatus may be provided based on: for example, but not limited to, using backside illuminated image sensor technology, for example, a first surface (e.g., but not limited to, an upper surface or a top surface) of a sample testing device may be used as a sample area and a second surface (e.g., but not limited to, a backside or a bottom surface) may be used for illumination and imaging.
In some examples, during an exemplary manufacturing process, after the silicon wafer is manufactured, the waveguides (e.g., waveguide layers as described above) may be transferred onto a glass wafer. In some examples, a silicon substrate (e.g., a substrate layer as described above) may be modified to allow backside access to the sample testing device. For example, additional openings may be formed on the back side of the sample testing device by an etching process.
While the above description provides an exemplary process for manufacturing a sample testing device, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary process may include one or more additional and/or alternative steps and/or elements. For example, additional layers may be added to further increase the optical coupling efficiency of the input and output of the sample testing device.
In various examples, the imaging component, lens component, and/or light source may be fixedly and/or removably integrated (e.g., without limitation, interfacing, connecting, etc.) with the sample testing device in various configurations and arrangements. The imaging component, lens component, and/or light source may be integrated via any available surface of the sample testing device. For example, the imaging component and the lens component may be fixedly and/or removably integrated with the sample testing device via one or more apertures, fittings, and/or connectors at a lateral end of the sample testing device. In other examples, the imaging component, lens component, and/or light source may be integrated with the sample testing device via one or more holes, fittings, and/or connectors on a bottom surface (e.g., without limitation, a back surface) or an upper surface of the sample testing device.
Fig. 14 illustrates a perspective view of an exemplary sample testing device 1400 according to various examples of the present disclosure. In some examples, exemplary sample testing device 1400 may include an alternatively configured imaging component 1407, lens component 1405, and/or light source 1401.
In the example shown in fig. 14, light source 1401 may be fixedly and/or removably integrated (e.g., without limitation, interfacing, connecting, etc.) with a bottom surface (e.g., without limitation, a back surface) of sample testing device 1400 via a connection to integrated optics 1403. Integrated optic 1403 may be fixedly and/or removably integrated via holes, fittings, connectors, and/or combinations thereof. In addition, imaging component 1407 and lens component 1405 may be directly and/or removably integrated (e.g., without limitation, interfacing, connecting, etc.) with a bottom surface (e.g., without limitation, a back surface) of sample testing device 1400 via different apertures, fittings, connectors, and/or combinations thereof.
In some examples, imaging component 1407 and lens component 1405 may include a microlens array integrated directly into a substrate layer or any other layer of sample testing device 1400. In examples where imaging component 1407, lens component 1405, and light source 1401 are integrated via a bottom surface (e.g., without limitation, a back surface) of sample testing device 1400, a user may interact with, grip, and/or hold a top surface of sample testing device 1400. Additionally, a top surface of the sample testing device 1400 may provide support and/or stabilize the sample testing device 1400. In some examples, an attachment may be provided on the top surface to improve the grip of the sample testing device 1400. In various examples, fixedly and/or removably integrating components (e.g., without limitation, imaging component 1407 and lens component 1405) with sample testing device 1400 reduces the space requirements of sample testing device 1400, thereby providing a compact and efficient solution.
Thus, light may be coupled into sample testing device 1400 through a bottom surface (e.g., without limitation, a back surface) of sample testing device 1400 via light source 1401. In some examples, light may enter waveguide 1409 between a top surface of sample testing device 1400 and a bottom surface (e.g., without limitation, a back surface) of sample testing device 1400 and may travel laterally through waveguide 1409 from an entry point (e.g., without limitation, via one or more optical channels) adjacent light source 1401/integrated optic 1403. In some examples, light may travel toward imaging component 1407/lens component 1405 at the opposite end of sample testing device 1400. In some examples, a processing component (e.g., a processor) may be electrically coupled to the imaging component 1407 and may be configured to analyze the imaging data (e.g., fringe data) to determine, for example, but not limited to, a change in refractive index within the waveguide 1409, as will be described in further detail herein.
Fig. 15 shows an alternative configuration of the example sample testing device of fig. 14 with an alternative configuration of imaging component 1508, lens component 1506, and light source 1502. As shown, the light source 1502 may be fixedly and/or removably integrated (e.g., without limitation, interfacing, connecting, etc.) with a bottom surface (e.g., without limitation, a back surface) of the sample testing device 1500 via a connection to the integrated optical component 1504. The integrated optical component 1504 can be directly and/or removably integrated via holes, fittings, connectors, and/or combinations thereof. Additionally or alternatively, the imaging component 1508 and the lens component 1506 may be directly and/or removably integrated (e.g., without limitation, interfacing, connecting, etc.) with the bottom surface of the sample testing device 1500 via different apertures, fittings, connectors, and/or combinations thereof.
In some examples, imaging component 1508 and lens component 1506 may include a microlens array integrated directly into a substrate layer or any other layer of sample testing device 1500. In examples where the imaging component 1508, the lens component 1506, and the light source 1502 are integrated via a bottom surface (e.g., without limitation, a back surface) of the sample testing device 1500, a user may interact with, grasp, and/or hold the top surface of the sample testing device 1500. Additionally or alternatively, a top surface of the sample testing device 1500 may provide support and/or stabilize the sample testing device 1500. In some examples, the sample testing device 1400 may include a support structure thereon for mounting/supporting the waveguide 1409. An exemplary support structure may include a structure disposed adjacent to at least one surface (e.g., a side surface) of the waveguide 1409.
Thus, light may be coupled into sample testing device 1500 through a bottom surface (e.g., without limitation, a back surface) of sample testing device 1500 via light source 1502. Light enters waveguide 1510 located between the top surface of sample testing device 1500 and the bottom surface (e.g., without limitation, the back surface) of sample testing device 1500 and travels laterally through waveguide 1510 from an entry point adjacent to light source 1502/integrated optical component 1504 (e.g., without limitation, via one or more optical channels) toward imaging component 1508/lens component 1506 at the opposite end of sample testing device 1500.
In various examples, the interferometry-based sample testing devices described herein (e.g., without limitation, dual-mode waveguide interferometer-based sample testing devices) may provide a "lab-on-a-chip" solution for mobile applications. However, practical integration may be limited by the capabilities of the light source and imaging (e.g., without limitation, fringe detection). For example, technical challenges may include designing a simple device that is capable of being integrated with a user computing device (e.g., without limitation, a mobile application) form factor.
Some examples of the present disclosure may overcome various technical challenges. For example, size reduction in combination with backside illumination and sensing may effectively reduce the chip sensor size and/or support component size. In some examples, the reduced-size low profile sensor module may be integrated with a mobile device (such as a mobile terminal for a mobile point-of-care application). In some examples, a backside illumination and interferometry based sample testing device with an integrated input light source and direct imaging sensor may achieve a total module height of less than 6 millimeters and thus may enable integration into a device such as a mobile phone. For example, an exemplary dual mode waveguide interferometer sample testing device can be integrated with a mobile device to provide a point-of-care application for rapid screening of viruses with reliable results.
In various examples, the sample testing device may include a mobile point-of-care component. The mobile point-of-care component may include an attachment configured to receive a user computing device (e.g., without limitation, a mobile device, a handheld terminal, a PDA, etc.) configured to attach to the sample testing device. For example, the mobile point-of-care component may be a mobile phone compatible form factor solution. The sample testing device may include an integrated and/or miniaturized component package configured to be compatible with user computing devices (e.g., without limitation, mobile devices, handheld terminals, PDAs, tablet computers, etc.) similar to point-of-sale products and devices.
Fig. 16A-16C illustrate various views of an exemplary mobile point-of-care component 1600 that may be suitable for integrating (e.g., without limitation, attaching) a sample testing device with a user computing device. Specifically, fig. 16A illustrates an exemplary profile view of a mobile point-of-care component 1600, fig. 16B illustrates an exemplary top view of the mobile point-of-care component, and fig. 16B illustrates an exemplary side view of the mobile point-of-care component. In some examples, an upper surface of the mobile point-of-care component 1600 may be configured to be removably integrated with a user computing device. For example, a user computing device (e.g., a mobile device) may be slid/inserted into an attachment of the mobile point-of-care component 1600 or adjacent to a surface of the mobile point-of-care component.
As shown in fig. 16B, the outline of the mobile point-of-care component 1600 may have a length of about 20 millimeters and a width of about 10 millimeters, corresponding to the form factor of an example user computing device (e.g., without limitation, a mobile device). The mobile point-of-care component 1600 can be fixedly or removably integrated with the sample testing device via the light source 1602/integrated optics 1604. For example, the mobile point-of-care component 1600 may be integrated with the sample testing device via a hole, fitting, connector, and/or combination thereof.
As shown in fig. 16C, the profile height "T" of the mobile point-of-care component 1600 may be about 6 millimeters, suitable for compatibility with a variety of conventionally sized user computing devices. As shown, the sample testing device may be positioned below the mobile point-of-care component 1600 adjacent to the integrated optical component. Other configurations may be implemented.
While the above description provides exemplary measurements of moving the instant check component, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary mobile point-of-care component has one or more measurements that may be less than or greater than those values described above.
In some examples, the light source 1602 and the integrated optical component 1604 may be integrated into a mobile point-of-care component 1600 component, a user computing device component, or the like. The output from the light source 1602/integrated optics 1604 may be transmitted directly to one or more processors of the user computing device (e.g., a mobile device standby camera port).
In some examples, mobile point-of-care component 1600 may integrate the sample testing device and the user computing device such that the hardware components may be shared between them. For example, the sample testing device and the user computing device may utilize the same sensors, optical components, etc. to reduce the number of hardware components in the sample testing device. In some examples, a user computing device chassis (e.g., without limitation, a mobile device chassis) may be positioned on or adjacent to the mobile point-of-care component 1600 using fasteners, retainers, brackets, connectors, cables, and the like.
In addition, mobile point-of-care component 1600 can include additional user device computing hardware and/or other subsystems (not depicted) for providing various user computing device functions. For example, an exemplary user computing device chassis (e.g., without limitation, a mobile device chassis) may be positioned on top of the mobile point-of-care component 1600 such that a user interface is provided (e.g., without limitation, accessible) to receive user input. In some examples, mobile point-of-care component 1600 may include hardware and software to enable integration with a sample testing device. In some examples, the sample testing device may include processing means to enable wireless communication with (e.g., to enable wireless transmission of data to) the computing device/entity. In some embodiments, the sample testing device may transmit data (e.g., images) to a user computing entity (e.g., a mobile device) by wired or wireless means. For example, the sample testing device may transmit images via the mobile device processor camera port using the MIPI serial imaging data connection.
In some examples, it should be appreciated that a user computing device (e.g., without limitation, a mobile device) may be integrated with the mobile point-of-care component 1600 and the sample testing device to serve as a back-facing apparatus. In such examples, user computing device optics, sensors, etc. may generally be used. For example, the user computing device may be integrated with additional custom circuitry and/or computing hardware (not depicted) housed by the mobile point-of-care component 1600, and/or with processing circuitry and/or conventional computing hardware of the user computing device (e.g., without limitation, with the CPU and/or memory via a bus) for further processing of captured and/or processed data from the sample testing device.
In some examples, the dual mode waveguide interferometer biosensor can exhibit high sensitivity in sample refractive index measurements. In addition, the results may also be highly sensitive to ambient temperature. Therefore, it is necessary to maintain a stable temperature during operation.
Some examples of the present disclosure may overcome various technical challenges. In some examples, the proposed thermally controlled waveguide interferometer sample testing apparatus described herein can be maintained at a constant temperature (e.g., within a temperature range) to ensure sensor output accuracy.
In some examples, heating/cooling components (e.g., without limitation, heating and/or cooling elements, plates, pads, etc.) may be provided to adjust the temperature of the waveguide sample testing apparatus. In some examples, an on-chip temperature sensor may be used to monitor the sample testing device/chip temperature. In some examples, a multi-point temperature sensor may be disposed at each corner of the sample testing device substrate layer to monitor uniformity and confirm thermal equilibrium.
In some examples, an insulating housing may be used to isolate the sensor chip from the surrounding environment, leaving only limited access and/or open areas for sample openings (or sample windows) and light input/output. Additional heating/cooling components (e.g., without limitation, heating and/or cooling pads) may be added to one or more surfaces (e.g., without limitation, upper surfaces) of the waveguide sample testing apparatus to further improve temperature uniformity. Exemplary sample testing devices may include resistive heating pads, built-in conductive coatings, additional Peltier cooling plates, and the like.
In some examples, a multi-point temperature sensor may be arranged to improve temperature measurement accuracy. In some examples, sample testing under different temperature conditions may be achieved by setting the temperature control to different values. In some examples, data may be collected regarding sample results and temperature. In some examples, testing may be facilitated due to minimal heating quality.
In some examples, the sample testing device may include a thermally controlled waveguide enclosure configured to maintain a constant temperature relative to the waveguide. The thermally controlled waveguide housing may be or include a housing or sleeve. The thermally controlled waveguide enclosure may include heating and/or cooling pads and/or an insulating enclosure. In some examples, the one or more sensors in the substrate layer may monitor and adjust the temperature of the waveguide during operation. For example, the temperature may be limited to a suitable range (e.g., without limitation, between 10 degrees celsius and 40 degrees celsius).
Fig. 17 illustrates an example thermally controlled waveguide housing 1710 that encapsulates an example waveguide 1700 (e.g., without limitation, embodied as an integrated chip). Waveguide 1700 (including a thermally controlled waveguide enclosure) can have a thickness in the range of 1 millimeter to 3 millimeters. The thermally controlled waveguide housing 1710 may be less than 0.2 millimeters thick. An encapsulation process (e.g., polymer overmolding) may be used to fabricate the exemplary thermally controlled waveguide housing 1710. In another example, an exemplary thermally controlled waveguide housing may include one or more directly coated surfaces of a sample testing device.
While the above description provides exemplary measurements of waveguide 1700 and thermally controlled waveguide housing 1710, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the example waveguide 1700 and the thermally controlled waveguide housing 1710 may have other values.
In some examples, the thermally controlled waveguide housing 1710 may include an insulating semiconductor material, a thermally conductive polymer, ceramic, silicon, or the like. Additionally and/or alternatively, the thermally controlled waveguide housing 1710 can be or include a film and/or coating, such as a silicon or silicon dioxide polymer. Waveguide 1700 may exhibit low thermal mass such that the temperature of waveguide 1700 may be controlled to a precise level (e.g., without limitation, within 1 degree celsius accuracy) in a short period of time. For example, the temperature of waveguide 1700 may be modulated/calibrated in less than 10 seconds.
While the above description provides exemplary materials and/or characteristics for the waveguide 1700 and the thermally controlled waveguide housing 1710, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the example waveguide 1700 and the thermally controlled waveguide housing 1710 may include other materials and/or have other characteristics.
Fig. 18 shows a side view of an exemplary waveguide 1800 and thermal control waveguide housing 1810. Additionally and/or alternatively, the thermally controlled waveguide housing 1810 may include one or more additional layers. For example, the thermally controlled waveguide housing 1810 may include an intermediate layer 1811 to provide insulation and/or promote electrical isolation. Additionally and/or alternatively, the intermediate layer 1811 may include a heating/cooling pad as described above in connection with fig. 17.
In some examples, thermally controlled waveguide housing 1810 may be formed using semiconductor/integrated circuit packaging techniques/processes (e.g., without limitation, thermally insulating polymer overmolding techniques/processes). The thermally controlled waveguide housing 1810 may include an insulating compound or material. The thermally controlled waveguide housing 1810 may include one or more holes that provide an opening for accessing and/or interfacing with the waveguide 1800. For example, the holes may provide access to an interface layer (not depicted) within the thermally controlled waveguide housing 1810. As shown, the waveguide 1800 may include a second aperture through which the light source 1802 and the integrated optical component 1804 may interface (e.g., without limitation, connect) with the waveguide 1800. In addition, the waveguide 1800 may include a third aperture through which the imaging component 1806 and the lens component 1808 may interface with (e.g., without limitation, connect with) the waveguide 1800. In some example examples, one or more films and/or coatings may be applied to the waveguide 1800 or the thermally controlled waveguide housing 1810 using a silicon process. In some examples, the film and/or coating may be applied to only the upper and bottom surfaces of the waveguide 1800 and/or the thermally controlled waveguide housing 1810. In such an example, thin edge leakage is negligible because the thickness of the waveguide 1800 may be small relative to its length and width.
In some examples, obtaining accurate test results from a waveguide may require controlled temperatures in the surrounding environment (e.g., without limitation, an entire laboratory, medical facility, etc.) to reduce or eliminate temperature interference with the test results. The example thermally controlled waveguide enclosure 1810 may facilitate individual level control of the waveguide using one or more temperature sensors (e.g., without limitation, a multi-point temperature sensor) integrated within the substrate layer. For example, the sense diode may be integrated (e.g., without limitation, bonded) within a substrate layer comprising silicon. In some examples, the sense diode may be integrated (e.g., without limitation, bonded) to a different waveguide layer. In some examples, the current through the sense diode may be monitored in order to increase or decrease the temperature associated with the waveguide 1800 substrate layer so that the waveguide 1800 may maintain a constant temperature to ensure sensor output accuracy as well as test stability and accuracy. In some examples, the waveguide may cover an area of approximately 0.5 square inches. The temperature of the waveguide/sample testing device can be continuously monitored and controlled. For example, the control algorithm in the exemplary chip may continuously monitor temperature data and provide optimal control in response to any temperature variations.
Although the above description provides examples of controlling the temperature associated with the waveguide, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, temperature control may be achieved by other means and/or via other devices.
In some examples, the dual mode waveguide interferometer may exhibit high sensitivity under biochemical refractive index test conditions. However, the results may be highly sensitive to temperature. For example, to achieve a desired level of test accuracy, the temperature stability requirement may be 0.001 degrees celsius, which may present a technical challenge in real world applications.
Some examples of the present disclosure may overcome various technical challenges. In some examples, by introducing a built-in reference channel, temperature-dependent measurement variations can be self-calibrated to eliminate temperature-dependent measurement errors. For example, a lab-on-a-chip sample testing device may consist of a dual mode waveguide interferometer with two other adjacent channels for reference. The closely arranged cladding reference channels of the same structure (e.g., without limitation, siO 2) may eliminate the need for precise temperature-dependent control and compensation. Additionally or alternatively, a closed reference cell may be included in a reference channel that is filled with a known reference biochemical solution to further improve accuracy. The biochemical solution may include pure water, known viruses, and the like. Temperature control may be combined with heating/cooling and temperature sensing via sensors to collect sample test results at different temperature conditions. In some examples, the temperature accuracy requirement need only be within a 1 degree celsius level.
In various examples, the sample testing device may include a waveguide configured to couple with and/or receive input from a light source using various methods such as diffraction gratings, end-fire, direct coupling, prism coupling. The waveguide may be or include an integrated chip.
In some examples, the waveguide may be or include a three-dimensional planar waveguide interferometer that includes multiple layers. In some examples, the waveguide may include at least a substrate layer (which defines the bottom of the sample testing device) with a waveguide layer deposited thereon. Additionally and/or alternatively, an interfacial layer may be deposited on or over the waveguide layer. The waveguide may be fabricated as a unitary body or component according to techniques similar to semiconductor fabrication techniques. In some examples, additional intermediate layers may be provided.
Fig. 19 illustrates an exemplary waveguide 1900 that includes a substrate layer 1920, an interface layer 1924 defining a top surface of the waveguide 1900, and a waveguide layer 1922 therebetween. In some embodiments, a flow channel plate may be positioned on the top surface of the waveguide 1900, the details of which are described herein.
The waveguide layer 1922 itself may include one or more layers and/or regions (e.g., without limitation, a film of transparent dielectric material such as silicon nitrate). Waveguide layer 1922 may include a transparent medium configured to laterally receive light from a first/input end of waveguide layer 1922 and couple the light to an opposite/distal end of waveguide layer 1922. Waveguide layer 1922 may be configured to implement a variety of propagation modes, such as a zero-order mode and a first-order mode. For example, waveguide layer 1922 having a stepped profile may correspond to a zero-order mode and a first-order mode.
As shown in fig. 19, the waveguide layer 1922 may include a unitary body having a first region having a first width/thickness (corresponding to the x-direction when the waveguide is viewed in fig. 19) and a second region having a second width/thickness different from the first region. As shown, waveguide layer 1922 may define a stepped profile with a first region corresponding to a first/lower profile and a second region corresponding to a second/higher profile. Each waveguide layer region may correspond to a different dispersion of light/energy therein and, thus, may correspond to a different refractive index than other regions and layers in the waveguide 1900.
During operation, when light is coupled into the waveguide 1900 and travels from a first region corresponding to a first/lower profile of the waveguide layer to a second region corresponding to a second/higher profile, the difference between the refractive index of the first region and the refractive index of the second region causes different dispersions of light corresponding to the zero order mode in the first region and the first order mode in the second region. As described above, the zero-order mode and the first-order mode correspond to two different light beams having different optical path lengths corresponding to different interference fringe patterns. For example, as described above, when there is at least a partial phase difference between the light beams reflected from the region corresponding to the zero-order mode and the region corresponding to the first-order mode, an interference fringe pattern may occur. An exemplary waveguide having a stepped profile may exhibit a phase difference when a traveling light beam reaches an intersection (i.e., a stepped portion) between two different regions. For example, the interference fringe pattern associated with the zeroth order mode may be a single bright spot surrounded by a dim edge, while the interference fringe pattern associated with the first order mode may be more than one bright spot (e.g., without limitation, two bright spots) each surrounded by a dim edge.
In some examples, additional regions with different widths/thicknesses may be included to provide additional step patterns.
The dispersion of light and corresponding interference fringe pattern may be detected and measured in a sensing layer/environment of the sample testing device, such as in a substrate layer (e.g., without limitation, using one or more sensors in the substrate layer). Additionally or alternatively, when surface conditions at the top surface of the sample testing device (e.g., in the interface layer) change (e.g., without limitation, when a medium is deposited thereon), such surface condition changes may cause a change in the refractive index and/or evanescent wave measured directly above the surface of the waveguide. Corresponding changes in the interference fringe pattern may be measured, detected, and/or monitored. In some examples, the interface layer over the waveguide layer may include one or more sample openings (or sample windows) and/or openings/windows configured to receive a medium (e.g., without limitation, a liquid, molecules, and/or combinations thereof) thereon. Thus, the output from the waveguide layer may change in response to the medium being located over the interface layer.
As shown in fig. 19 and described above, the waveguide layer 1922 may define a stepped profile. As shown, the thickness/width of the second region (corresponding to the higher profile/step) of waveguide layer 1922 may be greater than the thickness/width of the first region (corresponding to the lower profile/step). In some examples, the thickness/width of the second region may be at least twice the width of the first region.
Waveguides having a single optical channel/path can present technical challenges when used in test applications. For example, such a system may be sensitive to changes in environmental conditions (e.g., without limitation, temperature changes), which may obscure test results (e.g., without limitation, interference fringe patterns). These challenges can be addressed by including at least one reference channel in the waveguide and ensuring that the environmental conditions within the waveguide are the same during operation.
An exemplary waveguide may include at least one test optical channel (also referred to as a sample channel) and one reference channel, each including an optical path configured to limit light laterally through a waveguide layer in the waveguide. The output of each test/reference channel may be measured and/or monitored independently during operation to ensure consistency of the test and environmental conditions that may lead to inaccurate results (e.g., without limitation, interference fringe pattern inaccuracy caused by environmental conditions). The light source may be configured to uniformly illuminate all of the test/reference channels in the waveguide.
For each optical channel of the plurality of optical channels, small refractive index variations and/or induced refractive index variations (e.g., without limitation, variations in the dispersion of light along the corresponding optical path) may be measured and tested (e.g., without limitation, in the substrate layer) independently to identify the corresponding output (e.g., without limitation, interference fringe pattern) associated with each optical channel. The data describing the output may be captured and transmitted for further operations such as storage, analysis, testing, etc.
In some examples, the substrate layer may serve as a sensing layer/environment for the sample testing device. The substrate layer may be or include a semiconductor integrated circuit/chip (e.g., without limitation, a silicon oxide chip or wafer). Example integrated circuits/chips may include a plurality of sensors, transistors, resistors, diodes, capacitors, and the like. The substrate layer may have a lower refractive index than the waveguide layer described above. The substrate layer may include a protective sealing film that eliminates sensitivity therein to changes in the sensed environment.
The interface layer may include an optically transparent material such as glass or a transparent polymer coupled to and directly over the waveguide layer. Deposition of the medium on the surface of the interface layer may cause a change in refractive index in the underlying optical channel/waveguide layer.
The reference window associated with the reference channel may be covered, sealed, or may be accessible for receiving a deposit of a reference medium thereon (e.g., without limitation, air, water, known biochemical samples, etc.).
The sample window may be configured to receive a sample medium (e.g., without limitation, molecules, liquids, and/or combinations thereof) for testing. In some examples, a sample medium (e.g., without limitation, a biochemical sample) deposited on the sample window may interact with the surface and/or the medium on the surface. For example, by physical attraction (e.g., without limitation, surface tension) or chemical reaction (e.g., without limitation, chemical bonding, antibody reaction, etc.). The surface of the sample window may be configured to interact with a particular type of medium or a particular type of molecule in the medium. In some embodiments, the sample medium may be provided to a flow channel positioned over a sample window, the details of which are described herein.
Fig. 20A and 20B show side cross-sectional views of exemplary configurations of optical channels in a waveguide. As shown, each waveguide 2000A/2000B includes a substrate layer 2020A/2020B, a waveguide layer 2022A/2022B, and an interface layer 2024A/2024B.
Referring to fig. 20A, the waveguide layer 2022A may include a first sample channel 2010A, a first reference channel 2008A, and a second reference channel 2012A associated with a sample window 2002A in the interface layer 2024A. As shown, for testing purposes, the first reference channel 2008A and the second reference channel 2012A may be clad (e.g., without limitation, a silicon oxide clad reference in which there is no reference medium).
Referring to fig. 20B, the waveguide layer 2022B may include a first sample channel 2010B associated with a sample window 2002B in the interface layer 2024B, a first reference channel 2008B associated with a first reference window 2004B in the interface layer 2024B, and a second reference channel 2012B associated with a second reference window 2006B in the interface layer 2024B. For testing purposes, each reference window 2004B, 2006B may be sealed and contain the same or different reference media (e.g., without limitation, air, water, biochemical samples, etc.). Alternatively, in some examples, one reference channel may be clad and a second optical channel may be sealed therein with a medium in an associated reference window.
While the above description provides some example configurations, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, examples may include one or more additional and/or alternative elements. For example, fewer than two or more than two reference channels may be implemented.
Referring back to fig. 20A and 20B, the sample window 2002A/2002B may be configured to receive deposition of a sample medium (e.g., without limitation, molecules, biochemical samples, viruses, and/or the like) on a surface of the interface layer. Exemplary sample testing device components may be reusable, disposable, and/or include a combination of a reusable portion and a disposable portion. In some embodiments, sample window 2002A/2002B can include one or more biological or chemical elements (e.g., antibodies) disposed on a surface to attach certain molecules in a sample medium for testing, similar to those described above. In some embodiments, the sample window 2002A/2000B can be cleaned after each use (e.g., using distilled water, isopropyl alcohol, and/or the like). In some embodiments, the sample medium may be received via a flow channel, the details of which are described herein.
The substrate layer (e.g., without limitation, one or more sensors in the substrate layer of the waveguide) can detect and measure local changes in measured refractive index caused by changes in the direction of travel of light corresponding to different sample media deposited on the sample window 2002A/2002B.
The waveguide layer may include a plurality of sample channels, reference channels, sample windows, and/or combinations thereof. The sample and reference channels in the waveguide layer may be substantially parallel to each other and also associated with openings/windows in the upper interface layer.
Fig. 21-23 illustrate various views of an exemplary waveguide that may be fabricated according to methods similar to semiconductor fabrication techniques and as described herein.
Referring now to fig. 21, an exemplary waveguide 2100 includes a plurality of sample windows 2102, 2104, 2106, each of which is associated with a plurality of optical channels (not shown).
Fig. 22 shows a top view of an exemplary waveguide 2200 comprising a plurality of sample windows 2202, 2204, 2206, each associated with a plurality of buried optical channels 2208, 2210, 2212. Each exemplary optical channel 2208, 2210, 2212 may have a width less than 50nm, a length ranging between 1 millimeter and 5 millimeters, and a depth less than 1 micron, for example, between 0.1 microns and 0.3 microns. Each optical channel 2208, 2210, 2212 may be laterally spaced from an adjacent optical channel by about 0.1 millimeters.
Fig. 23 shows a side view of an exemplary waveguide 2300 having a width of less than about 1 millimeter thick (e.g., without limitation, between 0.2 millimeters and 0.3 millimeters).
Although the above description provides some example measurements, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, examples may include one or more elements having different measurements than those described above.
In some examples, the waveguides may be formed using fabrication techniques and/or processes similar to those used in semiconductor and integrated circuit fabrication.
Fig. 24 illustrates an exemplary fabrication method for producing a waveguide 2400 according to various examples of the present disclosure. Multiple layers/components may be coupled together/layered under suitable laboratory conditions to provide waveguide 2400. As shown, the substrate layer 2402, the intermediate layer 2404, the plurality of waveguide layers 2406, 2408, 2410, and the interface layer 2412 may be coupled together to create the waveguide 2400. In an exemplary fabrication process, after the silicon wafer is fabricated, the waveguide layers 2406, 2408, 2410 may be transferred onto a glass wafer.
"Edge-emitting" refers to a mechanism by which light is directed into a waveguide through its side surfaces (e.g., the "edges"). Edge-emitting waveguides face a number of technical challenges, including properly aligning the waveguide with the light source. This may be caused by a number of factors. For example, sub-micron dimensions of the waveguide cross-section may result in optical alignment requirements that exceed the capability of mass-produced products. For example, on-chip grating couplers may experience wafer processing challenges when aligned.
According to some examples of the present disclosure, an on-chip micro CPC (compound parabolic concentrator) lens array may reduce optical alignment requirements by more than ten times to allow mass production. For example, microlens arrays can be precisely produced using a silicon wafer process. In some embodiments, a single chip, direct edge-emitting waveguide (without additional couplers) may allow for a waveguide sensing product with reduced size and/or lower production costs.
In some embodiments, the micro-CPC lens array may be disposed at an input edge of the waveguide. The output end of each concentrator lens in the micro-CPC lens array may be aligned with one waveguide channel. The input end of each condenser lens may cover an input area to achieve high coupling efficiency. In some embodiments, the on-chip microlenses may be produced with high precision using a silicon process.
In some embodiments, a single chip, direct edge-emitting waveguide (without additional couplers) may reduce the complexity and cost of the application instrumentation while requiring only a minimum number of parts. In some embodiments, the micro-CPC lens array may increase the light input area by more than 3700 times. In some embodiments, the light source may be simplified with a collimation module to further reduce product size and cost.
Referring now to fig. 25, a portion of an exemplary sample testing device 3700 is illustrated. In the example shown in fig. 25, an exemplary sample testing apparatus 3700 includes a substrate 3701, a waveguide 3703 disposed on the substrate 3701, and a lens array 3705 disposed on the substrate 3701.
Similar to the substrate layers described above, the substrate 3701 can provide mechanical support for various components of the sample testing device. For example, the substrate 3701 may provide mechanical support for the waveguide 3703 and the lens array 3705.
In some embodiments, substrate 3701 may include materials such as, but not limited to, glass, silicon oxide, and polymers.
In some examples, waveguide 3703 and/or lens array 3705 may be disposed on top of substrate layer 3701 by various means, including, but not limited to, mechanically (e.g., a fastening clip) and/or chemically (such as using an adhesive material (e.g., glue)).
In some embodiments, the lens array 3705 is configured to direct light to an input edge of the waveguide 3703 (e.g., input edge 3707 shown in fig. 25).
In some embodiments, the lens array 3705 includes a Compound Parabolic Concentrator (CPC) lens array. For example, a Compound Parabolic Concentrator (CPC) lens array includes a plurality of concentrator lenses (e.g., concentrator lens 3705A, concentrator lens 3705B). In the example shown in fig. 25, the output end of each condenser lens is aligned with an optical channel of waveguide 3703 (e.g., an input opening of a corresponding optical channel), and the input end of each condenser lens is aligned with an input light source, the details of which are described herein.
In some embodiments, the lens array 3705 comprises a micro CPC lens array. In some embodiments, the lens array 3705 comprises an asymmetric CPC lens array. In some embodiments, the lens array 3705 comprises an asymmetric micro CPC lens array.
Referring now to fig. 26, a portion of a top view of an exemplary sample testing device 3800 is shown. In the example shown in fig. 26, exemplary sample testing device 3800 can include a lens array including, for example, but not limited to, condenser lens 3804. Exemplary sample testing device 3800 can also include a waveguide, which can include, for example, but is not limited to, optical channel 3802. As described above and in more detail herein, light may travel through an optical channel of a waveguide (e.g., optical channel 3802).
In the example shown in fig. 26, the output end of the condenser lens 3804 is aligned with the input edge of the optical channel 3802. Thus, the lens array may improve the accuracy of guiding light into the waveguide.
Referring now to fig. 27, a portion of a top view of an exemplary sample testing device 3900 is shown. In the example shown in fig. 27, the example waveguide 3917 of the example sample testing device 3900 may include a plurality of optical channels. For example, the waveguide 3917 may include a reference channel 3901, a reference channel 3903, a sample channel 3907, a sample channel 3909, a reference channel 3913, and a reference channel 3915. In some implementations, the exemplary waveguide 3917 may include one or more buried optical channels, wherein the lens array does not direct light into the buried optical channels. For example, the exemplary waveguide 3917 may include a buried reference channel 3905 and a buried reference channel 3911.
As will be described in greater detail herein, the sample channel 3907 and/or the sample channel 3909 may each include or share a sample window for receiving a sample to be tested. The reference channels 3901, 3903, 3913, 3915, 3905, and/or 3911 may be sealed and contain the same or different reference mediums (e.g., but not limited to air, water, biochemical samples, etc.) for testing purposes. Additionally or alternatively, in some examples, one or more of the reference channels may be clad and one or more of the reference channels may be media sealed in an associated reference window.
Referring to fig. 28A and 28B, an exemplary sample testing device 4000 is shown. Similar to those described above in connection with fig. 25, 26, and 27, exemplary sample testing device 4000 may include a substrate 4002, a waveguide 4004, and a lens array 4006. In some embodiments, the waveguide 4004 may include one or more optical channels (e.g., reference channel 4008). In some embodiments, the lens array 4006 can include one or more condenser lenses (e.g., condenser lens 4010).
In some embodiments, the lens array 4006 is configured to direct light to an input edge of the waveguide 4004. For example, each of these condenser lenses is configured to direct light into an input edge of an optical channel of waveguide 4004. As shown in the examples of fig. 28A and 28B, the output edge of the condenser lens 4010 is coupled to and aligned with the input edge of the reference channel 4008.
In some embodiments, the lens array 4006 is also aligned with the light source. For example, one or more optical elements may be implemented to direct light into the lens array (e.g., to the input edge of each of these condenser lenses).
Referring now to fig. 29, an exemplary sample testing device 4100 is shown. Similar to those described above, exemplary sample testing device 4100 can include a substrate 4101, a waveguide 4103, and a lens array 4105. The lens array 4105 may be configured to direct light to an input edge of the waveguide 4103, similar to those described above.
In the example shown in fig. 29, an exemplary sample testing device 4100 can include a light source 4107 and an integrated optical component 4109.
Similar to those described above, the light source 4107 may be configured to generate, emit light (including but not limited to a laser beam) and/or trigger the generation, and/or emission of light. The light source 4107 may be coupled to the integrated optic 4109, and light may travel from the light source 4107 to the integrated optic 4109. Similar to those described above, the integrated optic 4109 may collimate, polarize, and/or couple light to the lens array 4105.
Similar to those described above, the lens array 4105 may be configured to direct light to an input edge of the waveguide 4103. For example, each of the condenser lenses of the lens array 4105 is configured to direct light into an input edge of an optical channel (e.g., a reference channel or a sample channel) of the waveguide. The light travels through the corresponding reference channel or the corresponding sample channel and may be detected by the imaging component 4111. In some embodiments, an imaging component 4111 may be disposed on an output edge of the waveguide 4103 to collect interferometric data.
It should be noted that the scope of the present disclosure is not limited to what has been described above. In some embodiments of the present disclosure, features from the various figures may be substituted and/or combined. For example, while fig. 25, 26, 27, 28A, 28B, and 29 illustrate an exemplary lens array for directing light to an opening of a sample channel or a reference channel, one or more additional or alternative optical elements may be implemented to direct light to an opening of a sample channel or a reference channel, including but not limited to the integrated optical component 804 illustrated in fig. 4 described above.
A multi-channel waveguide (e.g., a waveguide comprising a plurality of optical channels) may include one or more beam splitter components (such as a Y-beam splitter, a U-beam splitter, and/or an S-beam splitter) to illuminate the plurality of optical channels. However, due to the silicon wafer process, many beam splitters may face technical limitations, challenges, and/or application constraints.
For example, fig. 30 shows a portion of an exemplary top view of a waveguide. In the example shown in fig. 30, the waveguide may include one or more Y-splitters. For example, the waveguide may include an exemplary Y-beam splitter 4200.
The Y beam splitter 4200 may be shaped like the letter "Y" and split one beam into two beams. For example, light may travel from the bottom of "Y" to the two top branches of "Y". Referring to the Y beam splitter 4200 shown in fig. 30, light may travel into the input edge 4203, be split into two parts, and exit from the output edges 4205 and 4207.
In some embodiments, one or more Y-beam splitters may be connected in parallel such that light may exit the output edge of one Y-beam splitter and enter the input edge of another Y-beam splitter. In the example shown in fig. 30, multiple Y-beam splitters may be connected to provide multiple light channels (e.g., sample channels and/or reference channels) as described herein.
However, the Y-beam splitter may face production limitations in providing a uniform light splitting structure. In addition, for more than two optical channels, multiple Y-beam splitters may be required, and excessive axial chip space may be required.
As another example, fig. 31 shows a portion of an exemplary top view of a waveguide. In the example shown in fig. 31, the waveguide may include one or more U-splitters. For example, the waveguide may include an exemplary U-beam splitter 4300.
The U beam splitter 4300 may be shaped similar to the letter "U" and split one beam into two beams. For example, light may travel from the bottom of the "U" to the two top branches of the "U". Referring to the U-beam splitter 4300 shown in fig. 31, light may travel into the input edge 4302, split into two parts, and exit from the output edge 4304 and the branch 4306.
In some embodiments, one or more U-splitters may be connected in parallel such that light may exit the output edge of one U-splitter and enter the input edge of another U-splitter. In the example shown in fig. 31, multiple U-beam splitters may be connected to provide multiple light channels (e.g., sample channels and/or reference channels) as described herein.
Similar to the Y beam splitter example described above, the U beam splitter may face production limitations in providing a uniform light splitting structure. The U-beam splitter may also provide a narrower spacing between the optical channels, which may result in optical interference between the optical channels.
As another example, fig. 32 shows a portion of an exemplary top view of a waveguide. In the example shown in fig. 32, the waveguide may include one or more S-splitters. For example, the waveguide may include an exemplary S-beam splitter 4400.
The S beam splitter 4400 may split one light beam into two light beams. Referring to the S-beam splitter 4400 shown in fig. 32, light may travel into the input edge 4401, be split into two parts, and exit from the output edges 4403 and 4405.
In some embodiments, one or more S-splitters may be connected in parallel such that light may exit the output edge of one S-splitter and enter the input edge of another S-splitter. In the example shown in fig. 32, multiple S-beam splitters may be connected to provide multiple light channels (e.g., sample channels and/or reference channels) as described herein.
Similar to the Y beam splitter example and the U beam splitter example described above, the S beam splitter may face production limitations in providing a uniform light beam splitting structure. The S-beam splitters may also require additional axial chip space for the S-transition and may be limited in directing light rays along the elongated cross-sectional angle between the S-beam splitters.
As described above, in some embodiments, the micro-CPC lens array may be disposed at the input edge of the waveguide. The output end of each concentrator lens in the micro-CPC lens array may be aligned with one optical channel. The input end of each condenser lens may cover an input area to achieve high coupling efficiency. In some embodiments, the on-chip microlenses may be produced with high precision using a silicon process.
Thus, according to various examples of the present disclosure, a flood-illuminated multichannel waveguide may flood-illuminate the multichannel in a direct end-fire manner through a micro-CPC lens array, thereby eliminating a beam splitter. In some embodiments, an oversized laser source may provide light into the micro CPC lens array. In some embodiments, light in the illuminated waveguide can be directed to the sensing portion by bending the optical channel, and the bending portion of the optical channel can compensate and optimize the uniformity of the light with minimal chip space requirements.
Referring now to fig. 33A and 33B, an exemplary top view 4500 of at least a portion of an exemplary waveguide 4502 is shown. Specifically, fig. 33B enlarges and shows a portion of the top view shown in fig. 33A (which is the optical channel 4504).
In some embodiments, the exemplary waveguide 4502 may be a flood irradiated multichannel waveguide.
In the example shown in fig. 33A, the waveguide 4502 may include an input edge 4506 for receiving light from a light source. The input edge 4506 of the waveguide 4502 may include a plurality of multi-channel input waveguide openings (also referred to herein as "input openings"), and each input opening of the plurality of input openings corresponds to an opening of an optical channel for receiving input light. For example, input edge 4506 may include input opening 4508.
In some embodiments, the input edge of the waveguide is configured to receive light. In some embodiments, each of the plurality of input openings is configured to receive light. For example, light may travel onto the input edge 4506, and the input edge 4506 may be configured to receive light. As described above, input edge 4506 can include input opening 4508. Thus, input opening 4508 may be configured to receive light. Light may travel through the corresponding optical channel 4504. In some embodiments, each optical channel of the plurality of optical channels (including optical channel 4504) is configured to direct light from a corresponding input opening through the corresponding optical channel.
In some embodiments, the input openings of the plurality of optical channels may have the same width. In some embodiments, the input openings of the plurality of optical channels may have different widths. For example, the different widths of the input openings may balance the energy received between the optical channels under a single gaussian distribution illumination.
In some implementations, the input opening of the optical channel may be perpendicular to the input edge of the waveguide. In some embodiments, the input opening of the optical channel may not be perpendicular to the input edge of the waveguide, which may, for example, eliminate the bending space required in other beam splitters (e.g., S-beam splitters).
In some embodiments, each optical channel of the plurality of optical channels includes a curved portion and a straight portion. For example, in the example shown in fig. 33A and 33B, the optical channel 4504 may include a curved portion 4510 and a straight portion 4512. In some embodiments, the straight portion 4512 is connected to the curved portion 4510, allowing light to travel from an input opening of an optical channel to an output opening of the optical channel.
In the example shown in fig. 33A and 33B, curved portion 4510 may be gradually offset from input opening 4508 and may provide a convergence angle for directing light through optical channel 4504. When the light reaches the end of curved portion 4510, the light may travel to straight portion 4512 and eventually exit optical channel 4504. Thus, the curved portion 4510 may provide a polynomial curve to couple the light beam into the sensor waveguide portion with optimal uniformity through redirection and compensation.
As shown in fig. 33A and 33B, the straight portions of the optical channels may be spaced apart from each other, thus creating a space between the ends of the optical channels. The separation distance between the ends of the optical channels may be determined based on processing power. For example, small intervals may have less energy loss in flood illumination. In some embodiments, flooding with an oversized illumination spot (e.g., oversized laser source) at the waveguide input may reduce alignment requirements due to slower beam convergence angles. For example, misalignment sensitivity may be more than ten times less than end-fire waveguide illumination for examples not implementing the present disclosure. While there may be energy loss from oversized illumination and gap energy loss between the inputs, examples of the present disclosure may provide adequate optical coupling efficiency for low power diode laser inputs and imaging component outputs with high signal-to-noise ratios.
Referring now to fig. 34, an exemplary sample testing device 4600 is shown. Similar to those described above, exemplary sample testing device 4600 may include light source 4601, integrated optics 4603, waveguide 4605, and imaging component 4607.
Similar to those described above, light source 4601 may be configured to generate, emit light (including, but not limited to, a laser beam) and/or trigger the generation, and/or emission of light. The light source 4601 may be coupled to the integrated optic 4603 and light may travel from the light source 4601 to the integrated optic 4603. Similar to those described above, the integrated optical component 4603 can collimate, polarize, and/or couple light to the waveguide 4605. For example, the integrated optical component 4603 may collimate, polarize, and/or couple light to each of the input openings of the plurality of optical channels within the waveguide 4605. The light travels through the plurality of optical channels (e.g., reference channels and/or sample channels) and may be detected by imaging component 4607. In some embodiments, imaging components 4607 may be disposed on the output edge of waveguide 4605 to collect interferometric data.
In the example shown in fig. 34, the waveguide 4605 may include a sensing portion 4609 on a top surface of the waveguide 4605. The sensing portion 4609 can include, for example, one or more sample windows for receiving sample channels of a sample to be tested and/or one or more reference windows for storing reference channels of the same or different reference media (e.g., without limitation, air, water, biochemical samples, etc.) for testing purposes.
In some embodiments, one or more optical channels may share a sample window, thus forming a combined sample channel. In some embodiments, one or more optical channels may share a reference window, forming a joint reference channel. In some embodiments, the sensing portion 4609 may correspond to a straight portion of the optical channel (e.g., without any curved portions).
It should be noted that the scope of the present disclosure is not limited to what has been described above. In some embodiments of the present disclosure, features from the various figures may be substituted and/or combined. For example, as described above, the plurality of optical channels described above may be implemented in a waveguide to create one or more sample channels and one or more reference channels, as described in other figures.
Waveguide edge inputs and outputs may require the addition of coupling components (such as, but not limited to, prisms or gratings) to the waveguide. In some embodiments, the prism may require additional space. In some embodiments, the grating may face wavelength dependence issues. Neither the prism nor the grating can support broadband and may suffer efficiency losses.
Direct edge coupling may be implemented to couple a prism or grating to a waveguide. However, direct edge coupling with the post-polished edge may cause production difficulties during the manufacturing process and may result in excessive mass production costs of the waveguide (e.g., packaged as a waveguide chip). Thus, there is a need for a design and/or mechanism for direct edge coupling that overcomes these challenges and allows for mass production of waveguide chips.
According to various examples of the present disclosure, a sample testing device is provided. In some embodiments, the sample testing device may include a direct edge coupling mechanism capable of achieving optical edge quality. For example, during the fabrication process, the edges of the waveguide may be etched to create recessed optical interface edges such that the waveguide maintains the optical quality of the light input and output surfaces at selected edges after dicing (e.g., finished chips). Since the post-polishing process is omitted, the optical surface quality of the edge surface can be ensured by the silicon wafer process. Thus, the waveguide can be mass produced (e.g., as a lab-on-a-chip product) with the highest efficiency.
In some embodiments, the surface of the optical interface edge may be achieved by etching at the end of the layer-by-layer fabrication process of the waveguide. The surface of the optical interface edge may be etched through all layers and may have optically clear quality to allow light to enter and exit the waveguide directly with minimal loss. In other words, the optical interface edge allows focused light to enter the waveguide directly from the light source and exit the waveguide directly to the imaging component (e.g., photosensor). In some implementations, optical components (such as lenses) may be added to further improve coupling efficiency.
Referring now to fig. 35A and 35B, an exemplary sample testing device 4700 is shown. In particular, the example sample testing device 4700 may be manufactured by various example processes described herein.
In the example shown in fig. 35A, the example sample testing device 4700 may include multiple layers. For example, exemplary sample testing device 4700 may include a substrate layer 4701, an intermediate layer 4703, a waveguide layer 4705, and an interface layer 4707, similar to those described above.
For example, the substrate layer 4701 may include materials such as, but not limited to, glass, silicon oxide, and polymers. The middle layer 4703 may be attached to the substrate layer 4701 by a plurality of fastening mechanisms and/or attachment mechanisms, including, but not limited to, chemical means (e.g., adhesive materials such as glue), mechanical means (e.g., one or more mechanical fasteners or methods such as welding, snap-fit, permanent and/or non-permanent fasteners), and/or suitable means.
In some embodiments, the waveguide layer 4705 includes a waveguide (e.g., a waveguide including one or more optical channels). For example, the waveguide layer of the sample testing device may include a layer comprising SiO2, a layer comprising Si3N4, and a layer comprising SiO 2. In some embodiments, the waveguide layer 4705 may be attached to the middle layer 4703 by a plurality of fastening mechanisms and/or attachment mechanisms, including, but not limited to, chemical means (e.g., adhesive materials such as glue), mechanical means (e.g., one or more mechanical fasteners or methods such as welding, snap-fit, permanent and/or non-permanent fasteners), and/or suitable means.
In some embodiments, interface layer 4707 may include one or more interface elements, such as, but not limited to, one or more sample windows and/or one or more reference windows, similar to those described above. In some embodiments, the interface layer 4707 may be attached to the waveguide layer 4705 by a plurality of fastening mechanisms and/or attachment mechanisms, including, but not limited to, chemical means (e.g., adhesive materials such as glue), mechanical means (e.g., one or more mechanical fasteners or methods such as welding, snap-fit, permanent and/or non-permanent fasteners), and/or suitable means.
In some embodiments, to achieve optical edge quality, a first edge of the intermediate layer, a first edge of the waveguide layer, a second edge of the intermediate layer, and a second edge of the waveguide layer may be etched during the method. Referring now to fig. 35B, various etched edges are shown.
In some embodiments, the middle layer 4703 may include a first edge 4709 and a second edge 4711. In some embodiments, light may enter the middle layer 4703 through the first edge 4709. In some embodiments, light may exit the middle layer 4703 through the second edge 4711.
In some embodiments, the waveguide layer 4705 may include a first edge 4713 and a second edge 4715. In some embodiments, light may enter the waveguide layer 4705 through the first edge 4713. In some embodiments, light may exit the waveguide layer 4705 through the second edge 4715.
In some embodiments, the interface layer 4707 may include a first edge 4717 and a second edge 4719. In some embodiments, light may enter the interface layer 4707 through the first edge 4717. In some embodiments, light may exit the interfacial layer 4707 through the second edge 4719.
During the method for the sample testing device 4700, after attaching the layers, the first edge 4709 of the middle layer 4703, the first edge 4713 of the waveguide layer 4705, and the first edge 4717 of the interface layer 4707 may be etched together such that the first edge 4709 of the middle layer 4703, the first edge 4713 of the waveguide layer 4705, and the first edge 4717 of the interface layer 4707 may be recessed from the edges of the substrate layer 4701. As shown in fig. 35B, light may travel into the waveguide layer 4705 through the input opening 4721 of the waveguide layer 4705. Thus, the etched first edge 4709 of the waveguide layer 4705 may become a recessed optical edge, which may provide improved optical quality with less optical loss.
Similarly, during the method for the sample testing device 4700, after attaching the layers, the second edge 4711 of the middle layer 4703, the second edge 4715 of the waveguide layer 4705, and the second edge 4719 of the interface layer 4707 may be etched together such that the second edge 4711 of the middle layer 4703, the second edge 4715 of the waveguide layer 4705, and the second edge 4719 of the interface layer 4707 may be recessed from the edges of the substrate layer 4701. As shown in fig. 35B, light may propagate out of waveguide layer 4705 through output opening 4723 of waveguide layer 4705. Thus, the etched second edge 4715 of the waveguide layer 4705 may become a recessed optical edge, which may provide improved optical quality with less optical loss.
In some embodiments, after etching the first edge 4709 of the middle layer 4703, the first edge 4713 of the waveguide layer 4705, and the first edge 4717 of the interface layer 4707, the method may further include coupling a light source to the first edge 4713 of the waveguide layer 4705. In some embodiments, after etching the second edge 4711 of the middle layer 4703, the second edge 4715 of the waveguide layer 4705, and the second edge 4719 of the interface layer 4707, the method may further include coupling an imaging component to the second edge 4715 of the waveguide layer 4705.
The light source may be configured to generate, emit light (including but not limited to a laser beam) and/or trigger the generation, and/or emission of light. For example, the light source may include, but is not limited to, a laser diode (e.g., a violet laser diode, a visible laser diode, an edge-emitting laser diode, a surface-emitting laser diode, etc.). As described above, light may be emitted from a light source and enter the sample testing device 4700 through the input opening 4721 on the first edge 4713 of the waveguide layer 4705. Since the first edge 4713 has been etched during the method, light can enter the waveguide layer 4705 with less loss. As described above, light may exit the sample testing device 4700 through the output opening 4723 on the second edge 4715 of the waveguide layer 4705. Since the second edge 4715 has been etched during the method, light can leave the waveguide layer 4705 with less loss.
Accordingly, the sample testing device 4700 may be designed with recessed edges for optical input and output (e.g., as a direct edge coupled waveguide chip). In some embodiments, a safety margin may be implemented during the etching process to ensure quality of the optical interface edge without causing damage during the process and handling.
In some embodiments, one or more layers of the sample testing device 4700 (e.g., the middle layer 4703, the waveguide layer 4705, and/or the interface layer 4707, together as a direct edge optical coupling component) may be registered with the surface of the substrate layer 4701 for high precision alignment.
In some embodiments, an index matching fluid may be applied to various edges to achieve high coupling efficiency for high numerical aperture optical applications. For example, a fluid having an index of refraction matching that of waveguide layer 4705 may be applied on first edge 4713 and/or second edge 4715. Additionally or alternatively, a fluid having an index of refraction matching the index of refraction of the middle layer 4703 may be applied on the first edge 4709 and/or the second edge 4711. Additionally or alternatively, a fluid having an index of refraction matching the index of refraction of the interface layer 4707 may be applied on the first edge 4717 and/or the second edge 4719.
In various embodiments of the present disclosure, an exemplary sample testing device may be in the form of a lab-on-a-chip (LOC) device that includes a microsensor chip (e.g., a waveguide layer) and an on-chip microfluidic (e.g., an on-chip fluidic layer). Manufacturing miniaturized additional microfluidic technologies presents technical difficulties and packaging microchips with microfluidic technologies is also technically challenging.
In some embodiments, an optical viral sensor with on-chip microfluidics can be precisely formed using a silicon wafer process by adding cover glass with built-in fluid input openings (or inlets) and output openings (or outlets) in a chip-scale sensor packaging process. Wafer-processed microfluidics may reduce costs associated with adding precision-molding fluids, and chip-scale packaging may eliminate the assembly process of precision-molding fluids.
Accordingly, various embodiments of the present disclosure may provide wafer level packaging processes with high precision and low cost, minimal sensor size for miniaturized instrument integration, glass surface fluidic interfaces with quick and easy connection and sealing, and/or direct edge optical input and output that simplify optical assembly.
Referring now to fig. 36, an exemplary device 4800 is shown. In some embodiments, exemplary device 4800 can be a waveguide with on-chip fluid, which can be fabricated according to embodiments of the present disclosure.
In the example shown in fig. 36, to fabricate example apparatus 4800, example methods may include producing waveguide layer 4801 and producing on-chip fluid layer 4803. As described herein, the on-chip fluid layer (or means for providing on-chip fluid) may also be referred to as a "flow channel plate".
In various embodiments of the present disclosure, waveguide layer 4801 can be generated or fabricated according to various examples described herein. For example, according to embodiments of the present disclosure, the waveguide layer 48101 may provide one or more waveguides including an optical channel (e.g., optical channel 4811).
As shown in fig. 36, on-chip fluid layer 4803 can include a plurality of flow channels that provide a flow path for sample media. In the example shown in fig. 36, the on-chip fluid layer 4803 may include a flow channel 4805, a flow channel 4807, and a flow channel 4809. Each of the flow channels 4805, 4807, and 4809 can be in the form of a gap connecting the input aperture to the output aperture.
In some embodiments, on-chip fluid layer 4803 can include a polymeric SU-8 material. Additionally or alternatively, the on-chip fluid layer 4803 can include other materials.
In some embodiments, an exemplary method may include attaching an on-chip fluid layer 4803 to a top surface of a waveguide layer 4801. In particular, the plurality of flow channels (e.g., flow channel 4805, flow channel 4807, and flow channel 4809) of the on-chip fluid layer 4803 can be aligned on top of the optical channels of the waveguide layer 4801 (e.g., flow channel 48107 can be aligned on top of the optical channels 4811).
Referring now to fig. 37, an exemplary device 4900 is shown. In particular, exemplary devices may be manufactured according to embodiments of the present disclosure.
In the example shown in fig. 37, to fabricate the example apparatus 4900, an example method may include: creating an adhesive layer 4906; attaching an adhesive layer 4906 on a top surface of device 4800; and attaching a cover glass layer 4908 on the top surface of the adhesive layer 4906. In some implementations, the device 4800 can be a waveguide with an on-chip fluid layer fabricated according to various examples described herein.
The adhesive layer 4906 may comprise a suitable material such as, but not limited to, silicon. In some embodiments, an adhesive material may be disposed on a top surface of adhesive layer 4906 and/or a bottom surface of adhesive layer 4906, such as, but not limited to, a chemical glue.
As shown in fig. 37, the adhesive layer 4906 may include a plurality of flow channels that provide flow paths for the sample medium. In the example shown in fig. 37, the adhesive layer 4906 may include a flow channel 4910, a flow channel 4912, and a flow channel 4914. Each of the flow channel 4910, the flow channel 4912, and the flow channel 4914 may be in the form of a gap connecting the input aperture to the output aperture.
In some embodiments, the plurality of flow channels of adhesive layer 4906 may be aligned with and/or overlap with the plurality of flow channels of the on-chip fluid layer of device 4800 as described above. As described above, the device 4800 can include an on-chip fluid layer on the top surface. After the adhesive layer 4906 is attached on the top surface of the apparatus 4800, each of the flow channels of the adhesive layer 4906 may be aligned with and/or overlap one of the flow channels of the on-chip fluid layer of the device 4800.
Referring back to fig. 37, the cover glass layer 4908 can include a material such as a glass material.
The cover glass layer 4908 may include one or more input openings and one or more output openings. For example, cover glass layer 4908 can include input opening 4916, input opening 4918, and input opening 4920. Sample media may enter through input opening 4916, input opening 4918, and input opening 4920. The cover glass layer 4908 may include an output opening 4922, an output opening 4924, and an output opening 4926. Sample media may exit through output opening 4922, output opening 4924, and output opening 4926.
In some embodiments, the input and output openings of the cover glass layer 4908 may be aligned with and/or overlap the input and output apertures of the flow channels in the adhesive layer 4906. As described above, each of the flow channels in the adhesive layer 4906 may connect an input aperture with an output aperture. After the cover glass layer 4908 is attached to the top surface of the adhesive layer 4906, each of the input openings of the cover glass layer 4908 may be aligned with and/or overlap one of the input holes of the adhesive layer 4906 and each of the output openings of the cover glass layer 4908 may be aligned with and/or overlap one of the output holes of the adhesive layer 4906.
Referring now to fig. 38, an exemplary apparatus 5000 is shown. In particular, exemplary device 5000 may be manufactured according to embodiments of the present disclosure.
In the example shown in fig. 38, to manufacture the example apparatus 5000, an example method may include producing the apparatus 4800 and attaching the cover glass member 5001 to the apparatus 4800. In some examples, device 4800 can be a waveguide with on-chip fluid fabricated according to various examples described herein. In some examples, the cover glass member 5001 can include a cover glass layer and an adhesive layer manufactured according to various examples described herein.
In some embodiments, the example device 5000 may be cut into individual sensors with protective films attached.
In various examples of the present disclosure, photonic integrated circuits may require precise alignment between optical input and output, which may limit their application in mass production and mass deployment. For example, lab-on-a-chip photonic integrated circuit devices may require field-available solutions and require precise alignment, which may limit their application.
As described above, various examples of the present disclosure may provide a sample testing device including a waveguide (e.g., a waveguide interferometer sensor). In many applications, the waveguide can only tolerate alignment errors of < +/-5 microns, < +/-2 microns, and < +/-10 microns in the X-direction (along the waveguide surface), Y-direction (perpendicular to the waveguide surface), and Z-direction (distance from the light source to the waveguide input end). However, many sensor packaging processes can only achieve die placement accuracy of +/-25 microns. Thus, the best-effort active alignment placement process may not meet this requirement with limited mass production capability and an effective solution is needed for field-usable applications in alignment.
According to various examples of the present disclosure, deep silicon edge etching techniques may be used, as described above. The etched edges may also provide alignment surface features to directly align the waveguide device to the micrometer and sub-micrometer levels. In some embodiments, the direct alignment apparatus may be used in mass production without alignment adjustment and may achieve high production efficiency. Furthermore, a direct insert assembly process may also be used in replacing the waveguide without the need for special tools.
In various examples of the present disclosure, a deep etching technique may be implemented on the substrate edge of the silicon waveguide to provide alignment features in the X and Z directions with relative alignment accuracy that may be as high as the level of silicon wafer process feature dimensions, which may be less than one tenth of a micron. In some implementations, the alignment features in the Z-direction may use the silicon top surface as a reference, whose relative accuracy may reach a level of silicon wafer film layer thickness, which may be less than one hundredth micron.
In some embodiments, the assembly mechanism for aligning the waveguides in the alignment arrangement may include pushing the waveguides to resiliently position in direct contact against the alignment features. In some embodiments, the final integrated alignment error is a combination of alignment feature error and contact gap between the waveguide and the alignment feature, which can reach submicron levels with clean contact surfaces.
In some implementations, a chip scale package may be used with the recessed cover glass to expose the alignment features. For example, a spring loaded seating interface may be designed to fix the waveguide relative to the alignment feature surface. In some embodiments, a fluid shim member (e.g., a silicone fluid shim) and a thermal pad may provide a compressive force for contact alignment without the need for additional mechanisms.
Referring now to fig. 39A, 39B, and 39C, exemplary views of exemplary waveguide holder components are shown. Specifically, fig. 39A shows an exemplary exploded view of an exemplary waveguide retainer component 5100, fig. 39B shows an exemplary top view of the exemplary waveguide retainer component 5100, and fig. 39C shows an exemplary oblique view of the exemplary waveguide retainer component 5100.
Referring back to fig. 39A, an exemplary waveguide retainer component 5100 may include a retainer cap element 5101 and a fluid shim element 5103.
In some embodiments, the retainer cap element 5101 can include one or more openings on a top surface of the retainer cap element 5101. For example, the retainer cap element 5101 may include an input opening 5105, an input opening 5107, and an input opening 5109. When the example waveguide holder member 5100 is in use, a sample or reference medium may travel through the input opening 5105, the input opening 5107, and/or the input opening 5109 and may enter the waveguide. The retainer cap element 5101 can include an output opening 5111, an output opening 5113, and an output opening 5115. When the example waveguide retainer member 5100 is in use, a sample may travel through the output opening 5111, the output opening 5113, and/or the output opening 5115 and may exit from the waveguide.
In some embodiments, the retainer covering element 5101 may include one or more alignment features on a side surface for aligning the light source. For example, the one or more alignment features may be in the form of surface depressions (e.g., surface depressions 5117 and 5119 shown in fig. 39A). When the light source is coupled to the waveguide to provide input light, the light source may include protrusions on its side surfaces, which may correspond to the surface indentations 5117 and 5119, thus enabling the light source to be properly aligned with the waveguide.
Referring back to fig. 39A, the fluid shim member 5103 can include one or more channels or inlets/outlets protruding from a top surface of the fluid shim member 5103. For example, the fluid shim member 5103 can include an inlet 5121, an inlet 5123, and an inlet 5125. The inlet 5121 can be coupled to the input opening 5107 of the retainer cap element 5101. The inlet 5123 can be coupled to the input opening 5109 of the retainer cap element 5101. The inlet 5125 can be coupled to the input opening 5105 of the retainer cap element 5101. When the example waveguide retainer member 5100 is in use, a sample or reference medium may travel through the input opening 5107 to the inlet 5121, through the input opening 5109 to the inlet 5123, and/or through the input opening 5105 to the inlet 5125, and may enter the waveguide. In the example shown in fig. 39A, the fluid shim element 5103 may include an outlet 5131, an outlet 5127, and an outlet 5129. The outlet 5131 can be coupled to the output opening 5111 of the retainer cap element 5101. The outlet 5127 can be coupled to the output opening 5113 of the retainer cap element 5101. The outlet 5129 can be coupled to the output opening 5115 of the retainer cap element 5101. When the example waveguide retainer member 5100 is in use, a sample or reference medium may travel through the outlet 5131 to the output opening 5111, through the outlet 5127 to the output opening 5113, and/or through the outlet 5127 to the output opening 5115 and may exit the waveguide.
Thus, the inlet 5121, inlet 5123, inlet 5125, outlet 5131, outlet 5127, and/or outlet 5129 can enable the fluid shim element 5103 to be secured to the retainer cap element 5101 while allowing sample or reference medium to travel therethrough. When in use, the fluid shim element 5103 may be positioned between the retainer cap element 5101 and the waveguide.
In some implementations, the fluid shim element 5103 can provide a compressive force on the waveguide to contact the alignment features of the waveguide retainer component 5100 (e.g., such that etched edges of the waveguide abut the alignment features, details of which are described herein).
Referring now to fig. 39B and 39C, various exemplary alignment features associated with the waveguide retainer component 5100 are shown.
For example, the waveguide retainer component 5100 may include at least an alignment feature 5133 and an alignment feature 5135. Specifically, the alignment features 5133 and 5135 may be in the form of protrusions from the inside surface of the waveguide retainer component 5100. In some embodiments, alignment features 5133 and 5135 may be referred to as X-direction alignment features because they are configured to align the waveguide in the X-direction (e.g., a direction parallel to the direction of the optical channels in the waveguide). For example, the waveguide may include one or more etched and/or recessed edges (details of which are described herein), and the etched and/or recessed edges may be urged against alignment features 5133 and/or alignment features 5135 (which may be resiliently contracted) of the waveguide holder component 5100 in an alignment arrangement in order to securely and correctly align the waveguide in the X-direction.
Additionally or alternatively, the waveguide retainer component 5100 may include at least an alignment feature 5137 and an alignment feature 5139. Specifically, the alignment features 5137 and 5139 may be in the form of grooves on the inner surface of the waveguide retainer component 5100. In some embodiments, alignment features 5133 and 5135 may be referred to as Y-direction alignment features because they are configured to align the waveguide in the Y-direction (e.g., a direction perpendicular to the direction of the optical channels in the waveguide), the details of which are described herein. For example, the waveguide may include one or more etched and/or recessed edges (details of which are described herein), and the etched and/or recessed edges may be urged against alignment features 5133 and/or alignment features 5135 (which may be resiliently contracted) of the waveguide holder component 5100 in an alignment arrangement in order to securely and correctly align the waveguide in the Y-direction.
Additionally or alternatively, the waveguide retainer component 5100 may include at least one alignment feature 5141. Specifically, the alignment feature 5141 may be in the form of a protrusion on the inside surface of the waveguide retainer component 5100. In some embodiments, the alignment feature 5141 may be referred to as a Z-direction alignment feature because it is configured to align the waveguide in the Z-direction (e.g., the direction from the light source to the input end of the waveguide). For example, the waveguide may include one or more etched and/or recessed edges (details of which are described herein), and the etched and/or recessed edges may be pushed against alignment features 5141 of the waveguide retainer component 5100 in an alignment arrangement in order to securely and properly align the waveguide in the Z-direction.
Referring now to fig. 40A, 40B, and 40C, an exemplary waveguide 5200 is illustrated. In various embodiments, the exemplary waveguide 5200 can comprise a waveguide layer element 5202 and a cover glass layer 5204 disposed on a top surface of the waveguide layer element 5202.
In some embodiments, the cover glass layer 5204 can include a transparent material, such as, but not limited to, glass. In some embodiments, the cover glass layer 5204 can include one or more openings. For example, the cover glass layer 5204 can include an input opening 5208, an input opening 5206, and/or an input opening 5210, and a sample can enter the waveguide 5200 through the input opening 5208, the input opening 5206, and/or the input opening 5210. The cover glass layer 5204 can include an output opening 5218, an output opening 5220, and/or an output opening 5222, and the sample can exit the waveguide 5200 through the output opening 5218, the output opening 5220, and/or the output opening 5222.
In some embodiments, a channel may connect an input opening with an output opening. For example, a sample or reference medium may enter through the input opening 5208, travel through the channel 5212, and exit from the output opening 5218. Additionally or alternatively, the sample or reference medium may enter through the input opening 5206, travel through the channel 5214, and exit from the output opening 5220. Additionally or alternatively, the sample or reference medium may enter through the input opening 5210, travel through the channel 5216, and exit from the output opening 5222.
In some embodiments, the cover glass layer 5204 can include at least one recessed edge. Referring now to fig. 40B and 40C, the edge 5224 of the cover glass layer 5204 can be recessed from the edge of the waveguide layer element 5202. The recessed edge 5224 can be manufactured by, for example, but not limited to, the exemplary etching process described above. In some implementations, the recessed edge 5224 of the cover glass layer 5204 can support and guide the proper alignment of the waveguide 5200.
For example, when the waveguide 5200 is properly aligned with the waveguide retainer component 5100 in the X-direction, the recessed edge 5224 can be pushed against the alignment features 5133 and 5135 of the waveguide retainer component 5100 shown in fig. 39B and 39C.
In some embodiments, waveguide layer element 5202 may include one or more waveguide layers and a substrate layer. As described above, the edge of the waveguide layer element 5202 can be etched.
For example, in the example shown in fig. 40B, the edge 5226 of the waveguide layer can be etched and become a recessed edge. In some embodiments, the recessed edges of the waveguide layer of the resulting waveguide layer element 5202 can support and guide the proper alignment of the waveguide 5200. For example, when the waveguide 5200 is properly aligned with the waveguide retainer component 5100 in the Y-direction, the etched edge 5226 can be pushed against the alignment features 5133 and 5135 of the waveguide retainer component 5100 shown in fig. 39B and 39C.
Additionally or alternatively, as described above, the input edge 5228 of the waveguide layer can be etched and become the edge of the recess. In some embodiments, the recessed edges of the waveguide layer of the resulting waveguide layer element 5202 can support and guide the proper alignment of the waveguide 5200. For example, when the waveguide 5200 is properly aligned with the waveguide retainer component 5100 in the Z-direction, the etched edge 5228 can be pushed against the alignment feature 5141 of the waveguide retainer component 5100 shown in fig. 39B and 39C.
Referring now to fig. 41A and 41B, exemplary views of an exemplary sample testing device 5300 are shown. In particular, exemplary sample testing device 5300 may include waveguide holder component 5301, waveguide 5303, and thermal pad 5305.
In some embodiments, the waveguide retainer member 5301 may be similar to the waveguide retainer member 5100 described above in connection with fig. 39A, 39B, and 39C. For example, the waveguide holder member 5301 may include at least one alignment feature. In some embodiments, the at least one alignment feature may support and guide the alignment of the waveguide 5303. In some embodiments, at least one etched edge of the waveguide 5303 may be pushed against at least one alignment feature of the waveguide holder member in an alignment arrangement.
In some embodiments, the thermal pad 5305 may be configured to provide thermal control of the waveguide 5303. In some embodiments, the thermal pad 5305 may provide a compressive force to the top surface of the waveguide 5303 for precise alignment.
Immunoassay-based sensors may be suitable for single-use only. For example, pregnancy detectors are a type of disposable lateral immunoassay device, and the costs associated with producing pregnancy detectors are low, which may justify the disposable nature of such detectors. However, in many applications, disposable sensors can result in wasted material and present challenges in dealing with possible biohazards. Thus, there is a need for a reusable sensor that is field-refurbishable.
According to various embodiments of the present disclosure, an optical immunoassay sensor (such as the various sample testing devices described herein) may continuously detect and monitor in real-time viruses in airborne aerosols or breath exhalates and nasal swabs or saliva.
In some embodiments, the refuelable optical immunoassay sensor may include a waveguide (e.g., a waveguide evanescent sensor) having a silicon nitride waveguide on a silicon oxide buffered silicon substrate. A silane layer may be added on top of the silicon oxide coated silicon nitride in the waveguide for antibody attachment. A waveguide with an optimal distance from the top of the antibody to the top of the silicon nitride can provide optimal detection sensitivity for antibody-induced virus binding activity.
In some embodiments, the waveguide may be irradiated with laser light from the light input end. Refractive index changes in the evanescent wave may introduce interference pattern changes in the output field, which may be captured by the imaging component. The data from the imaging component is then processed and reported along with the virus detection results.
In some embodiments, the antibody solution may be applied through a sample channel of an exemplary sample testing device described herein. After a period of incubation, distilled water or buffer solution is delivered through the sample channel to wash away unattached antibodies, leaving a uniform layer of antibodies on the sensing surface. For example, the buffer solution may be in the form of an aqueous solution that resists pH changes when acidic or basic substances (e.g., from a sample) are added to the buffer solution. For example, the buffer solution may comprise a mixture of weak acids and their conjugate bases, and vice versa. During testing, sample medium is supplied through the sample channel. The specifically targeted virus can be captured and form an adhesive and immobilized viral layer on the sensing surface. The sample testing device may then detect the presence of the virus and its concentration level.
In some embodiments, after positive detection of a particular virus, a cleaning fluid may be flushed through the sample channel to clean the sensing surface. After cleaning, antibody solution is again applied through the sample channel and the waveguide is ready for the next test.
As described above, a microfluidic (e.g., an on-chip fluid layer) may be disposed on the top surface of the waveguide, which may allow fluids (such as sample media and reference media) to flow on top of and be applied to the sensing region at optimal flow rates and concentrations for virus detection, while providing optimized cleaning and refreshing.
Referring now to fig. 42A, 42B, 42C, and 42D, an exemplary waveguide 5400 and associated methods are illustrated.
In the examples shown in fig. 42A, 42B, 42C, and 42D, the example waveguide 5400 may be an example sample testing device according to various examples of the present disclosure. For example, the waveguide 5400 can include a substrate layer comprising Si. The waveguide 5400 can include a waveguide layer disposed on top of a substrate layer and can include a SiO2 layer, a Si3N4 layer disposed on top of the SiO2 layer, and one or more SiO2 layers disposed on top of the SiO2 layer. The waveguide 5400 may further include a layer of SiH4 as shown in fig. 42A.
In some embodiments, the waveguide 5400 can include a fluidic component 5401 disposed on a top surface of the waveguide 5400. For example, the fluidic component 5401 may be an on-chip fluidic layer as described herein.
Referring now to fig. 42A, an antibody solution 5403 can be applied through a sample channel of a fluidic component 5401 and/or a waveguide 5400. For example, antibody solution 5403 may be injected through an input opening of a sample channel and exit from an output opening of the sample channel. In some embodiments, the antibody solution 5403 may include suitable antibodies based on the virus to be detected. In some embodiments, the waveguide 5400 can include a silane layer added on top of the silicon oxide coated silicon nitride for antibody attachment.
After application of the antibody solution, the antibody needs to be incubated for some time to adhere. After the incubation period has elapsed, a buffer solution (such as distilled water) may be delivered through the sample channel to wash away unattached antibodies.
Referring now to fig. 42B, a buffer solution in the form of water 5407 can be applied through the sample channel of the fluidic component 5401 and/or the waveguide 5400. For example, water 5407 can be injected through an input opening of a sample channel and exit from an output opening of the sample channel. The water 5407 can wash away unattached antibodies from the sample channel, leaving a uniform antibody layer 5405 on the sensing surface.
Although the above description provides an example of water as a buffer solution, it should be noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary buffer solution may include one or more additional and/or alternative chemicals and/or compounds.
Referring now to fig. 42C, during testing, a sample medium may be applied through the sample channel of the fluidic component 5401 and/or the waveguide 5400. For example, the sample medium may be injected through the input opening of the sample channel and exit from the output opening of the sample channel. In some embodiments, the sample may be supplied into buffer solution 5409. The specific targeted virus may be captured by antibody 5405, which may form an adhesive and immobilized viral layer on the sensing surface. The sample testing device may then detect the presence of the virus and its concentration level.
Referring now to fig. 42D, a cleaning solution 5411 can be flushed through the sample channel to clean the sensing surface (e.g., after positive detection of virus). In some embodiments, the cleaning solution 5411 can remove viruses and/or antibodies from the sensing surface. In some embodiments, cleaning solution 5411 may include suitable chemicals and/or compounds, including but not limited to ethanol. After cleaning, as shown in fig. 42A, antibody solution 5403 is again applied through the sample channel and the waveguide can be subjected to the next test.
The embodiment device may perform any of the various processes, methods, and/or computer-implemented methods for advanced sensing and processing described herein, e.g., as described herein with respect to the various figures herein. In some contexts, one or more embodiments may be configured with additional and/or alternative modules embodied in hardware, software, firmware, or a combination thereof, for performing all or some of such methods. For example, one or more embodiments include additional and/or alternative hardware, software, and/or firmware configured to perform one or more processes for processing interference fringe data embodying an interference fringe pattern in order to identify and/or classify unidentified sample media. In this regard, sample testing devices (such as those discussed herein and including but not limited to interferometers) may include or otherwise be communicatively linked with additional modules embodied in hardware, software, firmware and/or combinations thereof for performing such additional or alternative processing operations. It should be appreciated that in some embodiments, such additional modules embodied in hardware, software, firmware, and/or combinations thereof may additionally or alternatively perform one or more core operations with respect to the functionality of the sample testing device, such as activating and/or adjusting one or more light sources, activating and/or adjusting one or more imaging components. In at least one exemplary context, such additional and/or alternative modules embodied in hardware, software, firmware, and/or any combination thereof may be configured to perform the operations of the processes described below with respect to the various figures herein, which may be performed alone or in combination with hardware, software, and/or firmware of a sample testing device, or in combination with one or more hardware, software, and/or firmware modules of a sensing apparatus.
Although the components are described with respect to functional limitations, it should be appreciated that a particular implementation necessarily involves the use of particular hardware. It should also be understood that certain components described herein may include similar or common hardware. For example, both modules may use the same processor, network interface, storage medium, etc. to perform their associated functions such that each module does not require duplicate hardware. Thus, it should be understood that the use of the terms "module" and/or "circuit" as used herein with respect to components of any of the example apparatuses includes particular hardware configured to perform the functions associated with the particular modules described herein.
Additionally or alternatively, the terms "module" and/or "circuit" should be construed broadly to include hardware, and in some embodiments, software and/or firmware for configuring the hardware. For example, in some embodiments, "modules" and "circuitry" may include processing circuitry, storage media, network interfaces, input/output devices, support modules for interfacing with one or more other hardware, software, and/or firmware modules, and so forth. In some embodiments, other elements of the apparatus may provide or supplement the functionality of a particular module. For example, a processor (or multiple processors) may perform one or more operations and/or provide processing functions to one or more associated modules, a memory (or memories) may provide storage functions for one or more associated modules, and so on. In some embodiments, the one or more processors and/or the one or more memories are specifically configured to communicate in conjunction with each other for performing one or more of the operations described herein, e.g., as described herein with respect to the various figures herein.
FIG. 45 illustrates a block diagram of an exemplary apparatus for advanced sensing and processing in accordance with at least one exemplary embodiment of the present disclosure. In this regard, the apparatus 2700 as depicted may be configured to perform one, some, or all of the methods disclosed herein. In at least one example embodiment, the apparatus 2700 embodies an advanced interferometry apparatus configured to perform an interferometry process described herein and one or more of the advanced sensing and/or processing methods described herein with respect to the various figures.
As depicted, apparatus 2700 includes sample testing device 2706. The sample testing device may include and/or embody one or more devices embodied in hardware, software, firmware, or a combination thereof for projecting one or more interference fringe patterns associated with unidentified sample media and/or capturing sample interference fringe data representing the interference fringe patterns for processing. In some embodiments, for example, sample testing device 2706 comprises or is otherwise embodied as one or more interferometry devices and/or components thereof (e.g., at least one waveguide, at least one light source, at least one imaging component, support hardware for these components, and/or the like). In at least one example embodiment, sample testing apparatus 2706 is embodied by one or more of the devices described herein (e.g., with respect to the figures herein) and/or components thereof. For example, in some embodiments, the sample testing device is embodied as an interferometry apparatus configured as described herein with respect to these figures.
The apparatus 2700 also includes a processor 2702 and a memory 2704. The processor 2702 (and/or a coprocessor or any other processing circuitry that assists or is otherwise associated with the processor) may communicate with the memory 2704 via a bus for communicating information among the components of the device. Memory 2704 may be non-transitory and may include, for example, one or more volatile and/or non-volatile memories. In other words, for example, memory 2704 may be an electronic storage device (e.g., a computer-readable storage medium). The memory 2704 may be configured to store information, data, content, applications, instructions, and the like for enabling the apparatus 2700 to perform various functions in accordance with exemplary embodiments of the present disclosure. In this regard, the memory 2704 may be preconfigured to include computer-encoded instructions (e.g., computer program code) and/or be dynamically configured to store such computer-encoded instructions for execution by the processor 2702.
The processor 2702 can be embodied in any of a myriad of ways. In one or more embodiments, for example, the processor 2702 includes one or more processing devices, processing circuits, and the like that are configured to execute independently. Additionally or alternatively, in some embodiments, the processor 2702 may include one or more processing devices, processing circuits, and/or the like configured to operate in series. In some such embodiments, the processor 2702 includes one or more processors configured to communicate via a bus to implement independent execution of instructions, pipelining, and/or multithreading. Alternatively or in addition, in some embodiments, the processor 2702 is entirely embodied by electronic hardware circuitry specifically designed to perform the operations described herein. The use of the terms "processor," "processing module," and/or "processing circuit" may be understood to include a single-core processor, a multi-core processor, multiple processors within a device, other central processing units ("CPUs"), microprocessors, integrated circuits, field programmable gate arrays, application specific integrated circuits, and/or remote or "cloud" processors.
In an exemplary embodiment, the processor 2702 may be configured to execute computer-encoded instructions stored in one or more memories accessible to the processor 2702, such as memory 2704. Additionally or alternatively, the processor 2702 may be configured to perform hard-coded functions. Thus, whether configured by hardware or software, or by a combination thereof, the processor 2702 may represent an entity (e.g., physically embodied in circuitry) capable of performing operations according to embodiments of the present disclosure when configured accordingly. Alternatively, as another example, when the processor is embodied as an executor of software instructions, the instructions may configure the processor 2702 specifically to perform the algorithms and/or operations described herein when the instructions are executed.
In at least one example embodiment, the processor 2702 alone or in combination with the memory 2704 is configured to provide light source tuning functionality as described herein. In at least one example context, the processor 2702 is configured to perform one or more of the operations described herein with respect to fig. 50 and 51. For example, in at least one exemplary embodiment, the processor 2702 is configured to adjust temperature control to affect the sensing environment. Additionally or alternatively, in at least one example embodiment, the processor 2702 is configured to initiate a calibration setup event associated with the light source. Additionally or alternatively, in at least one example embodiment, the processor 2702 is configured to capture reference fringe data representative of a calibration fringe pattern in a calibration environment, such as a calibration fringe pattern projected via a reference channel of a waveguide. Additionally or alternatively, in at least one example embodiment, the processor 2702 is configured to compare the reference fringe data to stored calibration interferometer data, for example, to determine a refractive index offset between the reference fringe data and the stored calibration interferometer data. Additionally or alternatively, in at least one example embodiment, the processor 2702 is configured to tune the light source based on the refractive index offset. In one or more embodiments, the processor 2702 is configured to adjust a voltage level applied to the light source to adjust a light wavelength associated with the light source, and/or to adjust a current level applied to the light source to adjust a light wavelength associated with the light source. In some embodiments, processor 2702 may include or be associated with support hardware for adjusting one or more components of the sample testing device, such as adjusting drive current and/or voltage of one or more light sources to activate one or more imaging components and/or otherwise receive image data (e.g., interference fringe data) captured by the imaging components.
Additionally or alternatively, in at least one example embodiment, the processor 2702 alone or in conjunction with the memory 2704 is configured to provide refractive index processing functions, such as processing data and determining one or more refractive index profiles, as described herein. In at least one example context, the processor 2702 is configured to perform one or more of the operations described herein with respect to the various figures. For example, in at least one exemplary embodiment, processor 2702 is configured to receive first interference fringe data associated with a first wavelength of unidentified sample medium. Additionally or alternatively, in at least one example embodiment, processor 2702 is configured to receive second interference fringe data associated with a second wavelength that does not identify the sample medium. Additionally or alternatively, in at least one example embodiment, the processor 2702 is configured to derive refractive index profile data based on the first interference fringe data and the second interference fringe data. Additionally or alternatively, in at least one example embodiment, the processor 2702 is configured to determine sample identity data based on the refractive index profile data. In some embodiments, to receive the first and second interference fringe data, the processor 2702 is configured to trigger the light source to generate first projected light of a first wavelength and second projected light of a second wavelength, capture the first interference fringe data representing the first interference fringe pattern from the first projected light of the first wavelength, and capture the second interference fringe data representing the second interference fringe pattern based on the second projected light of the second wavelength. In some embodiments, to determine sample identity data based on the refractive index profile, the processor 2702 is configured to query the refractive index data based on the refractive index profile and/or the refractive index profile and the sample temperature, for example, wherein the sample identity data corresponds to a stored refractive index profile that best matches the refractive index profile data.
Additionally or alternatively, in at least one example embodiment, processor 2702 alone or in combination with memory 2704 is configured to provide interference fringe data processing functionality, such as processing interference fringe data and identifying and/or classifying a sample based on such processing, as described herein. In at least one example context, the processor 2702 is configured to perform one or more of the operations described herein with respect to the various figures. For example, in at least one exemplary embodiment, processor 2702 is configured to receive sample interference fringe data for unidentified sample media. Additionally or alternatively, in at least one example embodiment, the processor 2702 is configured to provide at least sample interference fringe data to the trained sample recognition model. Additionally or alternatively, in at least one example embodiment, the processor 2702 is configured to receive sample identity data associated with the sample interference fringe data from the sample identification model. In some such embodiments, the processor 2702 is additionally or alternatively configured to collect a plurality of interference fringe data associated with a plurality of known identity tags. In some such embodiments, additionally or alternatively, the processor 2702 is configured to store each of the plurality of interference fringe data in the training database with the plurality of known sample identity tags. In some such embodiments, additionally or alternatively, the processor 2702 is configured to train the trained sample recognition model according to a training database. Additionally or alternatively, in some embodiments, the processor 2702 is configured to determine an operating temperature associated with the sample environment and provide the operating temperature and sample interference fringe data to the trained sample identification model to receive sample identity data. In some embodiments, to receive sample interference fringe data for unidentified sample media, the processor 2702 is configured to trigger the light source to generate projected light of a determinable wavelength and capture sample interferometer data representing a sample interference fringe pattern associated with the projected light using the imaging component.
In at least one example embodiment, processor 2702 includes a first sub-processor configured to control some or all of the components of sample testing device 2706 and a second sub-processor to process interference fringe data captured by sample testing device 2706 and/or to adjust one or more components of sample testing device 2706 (e.g., to adjust the drive current and/or drive voltage of the light source). In some such embodiments, a first sub-processor may be located within sample testing device 2706 for controlling the various components described herein, and a second sub-processor may be located separately from sample testing device 2706 but communicatively linked to achieve the operations described herein.
FIG. 46 illustrates a block diagram of another example apparatus for advanced sensing and processing in accordance with at least one example embodiment of the present disclosure. In this regard, the apparatus 2800 as depicted may be configured to perform one, some, or all of the methods disclosed herein. In at least one example embodiment, apparatus 2800 embodies an advanced interferometry apparatus configured to perform an interferometry process described herein and one or more of the advanced sensing and/or processing methods described herein with respect to the various figures.
The apparatus 2800 may include various components, such as one or more imaging components 2806, one or more light sources 2808, one or more sensing optics 2810, a processor 2802, a memory 2804, a refractive index processing module 2812, a light source calibration module 2814, and a stripe data identification module 2816. In some embodiments, one or more components are entirely optional (e.g., refractive index processing module, light source calibration module, stripe data identification module, etc.), and/or one or more components may be partially or entirely embodied by another component and/or module associated with apparatus 2800 (e.g., refractive index processing module, light source calibration module, and/or stripe data identification module in combination with a processor). Components (such as processor 2802 and/or memory 2804) that are similarly named as those described with respect to fig. 45 may be configured similarly as described with respect to similarly named components of fig. 45. Similarly, imaging component 2806 can be embodied and/or similarly configured as similarly named components such as those described herein with respect to the various figures, light source 2808 can be embodied and/or similarly configured as similarly named components such as those described herein with respect to the various figures, and/or sensing optics 2810 can be embodied and/or similarly configured as similarly named components such as those described herein with respect to the various figures.
As shown, the apparatus 2800 includes an index of refraction processing module 2812. In some implementations, the refractive index processing module 2812 provides a light source tuning function as described herein, alone or in combination with one or more other components, such as the processor 2802 and/or memory 2804. In at least one exemplary context, the refractive index processing module 2812 is configured to perform one or more of the operations described herein with respect to fig. 50 and 51. For example, in at least one example embodiment, the refractive index processing module 2812 is configured to adjust temperature control to affect a sensing environment. Additionally or alternatively, in at least one example embodiment, the refractive index processing module 2812 is configured to initiate a calibration setup event associated with a light source. Additionally or alternatively, in at least one example embodiment, the refractive index processing module 2812 is configured to capture reference fringe data representative of a calibration fringe pattern in a calibration environment, such as a calibration fringe pattern projected via a reference channel of a waveguide. As described herein, the reference channel may include known materials associated with known and/or determinable refractive indices and/or operating temperatures of one or more wavelengths. Additionally or alternatively, in at least one example embodiment, the refractive index processing module 2812 is configured to compare the reference fringe data with stored calibration interferometer data, e.g., to determine a refractive index offset between the reference fringe data and the stored calibration interferometer data. Additionally or alternatively, in at least one example embodiment, the refractive index processing module 2812 is configured to tune the light source based on the refractive index offset. In one or more embodiments, the refractive index processing module 2812 is configured to adjust a voltage level applied to the light source to adjust a light wavelength associated with the light source and/or to adjust a current level applied to the light source to adjust a light wavelength associated with the light source. In some embodiments, refractive index processing module 2812 may include or be associated with support hardware for adjusting one or more components of a sample testing device, such as adjusting drive current and/or voltage of one or more light sources to activate one or more imaging components and/or otherwise receive image data captured by the imaging components.
As shown, the apparatus 2800 also includes a light source calibration module 2814. Additionally or alternatively, in at least one example embodiment, the light source calibration module 2814, alone or in combination with one or more other components (such as the processor 2802 and/or the memory 2804), is configured to provide refractive index processing functions, such as processing data and determining one or more refractive index curves, as described herein. In at least one example context, the light source calibration module 2814 is configured to perform one or more of the operations described herein with respect to fig. 47-49. For example, in at least one exemplary embodiment, light source calibration module 2814 is configured to receive first interference fringe data associated with a first wavelength for unidentified sample media. Additionally or alternatively, in at least one example embodiment, light source calibration module 2814 is configured to receive second interference fringe data associated with a second wavelength that does not identify the sample medium. Additionally or alternatively, in at least one example embodiment, the light source calibration module 2814 is configured to derive refractive index profile data based on the first and second interference fringe data. Additionally or alternatively, in at least one example embodiment, the light source calibration module 2814 is configured to determine sample identity data based on refractive index profile data. In some embodiments, to receive the first and second interference fringe data, the light source calibration module 2814 is configured to trigger the light source to generate first projected light of a first wavelength and second projected light of a second wavelength, capture the first interference fringe data representing the first interference fringe pattern from the first projected light of the first wavelength, and capture second interference fringe data representing the second interference fringe pattern based on the second projected light of the second wavelength. In some embodiments, to determine sample identity data based on the refractive index profile, the light source calibration module 2814 is configured to query the refractive index data based on the refractive index profile and/or the refractive index profile and sample temperature, e.g., where the sample identity data corresponds to a stored refractive index profile that best matches the refractive index profile data.
As shown, the apparatus 2800 also includes a stripe data identification module 2816. Additionally or alternatively, in at least one example embodiment, the fringe data identification module 2816, alone or in combination with one or more other components, such as the processor 2802 and/or the memory 2804, is configured to provide interference fringe data processing functions, such as processing interference fringe data and identifying and/or classifying samples based on such processing, as described herein. In at least one example context, stripe data identification module 2816 is configured to perform one or more of the operations described herein with respect to fig. 52-54. For example, in at least one exemplary embodiment, fringe data identification module 2816 is configured to receive sample interference fringe data for unidentified sample media. Additionally or alternatively, in at least one example embodiment, the fringe data identification module 2816 is configured to provide at least sample interference fringe data to a trained sample identification model. Additionally or alternatively, in at least one example embodiment, the fringe data identification module 2816 is configured to receive sample identity data associated with the sample interference fringe data from the sample identification model. In some such embodiments, additionally or alternatively, the fringe data identification module 2816 is configured to collect a plurality of interference fringe data associated with a plurality of known identity tags. In some such embodiments, additionally or alternatively, the fringe data identification module 2816 is configured to store each of the plurality of interference fringe data in the training database with the plurality of known sample identity tags. In some such embodiments, additionally or alternatively, stripe data identification module 2816 is configured to train a trained sample identification model according to a training database. Additionally or alternatively, in some embodiments, the fringe data identification module 2816 is configured to determine an operating temperature associated with the sample environment and provide the operating temperature and sample interference fringe data to the trained sample identification model to receive sample identity data. In some embodiments, to receive sample interference fringe data for an unidentified sample medium, the fringe data identification module 2816 is configured to trigger the light source to generate projected light of a determinable wavelength and capture sample interferometer data representing a sample interference fringe pattern associated with the projected light using the imaging component. It should be appreciated that in some embodiments, stripe data identification module 2816 can comprise a separate processor, a specially configured Field Programmable Gate Array (FPGA), and/or a specially configured Application Specific Integrated Circuit (ASIC), or the like.
In some embodiments, one or more of the foregoing components are combined to form a single module. A single combined module may be configured to perform some or all of the functions described herein with respect to the individual modules being combined to form the single combined module. For example, in at least one embodiment, refractive index processing module 2812, light source calibration module 2814, and/or stripe data identification module 2816, and processor 2802 are implemented by a single module. Additionally or alternatively, in some embodiments, one or more of the modules described above may be configured to perform one or more of the actions described with respect to such modules.
Some embodiments provided herein are configured for refractive index processing functions, such as processing data and determining one or more refractive index curves associated with unidentified sample media as described herein. In this regard, conventional implementations fail to accurately perform sample classification and/or identification using individual refractive index determinations. Thus, conventional implementations for sample classification and identification are deficient with respect to performing such classification and/or identification on unidentified samples using refractive index processing. In this regard, one or more embodiments are provided that are configured to determine a refractive index profile associated with an unidentified sample medium and/or to utilize the determined refractive index profile to identify and/or otherwise classify the unidentified sample medium. For example, in at least one exemplary context, apparatus 2700 and/or 2800 are configured to perform such functions based on captured data representing projected interference fringe patterns. It should be appreciated that the exemplary interference fringe patterns described with respect to fig. 45-54 may be embodied in a manner similar to that described herein with respect to the various figures.
FIG. 43 depicts an exemplary graphical visualization of a plurality of derived refractive index curves. For illustrative and exemplary purposes, the depicted refractive index profile may be associated with a water sample. In this regard, the refractive index profile may be determined from captured interference fringe data projected through the sample. As described herein, in some implementations, the refractive index profile associated with a particular medium (e.g., a known sample medium or an unidentified sample medium) can be derived based on any number of data points (e.g., any number of interference fringe data points) associated with the particular medium. For example, the refractive index profile associated with the identified sample medium or unidentified sample medium may be derived from the associated data points using one or more algorithms (e.g., mathematical calculations), interpolation, and the like.
As depicted, the various refractive index curves are also associated with various operating temperatures. For example, a first refractive index profile of the sample at an operating temperature of 5 degrees celsius (C), a second refractive index profile of the sample at an operating temperature of 10C, a third refractive index profile of the sample at a third operating temperature of 20C, and a fourth refractive index profile of the sample at a fourth operating temperature of 30C are depicted. It should be appreciated that any number of refractive index curves may be derived for various operating temperatures for a given sample. For example, in at least one exemplary context, a single refractive index profile of a sample at a single operating temperature is derived. In another exemplary context, multiple refractive index curves for a sample at multiple operating temperatures are derived.
In some embodiments, each refractive index profile is derived from a plurality of interference fringe data representing captured representations of interference fringe patterns produced by light having various wavelengths. For example, devices such as devices 2700 and/or 2800 may be configured to project a first beam of light at a first wavelength to produce a first interference fringe pattern for capture and processing. The apparatus may also capture first fringe data representing a first fringe pattern associated with the first wavelength and derive therefrom a first refractive index associated with the first wavelength. In some embodiments, the device may also correlate the first refractive index to both the first wavelength and the operating temperature. In this regard, the first wavelength may be predefined, driven by the device, and determinable therefrom (e.g., from memory), and/or determinable through communication with one or more light sources that produce light of the first wavelength.
The apparatus may be further configured to project a second beam of light at a second wavelength to produce a second interference fringe pattern for capture and processing. In this regard, the second interference fringe pattern may represent a different interference pattern due to a change in wavelength of light used to project the second interference fringe pattern. In this regard, the apparatus may also capture second interference fringe data representative of a second interference fringe pattern associated with a second wavelength and derive therefrom a second refractive index associated with the second wavelength. In some embodiments, the device may also correlate the second refractive index to both the second wavelength and the operating temperature. In this regard, the second wavelength may be predefined, driven by the device and determinable therefrom, and/or determinable by communication with one or more light sources producing light of the second wavelength.
In some embodiments, the device may similarly derive any number of additional refractive indices associated with any number of wavelengths. In this regard, each of the derived indices of refraction is used as a data point of a derived index of refraction curve associated with a given wavelength at a particular operating temperature. Thus, in some such implementations, the refractive index profile for a given operating temperature may be derived from various refractive indices, such as by algorithmic calculation and/or interpolation between determined refractive indices representing data points along the refractive index profile. In this regard, each refractive index associated with a particular operating temperature may be used as a data point along a refractive index curve corresponding to that operating temperature. Thus, in some exemplary contexts, multiple refractive index curves associated with multiple operating temperatures for a given sample medium may be generated, where each of these refractive index curves may be determined based on multiple interference fringe data, each representing a separate refractive index data point for a given sample, wavelength of light, and operating temperature.
In some embodiments, the apparatus may include and/or otherwise access a refractive index database that stores interference fringe data and/or data derived therefrom (e.g., modulation, frequency, and phase) representing refractive index data points for a particular sample, operating temperature, and wavelength. In this regard, the refractive index database may be populated with data points associated with known identity tags for a given sample. Further, based on the interference fringe data associated with each sample, one or more refractive index curves can be similarly determined and associated with known sample identity tags. For example, a database may be used to retrieve data associated with each sample identity tag and operating temperature, and based on interference fringe data associated with each sample identity tag and operating temperature, a corresponding refractive index profile may be derived. Thus, the newly derived refractive index profile associated with the unidentified sample medium and the known operating temperature may be compared to the refractive index profile derived for the sample of the known sample identity tag in the database to determine sample identity data associated with the unidentified sample medium, such as the sample identity tag. For example, the device may compare the newly derived refractive index profile of the unidentified sample medium with the refractive index profile of a known sample tag (e.g., where the refractive index profile of the known identity tag is stored in a refractive index database or derived from information stored therein). Furthermore, in some embodiments, the device may be configured to determine a refractive index profile at a particular operating temperature at which interference fringe data is captured for the unidentified sample medium that matches and/or best matches the newly derived refractive index profile for the unidentified sample medium at that operating temperature. In some embodiments, an unidentified sample medium is identified and/or classified based on, for example, sample identity data (e.g., a sample identity tag) associated with a refractive index curve that best matches the refractive index curve of the unidentified sample medium. It should be appreciated that the curve that matches and/or best matches the refractive index curve of the unidentified sample medium may be determined using any of a myriad of error calculation algorithms, distance algorithms, etc., and/or other custom algorithms for comparing the similarity of the two curves.
Fig. 47 illustrates a flowchart including exemplary operations of an exemplary process 2900 for refractive index processing, particularly for identifying sample identity data associated with unidentified sample media, in accordance with at least one exemplary embodiment of the present disclosure. It should be appreciated that the various operations form a process that may be performed via one or more computing devices and/or modules (e.g., computer-implemented methods) embodied in hardware, software, and/or firmware. In some implementations, the process 2900 is performed by one or more devices (e.g., devices 2700 and/or 2800 as described herein). In this regard, the apparatus may comprise or otherwise be configured with one or more memory devices having computer-encoded instructions stored thereon, and/or one or more processors (e.g., processing modules) configured to execute the computer-encoded instructions and perform the depicted operations. Additionally or alternatively, in some embodiments, computer program code for performing the operations depicted and described with respect to process 2900 may be stored on one or more non-transitory computer-readable storage media of a computer program product, for example, for execution via one or more processors associated with or otherwise executing with the non-transitory computer-readable storage media of the computer program product.
Process 2900 begins at block 2902. At block 2902, process 2900 includes receiving first interference fringe data for an unidentified sample medium, wherein first interference fringe information is associated with a first wavelength. In some such embodiments, the first interference fringe data embodies a captured representation of an interference fringe pattern produced by light of the first wavelength (e.g., via a waveguide). In some such embodiments, the first interference fringe data is captured by one or more imaging components associated with the projected first interference fringe pattern. Additionally or alternatively, in some embodiments, the first interference fringe data is received from another associated system, loaded from a database embodied on a local and/or remote memory device, or the like. In some embodiments, during capture of the first interference fringe data, the first interference fringe data is similarly associated with the operating temperature of the waveguide and/or unidentified sample medium. In some embodiments, the first interference fringe data can be used to derive a first interferometer index of refraction of the unidentified sample medium associated with the first wavelength and the operating temperature.
In some embodiments, the interference fringe data is indicative of a change in refractive index due to the introduction of the sample medium into the flow channel. In this regard, the interval between refractive indices due to the introduction of the sample medium may be calculated. For example, in the case where the amount of change is k times the original interval of the interference fringe pattern, the optical path difference may be equal to 2 kpi. In some implementations, with respect to a known geometry of the flow channel, the refractive index change can be calculated as an optical path difference of Δnl, where Δn is the refractive index change and L is the equivalent physical length of the optical path associated with the flow channel.
At block 2904, process 2900 further includes receiving second interference fringe data for the unidentified sample medium, wherein the second interferometer data is associated with a second wavelength. In this regard, in some implementations, the second interference fringe data embodies a captured representation of a second interference fringe pattern produced by light of the second wavelength (e.g., via a waveguide). In some implementations, the second light source can be activated to generate second light. In other embodiments, the same light source is adjusted to produce both the first light associated with the first interference fringe data and the second light associated with the second interference fringe data, for example, by adjusting the drive current and/or drive voltage to the light source from a first value associated with the first wavelength to a second value associated with the second wavelength. In some embodiments, the second interference fringe data is similarly associated with an operating temperature of the waveguide and/or unidentified sample medium during capture of the second interference fringe data, which may be the same or nearly the same (e.g., within a predetermined threshold) as the operating temperature during capture of the first interference fringe data. In some embodiments, the second interference fringe data can be used to derive a second interferometer index of refraction of the unidentified sample medium, wherein the second interferometer index of refraction is associated with a second wavelength and an operating temperature.
It should be appreciated that process 2900 may also include receiving any number of additional interference fringe data associated with the myriad wavelengths. For example, third interference fringe data associated with a third wavelength may be received and/or fourth interference fringe data associated with a fourth wavelength may be received. Any such additional fringe data may be received in a manner similar to the first fringe data and/or the second fringe data described above with respect to blocks 2902 and/or 2904.
At block 2906, the process 2900 further includes deriving refractive index profile data based on (i) first interference fringe data associated with the first wavelength and (ii) second interference fringe data associated with the second wavelength. In some such embodiments, for example, a first refractive index is derived from the first interference fringe data and a second refractive index is derived from the second interference fringe data. The first refractive index and the second refractive index may be used to derive refractive index profile data associated with unidentified sample media. In some embodiments, refractive index profile data is derived from the first and second fringe data using one or more algorithms and/or mathematical calculations. Alternatively or in addition, in some implementations, the refractive index profile data is derived based on interpolation between refractive indices. It should be appreciated that in the context of receiving one or more additional interference fringe data, refractive index profile data may also be derived based on the first interference fringe data, the second interference fringe data, and the one or more additional interference fringe data.
At block 2908, the process 2900 further includes determining sample identity data based on the refractive index profile data. In some embodiments, the sample identity data is determined by determining refractive index profile data that most closely matches known refractive index profile data of a sample associated with known sample identity data at the operating temperature. For example, if the sample refractive index profile data most closely corresponds to known refractive index profile data associated with a known sample identity tag (e.g., distilled water), the sample refractive index profile data may similarly be determined to embody the same known sample identity tag (e.g., representing distilled water). Where the sample refractive index profile data may match more than one known refractive index profile data, the determined sample identity data may embody statistical data based on similarity between the sample refractive index profile data and each known refractive index profile data. Exemplary embodiments for determining sample identity data based on refractive index profile data are described herein with respect to fig. 49.
FIG. 48 illustrates a flowchart including additional exemplary operations of an exemplary process 3000 for refractive index processing, particularly for receiving at least first interference fringe data associated with a first wavelength and second interference fringe data associated with a second wavelength of an unidentified sample medium, in accordance with at least one exemplary embodiment of the present disclosure. It should be appreciated that the various operations form a process that may be performed via one or more computing devices and/or modules (e.g., computer-implemented methods) embodied in hardware, software, and/or firmware. In some implementations, the process 3000 is performed by one or more devices (e.g., devices 2700 and/or 2800 as described herein). In this regard, the apparatus may comprise or otherwise be configured with one or more memory devices having computer-encoded instructions stored thereon, and/or one or more processors (e.g., processing modules) configured to execute the computer-encoded instructions and perform the depicted operations. Additionally or alternatively, in some embodiments, computer program code for performing the operations depicted and described with respect to process 3000 may be stored on one or more non-transitory computer-readable storage media of a computer program product, for example, for execution via one or more processors associated with or otherwise executing with the non-transitory computer-readable storage media of the computer program product.
As shown, process 3000 begins at either block 3002 or block 3004. In some embodiments, a process begins after one or more operations of another process, such as process 2900 described herein. Additionally or alternatively, in at least one embodiment, after completing the process shown with respect to process 3000, the flow returns to one or more operations of another process (such as process 2900). For example, as shown, in some embodiments, when block 3010 is completed, flow returns to block 2906.
In some implementations, the process 3000 begins at block 3002, for example, where a single light source is utilized to generate multiple interference fringe patterns associated with multiple wavelengths. At block 3002, process 3000 includes triggering light source generation: (i) A first projection light of a first wavelength, wherein the first projection light is associated with a first interferometer fringe pattern, and (ii) a second projection light of a second wavelength, wherein the second projection light is associated with a second interferometer fringe pattern. In this regard, the light source may be triggered first with a first drive current or drive voltage associated with a first wavelength and subsequently with a second drive current or drive voltage associated with a second wavelength. In other embodiments, the light source may generate a single light beam that is split and/or otherwise manipulated into two sub-beams by one or more optical components. One or more of these sub-beams may be manipulated to match the desired first and second wavelengths. It should be understood that the light source may be a component of a sample testing apparatus, waveguide, and/or the like as described herein, as described herein.
In other embodiments, process 3000 begins at block 3004, for example, where multiple light source components are utilized to generate light of different wavelengths associated with the first interferometer data and the second interferometer data. At block 3004, process 3000 includes triggering a first light source to generate a first projected light of a first wavelength, wherein the first projected light is associated with a first interference fringe pattern. In some embodiments, the first light source is triggered based on the first drive current or the first drive voltage such that the first light source generates the first light at the first wavelength. In some embodiments, the first projected light is manipulated by one or more optical components (e.g., components of a waveguide) to produce a first interference fringe pattern from the first projected light. In some embodiments, a processor and/or associated module of a sensing device as described herein is configured to generate one or more signals such that a first light source is triggered to an appropriate first wavelength.
At block 3006, process 3000 further includes triggering a second light source to generate a second projected light of a second wavelength, wherein the second projected light is associated with a second interference fringe pattern. In this regard, in some embodiments, the second light source is triggered based on the second drive current or the second drive voltage such that the second light source generates the second light at the second wavelength. In at least some such embodiments, the first drive current or voltage is different from the second drive current or voltage such that the light generated by the first light source and the second light source has different wavelengths. In some embodiments, the second projected light is manipulated by one or more optical components (e.g., components of a waveguide) to produce a second interference fringe pattern from the second projected light. In some embodiments, a processor and/or associated module of a sensing device as described herein is configured to generate one or more signals such that a second light source is triggered to an appropriate second wavelength.
After completing blocks 3004 or 3006, flow proceeds to block 3008. At block 3008, process 3000 includes capturing, using an imaging component, first interference fringe data representative of a first interference fringe pattern associated with a first wavelength. In this regard, the first interference fringe pattern is dependent on the first wavelength such that the captured data represents a different interference pattern for each different wavelength. The first interference fringe data can be processed to determine a refractive index associated with the interference pattern. In some embodiments, the imaging component is included in and/or otherwise associated with a sample testing device, waveguide, and/or the like, e.g., as described herein. In this regard, the imaging component may be triggered by one or more processors and/or associated modules associated therewith, e.g., as described herein. In at least one embodiment, the imaging component is embodied by a separate apparatus or sub-component thereof communicatively linked to one or more hardware, software, and/or firmware devices for processing such captured image data.
At block 3010, process 3000 includes capturing, using an imaging component, second interference fringe data representative of a second interference fringe pattern associated with a second wavelength. In this regard, the second interference fringe pattern is dependent on the second wavelength such that the captured data represents an interference pattern that is different from the first interferometer pattern associated with the first wavelength. The second interference fringe data can be processed to determine a second refractive index associated with the second interference pattern. In some embodiments, the imaging component is included in and/or otherwise associated with the same sample testing device, waveguide, and/or the like, e.g., as described herein. In this regard, the imaging component may be triggered by one or more processors and/or associated modules associated therewith, e.g., as described herein.
In some embodiments, first interference fringe data is captured when the projection of first light of a first wavelength is triggered and second interference fringe data is captured when the projection of second light of a second wavelength is triggered. In this regard, in some embodiments, block 3008 may occur in parallel with the one or more operations, for example, when the first light is projected at block 3002 or block 3004. Similarly, in some embodiments, block 3010 may occur in parallel with the one or more operations, such as when the first light is projected at block 3002 or block 3006.
Fig. 49 illustrates a flowchart including additional example operations of an example process 3100 for refractive index processing, particularly for determining sample identity data based on refractive index profile data, in accordance with at least one example embodiment of the present disclosure. It should be appreciated that the various operations form a process that may be performed via one or more computing devices and/or modules (e.g., computer-implemented methods) embodied in hardware, software, and/or firmware. In some implementations, process 3100 is performed by one or more devices (e.g., devices 2700 and/or 2800 as described herein). In this regard, the apparatus may comprise or otherwise be configured with one or more memory devices having computer-encoded instructions stored thereon, and/or one or more processors (e.g., processing modules) configured to execute the computer-encoded instructions and perform the depicted operations. Additionally or alternatively, in some embodiments, computer program code for performing the operations depicted and described with respect to process 3100 can be stored on one or more non-transitory computer-readable storage media of a computer program product, e.g., for execution via one or more processors associated with or otherwise executing with the non-transitory computer-readable storage media of the computer program product.
Process 3100 begins at block 3102. In some implementations, the process begins after one or more operations of another process (such as after block 2906 of process 2900 as described herein). Additionally or alternatively, in at least one embodiment, after completing the process shown with respect to process 3100, the flow returns to one or more operations of another process (such as process 2900).
At block 3102, process 3100 includes querying a refractive index database based on refractive index profile data, wherein the sample identity data corresponds to a stored refractive index profile in the refractive index database that best matches the refractive index profile data. In some embodiments, the refractive index database is further queried based on the operating temperature, such as the operating temperature at which the first and/or second interference fringe data representing the interference pattern of the unidentified sample medium is captured. In this regard, the refractive index database may be queried to identify data associated with the same operating temperature, and further derive associated refractive index profile data therefrom for comparison with sample refractive index profile data. The sample refractive index profile data may be compared to stored refractive index profiles retrieved from a database and/or derived from data retrieved from the database to determine a best match to the sample refractive index profile data. For example, in some embodiments, one or more error and/or distance algorithms may be utilized to determine a stored refractive index profile that best matches the refractive index profile of the unidentified sample medium. In this way, by determining the known refractive index profile associated with the known sample identity data and the best match to the sample refractive index profile, the sample identity data associated with the closest known refractive index profile may represent the identity and/or classification of the unidentified sample medium and/or statistical information associated therewith.
Some embodiments provided herein are configured for fine tuning a light source, such as to refine (or approach) the wavelength of light output by the light source to a desired wavelength. In this regard, the light source may be fine-tuned to account for environmental effects, such as differences in projected interference patterns due to shifts caused by operating temperatures. In at least one example environment, the devices 2700 and/or 2800 are configured to perform such functions to fine tune the light output of the light source.
FIG. 44 depicts an exemplary graphical visualization of variable adjustments for fine tuning the output of a light source. In this regard, the light source may be tuned as depicted in the visualization. For example, in at least one exemplary embodiment, as the output power of the light source increases, the wavelength of the light generated by the light source decreases. In this regard, the drive current may be adjusted (e.g., increased or decreased) to adjust the wavelength of light generated by the light source to or closer to (e.g., within an acceptable error threshold) the desired wavelength. For example, in the event that the operating temperature of the sample environment results in a decrease in the wavelength of light generated by the light source, the drive current to the light source may be adjusted to decrease the output power of the light source and increase the wavelength of light generated. The light source may be tuned such that the wavelength of the light output by the light source approximates and/or matches a desired and/or calibrated wavelength. It should be appreciated that in other embodiments, the drive voltage applied to the light source may be adjusted to achieve adjustment of the light source. In some embodiments, the light source includes or is otherwise associated with support hardware for adjusting the light source, such as by adjusting the current driving the light source.
Fig. 50 illustrates a flowchart of exemplary operations including an exemplary process 3200 for light source tuning, particularly for fine tuning the wavelength of light generated by a light source to calibrate the light source, in accordance with at least one exemplary embodiment of the present disclosure. It should be appreciated that the various operations form a process that may be performed via one or more computing devices and/or modules (e.g., computer-implemented methods) embodied in hardware, software, and/or firmware. In some implementations, process 3200 is performed by one or more devices (e.g., devices 2700 and/or 2800 as described herein). In this regard, the apparatus may comprise or otherwise be configured with one or more memory devices having computer-encoded instructions stored thereon, and/or one or more processors (e.g., processing modules) configured to execute the computer-encoded instructions and perform the depicted operations. Additionally or alternatively, in some embodiments, computer program code for performing the operations depicted and described with respect to process 3200 may be stored on one or more non-transitory computer-readable storage media of a computer program product, e.g., for execution via one or more processors associated with or otherwise executing with the non-transitory computer-readable storage media of the computer program product.
Process 3200 begins at block 3202. At block 3202, process 3200 further includes initiating a calibration setup event associated with the light source. In this regard, the calibration setup event may trigger the use of the reference channel to store data of the calibration data, such as calibrated reference interference data, for one or more later calibration operations. In some embodiments, the calibration setup event is initiated during factory setup of the device, computer program product, or the like. Alternatively or in addition, in some embodiments, the calibration setup event is initiated automatically, for example upon activation of the apparatuses 2700 and/or 2800, the sample testing device, and/or the like. Alternatively or in addition, the calibration setup event may be initiated automatically in response to activation of an operation for determining sample identity data associated with unidentified sample media. Alternatively or in addition, in one or more embodiments, the calibration setting event may be initiated in response to a user interaction, in particular indicative of initiation of the calibration setting event, for example in response to a predefined user interaction with one or more hardware, software and/or firmware components for initiating the calibration setting event.
At block 3204, process 3200 further includes capturing, in a calibrated environment, calibrated reference fringe data representing a calibrated fringe pattern, the calibrated fringe pattern projected via a reference channel of the waveguide. In this regard, the calibrated interference pattern may be projected through a reference medium (e.g., siO 2) located in the reference channel, which is used to output one or more reference interference fringe patterns for calibration purposes (e.g., for tuning and/or otherwise calibrating the wavelength output by the light source). In some embodiments, the calibrated environment includes a calibrated operating temperature. In this regard, the sample testing device, waveguide, and/or the like may be calibrated at an earlier operation (e.g., at block 3202 or prior to the beginning of process 3200). By projecting the interference fringe pattern through the reference channel of the waveguide, the interference fringe pattern represents a pre-calibration result that can be captured and compared to future conditions to determine if one or more properties of the device (e.g., the wavelength of light produced by the light source) have changed. Such properties may change over time for any one or more of a myriad of reasons, such as for degradation of one or more components of the device, changes in the operating environment, and the like.
At block 3206, process 3200 also includes storing the calibrated reference fringe data in local memory as stored calibrated fringe data. In this regard, stored calibration fringe data may be retrieved from local memory for use in subsequent calibration operations. For example, as described herein with respect to blocks 3210-3216. For example, the calibrated reference fringe data may include pre-calibrated fringe data for comparison with later captured fringe data to determine how to adjust one or more light sources to recalibrate or better calibrate the wavelength of light generated by the light sources. In some implementations, for example, the calibrated reference fringe data includes modulation data, frequency data, phase data, and/or combinations thereof associated with projecting the calibrated fringe pattern. It should be appreciated that the refractive index data points and/or refractive index curves associated with the calibrated fringe pattern may again be determined from the stored calibrated reference fringe data.
At block 3208, process 3200 further comprises adjusting temperature control, wherein adjusting the temperature sets the sample environment to a tuned operating temperature, and wherein the tuned operating temperature is within a threshold range from a desired operating temperature. The temperature controller may be a component of a sample testing apparatus (such as an interferometer apparatus), device 2700 and/or device 2800 and/or the like as described herein, which enables the operating temperature of the device when running to be changed. In this regard, the sample environment may be adjusted such that light projected through the sample medium (e.g., in the sample channel) is adjusted toward a desired and/or calibrated wavelength. For example, the waveguide may be calibrated to operate at a particular calibrated operating temperature. The tuned operating temperature may be coarsely tuned (e.g., within a threshold range) from a desired operating temperature corresponding to the calibrated operating temperature, such that precise temperature tuning via temperature control is not required.
At block 3210, the process 3200 further includes triggering a light source calibration event associated with the light source. In some implementations, the reference captured fringe data can be monitored to determine when the difference between the stored data and the captured data exceeds a predetermined threshold (e.g., the shift in refractive index exceeds a predetermined maximum shift before calibration occurs). Additionally or alternatively, in at least one embodiment, the light source calibration event is triggered upon determining that a predetermined time period has elapsed since the setup event and/or the previously triggered light source calibration event. Additionally or alternatively, in at least one embodiment, the light source calibration event is triggered automatically, for example at the beginning of an operation for identifying sample media as described herein. Additionally or alternatively, in at least one embodiment, the light source calibration event is initiated after initiating a predetermined and/or variable number of sample medium identification events.
At block 3212, the process 3200 further includes capturing reference interference fringe data representing a reference interference fringe pattern in the sample environment, the reference interference pattern projected via a reference channel of the waveguide. The reference fringe data may be captured similar to the calibrated reference fringe data described with respect to block 3204. Due to any of a variety of effects (time lapse, differences between calibrated and sample environments, degradation of one or more optical components, and/or the like), the projected reference interference pattern may be associated with a refractive index that differs from the refractive index of the pre-calibrated pattern represented by the stored calibration interference data.
At block 3214, the process 3200 further includes comparing the reference fringe data with stored calibration fringe data to determine a refractive index offset between the reference fringe data and the stored calibration interference data. In some embodiments, for example, the reference fringe data is processed to derive a first refractive index associated with a first fringe pattern represented by the reference fringe data. Similarly, for example, in some embodiments, the stored calibration interference data is processed to derive a second refractive index associated with a second interference fringe pattern represented by the stored calibration interference fringe data. In this regard, the first refractive index and the second refractive index may be compared to determine a refractive index offset between the two interference fringe patterns. In some such embodiments, the refractive index shift represents a change in the projected reference pattern due to an environmental change (e.g., an operating temperature change from a calibration temperature to a sample temperature), degradation of one or more optical and/or hardware device components, a change in the wavelength of light generated by the light source, and the like.
In this regard, in some embodiments, the refractive index offset is a result of waveguide structure and thermal variations. The equivalent length change associated with the refractive index offset may be derived therefrom and/or otherwise calculated. Thus, in some embodiments, the proportion of equivalent length variation is equal to the amount of wavelength proportional variation that should be adjusted via light source tuning as described herein to compensate for the offset.
At block 3216, the process 3200 further includes tuning the light source based on the index offset. In some implementations, the light source is tuned to adjust the wavelength of light output by the light generating component. For example, in at least one embodiment, one or more values associated with operating the light source are tuned or otherwise adjusted based on the refractive index offset between the reference interference fringe data and the stored calibration interference data. In this regard, by tuning the light source, the reference interference fringe pattern generated via the reference channel is adjusted to more closely match the calibration interference fringe pattern represented by the stored calibration interference data. Exemplary operations for tuning a light source are further described herein with respect to fig. 51.
Fig. 51 illustrates a flowchart including additional exemplary operations of an exemplary process 3300 for refractive index processing, particularly for tuning a light source, in accordance with at least one exemplary embodiment of the present disclosure. It should be appreciated that the various operations form a process that may be performed via one or more computing devices and/or modules (e.g., computer-implemented methods) embodied in hardware, software, and/or firmware. In some embodiments, process 3300 is performed by one or more devices (e.g., devices 2700 and/or 2800 as described herein). In this regard, the apparatus may comprise or otherwise be configured with one or more memory devices having computer-encoded instructions stored thereon, and/or one or more processors (e.g., processing modules) configured to execute the computer-encoded instructions and perform the depicted operations. Additionally or alternatively, in some embodiments, computer program code for performing the operations depicted and described with respect to process 3300 can be stored on one or more non-transitory computer-readable storage media of a computer program product, e.g., for execution via one or more processors that are associated with or otherwise executed with the non-transitory computer-readable storage media of the computer program product.
Process 3300 begins at block 3302 and/or block 3304. In some implementations, the process begins after one or more operations of another process (such as after block 3214 of process 3200 as described herein). Additionally or alternatively, in at least one embodiment, after completing the process shown with respect to process 3300, the flow returns to one or more operations of another process (such as process 3200).
At block 3302, process 3300 includes adjusting a voltage level applied to the light source to adjust a light wavelength associated with the light source. In this regard, by adjusting the voltage level applied to the light source, the light generated by the light source may similarly be varied based on the amount of adjustment, for example as depicted and described with respect to fig. 44. In some embodiments, the voltage level to be applied to the light source is stored in one or more components, such as in a cache memory, memory device, and/or the like. Alternatively or in addition, in some embodiments, the processor and/or associated module transmits one or more signals to the light source and/or support hardware to cause adjustment of the voltage level applied to the light source. In some such embodiments, the adjustment value (e.g., how much the voltage level applied to the light source is adjusted) is determined based on the refractive index offset between the reference interference fringe data and the stored calibration interference data. In this regard, the greater the offset between the two data (e.g., caused by a greater change in the operation of the waveguide and/or associated components), the greater the adjustment will be made to attempt to recalibrate the device.
Alternatively or in addition, in some embodiments, process 3300 begins at block 3304. At block 3304, process 3300 also includes adjusting a current level applied to the light source to adjust a light wavelength associated with the light source. In this regard, by adjusting the current level applied to the light source, the light generated by the light source may similarly be varied based on the amount of adjustment, for example as depicted and described with respect to fig. 44. In some embodiments, the current level to be applied to the light source is stored in one or more components for subsequent activation of the light source. In some embodiments, the processor and/or associated module transmits one or more signals to the light source and/or support hardware to cause adjustment of the current level applied to the light source. In some such embodiments, the adjustment value (e.g., how much to adjust the current level applied to the light source) is determined based on the refractive index offset. In this regard, the greater the offset between the two data (e.g., caused by a large change in the operation of the waveguide and/or associated components), the greater the adjustment that will be made when attempting to recalibrate the device. It should be appreciated that in some embodiments, hardware, software, and/or firmware is included to drive the applied current level to trigger the light source, which is preferred over other properties (such as voltage, resistance, etc.).
It should be appreciated that in some embodiments, both the voltage and current are adjusted to effect a change in wavelength associated with the light source. Thus, in some embodiments, process 3300 includes both blocks 3302 and 3304. In other implementations, only one of the voltage and/or current is driven to effect tuning of the light source.
Some embodiments provided herein are configured for processing interference fringe data to enable sample identification and/or classification using one or more statistics and/or machine learning modules associated with at least one exemplary embodiment described herein. In this regard, features of the interference fringe data representing the generated interference fringe pattern may be processed through one or more statistical, machine learning, and/or algorithmic models.
By utilizing statistical, machine learning, and/or algorithmic models, such models may be utilized to determine sample identity data (e.g., sample tag data and/or statistical information, such as one or more confidence scores associated therewith) of unidentified sample media. In this regard, such implementations may be utilized even in cases where other attempted sample identity data determinations may be unsuccessful. Such image-based classification and/or identification may be used, for example, even in cases where the refractive index change in the sample medium under test may be insufficient to identify such sample identity data.
It should be appreciated that embodiments may include machine learning models, statistical models, and/or other models trained from any one or more of a myriad of types of interference fringe data. For example, in at least one embodiment, a model (e.g., a sample recognition model) is trained based on interference fringe data comprising an original representation of the captured interference pattern. Alternatively or in addition, in at least one embodiment, the model is trained based on interference fringe data comprising refractive index data and/or data associated therewith, such as modulation, frequency, and/or phase. The type of data used for training may be selected based on one or more factors, such as the particular task to be performed, available training data, and the like. In this regard, by receiving interference fringe data and/or associated input data (such as operating temperatures), the model may provide data indicative of a statistically best matching tag associated with the input data based on corresponding interference fringe data corresponding to the same or similar operating temperatures.
In some such embodiments, the sample testing device (e.g., a waveguide) is configured to capture interference fringe data associated with the sample medium being tested in order to perform identification and/or classification of the sample medium. The captured interference fringe data may also be associated with a known and/or determinable operating temperature and/or a wavelength associated with light generated by the light source. Thus, the captured interference fringe data and/or data derived therefrom may be input into a trained sample identification model (e.g., embodied by one or more statistical, algorithmic, and/or machine learning models) alone or in combination with operating temperature values and/or determined wavelengths to improve the generation of sample identity data associated with the sample medium.
In some embodiments, the trained sample recognition model is trained from a plurality of data samples (e.g., classified known samples) associated with known sample identity tags. In this regard, the training database may be configured to include data associated with any number of known sample media, such as interference fringe data. In at least one exemplary context, the training database is configured to store the processed captured representation of the interference fringe pattern, for example by storing modulation values, frequency values, and/or phase values, to minimize the required storage space while maintaining all of the raw information available via the interference fringe pattern. In this regard, the raw fringe data may then be back-reconstructed into the test sample effective temperature-spectral refractive index distribution in the sampling region. Additionally or alternatively, in some embodiments, the training database includes interference fringe data associated with such known sample media at various operating temperatures and/or associated with various wavelengths. In this regard, the training database may be used to train a sample identification model to identify any number of sample media, and further identify such sample media based on interference fringe data associated with varying temperatures and/or wavelengths. In other embodiments, the training database may include any number of additional data types, such as sample density profiles, particle counts, average size and/or dimensions of the sample media, and the like.
In at least one exemplary context, the interference fringe data processing of the advanced sample identification methods described herein can be used for virus identification, such as identifying novel COVID-19 that are different from other viruses. In this regard, sensing devices such as waveguide interferometer biosensors described herein can be used to capture interference fringe data associated with sample media (e.g., viral specimens) at various spectral wavelengths and temperature conditions. The collected viral spectral refractive index data may be collected and stored in a training database for refining and/or otherwise training one or more sample identification models to identify different sample identities (e.g., virus types) with high matching accuracy that improves as the collected data set expands. In this regard, an inverse transformation algorithm may be constructed to reconstruct the refractive index change curve in the test region, and a sample identification model (e.g., neural network) may be used to classify when trained via the collected training database to output the determined identity tags, confidence scores associated with such tags. Such sample identity data (e.g., identity tags and/or confidence scores in some embodiments) associated with the tested unidentified sample medium may be displayed to a user for viewing.
FIG. 52 illustrates a flowchart of exemplary operations including an exemplary process 3400 for interference fringe data processing for advanced sample identification, particularly using a trained sample identification module, in accordance with at least one exemplary embodiment of the present disclosure. It should be appreciated that the various operations form a process that may be performed via one or more computing devices and/or modules (e.g., computer-implemented methods) embodied in hardware, software, and/or firmware. In some implementations, the process 3400 is performed by one or more devices (e.g., devices 2700 and/or 2800 as described herein). In this regard, the apparatus may comprise or otherwise be configured with one or more memory devices having computer-encoded instructions stored thereon, and/or one or more processors (e.g., processing modules) configured to execute the computer-encoded instructions and perform the depicted operations. Additionally or alternatively, in some embodiments, computer program code for performing the operations depicted and described with respect to process 3400 may be stored on one or more non-transitory computer-readable storage media of the computer program product, e.g., for execution via one or more processors associated with or otherwise executing with the non-transitory computer-readable storage media of the computer program product.
The process 3400 begins at block 3402. At block 3402, the process 3400 includes collecting a plurality of interference fringe data associated with a plurality of known identity tags. In this regard, a sample testing device (such as apparatus 2700 or 2800 described herein) may be used to generate an interference fringe pattern of a sample medium having a known identity (e.g., associated with a known identity tag). The captured interference fringe data may be stored locally and/or transmitted over a wired and/or wireless communication network to another system, such as an external server, for storage and/or processing of the data. For example, in some embodiments, the captured interference fringe data is transmitted over a wireless communication network (e.g., the internet) accessible to the sample testing device for storage in a central database server along with sample identity data (e.g., known identity tags) provided by the user. In this way, the collected interference fringe data each corresponds to sample identity data known to the user to be correct, such as a known identity tag. Thus, such data may be used to train one or more models with statistical certainty. The central database server may be further configured to train one or more models based on such data and/or communicate with another server, device, system, etc. configured to perform such model training. The server, device, system, and/or the like performing model training may additionally or alternatively be configured to provide a trained model for use by the sample testing device and/or associated processing apparatus (e.g., apparatus 2700 and/or 2800). It should be appreciated that as the number of collected fringe data increases, models trained from such data may operate with increased accuracy, as opposed to training with small data sets.
At block 3404, the process 3400 further includes storing, in a training database, each of the plurality of interference fringe data with the plurality of known sample identity tags. In this regard, each interference fringe data and/or data derived therefrom (e.g., which represents interference fringe data) may be stored to a training database along with additional data values embodying known identity tags. Thus, each data record stored in the training database may be retrieved along with the corresponding correct identity tag of the associated sample medium. In some embodiments, each of the plurality of interference fringe data is further stored with a corresponding wavelength of light used to generate the corresponding interference fringe pattern and/or a sample temperature at which the interference fringe pattern projection and subsequent capture occurs.
At block 3406, the process 3400 further includes training a trained sample recognition model from a training database. In this regard, training may involve fitting a sample identification model to data represented in a training database. It should be appreciated that such operations may include partitioning the training database into one or more data sub-packets, such as a training set and one or more test sets, and the like. Thus, upon completion of the training model, the trained sample identification model is configured to generate identity tag data for the newly provided interference fringe data, wavelength, and/or temperature (such as for unidentified sample media). The trained sample identification model may be stored on and/or otherwise made accessible by the sample testing device for identifying and/or otherwise classifying unidentified sample media.
It should be appreciated that blocks 3402-3406 embody a sub-process for training the recognition of the trained sample. Accordingly, such blocks may be performed alone or in combination with the remaining blocks depicted and described with respect to process 3400.
At block 3408, the process 3400 further includes: sample interference fringe data is received for the unidentified sample medium, the sample interference fringe data being associated with a determinable wavelength. In some such embodiments, the interference fringe data embodies a captured representation of an interference fringe pattern produced by light of determinable wavelength (e.g., via a waveguide and/or other sample testing device). In some embodiments, the determinable wavelength may be determined based on communication with the light source and/or one or more associated components (e.g., a processor configured to control the light source and/or associated modules), as described herein. As described, in some such embodiments, the interference fringe data is captured by one or more imaging components associated with the projected interference fringe pattern. Additionally or alternatively, in some embodiments, the interference fringe data is received from another associated system, is loaded from a database embodied on a local and/or remote memory device, and so forth. In some embodiments, during capture of the interference fringe data, the interference fringe data is similarly associated with the operating temperature of the waveguide and/or unidentified sample medium.
At block 3410, the process 3400 further includes providing at least sample interference fringe data to the trained sample recognition model. At block 3412, the process 3400 further includes receiving sample identity data associated with the unidentified sample medium from the trained sample identification model. In this regard, the trained sample recognition model is configured to generate sample identity data based on processing the sample interference fringe data. It should be appreciated that in this regard, the trained sample identification model may analyze the various features embodied in the data and determine sample identity data and/or statistical information associated with the sample identity data that is most likely to be used for unidentified samples. For example, in at least one exemplary embodiment, the trained sample identification model generates and/or otherwise outputs sample identity data that includes a sample identity tag for the most likely classification of unidentified sample media (e.g., which is associated with the highest statistical probability). In at least one exemplary embodiment, the trained sample identification model generates and/or otherwise outputs statistical sample identity data representing a likelihood that an unidentified sample medium corresponds to each of the one or more sample identity tags. For example, in the context of virus classification, the statistical sample identity data may include a first likelihood that the virus sample is an influenza virus, not a common cold virus, based on the corresponding interference fringe data. It should be appreciated that in some embodiments, the trained sample identification model is provided with sample interference fringe data and additional data, such as operating temperature data as described herein. In at least one exemplary embodiment, the trained sample recognition model comprises a deep neural network. In some example embodiments, the trained sample recognition model includes a convolutional neural network.
Fig. 53 illustrates a flowchart including additional exemplary operations of an exemplary process 3500 for interference fringe data processing for advanced sample identification, particularly for receiving at least interference fringe data associated with determinable wavelengths of unidentified sample media, in accordance with at least one exemplary embodiment of the present disclosure. It should be appreciated that the various operations form a process that may be performed via one or more computing devices and/or modules (e.g., computer-implemented methods) embodied in hardware, software, and/or firmware. In some embodiments, process 3500 is performed by one or more devices (e.g., devices 2700 and/or 2800 as described herein). In this regard, the apparatus may comprise or otherwise be configured with one or more memory devices having computer-encoded instructions stored thereon, and/or one or more processors (e.g., processing modules) configured to execute the computer-encoded instructions and perform the depicted operations. Additionally or alternatively, in some embodiments, computer program code for performing the operations depicted and described with respect to process 3500 can be stored on one or more non-transitory computer-readable storage media of a computer program product, e.g., for execution via one or more processors associated with or otherwise executing with the non-transitory computer-readable storage media of the computer program product.
As shown, process 3500 begins at block 3502. In some embodiments, the process begins after one or more operations of another process (such as after block 3406 of process 3400 as described herein). Additionally or alternatively, in at least one embodiment, after completing the process shown with respect to process 3500, the flow returns to one or more operations of another process, such as process 3400. For example, as shown, in some embodiments, when block 3504 is completed, flow returns to block 3410.
As shown, process 3500 begins at block 3502. At block 3502, the process 3500 includes receiving sample interference fringe data for an unidentified sample medium including: the trigger light source generates projected light of a determinable wavelength, wherein the projected light is associated with the sample interference fringe pattern. In this regard, the sample interference fringe pattern is associated with an unidentified sample. In some embodiments, the light source is triggered based on a drive current or drive voltage such that the light source produces light of a determinable wavelength. In some embodiments, the projected light is manipulated by one or more optical components (e.g., a waveguide or other component of a sample testing device) to produce a sample interference fringe pattern from the projected light. In some embodiments, a processor and/or associated module of a sensing device as described herein is configured to generate one or more signals to cause a trigger light source to reach an appropriately determinable wavelength.
At block 3504, the process 3500 includes capturing sample interference fringe data representing a sample interference fringe pattern associated with the determinable wavelength using the imaging component. In this regard, the sample interference fringe pattern is dependent on the determinable wavelength such that the captured data represents a particular interference pattern corresponding to the determinable wavelength. In some embodiments, the imaging component is included in and/or otherwise associated with a sample testing device, waveguide, and/or the like, e.g., as described herein. In this regard, the imaging component may be triggered by one or more processors and/or associated modules associated therewith, e.g., as described herein. The captured sample interference fringe data may then be input into a trained sample recognition module to identify and/or otherwise classify unidentified samples.
FIG. 54 illustrates a flowchart including additional exemplary operations of an exemplary process 3600 for interference fringe data processing for advanced sample identification, particularly for generating sample identity data based on at least sample interference fringe data and operating temperature, in accordance with at least one exemplary embodiment of the present disclosure. It should be appreciated that the various operations form a process that may be performed via one or more computing devices and/or modules (e.g., computer-implemented methods) embodied in hardware, software, and/or firmware. In some embodiments, process 3600 is performed by one or more devices (e.g., devices 2700 and/or 2800 as described herein). In this regard, the apparatus may comprise or otherwise be configured with one or more memory devices having computer-encoded instructions stored thereon, and/or one or more processors (e.g., processing modules) configured to execute the computer-encoded instructions and perform the depicted operations. Additionally or alternatively, in some embodiments, computer program code for performing the operations depicted and described with respect to process 3600 may be stored on one or more non-transitory computer-readable storage media of a computer program product, for example, for execution via one or more processors that are associated with or otherwise execute with the non-transitory computer-readable storage media of the computer program product.
As shown, process 3600 begins at block 3602. In some embodiments, the process begins after one or more operations of another process (such as after block 3408 of process 3400 as described herein). Additionally or alternatively, in at least one embodiment, after completing the process shown with respect to process 3600, the flow returns to one or more operations of another process, such as process 3400. For example, as shown, in some embodiments, when block 3604 is completed, flow returns to block 3412.
As shown, process 3600 begins at block 3602. At block 3602, process 3600 includes determining an operating temperature associated with a sample environment. In some embodiments, the sample environment includes a defined sample channel within which unidentified sample medium is located for testing (e.g., for identification purposes), and/or through which light is projected. In some embodiments, a temperature monitoring device (such as one or more temperature monitoring hardware devices) is used to monitor and/or otherwise determine the operating temperature. It should be appreciated that during testing without identifying the sample medium, the operating temperature may be read from such a temperature monitoring device for the purpose of determining the operating temperature associated with the sample environment and/or otherwise associated with the sample medium. In other embodiments, the operating temperature is predetermined. In other embodiments, the sample environment may include an operating temperature associated with the entirety of the sample testing device, the waveguide, an associated apparatus (such as apparatus 2700 or 2800), and the like. It should be appreciated that in some embodiments, temperature sensors associated with sample testing devices, waveguides, etc. may be used to monitor and/or otherwise control the operating temperature for testing the sample media, as described herein.
At block 3604, the process 3600 further includes providing operating temperature and sample interference fringe data to the trained sample recognition model, wherein sample identity data is received in response to the operating temperature and the sample interference fringe data. In this regard, the trained sample recognition model may be configured to generate and/or otherwise output sample identity data for unidentified samples based on such input data. Thus, the trained sample identification model is configured to accurately output the sample identity tag and/or statistical information associated therewith for each unidentified sample medium while accounting for shifts in interference fringe patterns associated with changes in the operating temperature of the sample environment. In other embodiments, the trained sample recognition model may be trained to further receive one or more additional input data elements, such as wavelengths associated with sample interference fringe data, and so forth, as described herein.
Dual mode waveguide interferometer sensors can have the advantages of high sensitivity and low manufacturing process requirements, and silicon wafer processes can be implemented to mass produce dual mode interferometer sensors. However, many dual-mode interferometer fringe analyses based on dual-mode interferometer sensors may have limitations. For example, dual mode interferometer fringe analysis based on fringe offset ratios does not provide accurate results.
In accordance with various embodiments of the present disclosure, an enhanced dual mode waveguide interferometer fringe pattern analysis process may be provided, where the enhanced analysis process may include additional feature extraction. For example, rather than calculating the ratio of the amplitudes sampled on both sides of the fringe pattern, statistical measures may be used to extract pattern amplitude (sum), pattern center offset (average), pattern distribution width (standard deviation), pattern profile asymmetry (skewness), and/or pattern distribution outliers (kurtosis). The enhanced analytical process may increase dual mode interferometer sensitivity by detecting detailed differences between the test sample and the reference medium.
Referring now to fig. 55, an exemplary diagram illustrating an exemplary infrastructure 5500 is shown.
In the example shown in fig. 55, light source 5501 may provide light to sample testing device 5503. In some examples, the light source 5501 may be configured to generate, emit light, and/or trigger the generation, and/or emission of light. Exemplary light sources 5501 may include, but are not limited to, laser diodes (e.g., violet laser diodes, visible laser diodes, edge-emitting laser diodes, surface-emitting laser diodes, etc.). In some examples, the light source 5501 may be configured to generate light having a spectral purity within a predetermined threshold. For example, the light source 5501 may include a laser diode that may generate a single frequency laser beam. Additionally or alternatively, the light source 5501 may be configured to generate light having a spectral purity difference. For example, the light source 5501 may include a laser diode that may generate a wavelength tunable laser beam. In some examples, the light source 5501 may be configured to generate light having a broad spectrum.
In some embodiments, the sample testing device 5503 may include a waveguide (e.g., a bimodal waveguide). As light travels through sample testing device 5503, an interference fringe pattern may be generated at the output end of sample testing device 5503, as described herein. In the example shown in fig. 55, a region imaging component 5505 may be disposed at the output of the sample testing device 5503 to directly capture an image 5507 of the interference fringe pattern to generate interference fringe data.
According to various examples of the present disclosure, the interference fringe data and interference fringe patterns may be analyzed using a statistical process to obtain one or more statistical metrics. Exemplary statistical metrics may include, but are not limited to, a sum associated with the interference fringe data/interference fringe pattern, an average associated with the interference fringe data/interference fringe pattern, a standard deviation associated with the interference fringe data/interference fringe pattern, a skewness associated with the interference fringe data/interference fringe pattern, and/or a kurtosis value associated with the interference fringe data/interference fringe pattern. By comparing these statistical metrics associated with the unidentified sample medium with the statistical metrics associated with the identified reference medium, the identity of the unidentified sample medium may be determined and the result may have a higher accuracy and a higher confidence level.
Referring now to fig. 56, 57, and 58, exemplary methods associated with examples of the present disclosure are shown.
Referring now to fig. 56, an exemplary process 5600 begins at step/operation 5602.
At block 5604, the process 5600 may include receiving interference fringe data for an identified reference medium.
In some embodiments, the interference fringe data embodies a captured representation of an interference fringe pattern produced by light and via a sample testing device (e.g., a waveguide) according to embodiments of the present disclosure. In some embodiments, fringe data is captured by one or more imaging components associated with the projected interference fringe pattern. Additionally or alternatively, in some embodiments, the interference fringe data is received from another associated system, is loaded from a database embodied on a local and/or remote memory device, and so forth.
In some embodiments, the interference fringe data can be used to derive one or more statistical metrics, as described herein.
At block 5606, the process 5600 may include calculating a plurality of statistical metrics based on the interference fringe data.
In some embodiments, process 5600 can include calculating a sum associated with the interference fringe data. The sum may represent the area under the pattern distribution (e.g., the total energy received as a result of optical efficiency).
In some embodiments, process 5600 can include calculating an average associated with the interference fringe data. The average value may represent a center shift of the pattern. For example, the average value may represent the total path length difference between the two modes of the waveguide caused by the refractive index change.
In some embodiments, process 5600 can include calculating a standard deviation associated with the interference fringe data. The standard deviation may represent the width of the pattern, including the change in refractive index over the sample area.
In some embodiments, process 5600 can include calculating a skewness associated with the interference fringe data. The skewness may represent symmetry of the pattern, including any additional sample response differences in the two modes of the waveguide.
In some embodiments, process 5600 can include calculating kurtosis values associated with the interference fringe data. Kurtosis values may represent the shape of the pattern and identify additional outliers of the sample response (e.g., the degree to which the shape is peaked or flattened).
At block 5608, the process 5600 may include storing the plurality of statistical metrics in a database.
At block 5610, the process 5600 ends.
Referring now to fig. 57, an exemplary process 5700 may begin at block 5701.
At block 5703, process 5700 can include receiving interference fringe data for unidentified sample medium.
In some embodiments, the interference fringe data embodies a captured representation of an interference fringe pattern produced by light and via a sample testing device (e.g., a waveguide) according to embodiments of the present disclosure. In some embodiments, fringe data is captured by one or more imaging components associated with the projected interference fringe pattern. Additionally or alternatively, in some embodiments, the interference fringe data is received from another associated system, is loaded from a database embodied on a local and/or remote memory device, and so forth.
At block 5705, the process 5700 can include calculating at least one statistical metric based on interference fringe data.
In some implementations, the process 5700 can include calculating a sum associated with interference fringe data. The sum may represent the area under the pattern distribution (e.g., the total energy received as a result of optical efficiency).
In some embodiments, process 5700 can include calculating an average associated with interference fringe data. The average value may represent a center shift of the pattern. For example, the average value may represent the total path length difference between the two modes of the waveguide caused by the refractive index change.
In some implementations, the process 5700 can include calculating a standard deviation associated with interference fringe data. The standard deviation may represent the width of the pattern, including the change in refractive index over the sample area.
In some implementations, the process 5700 can include calculating skewness associated with interference fringe data. The skewness may represent symmetry of the pattern, including any additional sample response differences in the two modes of the waveguide.
In some implementations, the process 5700 can include calculating kurtosis values associated with interference fringe data. Kurtosis values may represent the shape of the pattern and identify additional outliers of the sample response (e.g., the degree to which the shape is peaked or flattened).
At block 5707, process 5700 can include comparing the at least one statistical metric to one or more statistical metrics associated with one or more identified media.
For example, process 5700 can include comparing a sum associated with interference fringe data for an unidentified sample medium to one or more sums each associated with interference fringe data for an identified reference medium, and calculating one or more differences. The process 5700 can include determining whether each of these differences satisfies a threshold, details of which are described in connection with at least fig. 58.
Additionally or alternatively, the process 5700 can include comparing an average associated with interference fringe data for an unidentified sample medium with one or more averages each associated with interference fringe data for an identified reference medium, and calculating one or more differences. The process 5700 can include determining whether each of these differences satisfies a threshold, details of which are described in connection with at least fig. 58.
Additionally or alternatively, the process 5700 can include comparing a standard deviation associated with interference fringe data for unidentified sample media to one or more standard deviations each associated with interference fringe data for an identified reference medium, and calculating one or more differences. The process 5700 can include determining whether each of these differences satisfies a threshold, details of which are described in connection with at least fig. 58.
Additionally or alternatively, the process 5700 can include comparing the bias associated with interference fringe data for unidentified sample media to one or more bias each associated with interference fringe data for an identified reference media, and calculating one or more differences. The process 5700 can include determining whether each of these differences satisfies a threshold, details of which are described in connection with at least fig. 58.
Additionally or alternatively, the process 5700 can include comparing kurtosis values associated with interference fringe data for unidentified sample media with one or more bias values each associated with interference fringe data for an identified reference media, and calculating one or more differences. The process 5700 can include determining whether each of these differences satisfies a threshold, details of which are described in connection with at least fig. 58.
Additionally or alternatively, other statistical metrics may be used.
At block 5709, the process 5700 can include determining sample identity data based on the at least one statistical metric and the one or more statistical metrics.
In some embodiments, the sample identity data may provide an identity of the unidentified sample medium (e.g., a type of virus in the sample medium). In some embodiments, the sample identity data may be determined based on differences between statistical measures associated with interference fringe data for unidentified sample media and one or more statistical measures each associated with interference fringe data for identified reference media, the details of which are described in connection with at least fig. 58.
At block 5711, process 5700 ends.
Referring now to fig. 58, an exemplary process 5800 may begin at block 5802.
At block 5804, process 5800 may include determining whether a difference between the at least one statistical metric and the one or more statistical metrics meets a threshold.
For example, process 5800 may include determining whether a difference between a sum associated with an unidentified sample medium and a sum associated with an identified reference medium meets a threshold. For example, the threshold may be a predetermined value based on the error margin of the system, and when the difference is less than the threshold, the difference satisfies the threshold.
Additionally or alternatively, process 5800 may include determining whether a difference between an average associated with the unidentified sample medium and an average associated with the identified reference medium meets a threshold. For example, the threshold may be a predetermined value based on the error margin of the system, and when the difference is less than the threshold, the difference satisfies the threshold.
Additionally or alternatively, process 5800 may include determining whether a difference between a standard deviation associated with the unidentified sample medium and a standard deviation associated with the identified reference medium meets a threshold. For example, the threshold may be a predetermined value based on the error margin of the system, and when the difference is less than the threshold, the difference satisfies the threshold.
Additionally or alternatively, process 5800 may include determining whether a difference between the skewness associated with the unidentified sample medium and the skewness associated with the identified reference medium meets a threshold. For example, the threshold may be a predetermined value based on the error margin of the system, and when the difference is less than the threshold, the difference satisfies the threshold.
Additionally or alternatively, process 5800 may include determining whether a difference between a kurtosis value associated with an unidentified sample medium and a kurtosis value associated with an identified reference medium meets a threshold. For example, the threshold may be a predetermined value based on the error margin of the system, and when the difference is less than the threshold, the difference satisfies the threshold.
Additionally or alternatively, other statistical metrics may be used.
At block 5806, process 5800 may include: sample identity data is determined based on the identity data of the identified reference medium associated with the one or more statistical metrics in response to determining that the difference between the at least one statistical metric and the one or more statistical metrics satisfies a threshold.
For example, if the difference between the sum of unidentified sample medium and the sum of reference medium a meets its corresponding threshold, process 5800 may include determining that unidentified sample medium is associated with reference medium a (e.g., unidentified sample medium has the same virus type as reference medium a).
Additionally or alternatively, if the difference between the average of the unidentified sample medium and the average of reference medium a meets its corresponding threshold, process 5800 may include determining that the unidentified sample medium is associated with reference medium a (e.g., the unidentified sample medium has the same virus type as reference medium a).
Additionally or alternatively, if the difference between the standard deviation of the unidentified sample medium and the standard deviation of reference medium a meets its corresponding threshold, process 5800 may include determining that the unidentified sample medium is associated with reference medium a (e.g., the unidentified sample medium has the same virus type as reference medium a).
Additionally or alternatively, if the difference between the skewness of the unidentified sample medium and the skewness of reference medium a meets its corresponding threshold, process 5800 may include determining that the unidentified sample medium is associated with reference medium a (e.g., the unidentified sample medium has the same virus type as reference medium a).
Additionally or alternatively, if the difference between the kurtosis value of the unidentified sample medium and the kurtosis value of reference medium a meets its corresponding threshold, process 5800 may include determining that the unidentified sample medium is associated with reference medium a (e.g., the unidentified sample medium has the same virus type as reference medium a).
In some examples, process 5800 may include determining that more than one difference satisfies its corresponding threshold. In such examples, process 5800 may determine identity data based on a reference medium associated with a maximum number of statistical metrics meeting a threshold. For example, if three of the differences between the statistical measures of unidentified sample medium and the statistical measures of reference medium a meet their corresponding thresholds and four of the differences between the statistical measures of unidentified sample medium and the statistical measures of reference medium B meet their corresponding thresholds, process 5800 may determine that unidentified sample medium is associated with reference medium B.
At block 5808, process 5800 ends.
It should be noted that the scope of the present disclosure is not limited to what has been described above. In some embodiments of the present disclosure, features from the various figures may be substituted and/or combined. For example, the statistical metrics described in connection with fig. 55-58 may be used in connection with the exemplary processes described above in connection with fig. 47-54. For example, statistical metrics may be used to train the sample recognition model described above in connection with fig. 52.
Fluid virus detection may require complex operations (such as laboratory testing) or slow response times or limited sensitivity (such as paper-based testing). There is a need for a simple, fast and accurate fluid viral sensor for clinical or public use.
According to various embodiments of the present disclosure, a universal fluid virus sensor is provided. The universal fluid virus sensor may optically sense fluid refractive index changes based on an immunoassay. A micro-device with a disposable reusable sensor cartridge may report results within minutes.
Referring now to fig. 59, an exemplary exploded view of an exemplary sensor cartridge 5900 is provided. In the example shown in fig. 59, an exemplary sensor cartridge 5900 may include a cover layer 5901, a waveguide 5903, and a substrate layer 5905.
Similar to the various examples described herein, the waveguide 5903 may include a sample opening 5907 on the first surface. Similar to the various sample openings described herein, sample opening 5907 may be configured to receive a sample medium.
Similar to the various examples described herein, a cladding layer 5901 may be coupled to the waveguide 5903. In some examples, the coupling between the cover layer 5901 and the waveguide 5903 may be achieved via at least one sliding mechanism. For example, the cross-section of the cover layer 5901 may be shaped like the letter "n". A sliding guard may be attached to the inner surface of each leg of the cover layer 5901, and a corresponding rail may be attached to one or more side surfaces of the waveguide 5903. Thus, the cover layer 5901 is slidable between a first position defined by the slide guard and the rail and a second position, details of which are shown in fig. 60A, 60B, 61A, and 61B.
Referring back to fig. 59, the waveguide 5903 may be securely fastened to the substrate layer 5905. For example, the waveguide 5903 may include an input window 5909 and an output window 5911. Each of the input window 5909 and the output window 5911 is in the form of a rib protruding from a surface of the substrate layer 5905. The waveguide 5903 may be snap fit between the input window 5909 and the output window 5911, and light may travel into the waveguide 5903 through the input window 5909 and exit from the output window 5911. Thus, the input window 5909 and the output window 5911 may each provide an optically clear path for light to travel.
In some embodiments, the substrate layer 5905 may include a thermally conductive material for temperature sensing and control. For example, the substrate layer 5905 may include a glass material. Additionally or alternatively, the substrate layer 5905 may include other materials.
In some embodiments, exemplary sensor cartridge 5900 may have a length of 1.3 inches, a width of 0.4 inches, and a height of 0.1 inches. In some embodiments, the dimensions of the exemplary sensor cartridge 5900 may be other values.
Referring now to fig. 60A and 60B, exemplary views of an exemplary sensor cartridge 6000 are provided. In particular, exemplary sensor cartridge 6000 includes cover layer 6006, waveguide 6004, and substrate layer 6002, similar to those described above.
In the example shown in fig. 60A and 60B, the cover layer 6006 is in a first position (e.g., an "open position"). As shown, when cover 6006 is in the first position, opening 6008 of cover 6006 can overlap with opening 6010 of waveguide 6004. As described above, the waveguide 6004 can include antibodies for attracting molecules in a sample medium and/or include a reference medium for temperature control. The opening 6008 receives a sample medium to be tested, such as buffered saliva, nasal swabs, and throat swabs.
Referring now to fig. 61A and 61B, an exemplary view of an exemplary sensor cartridge 6100 is provided. In particular, the exemplary sensor cartridge 6100 includes a cover layer 6105, a waveguide 6103, and a substrate layer 6101, similar to those described above.
In the example shown in fig. 61A and 61B, the cover 6105 is in a second position (e.g., a "closed position"). As shown, when the cover layer 6105 is in the second position, the opening 6107 of the cover layer 6105 may not overlap with the opening 6109 of the waveguide 6103.
In some embodiments, an exemplary sensor cartridge 6100 in a closed position may be inserted into a slot of an analyzer device, the details of which are described herein.
Referring now to fig. 62, an exemplary view 6200 is illustrated. In particular, the example view 6200 illustrates an example sensor cartridge 6202 and an analyzer device 6204. The exemplary sensor cartridge 6202 may be similar to the various exemplary sensor cartridges described herein.
The analyzer device 6204 may include a slot base 6206 for securely fastening the sensor cartridge 6202 to the analyzer device 6204 (e.g., without limitation, by a snap-fit mechanism).
In some embodiments, the slot base 6206 can include a thermal pad (e.g., the thermal pad can include one or more temperature sensors embedded therein) that provides temperature sensing capabilities. The thermal pad may monitor and control the temperature of the sensor cartridge 6202 to ensure accuracy of measurement of the reflectance of the sample.
In some embodiments, the analyzer device 6204 can include one or more optical windows (e.g., optical window 6208) disposed perpendicular to a surface of the slot base 6206. When the sensor cartridge 6202 is inserted onto the slot base 6206, an optical window (e.g., optical window 6208) can be aligned with an input window of the exemplary sensor cartridge 6202 such that the analyzer device 6204 can provide light to the exemplary sensor cartridge 6202 and/or another optical window (e.g., optical window 6208) can be aligned with an output window of the exemplary sensor cartridge 6202 such that the analyzer device 6204 can receive the interference disruption pattern.
In the example shown in fig. 62, the analyzer device 6204 may include a light indicator 6210 disposed on the surface, which may indicate the optical sensing result. For example, the light indicator 6210 may adjust its color and/or flash based on whether the analyzer device 6204 is ready, whether the analyzer device 6204 is busy, whether a virus is determined, whether an error exists, and the like.
In some embodiments, the analyzer device 6204 may include a plurality of circuits disposed therein. For example, the analyzer device 6204 may include processing circuitry for analyzing the interference destruction pattern. The analyzer device 6204 may include communication circuitry for transmitting the analysis data to other devices (such as a mobile phone or tablet) via wired or wireless means (such as via Wi-Fi, bluetooth, and/or the like). In some embodiments, the circuit may be powered by one or more batteries suitable for wireless charging.
In some embodiments, the analyzer device 6204 may be hermetically sealed such that it is gas impermeable. In particular, the optical interface implemented through the optical window between the sensor cartridge 6202 and the analyzer device 6204 may reduce the need for a wired connection while enabling the analyzer device 6204 to be hermetically sealed for sterilization.
In some embodiments, the analyzer device 6204 may include a built-in total internal reflection automatic UV sterilizer for sterilizing the surface of the analyzer device 6204. For example, a UV sterilizer may be disposed within the analyzer device 6204. As described above, the analyzer device 6204 may transmit data wirelessly, thus providing non-contact operation and reducing the risk of contamination.
Referring now to fig. 63A, 63B, and 63C, exemplary views of an exemplary sensor cartridge 6301 that has been inserted into an analyzer device 6303 are shown. Specifically, fig. 63A shows an exemplary prospective view, fig. 63B shows an exemplary top view, and fig. 63C shows an exemplary side view.
In some embodiments, the analyzer device 6303 may have a length of 80 millimeters, a width of 40 millimeters, and a height of 10 millimeters. In some embodiments, the size of the analyzer device 6303 may be other values.
It should be noted that the scope of the present disclosure is not limited to what has been described above. In some embodiments of the present disclosure, features from the various figures may be substituted and/or combined. For example, various features associated with a sample testing device including a sliding cover (e.g., sliding mechanism) as shown in fig. 10-13 may be implemented in the above-described exemplary sensor cartridge.
Integrated airborne virus detection may provide early warning in the field. For example, the integrated airborne virus detection system may be integrated into an HVAC system or AC unit. However, due to the low potential concentration levels of viruses in air, technical challenges exist in detecting airborne viruses, and the requirement for high aerosol sampling efficiency and high virus detection sensitivity may limit the application of point-of-care devices for detecting airborne viruses. Thus, there is a need for a compact aerosol virus detection device that provides real-time virus detection capabilities.
Some electrostatic precipitator aerosol samplers may include high voltage electrodes, grid ground and a liquid collector. Such samplers may be limited in implementation due to grid grounding requirements. In various embodiments of the present disclosure, the integrated sensor may use a waveguide as part of an electrostatic precipitator to eliminate the ground grid requirements in the aforementioned precipitator. For example, the metal top of the waveguide may collect aerosol particles directly without a liquid collector and/or a fluidic system to maximize collection efficiency.
Some waveguide interferometers may have a non-conductive dielectric top surface with a non-window area masked with an opaque oxide, and the sample medium may be delivered by a fluid added on top of the waveguide interferometer. In various embodiments of the present disclosure, the integrated electrostatic precipitator waveguide may comprise a metal layer at the top surface for non-window area masking without requiring additional processing. The metal layer may be connected to system ground and serve as an electrostatic precipitator ground. The aerosol sample can be deposited directly on the sensing surface without the need for an additional air-liquid interface, thereby minimizing collection efficiency losses and improving detection accuracy.
Thus, the direct interface design of the sample testing device in various embodiments of the present disclosure may allow for bioaerosol particle collection, biochemical virus binding, and virus detection on a single lab-on-a-chip structure. The air flow tunnel of the sample testing device may provide an electric field formed by the positive electrode and a metal layer (also referred to as a grounded mesh layer) on the top surface of the waveguide. Electrostatic precipitation may push an airborne bioaerosol to the top surface of the waveguide. The precoated antibodies on the waveguides can bind and immobilize specific viral particles, and the waveguides can detect viruses based on refractive index changes.
According to various embodiments of the present disclosure, an exemplary sample testing device may include a waveguide (e.g., a dual mode waveguide interferometer sensor) and a sampler component (e.g., an electrostatic aerosol sampler). The sampler component may provide an electrostatic flow tunnel that may bind airborne viruses to the surface of the waveguide. In some embodiments, the sampler component may enable compact in-situ collection of the bioaerosol. In some embodiments, the waveguide may provide a lab-on-a-chip structure to detect viruses based on potential refractive index changes due to airborne viruses.
Referring now to fig. 64A, 64B, and 64C, an exemplary sample testing device 6400 is shown.
As shown in fig. 64A and 64B, an exemplary sample testing device 6400 may include a waveguide 6401 and a sampler member 6403.
In some embodiments, the sampler member 6403 may be disposed on a top surface of the waveguide 6401. In some examples, the sampler component 6403 may be disposed onto a side surface of the waveguide 6401 by one or more fastening mechanisms and/or attachment mechanisms, including, but not limited to, chemical means (e.g., adhesive materials such as glue), mechanical means (e.g., one or more mechanical fasteners or methods such as welding, snap-fit, permanent and/or non-permanent fasteners), and/or suitable means.
In the example shown in fig. 64A, the cross-section of the sampler member 6403 may take a shape similar to the inverted letter "U" in the english alphabet. Thus, the sampler member 6403 may provide a flow tunnel 6407 that allows air to flow therethrough. In some embodiments, the flow tunnel may be an electrostatic flow tunnel. Referring now to fig. 65A and 65B, exemplary views of exemplary sample testing device 6500 are shown.
Fig. 65A illustrates an exemplary cross-sectional view of an exemplary sample testing device 6500 taken along the width of the exemplary sample testing device 6500. An exemplary sample testing device 6500 can include a sampler member 6501 disposed on a top surface of a waveguide 6503. In the example shown in fig. 65A, an example sampler component 6501 may include an anode element 6505. In some embodiments, the anode element 6505 may be in the form of a positively chargeable electrode. In some embodiments, the top surface of the waveguide 6503 may include a layer connected to ground. Thus, the top surfaces of the anode element 6505 and the waveguide 6503 may create an electric field in the flow tunnel.
Referring now to fig. 65B, another exemplary cross-sectional view of an exemplary sample testing device 6500 is shown taken along the length of the exemplary sample testing device 6500. As air flows through the flow tunnel (e.g., in the direction indicated by the arrows), the electric field generated by the anode element 6505 and the top surface of the waveguide 6503 may cause the aerosol within the flow tunnel to be attracted to or bind to the top surface of the waveguide 6503.
Referring back to fig. 64A and 64B, the sampler member 6403 may include an anode element 6405 similar to the anode element 6505 described above. For example, the anode element 6405 and the top surface of the waveguide 6401 may generate an electric field within the flow tunnel 6407 of the sampler component 6403, and the aerosol in the flow tunnel 6407 may be attracted to or bonded to the top surface of the waveguide 6401.
In some embodiments, the anode element 6405 may be embedded within the sampler component 6403. For example, the anode element 6405 may be embedded in a central middle portion of the sampler member 6403. In some embodiments, the anode element 6405 may be in contact with air in the flow tunnel 6407.
Referring now to fig. 64C, an exploded view of an exemplary sample testing device 6400 is shown. Specifically, fig. 64C shows the various layers associated with waveguide 6401.
For example, the waveguide 6401 may include a silicon substrate layer 6411. The waveguide 6401 may include a SiO2 cladding layer 6413 disposed on top of a silicon substrate layer 6411. The waveguide 6401 may include a Si3N4 waveguide core layer 6415 (which may provide one or more waveguide elements) disposed on top of a SiO2 cladding layer 6413. The waveguide 6401 may include a SiO2 planar layer 6417 disposed on top of a Si3N4 waveguide core layer 6415. The waveguide 6401 may include a polysilicon light shielding layer 6419 (which may shield stray light) disposed on top of the SiO2 planar layer 6417. The waveguide 6401 may include a SiO2 cladding window layer 6421 disposed on top of a polysilicon light-shielding layer 6419. The waveguide 6401 may include an aluminum mesh layer 6423 (which may be connected to ground) disposed on top of a SiO2 cladding window layer 6421.
In order to protect passengers from airborne viruses (such as, but not limited to, SARS-COV-II), it is desirable to provide effective, real-time monitoring of the air in the aircraft cabin to detect airborne viruses.
According to various embodiments of the present disclosure, an airborne bioaerosol virus sensor may be deployed in an aircraft cabin with minimal impact on flight operations. In some embodiments, the airborne bioaerosol virus sensor may be in the form of plug-in devices that may be added to an AC outlet (e.g., an AC outlet near the seat bottom) to monitor bioaerosols in the air of the aircraft cabin. Thus, real-time monitoring and control may be utilized to improve flight safety.
Referring now to fig. 66A, 66B, 66C, and 66D, an exemplary sample testing device 6600 is shown. In particular, the exemplary sample testing device 6600 may provide the airborne bioaerosol virus sensor described above.
Referring now to fig. 66A, an exemplary sample testing device 6600 can include a housing component 6601.
In some embodiments, the housing component 6601 may include a plurality of airflow opening elements 6605, allowing air to circulate into the sample testing device 6600, the details of which are described herein.
In some embodiments, the housing component 6601 may include an electrical outlet element 6607 disposed on the front surface. As described above, the sample testing device 6600 may be plugged into an AC outlet. When another device is plugged into the outlet element 6607, the outlet element 6607 may transfer power from the AC outlet to the other device.
Referring now to fig. 66B, an exemplary sample testing device 6600 can include a base member 6603. As shown, the housing component 6601 may be securely fastened to the base component 6603.
As described above, the exemplary sample testing device 6600 may be plugged into an AC outlet. In the example shown in fig. 66B, the base member 6603 may include a power plug element 6609. When the power plug element 6609 is plugged into an AC outlet, power may flow from the AC outlet to the sample testing device 6600 and may power the sample testing device 6600. As described above, the housing member 6601 can include an electrical outlet element 6607 disposed on the front surface. In such an example, the example sample testing device 6600 may also pass current to another device plugged into the electrical outlet element 6607.
Referring now to fig. 66C, an exploded view of an exemplary sample testing device 6600 is shown.
In some embodiments, the example sample testing device 6600 can include a blower element 6611 disposed on an inner surface of the base member 6603. In some embodiments, the blower element 6611 may include one or more devices that generate an airflow, such as, but not limited to, a fan. In some embodiments, the blower element 6611 may be positioned on the base member 6603 corresponding to the position of the airflow opening element 6605 on the housing member 6601. In such examples, when the blower element 6611 is energized and is operating, the blower element 6611 may generate an airflow, wherein air may flow into the sample testing device 6600 through the airflow opening element 6605, travel within the sample testing device 6600 (details of which are described herein), and exit the sample testing device 6600 through an opening (e.g., through the airflow opening element 6605 and/or another opening).
Referring now to fig. 66D, an exemplary view of the base member 6603 is shown.
As disclosed above, the blower element 6611 may be disposed on an inner surface of the base member 6603. An aerosol sampler member 6613 may be connected to the blower element 6611 to sample aerosols from the air.
For example, the aerosol sampler component 6613 may provide a tunnel that allows air to flow from the blower element 6611 onto the exemplary waveguide 6619. In some embodiments, the aerosol sampler component 6613 may generate an electric field to bind or attract the aerosol to the waveguide 6619, similar to those described herein.
In some embodiments, the light source 6615 may provide input light to the waveguide 6619 through the integrated optic 6617.
Similar to those described above, the light source 6615 may be configured to generate, emit light (including but not limited to a laser beam) and/or trigger the generation, and/or emission of light. The light source 6615 may be coupled to the integrated optic 6617 and light may travel from the light source 6615 to the integrated optic 6617. Similar to those described above, the integrated optical component 6617 can collimate, polarize, and/or couple light to the waveguide 6619. For example, the integrated optical component 6617 may be disposed on a top surface of the waveguide 6619 and may direct light through an input opening of the waveguide 6619.
In some embodiments, the sample testing device 6600 can include a lens component 6621 disposed on a top surface of the waveguide 6619. For example, the lens component 6621 can at least partially overlap with the output opening of the waveguide 6619 such that light exiting the waveguide 6619 can pass through the lens component 826.
In some examples, lens component 6621 can include one or more optical imaging lenses, such as, but not limited to, one or more lenses having a spherical surface, one or more lenses having a parabolic surface, and the like. In some examples, the lens component 6621 can redirect and/or adjust the direction of light exiting the waveguide 6619 toward the imaging component 6623. In some examples, the imaging component 6623 can be disposed on an inner surface of the base component 6603.
The imaging component 6623 may be configured to detect interference fringe patterns similar to those described above. For example, imaging component 6623 can include one or more imagers and/or image sensors (such as integrated 1D, 2D, or 3D image sensors). Various examples of image sensors may include, but are not limited to, contact Image Sensors (CIS), charge Coupled Devices (CCD) or Complementary Metal Oxide Semiconductor (CMOS) sensors, photodetectors, one or more optical components (e.g., one or more lenses, filters, mirrors, beam splitters, polarizers, etc.), auto-focusing circuitry, motion tracking circuitry, computer vision circuitry, image processing circuitry (e.g., one or more digital signal processors configured to process images to improve image quality, reduce image size, increase image transmission bit rate, etc.), a checker, a scanner, a camera, any other suitable imaging circuitry, or any combination thereof.
In some embodiments, the imaging component 6623 can be electrically coupled to the sensor board element 6625. In some embodiments, the sensor board element 6625 may include circuitry such as, but not limited to, processor circuitry, memory circuitry, and communication circuitry.
For example, the processor circuit may communicate with the memory circuit via a bus for communicating data/information, including data generated by the imaging component 6623. The memory circuit is non-transitory and may include, for example, one or more volatile and/or non-volatile memories. The processor circuit may perform one or more of the example methods described herein to detect the presence of a virus based on data generated by the imaging component 6623.
In some embodiments, the processor circuit may generate a warning signal when the processor circuit determines that a virus is present in the air. The processor circuit may communicate the alert signal to the communication circuit over the bus, and the communication circuit may transmit the alert signal to another device (e.g., a central controller on the aircraft) via wired or wireless means (e.g., wi-Fi).
In some embodiments, one or more actions may be taken based on the alert signal. For example, a central controller on the aircraft may regulate airflow in the aircraft to remove viruses. Additionally or alternatively, the central controller may present a warning message on the display and one or more crewmembers may begin disinfecting the aircraft and/or replacing the waveguide 6619.
While the above description provides an exemplary implementation of the sample testing device 6600 within an aircraft, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the example sample testing device 6600 can be implemented in other environments and/or situations.
According to various embodiments of the present disclosure, a multi-channel waveguide may simultaneously test multiple fluid samples to provide accurate results with multiple references, which may require highly synchronized delivery and control of multiple fluids into a fluid cap. However, providing simultaneous delivery and control of multiple fluids can be technically challenging. For example, some systems may utilize multiple pumps, where each pump is configured to deliver one type of fluid (e.g., sample medium for testing, known reference medium for reference, etc.) into one flow channel. Such systems may require one or more separators and/or cylinders connected to a pump in order to simultaneously deliver multiple fluids (such as sample media and/or reference media) to different channels. However, a system implementing multiple separators and/or cylinders may result in non-uniform delivery of fluid (such as sample medium and/or reference medium) between channels, resulting in differences in test results and providing an unreliable solution for sample testing.
According to various embodiments of the present disclosure, a single pump, multi-channel fluid system is provided. In some embodiments, a single pump delivers the buffer solution continuously, which flows through multiple flow channels in series. Each of the flow channels is formed between the fluid cover, the flow channel plate, and the waveguide. In some embodiments, multiple fluids (including sample media and reference media) are preloaded and/or injected into a valve of a single pump multichannel fluid system. In some embodiments, when testing of the sample medium is performed, the valve is switched to insert a fluid (such as, but not limited to, the sample medium, a reference medium, and/or the like) into the flow of buffer solution through the flow channel. In some embodiments, the length of tubing between the valve and the flow channels is predetermined based on the timing for switching the different valves such that each flow channel will receive fluid at the same time, providing more accurate results for testing and further analysis.
Thus, according to examples of the present disclosure, an exemplary single pump multi-channel fluid system may provide buffer solution to all channels at the same pressure, the same temperature, and at the same flow rate. In some embodiments, a plurality of valves (each of which is connected to a flow channel by a buffer circuit) may be provided for injecting fluids (such as, but not limited to, sample media, reference media) into an exemplary single pump multi-channel fluid system, which may ensure that the volumes of all injected fluids are consistent. In some embodiments, fluid sensing and analysis accuracy is provided for the same time by synchronizing the timing for switching the valve based on the length of the buffer loop between the valve and the flow channel.
Referring now to fig. 67A and 67B, an exemplary configuration associated with an exemplary valve 6700 is shown. In the example shown in fig. 67A and 67B, the exemplary valve is a 2-configuration 6-port valve.
Specifically, fig. 67A shows an example valve 6700 in a first configuration, and fig. 67B shows an example valve 6700 in a second configuration. In some embodiments, the example valve 6700 can include a first port 6701, a second port 6702, a third port 6703, a fourth port 6704, a fifth port 6705, and a sixth port 6706.
In the example shown in fig. 67A, when in the first configuration, the first port 6701 and the second port 6702 are connected within the example valve 6700. In other words, when in the first configuration, fluid may flow into the example valve 6700 through the first port 6701 and out of the example valve 6700 through the second port 6702, or may flow into the example valve 6700 through the second port 6702 and out of the example valve 6700 through the first port 6701.
Similarly, when in the first configuration, the third port 6703 and the fourth port 6704 are connected within the example valve 6700. In other words, when in the first configuration, fluid may flow into the example valve 6700 through the third port 6703 and out of the example valve 6700 through the fourth port 6704, or may flow into the example valve 6700 through the fourth port 6704 and out of the example valve 6700 through the third port 6703.
Similarly, when in the first configuration, the fifth port 6705 and the sixth port 6706 are connected within the example valve 6700. In other words, when in the first configuration, fluid may flow into the example valve 6700 through the fifth port 6705 and out of the example valve 6700 through the sixth port 6706, or may flow into the example valve 6700 through the sixth port 6706 and out of the example valve 6700 through the fifth port 6705.
In the example shown in fig. 67B, the first port 6701 and the sixth port 6706 are connected within the example valve 6700 when in the second configuration. In other words, when in the second configuration, fluid may flow into the example valve 6700 through the first port 6701 and out of the example valve 6700 through the sixth port 6706, or may flow into the example valve 6700 through the sixth port 6706 and out of the example valve 6700 through the first port 6701.
Similarly, when in the second configuration, the third port 6703 and the second port 6702 are connected within the example valve 6700. In other words, when in the second configuration, fluid may flow into the example valve 6700 through the third port 6703 and out of the example valve 6700 through the second port 6702, or may flow into the example valve 6700 through the second port 6702 and out of the example valve 6700 through the third port 6703.
Similarly, when in the second configuration, the fifth port 6705 and the fourth port 6704 are connected within the example valve 6700. In other words, when in the second configuration, fluid may flow into the example valve 6700 through the fifth port 6705 and out of the example valve 6700 through the fourth port 6704, or may flow into the example valve 6700 through the fourth port 6704 and out of the example valve 6700 through the fifth port 6705.
In the example shown in fig. 67A and 67B, the first port 6701 is always connected to the fourth port 6704 through the sample loop 6708, whether the example valve 6700 is in the first configuration (fig. 67A) or the second configuration (fig. 67B). In other words, when in the first configuration or the second configuration, fluid may flow into the first port 6701, through the sample loop 6708, and out of the fourth port 6704, or may flow into the fourth port 6704, through the sample loop 6708, and out of the first port 6701.
In some embodiments, the example valve 6700 may receive fluid through the second port 6702.
For example, in the first configuration shown in fig. 67A, the second port 6702 may be connected to a fluid source configured to inject a fluid (e.g., without limitation, a sample medium or a reference medium) into the example valve 6700. As described above, in the first configuration, the second port 6702 is connected to the first port 6701, which in turn is connected to the sample loop 6708. Thus, fluid may flow through sample loop 6708 and reach fourth port 6704. As described above, in the first configuration, the fourth port 6704 is connected to the third port 6703. Thus, fluid may exit the valve 6700 through the third port 6703.
After the example fluid is injected into the second port 6702 and the sample circuit 6708 when the example valve 6700 is in the first configuration, the example valve 6700 may be switched to the second configuration as shown in fig. 67B. As described above, in the second configuration, the fourth port 6704 is connected to the fifth port 6705. In some embodiments, the fifth port 6705 may receive buffer solution from a pump or from a previous flow channel through a buffer circuit, the details of which are described herein.
As described above, the fifth port 6705 is connected to the fourth port 6704, which in turn is connected to the sample loop 6708. Thus, after the example valve 6700 is switched to the second configuration, the buffer solution received from the fifth port mixes with the example fluid in the sample loop 6708 at the fourth port 6704. As described above, in the second configuration, the fourth port 6704 is connected to the fifth port 6705. Thus, fluid may exit the example valve 6700 through a sixth port 6706, which may be connected to a flow channel, details of which are described herein.
Referring now to fig. 68, an exemplary single pump, multi-channel fluid system 6800 is shown.
In the example shown in fig. 68, the example single-pump, multi-channel fluidic system 6800 includes a pump 6802 that delivers buffer solution to one or more flow channels (including, but not limited to, a first flow channel 6808, a second flow channel 6816 … …, and a last flow channel 6824). In some embodiments, one or more flow channels of the exemplary single pump, multi-channel fluidic system 6800 are connected in series. For example, the first flow channel 6808 is connected to the second flow channel 6816 through a second valve 6812, as shown in fig. 68. In some embodiments, the use of a single pump (rather than multiple pumps) provides the technical advantage of having the same flow rate across different flow channels.
In some embodiments, an exemplary single pump multi-channel fluid system may include one or more valves. In some embodiments, each of the one or more valves may connect a flow channel to a pump, or may connect two flow channels. In the example shown in fig. 68, a first valve 6804 is connected to the pump 6802 and the first flow channel 6808, a second valve 6812 is connected to the first flow channel 6808 and the second flow channel 6816, and so on.
In some embodiments, to operate the example single pump multi-channel fluidic system 6800 shown in fig. 68, buffer solution may be provided to the one or more flow channels (e.g., first flow channel 6808, second flow channel 6816 … …, and last flow channel 6824) by pump 6802, and example fluid (e.g., but not limited to sample medium or reference medium) may be provided to the one or more flow channels (e.g., first flow channel 6808, second flow channel 6816 … …, and last flow channel 6824) by the one or more valves (e.g., first valve 6804, second valve 6812 … …, and last valve 6820).
In accordance with examples of the present disclosure, an exemplary method of operating an exemplary single pump, multi-channel fluid system 6800 is provided.
In some embodiments, the example method may include switching the one or more valves (e.g., the first valve 6804, the second valves 6812 and … …, and the last valve 6820) of the example single-pump, multi-channel fluid system 6800 to the first configuration. As described above, in the first configuration, the fifth port of the valve is connected to the sixth port of the valve, while the first port is connected to the fourth port through the sample loop.
In some embodiments, an exemplary method may include injecting a buffer solution into the first valve 6804 via the pump 6802. In some embodiments, the example pump 6802 is connected to a fifth port of the first valve 6804. In some embodiments, the sixth port of the first valve 6804 is connected to the first flow channel 6808. As described above, in the first configuration, the fifth port of the first valve 6804 is connected to the sixth port of the first valve 6804. Thus, the buffer solution flows from the example pump 6802 through the first valve 6804 and to the first flow channel 6808.
As described above, the first flow channel 6808 is connected to the second flow channel 6816 via one or more components. In the example shown in fig. 68, the first flow channel 6808 is connected to a first buffer circuit 6810, which in turn is connected to a second valve 6812, which in turn is connected to a second flow channel 6816. In some embodiments, the length of the first buffer circuit 6810 may be determined based on the timing of switching the second valve 6812 from the first configuration to the second configuration, the details of which are described herein.
The sixth port of the second valve 6812 is connected to the second flow passage 6816, similar to those described above. As described above, in the first configuration, the fifth port of the second valve 6812 is connected to the sixth port of the second valve 6812. Thus, the buffer solution flows from the first buffer circuit 6810 through the second valve 6812 and reaches the second flow channel 6816.
In some embodiments, one or more sets of valves and flow channels may be connected in series such that buffer solution may flow through the various flow channels from the example pump 6802 to the final buffer circuit 6818. Similar to those described above, the last buffer circuit 6818 is connected to the last valve 6820, which in turn is connected to the last flow channel 6824. In some embodiments, the last flow channel 6824 is the last flow channel in a series of flow channels of the exemplary single pump, multi-channel fluid system 6800.
In some embodiments, when the first valve 6804 is in the first configuration, the example method further includes providing a first fluid (e.g., without limitation, a sample medium or a reference medium) to the first valve 6804 through a second port of the first valve 6804. As described above, when the first valve 6804 is in the first configuration, the second port of the first valve 6804 is connected to the first port of the first valve 6804, and the first port of the first valve 6804 is connected to the fourth port of the first valve 6804 through the first sample loop 6806. Thus, the first fluid may flow into the first sample loop 6806.
Additionally or alternatively, when the second valve 6812 is in the first configuration, the example method further includes providing a second fluid (e.g., without limitation, a sample medium or a reference medium) to the second valve 6812 through a second port of the second valve 6812. As described above, when the second valve 6812 is in the first configuration, the second port of the second valve 6812 is connected to the first port of the second valve 6812, and the first port of the second valve 6812 is connected to the fourth port of the second valve 6812 through the second sample loop 6814. Thus, the second fluid may flow into the second sample loop 6814.
Additionally or alternatively, when the last valve 6820 is in the first configuration, the example method further includes providing a last fluid (e.g., without limitation, a sample medium or a reference medium) to the last valve 6820 through a second port of the last valve 6820. As described above, when the last valve 6820 is in the first configuration, the second port of the last valve 6820 is connected to the first port of the last valve 6820, and the first port of the last valve 6820 is connected to the fourth port of the last valve 6820 through the last sample loop 6822. Thus, the last fluid may flow into the last sample loop 6822.
In some embodiments, the exemplary method further comprises switching the first valve 6804 from the first configuration to the second configuration. As described above, after the first valve 6804 is switched from the first configuration to the second configuration, the first port of the first valve 6804 is no longer connected to the second port of the first valve 6804. Conversely, when the first valve 6804 is in the second configuration, the first port is connected to the sixth port of the first valve 6804 and the fifth port is connected to the fourth port of the first valve 6804. Thus, after the first valve 6804 is switched to the second configuration, the buffer solution may be continuously injected into the first valve 6804 through the fifth port (which is connected to the fourth port when the first valve 6804 is in the second configuration). The buffer solution may then exit the fourth port and flow through the first sample loop 6806.
As described above, the first sample loop 6806 is connected to the first port and may contain a first fluid. The buffer solution may be combined with the first fluid and flowed to the first port. As described above, when the first valve 6804 is in the second configuration, the first port is connected to the sixth port, and the buffer solution may exit the first valve 6804 through the sixth port. As described above, the sixth port of the first valve 6804 is connected to the first flow channel 6808, and the buffer solution having the first fluid may flow through the first flow channel 6808.
As described above, after the buffer solution exits the first flow channel 6808, the buffer solution may further flow through the first buffer circuit 6810. In some embodiments, the exemplary method further comprises switching the second valve 6812 from the first configuration to the second configuration.
As described above, after the second valve 6812 is switched from the first configuration to the second configuration, the first port of the second valve 6812 is no longer connected to the second port of the second valve 6812. Conversely, when the second valve 6812 is in the second configuration, the first port is connected to the sixth port of the second valve 6812 and the fifth port is connected to the fourth port of the second valve 6812. Thus, after the second valve 6812 is switched to the second configuration, the buffer solution may flow from the first buffer circuit 6810 to the second valve 6812 through the fifth port (which is connected to the fourth port when the second valve 6812 is in the second configuration). The buffer solution may then leave the fourth port and flow through the second sample loop 6814.
As described above, the second sample loop 6814 is connected to the first port and may contain a second fluid. The buffer solution may be combined with the second fluid and flowed to the first port. As described above, when the second valve 6812 is in the second configuration, the first port is connected to the sixth port, and the buffer solution may exit the second valve 6812 through the sixth port. As described above, the sixth port of the second valve 6812 is connected to the second flow passage 6816, and the buffer solution having the second fluid may flow through the second flow passage 6816.
In some embodiments, the first buffer circuit 6810 may enable a mixture of buffer solution and first fluid to enter the first flow channel 6808 at the same time that a mixture of buffer solution and second fluid enters the second flow channel 6816. In some embodiments, the first buffer circuit 6810 may prevent the first fluid from mixing with the second fluid. To achieve the above, the length of the first buffer circuit 6810 may be calculated based at least in part on a time period between a time when the first valve 6804 is switched from the first configuration to the second configuration and a time when the second valve 6812 is switched from the first configuration to the second configuration. For example, the length L of the first buffer loop 6810 may be calculated based on the following equation:
In the above example, T is the period of time between the time when the first valve 6804 is switched from the first configuration to the second configuration and the time when the second valve 6812 is switched from the first configuration to the second configuration. Q is the flow rate of the buffer solution injected by pump 6802. r is the radius of the first buffer loop 6810. As described in the above equation, the length L of the first buffer circuit 6810 is equal to the flow rate (during the period between the time the first valve 6804 is switched from the first configuration to the second configuration and the time the second valve 6812 is switched from the first configuration to the second configuration) divided by the cross-sectional area of the first buffer circuit 6810. In some embodiments, the length L of the first buffer circuit 6810 prevents the buffer solution that has mixed with the first fluid (and exited the first flow channel 6808) from interacting with the second fluid (after the second valve 6812 switches from the first configuration to the second configuration) while enabling the mixture of buffer solution and first fluid to enter the first flow channel 6808 at the same time as the mixture of buffer solution and second fluid enters the second flow channel 6816.
In some embodiments, the example single pump multi-channel fluid system 6800 further includes one or more additional valves connected in series, and the example method further includes sequentially switching each of the one or more additional valves.
For example, as shown in fig. 68, the exemplary single pump, multi-channel fluid system 6800 further includes a last buffer circuit 6818. The last buffer circuit 6818 connects the penultimate flow channel to the last valve 6820, and the last valve 6820 connects to the last flow channel 6824. In some embodiments, the exemplary method further includes switching the last valve 6820 from the first configuration to the second configuration. As described above, after the last valve 6820 is switched from the first configuration to the second configuration, the first port of the last valve 6820 is no longer connected to the second port of the last valve 6820. Conversely, when the last valve 6820 is in the second configuration, the first port is connected to the sixth port of the last valve 6820 and the fifth port is connected to the fourth port of the last valve 6820. Thus, after the last valve 6820 is switched to the second configuration, buffer solution may flow from the last buffer circuit 6818 to the last valve 6820 through a fifth port (which is connected to the fourth port when the last valve 6820 is in the second configuration). The buffer solution may then exit the fourth port and flow through the last sample loop 6822. As described above, the last sample loop 6822 is connected to the first port and may contain the last fluid. The buffer solution may be combined with the last fluid and flowed to the first port. As described above, when the last valve 6820 is in the second configuration, the first port is connected to the sixth port and the buffer solution can exit the last valve 6820 through the sixth port. As described above, the sixth port of the last valve 6820 is connected to the last flow channel 6824, and the buffer solution can flow through the last flow channel 6824.
In some embodiments, the last buffer circuit 6818 may enable a mixture of buffer solution and penultimate fluid to enter the penultimate flow channel at the same time that the mixture of buffer solution and penultimate fluid enters the last flow channel 6824. In some embodiments, the last buffer circuit 6818 may prevent the penultimate fluid from mixing with the last fluid. To achieve the above, the length of the last buffer loop 6818 may be calculated based at least in part on the time period between the time the penultimate valve is switched from the first configuration to the second configuration and the time the penultimate valve 6820 is switched from the first configuration to the second configuration. For example, the length L of the last buffer loop 6818 may be calculated based on the above equation.
Thus, according to various embodiments of the present disclosure, the exemplary single pump multi-channel fluid system 6800 enables simultaneous delivery of multiple fluids into their corresponding flow channels.
Referring now to fig. 69A and 69B, exemplary views associated with an exemplary multi-channel waveguide apparatus 6900 are shown. Specifically, fig. 69A shows an exemplary perspective view of a multi-channel waveguide apparatus 6900, and fig. 69B shows an exemplary exploded view of the multi-channel waveguide apparatus 6900.
As shown in fig. 69A and 69B, the multi-channel waveguide apparatus 6900 can include a fluid cover 6907 secured to the multi-channel waveguide 6905. In some embodiments, the multi-channel waveguide apparatus 6900 includes a multi-channel waveguide 6905 disposed on a top surface of an insulating base 6903. In some embodiments, the multichannel waveguide 6905 is based on one or more examples of the waveguides described above. For example, the multichannel waveguide 6905 may include one or more sample channels and/or one or more reference channels, similar to those described above. In some embodiments, similar to the various insulating components described above, the insulating base 6903 prevents ambient temperature from interfering with the multichannel waveguide 6905.
In the example shown in fig. 69A and 69B, the fluid cover 6907 is secured to the multichannel waveguide 6905 by one or more screws (such as, but not limited to, screw 6909A, screw 6909B, screw 6909C, screw 6909D). For example, the fluid cover 6907 may include one or more threaded holes (such as, but not limited to, threaded holes 6913A, 6913C, 6913D), and each of the one or more screws may pass through the one or more threaded holes, wherein threads on an inner side of the threaded holes engage threads of the screws.
In some embodiments, a flow channel plate 6915 may be positioned between the fluid cover 6907 and the multichannel waveguide 6905. In particular, the flow channel plate 6915 may include one or more grooves etched on a surface of the flow channel plate 6915. When the flow channel plate 6915 is positioned below the fluid cover 6907, the bottom surface of the fluid cover 6907 and the one or more grooves form one or more flow channels. When the flow channel plate 6915 is positioned over the multichannel waveguide 6905 (e.g., based on one or more alignment techniques described herein), each of the one or more flow channels may be positioned over one of the sample channels or one of the reference channels of the multichannel waveguide 6905. In some embodiments, an inlet tube and an outlet tube may be connected to each of the flow channels such that sample medium, reference medium, and/or buffer solution may flow through the inlet tube to each of the flow channels and exit from each of the flow channels through the outlet tube.
For example, an inlet tube 6911A may be inserted through the fluid cover 6907 and connected to a first end of a flow channel on the flow channel plate 6915, and an outlet tube 6911B may be inserted through the fluid cover 6907 and connected to a second end of the flow channel on the flow channel plate 6915. In this example, the sample medium or reference medium may flow through the flow channel from the inlet tube 6911A and exit from the outlet tube 6911B. In some embodiments, the inlet tube 6911A is connected to a sixth port of the valve, similar to those described above. In some embodiments, outlet tube 6911B is connected to a buffer circuit, similar to those described above.
Additionally or alternatively, an inlet tube 6911C may be inserted through the fluid cover 6907 and connected to a first end of a flow channel on the flow channel plate 6915, and an outlet tube 6911D may be inserted through the fluid cover 6907 and connected to a second end of the flow channel on the flow channel plate 6915. In this example, the sample medium or reference medium may flow through the flow channel from the inlet tube 6911C and exit from the outlet tube 6911D. In some embodiments, the inlet tube 6911C is connected to a sixth port of the valve, similar to those described above. In some embodiments, outlet tube 6911D is connected to a buffer circuit, similar to those described above.
Additionally or alternatively, an inlet tube 6911E may be inserted through the fluid cover 6907 and connected to a first end of a flow channel on the flow channel plate 6915, and an outlet tube 6911F may be inserted through the fluid cover 6907 and connected to a second end of the flow channel on the flow channel plate 6915. In this example, the sample medium or reference medium may flow through the flow channel from the inlet tube 6911E and exit from the outlet tube 6911F. In some embodiments, the inlet tube 6911E is connected to a sixth port of the valve, similar to those described above. In some embodiments, outlet tube 6911F is connected to a buffer circuit, similar to those described above.
Referring now to fig. 70A, 70B, 70C, and 70D, exemplary views associated with exemplary flow channel plate 7000 are shown. Specifically, fig. 70A shows an exemplary perspective view of flow channel plate 7000, fig. 70B shows an exemplary top view of flow channel plate 7000, fig. 70C shows an exemplary side view of flow channel plate 7000, and fig. 70D shows another exemplary side view of flow channel plate 7000.
In the example shown in fig. 70A, 70B, 70C, and 70D, the example flow channel plate 7000 includes a first flow channel 7002, a second flow channel 7004, and a third flow channel 7006. As described above, each of the first, second, and third flow channels 7002, 7004, and 7006 are formed between etched grooves on a surface of the flow channel plate 7000 and a bottom surface of a fluid cover under which the example flow channel plate 7000 is positioned.
As shown in fig. 70B, in some embodiments, the first flow channel 7002 and/or the third flow channel 7006 may have a length L2 of 16 centimeters. In some embodiments, the second flow channel 7004 may have a length L1 of 21 centimeters. In some embodiments, the example flow channel plate 7000 may have a length L3 of 25.6 cm. In some embodiments, the example flow channel plate 7000 may have a width W2 of 5.3 cm. In some embodiments, the distance W1 between the first flow channel 7002 and the second flow channel 7004 (and/or the distance between the second flow channel 7004 and the third flow channel 7006) is 0.9 centimeters. In some embodiments, one or more of the above-mentioned measurements may be other values.
In some embodiments, the diameter D3 of the end of the flow channel is 0.6 cm, as shown in fig. 70C. In some embodiments, diameter D3 may be other values.
As shown in fig. 70D, in some embodiments, the etch depth D1 of each flow channel is 0.2 cm. In some embodiments, the width D2 of the flow channel plate 7000 is 0.5 millimeters. In some embodiments, one or more of the above-mentioned measurements may be other values.
Referring now to fig. 71 and 72, exemplary graphs showing exemplary test results are provided. Specifically, a graph 7100 shown in fig. 71 shows an exemplary original signal containing noise, and a graph 7200 shown in fig. 72 shows an exemplary processed signal from which noise has been removed.
As shown in fig. 71 and 72, exemplary signals from three flow channels are shown. For example, curve 7101 of fig. 71 shows an exemplary raw signal generated by an exemplary imaging component based on detection of a sample medium or a reference medium in a first flow channel, and curve 7202 of fig. 72 shows an exemplary processed signal based on the raw signal from the first flow channel. As another example, curve 7103 of fig. 71 shows an exemplary raw signal generated by an exemplary imaging component based on detecting a sample medium or a reference medium in a second flow channel, and curve 7204 of fig. 72 shows an exemplary processed signal based on the raw signal from the second flow channel. As another example, curve 7105 of fig. 71 shows an exemplary raw signal generated by an exemplary imaging component based on detecting a sample medium or a reference medium in a third flow channel, and curve 7206 of fig. 72 shows an exemplary processed signal based on the raw signal from the third flow channel.
In the examples shown in fig. 71 and 72, the three channel example may allow for testing of sample media using at least a first reference medium as a negative reference (e.g., distilled water) and a second reference medium as a positive reference (e.g., target virus substitute). For example, the sample medium, the first reference medium, and the second reference medium may be a first fluid, a second fluid, and a third fluid, respectively, which may be injected into a first valve, a second valve, and a third valve, respectively, of a single pump, multi-channel fluid system. Pumps may be used to inject the buffer solution into a single pump multichannel fluid system.
In some embodiments, three different fluids (e.g., one sample medium and two reference mediums) may travel through the three flow channels after the valve is switched. In some embodiments, signals from three flow channels may be used to quantitatively provide test results based on processing using positive and negative references. When multi-channel testing is performed under the same conditions, common noise and variations (such as sensing system heat, structural variations, and drift) can be eliminated by processing signals from different channels, as shown in graph 7200 of FIG. 72.
Although the above description provides some examples using three flow channels, it should be noted that the scope of the present disclosure is not limited to the above description. For example, in some embodiments, a single flow channel may be implemented in an exemplary flow channel plate, and the single flow channel may be positioned on top of the waveguide to cover one or more sample channels and/or one or more reference channels in the waveguide. In some embodiments, more flow channels may be arranged with different target alternatives to have multiple results in one test. In some embodiments, multiple sensors may be arranged in each channel to provide error correction and noise reduction. In some implementations, embedded sensing regions may be added to provide an absolute reference to compensate for sensor signal changes with signals from the surrounding environment.
As described above, an exemplary sample testing device according to embodiments of the present disclosure may implement a light source that emits a laser beam toward a waveguide. It is noted that optical waveguide-based devices find use in a variety of applications involving biosensing, quantum computing, communications and data processing. In some of these applications, the waveguide is a permanent part of the system. In other applications, however, particularly in biosensing applications, the waveguide may need to be removable and disposable, which presents some technical challenges, as the laser must typically be correctly coupled into the waveguide before it can be used. Proper coupling of the laser to the waveguide typically requires alignment of the waveguide to the focal point of the laser (or to another waveguide in which the fiber or light has been confined) with an error within a few microns. This requirement may be beyond the tolerance that can be achieved by machining or manufacturing of the mechanical parts.
Thus, the waveguide needs to be actively aligned with the light source after it is inserted into the system. However, manual alignment can be time consuming and require a skilled operator. In addition, the various shocks and vibrations associated with normal use (e.g., placing the device on a table, the device being bumped by an elbow, running a noisy machine near the device) may cause the waveguide to move at least a few microns relative to the light source, requiring repeated alignment procedures.
According to various embodiments of the present disclosure, a laser alignment system is provided that provides for automatic alignment of a laser to a waveguide. For example, various embodiments of the present disclosure may include features that may provide a signal to the auto-alignment system even when the laser source is initially severely misaligned with the waveguide. Various embodiments of the present disclosure may allow for the use of lower cost actuators (which may drift over time) during alignment by providing feedback signals (which may be used to correct for drift).
Various embodiments of the present disclosure may provide various technical advantages over other systems, including but not limited to providing feedback even when the laser is severely misaligned with the waveguide. Various embodiments of the present disclosure are compatible with inexpensive high-drift actuators used in continuous active servo control processes.
In various embodiments of the present disclosure, an exemplary method is provided. The exemplary method may include patterning at least some of the optical features on the waveguide chip and patterning some of the optical features on a holder in which the waveguide chip is mounted. In some embodiments, when the laser source emits laser light on one of the optical features, the optical feature may cause a redirection of the laser light (e.g., only high spatial frequency or low spatial frequency light is redirected) and/or a change in its characteristics (e.g., a change in light intensity). In some embodiments, an imaging component (such as a camera pixel array or one or more photodiodes) as described above may be positioned at a particular location to detect the laser light. In some embodiments, the camera pixel array or one or more photodiodes may convert the detected laser light into signals, which may be transmitted to a processor. Based on these signals, the processor may send control signals to the actuator or motor to move the light source such that the light source is properly aligned with the waveguide (additionally or alternatively, to move the waveguide such that the waveguide is properly aligned with the light source).
For example, based on these signals, the processor may send control signals to the actuator or motor, indicating in which direction the light source should move in the "horizontal" dimension (e.g., in the plane of the waveguide chip). In some implementations, the laser light may be redirected from a grating coupler patterned into the waveguide itself, such that the laser source may be realigned to the waveguide leading to the grating coupler even if the laser source is initially very misaligned in the horizontal dimension. In some embodiments, the grating coupler may redirect these lasers vertically onto the camera pixel array or one or more photodiodes and the resulting signal is different when the laser source is aligned with one side of the waveguide chip than when the laser source is aligned with the other side of the waveguide chip. Thus, the signals generated by the camera pixel array or one or more photodiodes may indicate: in order to be properly aligned (e.g., to an input coupler configured to receive the laser light and direct it to the waveguide chip), the laser source (or waveguide chip) needs to be moved in which way.
Additionally or alternatively, in the "vertical" dimension (e.g., in a plane perpendicular to the waveguide chip), signals are reflected from portions of the mount below the chip onto one or more photodiodes or camera pixel arrays in a different manner than from portions of the mount above the chip.
Referring now to fig. 73A, 73B, and 73C, exemplary diagrams illustrating exemplary methods of aligning a laser source to a waveguide chip in a vertical dimension are shown. In particular, the exemplary methods shown in fig. 73A, 73B, and 73C may align a laser source with a waveguide chip in a vertical direction based on signals detected by a camera pixel array. In some embodiments, the examples shown herein may provide a number of technical advantages, including, but not limited to, providing robust alignment against background light contamination, accommodating laser intensity variations, and avoiding interference from stray reflections or scattering.
In the examples shown in fig. 73A, 73B, and 73C, a waveguide mount 7301, a waveguide chip including a plurality of layers (e.g., a first layer 7303 and a second layer 7305), and a fluid cap 7307 are shown. In some embodiments, the waveguide chip is mounted on the top surface of the waveguide mount 7301. In some embodiments, a fluid cap 7307 is mounted on the top surface of the waveguide chip. In some embodiments, the second layer 7305 is mounted on a top surface of the first layer 7303.
In some embodiments, the waveguide mount 7301 and the waveguide chip may have different reflectivities that reflect laser light. For example, waveguide mount 7301 may have a 95% reflectivity. Additionally or alternatively, the first layer 7303 of the waveguide chip may include silicon and have a reflectivity of 40%. Additionally or alternatively, the second layer 7305 of the waveguide chip may comprise silicon oxide having a reflectivity of 4%.
Referring now to fig. 73A, in some embodiments, an exemplary method may include aiming a laser source 7309 at a waveguide mount 7301. Specifically, the laser source 7309 may emit laser light, and the laser light may travel through the beam splitter 7311 and collimator 7313, similar to those described above. Since the laser source 7309 is aimed at the waveguide mount 7301 and the waveguide mount 7301 has a 95% reflectivity, the waveguide mount 7301 can reflect the laser light back to the beam splitter 7311 and the beam splitter 7311 redirects the laser light upward in the vertical dimension toward the imaging component 7317 (e.g., camera pixel array).
In some embodiments, an exemplary method may include maximizing the brightness of the laser light detected by imaging component 7317 based on tilting and/or tilting beam splitter 7311.
In some embodiments, an exemplary method may include moving the laser source 7309 upward in a vertical dimension. In the example shown in fig. 73A, a laser source 7309, a beam splitter 7311, and a collimator 7313 are fixed within a laser housing 7315 and aligned with one another. In some embodiments, the laser housing 7315 is movably positioned on the vertical support wall 7321. For example, the laser housing 7315 may be attached to one or more slide mechanisms (e.g., the slider/rail mechanisms described above), and the position of the laser housing 7315 on the one or more slide mechanisms is controlled by one or more actuators or motors (e.g., the actuators or motors may control the position of the slider on the rail). As described above, the actuator or motor is controlled by the processor, and the exemplary method may include transmitting a control signal from the processor to the actuator or motor such that the laser source 7309 moves upward in the vertical dimension.
In some embodiments, one or more horizontal support walls (e.g., horizontal support wall 7319 and horizontal support wall 7323) are disposed on an inner surface of vertical support wall 7321. In the example shown in fig. 73A, 73B, and 73C, the imaging part 7317 is mounted on the horizontal support wall 7319.
In some embodiments, an exemplary method may include moving, by a processor, a laser source or an optical element that refracts or reflects the laser source in a vertical dimension until a change in back reflected power from a surface is detected. In some embodiments, the characteristic reflectivity of the dielectric embedded waveguide may be used as a signal to indicate when the laser is incident on the film. For example, as the laser source 7309 continues to move upward in the vertical dimension, laser light emitted by the laser source 7309 reaches the first layer 7303. As described above, the first layer 7303 has a reflectivity of 40% compared to a reflectivity of 95% of the waveguide mount 7301. Thus, as the laser source 7309 moves in the vertical dimension upward from aiming waveguide mount 7301 to aim at the first layer 7303, the light received by the imaging assembly 7317 becomes darker.
In some embodiments, as the laser source 7309 continues to move upward in the vertical dimension, the laser light emitted by the laser source 7309 reaches the second layer 7305, as shown in fig. 73B. As described above, the second layer 7305 has a reflectivity of 4% compared to the reflectivity of 40% of the first layer 7303. Thus, as the laser source 7309 moves in the vertical dimension upward from aiming at the first layer 7303 to aiming at the second layer 7305, the light received by the imaging assembly 7317 becomes darker.
In some embodiments, once the laser light emitted by the laser light source 7309 reaches the second layer 7305, the imaging component 7317 may detect a grating coupler spot due to the laser light reflected from the grating coupler etched at the second layer 7305. In some embodiments, the laser light reflected from the grating coupler travels through a collimator 7316 mounted on imaging assembly 7317, forming one or more grating coupler spots that are detected by imaging assembly 7317.
In some embodiments, once the imaging component detects the one or more grating coupler light spots, the exemplary method further includes stopping the vertical movement of the laser source 7309 and initiating the horizontal movement of the laser source 7309. In some embodiments, once the one or more grating coupler light spots are present, the processor may determine that the laser source 7309 is properly aligned in the vertical dimension and may begin alignment of the laser source in the horizontal dimension. Details associated with alignment in the horizontal dimension are further described in connection with at least fig. 74, 75A, and 75B.
In some embodiments, as the laser source 7309 is continuously moved upward in the vertical dimension, the laser source 7309 may inadvertently move from aiming the second layer 7305 to aiming the fluid cover 7307, as shown in fig. 73C. In some embodiments, the fluid cap 7307 may include additional gratings on the surface. When the laser source 7309 emits laser light toward the fluid cap 7307, the imaging assembly 7317 may detect additional spots due to the laser light redirected by additional gratings on the surface of the fluid cap 7307. In some embodiments, these additional spots occur at different locations from and remote from the grating coupler spots detected by the imaging assembly when the laser is aimed at the second layer 7305. Based on these positions, the processor may determine that the laser source 7309 has moved upward and past the second layer 7305, and may cause the laser source 7309 to move downward in the vertical dimension.
Referring now to fig. 74, an exemplary top view 7400 of an exemplary waveguide chip 7402 is shown. In particular, the exemplary top view 7400 shows exemplary grating coupler patterns on the exemplary waveguide chip 7402 that can facilitate alignment of the laser sources in the horizontal dimension as described above.
In the example shown in fig. 74, an exemplary waveguide chip 7402 may include an optical channel 7404 that corresponds to the correct channel (e.g., a sample channel or a reference channel of a waveguide) that the laser source should be aimed at when the laser source is properly aligned. In some embodiments, a fluid cap 7405 may be disposed on a top surface of the exemplary waveguide chip 7402.
In some embodiments, the exemplary waveguide chip 7412 may include one or more additional alignment channels such as, but not limited to, alignment channels 7406, alignment channels 7418, alignment channels 7410, alignment channels 7412, alignment channels 7414, and alignment channels 7416.
In some embodiments, each of the alignment channels may include one or more grating couplers etched on the alignment channel (e.g., grating coupler 7418 of alignment channel 7406). In some embodiments, each of the grating couplers redirects laser light at a particular spatial frequency. As described above, the redirected laser light may also form one or more grating coupler spots as detected by the imaging component. Thus, based on the detected spatial frequency of the grating coupler spot, the processor may cause movement of the laser source in the horizontal dimension such that the laser source is properly aligned with the waveguide chip.
In the example shown in fig. 74, the optical channel 7404 may divide the waveguide chip 7402 into two sides: one or more alignment vias (including alignment via 74106, alignment via 7418, alignment via 7410) are etched on a first side of the optical via 7414, while one or more alignment vias (including alignment via 7412, alignment via 7414, alignment via 7416) are etched on a second side of the optical via 7414. In some embodiments, the alignment channels etched on the first side of the optical channel 7404 may include grating couplers that redirect laser light at a different spatial frequency than the spatial frequency of the grating couplers from the alignment channels etched on the second side of the optical channel 7404.
For example, alignment vias 74106, 7408, 7410 may include grating couplers that redirect laser light at low spatial frequencies, and alignment vias 7412, 7414, 7416 may include grating couplers that redirect laser light at high spatial frequencies.
Referring now to fig. 75A and 75B, exemplary diagrams illustrating an exemplary method of aligning a laser source to a waveguide chip in a horizontal dimension are shown. In particular, the exemplary methods shown in fig. 75A and 75B may align a laser source with a waveguide chip in the horizontal dimension based on signals detected by the camera pixel array.
Similar to waveguide chip 7402 described above in connection with fig. 74, waveguide chip 7503 shown in fig. 75A and 75B may include optical channels 7511 that correspond to the correct channels (e.g., sample channels or reference channels of a waveguide) that the laser source should be aimed at when the laser source is properly aligned. Exemplary waveguide chip 75103 may include one or more additional alignment channels such as, but not limited to, alignment channels 7505, 7507, and 7509 positioned on a first side of optical channel 7511, and alignment channels 7513, 7515, and 7517 positioned on a second side of optical channel 7511.
Similar to those described above, alignment channels 7505, 7507, and 7509 may redirect laser light at high spatial frequencies, while alignment channels 7513, 7515, and 7517 may redirect laser light at low spatial frequencies. In some implementations, each of the alignment channels 7505, 7507, and 7509, 7513, 7515, and 7517 can redirect laser light at different spatial frequencies.
In some embodiments, an exemplary method may include moving a laser source or an optical element from which the laser source is refracted or reflected in a horizontal dimension to either side of a target region in a direction indicated by a pattern of light diffracted from a grating formed in one or more waveguides to couple into a main functional waveguide or a main channel of a waveguide. In some embodiments, the position or spatial frequency of the grating on one side of the target area is different from the position or spatial frequency of the grating on the other side of the target area, as described herein. For example, the laser source 7501 may be moved in a horizontal dimension by an actuator or motor and the imaging component may detect one or more grating coupler spots, as described above. For example, when the imaging component detects one or more grating coupler spots having a high spatial frequency, the processor may determine that the laser source 7501 has moved too far to the left and may move the laser source 7501 toward the right as shown in fig. 75A. As used herein, the opposite sides of "left" and "right" are based on viewing from the direction of the laser light from the laser source 7501 toward the waveguide chip 7503. As another example, when the imaging component detects one or more grating coupler light spots having a low spatial frequency, the processor may determine that the laser source 7501 has moved too far to the right and may move the laser source 7501 toward the left as shown in fig. 75B. In some implementations, each of the alignment channels 7505, 7507, and 7509, 7513, 7515, and 7517 can redirect laser light at different spatial frequencies. In such embodiments, the processor may determine the position of the laser source 7501 based on the detected spatial frequency and may cause the laser source 7501 to move accordingly. In some implementations, the processor can cause the laser source to continuously move in the horizontal dimension until the laser source 7501 is properly aligned in the horizontal dimension.
Referring now to fig. 76A, 76B, and 76C, exemplary diagrams illustrating an exemplary method of aligning a laser source to a waveguide chip in a vertical dimension are shown. Specifically, the exemplary methods shown in fig. 76A, 76B, and 76C may align a laser source with a waveguide chip in a vertical direction based on signals detected by one or more photodiodes.
In the examples shown in fig. 76A, 76B, and 76C, a waveguide mount 7601, a waveguide chip including a plurality of layers (e.g., a first layer 7603 and a second layer 7605), and a fluid cap 7607 are shown. In some embodiments, the waveguide chip is mounted on the top surface of the waveguide mount 7601. In some embodiments, a fluid cap 7607 is mounted on the top surface of the waveguide chip. In some embodiments, the second layer 7605 is mounted on a top surface of the first layer 7603.
In some embodiments, the waveguide mount 7601 and the waveguide chip may have different reflectivities that reflect laser light. For example, the waveguide mount 7601 may have a 95% reflectivity. Additionally or alternatively, the first layer 7603 of the waveguide chip may include silicon and have a reflectivity of 40%. Additionally or alternatively, the second layer 7605 of the waveguide chip may comprise silicon oxide having a reflectivity of 4%.
Referring now to fig. 76A, in some embodiments, an exemplary method may include aiming a laser source 7609 at a waveguide mount 7601. In particular, the laser source 7609 may emit laser light, and the laser light may travel through a beam splitter, similar to those described above. Since the laser source 7609 is aimed at the waveguide mount 7601 and the waveguide mount 7601 has a 95% reflectivity, the waveguide mount 7601 can reflect the laser light based on the beam splitter 7611 and the beam splitter 7611 redirects the laser light upward in the vertical dimension toward the photodiode 7616.
In some embodiments, the exemplary method may include moving the laser source 7609 upward in the vertical dimension. In the example shown in fig. 76A, the laser source 7609 and the beam splitter 7611 are fixed within the laser housing 7615 and aligned with each other. In some embodiments, the laser housing 7615 is movably positioned on the vertical support wall 7621. For example, the laser housing 7615 may be attached to one or more slide mechanisms (e.g., the slider/rail mechanisms described above), and the position of the laser housing 7615 on the one or more slide mechanisms is controlled by one or more actuators or motors (e.g., the actuators or motors may control the position of the slider on the rail). As described above, the actuator or motor is controlled by a processor, and an exemplary method may include transmitting a control signal from the processor to the actuator or motor such that the laser source 7609 moves upward in the vertical dimension.
In some embodiments, one or more horizontal support walls (e.g., horizontal support wall 7619 and horizontal support wall 7623) are disposed on an inner surface of vertical support wall 7621. In the example shown in fig. 76A, 76B, and 76C, one or more photodiodes 7614 are mounted on a horizontal support wall 7619.
In some embodiments, the laser light emitted by the laser light source 7609 reaches the first layer 7603 as the laser light source 7609 continues to move upward in the vertical dimension. As described above, the first layer 7603 has a reflectivity of 40% (compared to 95% reflectivity of the waveguide mount 7601). Thus, as the laser source 7609 moves in the vertical dimension up from the targeting waveguide mount 7601 to the targeting first layer 7603, the light received by the photodiode 7616 becomes darker.
In some embodiments, as the laser source 7609 continues to move upward in the vertical dimension, the laser light emitted by the laser source 7609 reaches the second layer 7605, as shown in fig. 76B. As described above, the second layer 7605 has a reflectivity of 4% compared to the reflectivity of 40% of the first layer 7603. Thus, as the laser source 7609 moves in the vertical dimension up from aiming at the first layer 7603 to aiming at the second layer 7605, the light received by the photodiode 7616 becomes darker.
In some implementations, the processing circuitry may determine that the laser source 7609 is aiming at the second layer 7605 based on the detected reflectivity.
Referring now to fig. 77, an exemplary diagram 7700 is shown. In particular, exemplary graph 7700 shows an exemplary relationship between back reflected signal power (e.g., as detected by photodiode 7616 shown in fig. 76A-76C) and the position of a laser source (e.g., laser source 7609) in the vertical dimension.
In the exemplary graph 7700, an exemplary threshold value for the back-reflected signal power is set to 4%, which corresponds to the reflectivity of the second layer. In some embodiments, the back-reflected signal power may be calculated by dividing the power of the optical signal detected by the photodiode by the power of the light emitted by the laser source. In some embodiments, a power monitor diode is implemented to distinguish between laser power changes and reflectivity changes.
In some embodiments, the processor may cause the laser source to move upward in the vertical dimension (as shown in fig. 76A) when the detected back-reflected signal power is greater than 4%. When the detected back reflection signal power is below 4%, the processor may cause the laser source to move downward in the vertical dimension (as described in further detail at least in connection with fig. 76C). In some embodiments, the processor determines that the laser source is properly aligned in the vertical direction when the detected back-reflected signal power is about 4% (e.g., within 15 um).
Referring back to fig. 76B, in some embodiments, once the processor determines that the laser source 7609 is aiming at the second layer 7605, the exemplary method further includes stopping the vertical movement of the laser source 7609 and initiating the horizontal movement of the laser source 7609. In some embodiments, the processor may determine that the laser source 7609 is properly aligned in the vertical dimension and may begin alignment of the laser source in the horizontal dimension. Details associated with alignment in the horizontal dimension are further described in connection with at least fig. 78, 79A, and 79B.
In some embodiments, as the laser source 7609 is continuously moved upward in the vertical dimension, the laser source 7609 may inadvertently move from aiming the second layer 7605 to aiming the fluid cover 7607, as shown in fig. 76C. In some embodiments, the fluid cap 7607 may have a low reflectivity and the photodiode 7616 may detect little reflected light, indicating a back reflected signal power below a threshold, as shown in fig. 77. In this example, the processor may determine that the laser source 7609 has moved too far upward and past the second layer 7605, and may cause the laser source 7609 to move downward in the vertical dimension.
Referring now to fig. 78, an exemplary top view 7800 of an exemplary waveguide chip 7802 is shown. In particular, the exemplary top view 7800 shows exemplary grating coupler patterns on the exemplary waveguide chip 7802 that may facilitate alignment of the laser sources in the horizontal dimension as described above.
In the example shown in fig. 78, an exemplary waveguide chip 7802 may include an optical channel 7804 that corresponds to the correct channel (e.g., a sample channel or a reference channel of a waveguide) that the laser source should be aimed at when the laser source is properly aligned. In some embodiments, a fluid cap 7805 may be disposed on a top surface of the exemplary waveguide chip 7802.
In some embodiments, the exemplary waveguide chip 7802 may include one or more additional alignment channels, such as, but not limited to, alignment channel 7806, alignment channel 7808, alignment channel 7810, alignment channel 7812, alignment channel 7814, and alignment channel 7816. In some embodiments, each of the alignment channels may include one or more grating couplers etched on the alignment channel (e.g., grating coupler 7818 of alignment channel 7806).
In the example shown in fig. 78, the optical channel 7804 may divide the waveguide chip 7802 into two sides: one or more alignment channels (including alignment channel 7806, alignment channel 7808, alignment channel 7810) are etched on a first side of optical channel 7804, while one or more alignment channels (including alignment channel 7812, alignment channel 7814, alignment channel 7816) are etched on a second side of optical channel 7804. In some implementations, the alignment channels etched on the first side of the optical channel 7804 may include grating couplers positioned in their respective alignment channels at a different location than the respective locations of the grating couplers in the alignment channels on the second side of the optical channel 7804.
For example, alignment channels 7806, 7808, and 7810 may include grating couplers positioned closer to the laser source than grating couplers in alignment channels 7812, 7814, and 7816. As described above, each grating coupler may redirect the laser light (e.g., upward in the vertical dimension). In some embodiments, one or more photodiodes are positioned over each of the grating couplers to receive laser light reflected from each of the grating couplers. In some embodiments, the processor may align the laser source in the horizontal dimension based on which of the one or more photodiodes detected the reflected laser light.
Referring now to fig. 79A and 79B, exemplary diagrams illustrating an exemplary method of aligning a laser source to a waveguide chip in a horizontal dimension are shown. In particular, the exemplary methods shown in fig. 79A and 79B may align a laser source with a waveguide chip in a horizontal dimension based on signals detected by one or more photodiodes.
Similar to the waveguide chip 7802 described above in connection with fig. 78, the waveguide chip 7903 shown in fig. 79A and 79B may include an optical channel 7911 that corresponds to the correct channel (e.g., sample channel or reference channel of the waveguide) that the laser source should be aimed at when the laser source is properly aligned. Exemplary waveguide chip 7903 may include one or more additional alignment channels such as, but not limited to, alignment channel 7905, alignment channel 7907, and alignment channel 7909 positioned on a first side of optical channel 7911, and alignment channel 7913, alignment channel 7915, and alignment channel 7917 positioned on a second side of optical channel 7911.
As shown in fig. 79A and 79B, the grating couplers of alignment channels 7905, 7907 and 7909 are positioned closer to laser source 7901 than the grating couplers of alignment channels 7913, 7915 and 7917. In some embodiments, one or more photodiodes may be positioned over the grating couplers of alignment channels 7905, 7907, and 7909, and one or more photodiodes may be positioned over the grating couplers of alignment channels 7913, 7915, and 7917.
In some embodiments, the laser source 7901 may be moved in the horizontal dimension by an actuator or motor and the one or more photodiodes may detect one or more signals, as described above. For example, when the one or more photodiodes positioned above the grating coupler of the alignment channel 7907 detects reflected laser light, the processor may determine that the laser source 7901 has moved too far to the left and may move the laser source 7051 toward the right as shown in fig. 79A. As used herein, the opposite sides of "left" and "right" are based on viewing from the direction of the laser light from the laser source 7901 toward the waveguide chip 7903. As another example, when the one or more photodiodes positioned above the grating coupler of the alignment channel 7913 detects reflected laser light, the processor may determine that the laser source 7901 has moved too far to the right and may move the laser source 7901 toward the left as shown in fig. 79B. In some embodiments, the processor may cause the laser source to continuously move in the horizontal dimension until the laser source 7901 is properly aligned based on all photodiodes not detecting any reflected laser light.
In some embodiments, an exemplary method for aligning a laser source with a waveguide chip is provided. In some embodiments, the actuator or motor may cause the laser source to move in a direction as determined by the processor by a step size of about 100um when the laser source is aligned to the waveguide in the vertical or horizontal dimension, and stop when a threshold is met based on the above example (e.g., when the spatial frequency changes or when the photodiode detects reflected light). In some embodiments, examples of the present disclosure may engage a fine control motor. Additionally or alternatively, when aligning the laser source to the waveguide in the vertical or horizontal dimension, the actuator or motor may continuously scan the laser source in a direction as determined by the processor until the target threshold is crossed. Once the target threshold is crossed, the processor may move the laser source in the opposite direction until the target threshold is crossed again. This process may be repeated to determine the optimal position for aligning the laser source (e.g., the exact position that crosses the target threshold).
One of the many technical challenges associated with sample testing (e.g., when testing for the presence of viruses in collected samples) is a false negative or false positive reading. For example, in antigen or molecular testing, it is desirable to identify and eliminate false negative readings. When the test result of a sample (e.g., collected by a swab or breath/aerosol sampling device) is negative, it can be challenging to determine if the result is negative because there are no viral components in the collected sample, or if the result is negative because the amount of collected sample is insufficient.
Various embodiments of the present disclosure may overcome the technical challenges mentioned above. For example, during sample collection of a respiratory aerosol for virus testing, the collected sample may include one or more proteins, biochemicals, or enzymes that are naturally present in the respiratory aerosol, whether or not viral components are present (e.g., whether or not the respiratory aerosol is infected with a virus). The concentration levels of these proteins, biochemicals and/or enzymes in the collected sample may be analyzed, which may provide a basis for determining whether a sufficient amount of the sample has been collected. Thus, various embodiments of the present disclosure may reduce or eliminate the possibility of reporting false negative results.
Referring now to FIG. 80, an exemplary diagram 8000 is shown. Specifically, exemplary diagram 8000 shows sample medium flowing through flow channel 8002 of the waveguide in the direction indicated by arrow 8008. For example, the waveguide may be configured to receive a sample medium comprising a non-viral indicator of a biological component and a viral indicator of the biological component.
In some embodiments, the collected sample medium may include both viral indicator 8004 of biological components and non-viral indicator 8006 of biological components. In the present disclosure, the term "viral indicator of a biological component" refers to a protein/biochemical/enzyme in a collected sample that indicates the presence of the biological component in the collected sample to be detected by a sample testing device. Examples of viral indicators of biological components may include, but are not limited to, viruses to be detected by the sample testing device, protein fragments associated with viruses to be detected by the sample testing device, and/or biomarkers associated with a viral state or condition. The term "non-viral indicator of a biological component" refers to a protein/biochemical/enzyme that is always present in a collected sample, regardless of whether the biological component to be detected by the sample testing device is present in the collected sample. Examples of non-viral indicators of biological components may include, but are not limited to, certain amino acids, certain volatile organic compounds, and/or the like that are always present in exhaled breath.
Referring now to FIG. 81, an exemplary method 8100 is illustrated. In particular, exemplary method 8100 illustrates utilizing the minimum feasible concentration of proteins, biochemicals, and/or enzymes to determine whether a sufficient amount of sample has been collected. Once the minimum concentration is confirmed in the collected sample, it can be determined that a sufficient amount of the sample has been collected for accurate testing.
The exemplary method 8100 begins at step/operation 8101 and proceeds to step/operation 8103. At step/operation 8103, the example method 8100 includes detecting a non-viral indicator of a biological component in the collected sample and/or determining a concentration level of the non-viral indicator of the biological component in the collected sample.
In some embodiments, exemplary method 8100 may implement various sample testing devices according to the present disclosure to detect non-viral indicators of biological components in a collected sample. For example, the collected sample may be provided to a flow channel as described herein. In some embodiments, the flow channel may be configured to detect a concentration level of a non-viral indicator of a biological component. For example, the flow channel may detect a non-viral indicator in the collected sample that includes 0.5 mass/milliliter of the biological component.
Referring back to fig. 81, at step/operation 8105, the example method 8100 includes determining whether the concentration level of the non-viral indicator of the biological component meets a threshold.
In some embodiments, the threshold value may be determined based on a non-viral indicator of the biological component to be tested and/or a viral indicator of the biological component. For example, if a non-viral indicator of a certain type of biological component typically has a concentration level in the collected sample of between 1 mass/ml, the threshold may be set to 1 mass/ml. As another example, if detecting a viral indicator of a certain type of biological component requires that the non-viral indicator of the biological component be at a concentration level of at least 2 mass/ml, the threshold may be adjusted based on the concentration level of 2 mass/ml.
In some embodiments, the threshold value may be determined based on collecting multiple samples and calculating an average or universal concentration level of the non-viral indicator of the biological component in the samples. In some embodiments, the threshold may be determined in other ways.
Referring back to fig. 81, if at step/operation 8105 the concentration level of the non-viral indicator of the biological component meets the threshold, then the exemplary method 8100 proceeds to step/operation 8107. At step/operation 8107, an exemplary method 8100 includes detecting an amount of a viral indicator of a biological constituent.
Continuing with the above example, if the threshold is 0.2 mass/ml and the concentration level of the non-viral indicator of the biological component detected at step/operation 8103 is 0.5 mass/ml, the concentration level of the non-viral indicator of the biological component satisfies the threshold. In other words, a sufficient amount of sample has been collected to ensure accurate testing.
In some embodiments, exemplary method 8100 may implement various sample testing devices according to the present disclosure to detect the amount of a viral indicator of a biological component in a collected sample. For example, the collected sample may be provided to a flow channel as described herein. In some embodiments, the flow channel may be configured to detect a concentration level of a viral indicator of a biological component.
Referring back to fig. 81, if at step/operation 8105 the amount of the non-viral indicator of the biological component does not meet the threshold, then the example method 8100 proceeds to step/operation 8109. At step/operation 8109, an exemplary method 8100 includes transmitting an alert signal.
Continuing with the above example, if the threshold is 1 mass/milliliter and the concentration level of the non-viral indicator of the biological component detected at step/operation 8103 is 0.5 mass/milliliter, the concentration level of the non-viral indicator of the biological component does not satisfy the threshold. In other words, a sufficient amount of sample was not collected.
In some embodiments, the alert signal may be generated by a processor and transmitted to a display device (such as, but not limited to, a computer display). For example, the warning signal may cause the display device to present a message warning the user that a sufficient amount of sample has not been collected and/or that the test results may be inaccurate. In some embodiments, the user may discard the collected sample and may initiate collection of a new sample.
Referring back to fig. 81, after step/operation 8107 and/or step/operation 8109, the exemplary method 8100 ends at step/operation 8111.
Referring now to fig. 82, an exemplary method 8200 is illustrated. In particular, the exemplary method 8200 illustrates using the concentration levels of non-viral indicators of biological components to calculate relative concentration levels of viral indicators of biological components in different collected samples.
The exemplary method 8200 begins at step/operation 8202 and proceeds to step/operation 8204. At step/operation 8204, an exemplary method 8200 includes detecting a concentration level of a non-viral indicator of a biological component in a plurality of collected samples.
Similar to those described above in connection with at least step/operation 8103 of fig. 81, in some embodiments, the exemplary method 8200 may be practiced with various sample testing devices according to the present disclosure to detect concentration levels of non-viral indicators of biological content in a collected sample.
For example, the exemplary method 8200 can determine that a first collected sample comprises a non-viral indicator of a biological component of 0.8 mass/milliliter and a second collected sample comprises a non-viral indicator of a biological component of 1.8 mass/milliliter.
At step/operation 8206, the exemplary method 8200 comprises detecting a concentration level of a viral indicator of a biological component in a plurality of collected samples.
Similar to those described above in connection with at least step/operation 8107 of fig. 81, in some embodiments, the exemplary method 8200 can be implemented to detect a concentration level of a viral indicator of biological content in a collected sample according to various sample testing devices of the present disclosure.
For example, the exemplary method 8200 can determine that a first collected sample comprises a viral indicator of a biological component of 0.4 mass/milliliter and a second collected sample comprises a viral indicator of a biological component of 0.6 mass/milliliter.
Referring back to fig. 82, at step/operation 8208, the exemplary method 8200 includes calculating a relative concentration level of a viral indicator of a biological component in a plurality of collected samples.
In the present disclosure, the term "relative concentration level of a viral indicator of a biological component" refers to a normalized concentration level of a viral indicator of a biological component in a collected sample of a plurality of collected samples based on concentration levels of a non-viral indicator of a biological component in the plurality of collected samples. In some embodiments, the concentration level of the non-viral indicator of the biological component may serve as a standard for normalizing the concentration levels of the viral indicators of the biological components in different collected samples. In some embodiments, the relative concentration level of the viral indicator of the biological component can be calculated based on the following equation:
In the above equation, C c represents the relative concentration level of the viral indicator of the biological component, C v represents the concentration level of the viral indicator of the biological component, and C nv represents the concentration level of the non-viral indicator of the biological component.
Continuing from the example above, the first collected sample has a non-viral indicator of a biological component of 0.8 mass/ml and a viral indicator of a biological component of 0.4 mass/ml. Thus, the relative concentration level of the viral indicator of the biological component of the first collected sample is 0.5. The second collected sample had a non-viral indicator of a biological component of 1.8 mass/ml and a viral indicator of a biological component of 0.6 mass/ml. Thus, the relative concentration level of the viral indicator of the biological component of the second collected sample is 0.33. In such an example, the first collected sample has a higher relative concentration level of the viral indicator of the biological component than the second collected sample, which indicates that the first collected sample may be more infectious than the second collected sample.
Referring back to fig. 82, after step/operation 8208, exemplary method 8100 ends at step/operation 8210.
Many multi-channel waveguide illumination face technical challenges such as, but not limited to, input beam splitters causing laser non-uniformity between channels, optical inefficiency, high input power requirements, and so forth. For example, the greater the number of channels, the higher the total input power required to illuminate the channels, and the total input power required may be too high to be practical. Thus, there is a need for an alternative optical input method for a multi-channel waveguide.
In various embodiments of the present disclosure, a sample testing device (such as a multichannel waveguide biosensor) can detect multiple virus types simultaneously to effectively overcome the technical challenges associated with detecting viral variants. In some embodiments, an exemplary sample testing device (such as a scanning multi-channel waveguide biosensor) uses a laser beam that is scanned through each waveguide channel to provide input to the waveguide channels. With a scanning laser beam input, only one channel is illuminated at a time, which ensures that the input power of the laser beam to each channel in the waveguide is the same. Thus, various embodiments of the present disclosure provide a mechanism to provide laser beam inputs with the same power to multiple channels. In some embodiments, an exemplary sample testing device (such as a scanning multichannel waveguide biosensor) may provide linear scanning (optionally, as well as piezoelectric actuators) with pitch control and roll control, which may meet multichannel waveguide input alignment requirements. Accordingly, various embodiments of the present disclosure provide electromagnetic scanning and alignment control that provides a low cost solution. In addition to various advantages such as input power efficiency, providing lasers to one channel at a time also eliminates crosstalk and unwanted interference between adjacent channels, which provides a clean signal that improves the sensitivity of low concentration biological detection.
Referring now to fig. 83A-83E, various exemplary views associated with a sample testing device 8300 are shown. Specifically, fig. 83A shows an exemplary perspective view of sample testing device 8300.
Fig. 83B illustrates another exemplary perspective view of sample testing device 8300. Fig. 83C shows an exemplary side view of sample testing device 8300. Fig. 83D shows an exemplary top view of sample testing device 8300. Fig. 83E illustrates an exemplary cross-sectional view of sample testing device 8300 taken along line A-A' shown in fig. 83C and viewed in the direction indicated by the arrow.
Referring now to fig. 83A and 83B, an exemplary sample testing device 8300 includes a waveguide platform 8301. In some embodiments, the aiming control mount 8303 and the waveguide mount 8317 are disposed on a top surface of the waveguide platform 8301. In some embodiments, the aiming control mount 8303 is disposed adjacent to the waveguide mount 8317.
In some embodiments, the laser source 8305 is disposed on a top surface of the aiming control mount 8303. In some embodiments, the laser source 8305 may include a laser diode configured to emit a laser beam, similar to those described herein. In some embodiments, the laser light from the laser diode of the laser source 8305 is collimated with a collimating lens 8307, as shown in fig. 83E. In some embodiments, the collimated laser beam is reflected by a scanning element 8309 (which may include an electromagnetic scanning mirror) to form a linearly scanned laser beam. In some embodiments, the scanned laser beam is refocused with various lenses (such as f-theta lenses). For example, as shown in fig. 83A, 83B, 83D, and 83E, the scanning laser beam is refocused by a focusing lens 8311, and then refocused by a field lens 8313.
In some embodiments, the scanning element 8309 is mounted on the aiming control base 8303. In some embodiments, the aiming control base 8303 may include at least two electromagnetic actuators (such as electromagnetic actuator 8327 and electromagnetic actuator 8329) for pitch control and roll control of the aiming control base 8303. In some embodiments, the electromagnetic actuator may adjust the pitch and roll of the aiming control mount 8303 such that the laser beam reflected from the scanning element 8309 may be aligned with the input end of the waveguide 8331.
For example, referring now to fig. 83C, the aiming control base 8303 may include bearing balls 8335 interposed between a bottom surface of a top portion 8337 of the aiming control base 8303 and a top surface of a bottom portion 8339 of the aiming control base 8303. In this example, components such as a laser source 8305 and a scanning element 8309 are disposed on a top surface of a top portion 8337 of the aiming control base 8303. Additionally or alternatively, each of the electromagnetic actuators may include a retaining spring between the top portion 8337 and the bottom portion 8339. In some embodiments, the retaining spring is configured to adjust the distance between the top portion 8337 and the bottom portion 8339 at a given position. For example, each of the retaining springs 8341 (of the electromagnetic actuator 8327) and the retaining springs 8345 (of the electromagnetic actuator 8329) may adjust the distance between the top portion 8337 and the bottom portion 8339 at their respective positions, thereby adjusting the pitch and roll of the aiming control base 8303.
Additionally or alternatively, the aiming control mount 8303 may include one or more piezoelectric actuators configured to adjust the position of the aiming control mount 8303 relative to the waveguide mount 8317.
In some embodiments, the waveguide pedestal 8317 includes a waveguide 8331 having a plurality of channels. In some embodiments, the multi-channel waveguide may include a plurality of channels that may be arranged in three groups, namely, a negative reference channel 8333A, a sample channel 8333B, and a positive reference channel 8333C. Similar to those described above, each set includes open window channels and/or buried reference channels. For example, sample channel 8333B may comprise an open window channel coated with various antibodies of interest for detecting multiple viral variants in one test. In some embodiments, the negative reference channel 8333A and the positive reference channel 8333C include buried reference channels that are pre-arranged to provide a real-time reference to eliminate thermal and structural disturbances that may cause waveguide signal variations and drift, thereby ensuring high sensitivity for low concentration virus detection, similar to those described above.
In some embodiments, the refocused scanning beam illuminates the waveguide 8331 on a channel-by-channel basis. In the example shown in fig. 83D, a scanned beam may illuminate channel 8333A, followed by channel 8333B, and then channel 8333C. In some embodiments, the scanning element 8309 is configured to adjust the angle of the laser beam from the laser source 8305 to form a scanning beam, the details of which are described herein.
In some embodiments, the sample testing device 8300 further comprises a fluid cap 8319. Similar to those described above, a fluid cap 8319 is disposed on the top surface of the waveguide base 8317, thereby forming a plurality of flow channels. In some embodiments, each of the flow channels may include at least one inlet (e.g., inlet 8321A) configured to receive a sample and provide the sample to the flow channel and at least one outlet (e.g., outlet 8321B) configured to expel the sample from the flow channel.
In some embodiments, each flow channel of the plurality of flow channels is disposed on top of at least one of the channels (negative reference channel, sample channel, and/or positive reference channel) of the waveguide 8331. For example, referring now to fig. 83D, in some embodiments, the negative reference channel 8333A is covered with a reference medium from the corresponding flow channel that is free of virus. In some embodiments, sample channel 8333B is covered with sample medium for detection from the corresponding flow channel. In some embodiments, the positive reference channel 8333C is covered with a target viral surrogate from the corresponding flow channel.
In some embodiments, the sample testing device 8300 further comprises an imaging component 8347 configured to detect interference fringe patterns, similar to those described above.
In some embodiments, the sample testing device 8300 further comprises an insulator 8315 disposed between the waveguide platform 8301 and the waveguide base 8317. In some embodiments, the thermal insulator 8315 includes a thermal insulating material that can minimize or reduce the effects on the interference fringe pattern caused by temperature fluctuations. Additionally or alternatively, the sample testing device 8300 includes a thermal sensor 8325 in electronic communication with the heating/cooling pad 8323. For example, based on the temperature detected by the thermal sensor 8325, the processor may adjust the temperature of the heating/cooling pad 8323 to minimize or reduce disturbances caused by temperature fluctuations.
In some embodiments, the dimensions of the sample testing device 8300 can be designed based on system requirements. For example, the sample testing device 8300 shown in fig. 83D may have a width W of 26 millimeters and a length L of 76 millimeters. In some embodiments, the width and/or length of the sample testing device 8300 can be other values.
Referring now to fig. 84A-84D, various exemplary views associated with the aiming control base 8400 are shown. Specifically, fig. 84A shows an exemplary perspective view of the aiming control base 8400.
Fig. 84B illustrates another exemplary perspective view of the aiming control base 8400. Fig. 84C illustrates an exemplary side view of the aiming control base 8400. Fig. 84D illustrates an exemplary top view of the aiming control base 8400.
Similar to those described above in connection with fig. 83A-83E, the aiming control mount 8400 may include at least a laser source 8401 configured to emit a laser beam. In some embodiments, the laser beam travels to a scanning element 8403 that redirects the laser beam toward a focusing lens 8405. In some embodiments, after passing through the focusing lens 8405, the laser beam further passes through the field lens 8407 and reaches the input end of the waveguide, similar to those described above.
In some embodiments, the aiming control base 8400 may include one or more electromagnetic actuators (e.g., electromagnetic actuator 8411 and electromagnetic actuator 8409). In the example shown in fig. 84C, the aiming control base may include bearing balls 8413, and each of the one or more electromagnetic actuators may include one or more retaining springs (e.g., retaining springs 8415 and 8417) configured to adjust a distance between a top portion 8442 and a bottom portion 8444 of the aiming control base 8400 at one or more positions of the aiming control base 8400 in order to control the roll and pitch of the aiming control base 8400, similar to those described above.
In some embodiments, the dimensions of the aiming control base 8400 may be designed based on system requirements. For example, as shown in fig. 84C, the height H of the aiming control base 8400 may be 13 millimeters. Additionally or alternatively, as shown in fig. 84D, the length L of the aiming control base 8400 may be 36 millimeters and/or the width of the aiming control base 8400 may be 26 millimeters. Additionally or alternatively, the height, length, and/or width of the aiming control base 8400 may be other values.
Referring now to fig. 85A-85E, various exemplary views associated with a scanning element 8500 are shown. In particular, fig. 85A shows an exemplary perspective view of a scanning element 8500. Fig. 85B illustrates another example exploded view of a scan element 8500. Fig. 85C shows another example exploded view of a scan element 8500. Fig. 85D illustrates an example side view of an example element 8500. Fig. 85E illustrates an exemplary perspective view of a resonant flexure 8507 of the scan element 8500.
In the example shown in fig. 85A-85E, an exemplary scanning element 8500 includes a substrate 8501, a coil 8503, a magnet 8505, a resonant flexure 8507, a scanning mirror 8509, and a spacer 8511.
As shown in fig. 85A and 85B, a coil 8503 is provided over the surface of the substrate 8501. As shown in fig. 85B, 85C, and 85D, a magnet 8505 is provided on a first surface of the resonance flexible member 8507, and a scanning mirror 8509 is provided on a second surface of the resonance flexible member 8507 opposite to the first surface. In some embodiments, the spacer 8511 attaches the substrate 8501 to the resonant flexure 8507 and aligns the magnet 8505 within the central ring formed by the coil 8503.
In some embodiments, when an electric current is passed through the coil 8503, an electromagnetic field is formed, causing the magnet 8505 to move toward or away from the coil 8503. In some embodiments, the strength of the electromagnetic field is controlled by the amount of current through coil 8503. Thus, by adjusting the current in coil 8503, the movement of magnet 8505 can be adjusted. Because the magnet 8505 is disposed on the resonant flexible member 8507, which in turn attaches the scan mirror 8509, the position of the scan mirror 8509 can be adjusted based on the strength of the electromagnetic field. Thus, by adjusting the current in coil 8503, the position of scan mirror 8509 can be adjusted, which in turn directs the laser beam to scan channel by channel, as described above.
Fig. 85E illustrates an exemplary resonating flexible member 8507. In some embodiments, the surface of the resonant flexible member 8507 includes a first portion 8513 attached to the spacer 8511 and a third portion 8517 attached to the magnet 8505. In some embodiments, the resonant flexible member 8507 includes an intermediate hinge 8515 between the first portion 8513 and the third portion 8517. In some embodiments, intermediate hinge 8515 is flexible.
In some embodiments, the dimensions of the resonant flexible member 8507 may be designed based on system requirements. For example, the resonant flexible member 8507 may have a length L of 11 millimeters and a width W of 5.6 millimeters. In some embodiments, the length L and/or the width W may be other values.
In various applications, sample testing devices (such as waveguide virus sensors) require microfluidics to deliver sample media and reference media at controlled flow rates and injection timing. Various embodiments of the present disclosure provide an integrated waveguide viral sensor cartridge (also referred to as a "waveguide cartridge") that includes a waveguide, a flow channel, a cartridge body, and a fluidic cap configured to provide controlled flow rates and injection timing of sample media and reference media. In some embodiments, the waveguide box allows for quick insertion applications using alignment features. In some embodiments, the closed and sealed waveguide cassette is disposable according to a biohazard control protocol to meet clinical use requirements.
Referring now to fig. 86A-86F, an exemplary waveguide box 8600 is shown. Specifically, fig. 86A shows an exemplary perspective view of a waveguide box 8600 from the top. Fig. 86B shows an exemplary perspective view of the waveguide box 8600 from the bottom. Fig. 86C shows an exemplary exploded view of a waveguide box 8600. Fig. 86D shows an exemplary top view of a waveguide box 8600. Fig. 86E shows an example side view of a waveguide box 8600. Fig. 86F shows an example side low view of the waveguide box 8600. In some embodiments, waveguide cassette 8600 can be a single-use cassette. In some embodiments, the waveguide box 8600 can be implemented with a sample collector and receive samples, such as breath/breath aerosol samples (e.g., exhaled aerosol) and/or nasal swab samples.
As shown in fig. 86C, an exemplary waveguide cassette 8600 includes a waveguide 8601, a flow channel plate 8603, a cassette body 8605, a fluid cover 8607, an emissions filter 8609, and a cassette cover 8611. In some embodiments, the flow channel plate 8603 may be embodied as a flow gasket according to various examples described herein.
In some implementations, one or more laser alignment methods, apparatus, and/or systems may be implemented to align the waveguide 8601 and/or the waveguide box 8600 to a laser source in order to reduce system turn-around time (e.g., less than five minutes). In some embodiments, the temperature of the waveguide 8601 can be kept consistent throughout the sample testing period by implementing one or more of the temperature control techniques described herein. In some embodiments, the bottom surface of the flow channel plate 8603 is disposed on the top surface of the waveguide 8601. In some implementations, each of the flow channels in the flow channel plate 8603 is aligned with one of the sample channel or the reference channel in the waveguide 8601, similar to those described above.
In some embodiments, the bottom surface of the cartridge body 8605 is disposed on the top surface of the flow channel plate 8603. As further described herein, the bottom surface of the cartridge body 8605 includes a plurality of inlet and outlet ports. In some embodiments, each of the output ports provides a sample medium or a reference medium to one of the flow channels in the flow channel plate 8603, and each of the input ports receives a sample medium or a reference medium from one of the flow channels in the flow channel plate 8603, the details of which are described herein.
In the example shown in fig. 86C, cartridge body 8605 includes buffer reservoir 8613, reference port 8619, sample port 8625, and drain chamber 8631.
In some embodiments, a fluid cover 8607 is disposed on a top surface of the cartridge body 8605. In some embodiments, the fluid cap 8607 includes an actuator push 8615, a reference injection tube 8621, and a sample injection tube 8627. In some embodiments, the actuator push 8615 is aligned on top of the buffer reservoir 8613 of the cartridge body 8605. In some embodiments, the reference injection tube 8621 is aligned on top of the reference port 8619. In some embodiments, the sample injection tube 8627 is aligned on top of the sample port 8625.
In some embodiments, an emissions filter 8609 is disposed on a top surface of the cartridge body 8605. In some embodiments, the vent filter 8609 is aligned to cover the vent chamber 8631 of the cartridge body 8605.
In some embodiments, a cap 8611 is provided on top of the fluid cap 8607 and/or the emissions filter 8609. In some embodiments, the cartridge cover 8611 includes an actuator opening 8617, a reference opening 8623, a sample opening 8629, and a drain opening 8633. In some embodiments, the actuator opening 8617 is aligned on top of the actuator pusher 8615. In some embodiments, the reference opening 8623 is aligned on top of the reference injection tube 8621. In some embodiments, the sample opening 8629 is aligned on top of the sample injection tube 8627. In some embodiments, the drain opening 8633 is aligned on top of the drain filter 8609.
In the example shown in fig. 86B, the corners of the waveguide 8601 are exposed from the box body 8605, allowing for optical alignment. In some embodiments, the bottom surface of waveguide 8601 is also cleaned to contact a heating/cooling pad for temperature control.
In some embodiments, a thermal fusion bonding method that only locally heats may be implemented when assembling the waveguide box 8600 to prevent damage to the bio-active waveguide 8601. Additionally or alternatively, other methods may be implemented when assembling the waveguide box 8600.
For example, the waveguide cassette 8600 may be pre-assembled with a cassette body 8605, a fluid cover 8607, an emissions filter 8609, and a cassette cover 8611. Final assembly is performed by heat-fusing the bio-active waveguide 8601 and sealing the flow channel plate 8603 between the cartridge body 8605 and the waveguide 8601. In some embodiments, the waveguide box 8600 is then filled with PBS buffer solution (except for the drain/waste chamber) that is included in the buffer reservoir 8613 and in the flow channels of the flow channel plate 8603.
When using the waveguide box 8600, the waveguide box 8600 is placed in the reading instrument by optical alignment with direct reference to the waveguide edge features. Injection is then performed, wherein the reference medium is injected through reference port 8619 and then the sample medium is injected through sample port 8625. After injection, the deformable actuator push 8615 is then pushed down, which in turn pushes the buffer solution in the buffer reservoir 8613 to move through the flow channel. In the three-channel example shown in fig. 86A to 86F, the order of flow is the same as the order of PBS buffer, fluid, and then PBS buffer. The fluid includes a target surrogate in a positive reference channel (e.g., a positive reference medium), a non-viral PBS in a negative reference channel (e.g., a negative reference medium), and a patient sample in a sample channel (e.g., a sample medium). The serial flow path provides synchronization signals from the reference channel and the sample channel in order to accurately derive test results, the details of which are described herein.
In some implementations, the dimensions of the waveguide box 8600 can be designed based on system requirements. For example, the width W of the waveguide box 8600 as shown in fig. 86D may be 74 millimeters. Additionally or alternatively, the height H of the waveguide box 8600 as shown in fig. 86E may be 68 millimeters. Additionally or alternatively, the length L of the waveguide box 8600 as shown in fig. 86E may be 31 millimeters. Additionally or alternatively, the width W' of the waveguide 8601 may be 44 millimeters. Additionally or alternatively, the width W, the height H, the length L, and/or the width W' may be other values.
Referring now to fig. 87A-87C, an exemplary waveguide 8700 is shown. Specifically, fig. 87A shows an exemplary perspective view of waveguide 8700. Fig. 87B shows an exemplary top view of waveguide 8700. Fig. 87C shows an example side view of waveguide 8700.
In the example shown in fig. 87A-87C, an exemplary waveguide 8700 includes multiple channels for sample and reference media. For example, the exemplary waveguide 8700 can include a first channel 8701, a second channel 8703, and a third channel 8705. In some embodiments, the first channel 8701 and the third channel 8705 are reference channels (e.g., buried channels). In some embodiments, the second channel 8703 is a sample channel (e.g., an open channel). For example, the second channel 8703 can include a bioassay reagent immobilized on a surface to detect and/or capture pathogens (such as SARS-CoV2 pathogens) in a sample, similar to those described above. The capture causes a refractive index change that alters the propagation of the laser light down waveguide 8700, similar to those described above. Very little sample preparation is required to test a sample using the exemplary waveguide 8700 due to the evanescent transduction mechanism. In some embodiments, the first channel 8701 and the third channel 8705 can provide parallel positive and negative control assays that allow for real-time noise cancellation and quantification of viral load present in the sample. Due to the evanescent transduction mechanism, very little sample preparation is required for diagnosis. In some embodiments, the exemplary waveguide 8700 can include fewer than three or more than three channels. For example, exemplary waveguide 8700 may include eight optical channels in an active state for use when testing one or more samples.
As shown in fig. 87B and 87C, in some embodiments, the length L1 of the exemplary waveguide 8700 is 31000 microns. In some embodiments, the total length L2 of the channels in the exemplary waveguide 8700 is 30000 microns. In some embodiments, the length L3 of the open window portion of each channel is 15000 microns. In some embodiments, the buried portion of each channel has a length L4 of 8000 microns. In some embodiments, the width W of the exemplary waveguide 8700 is 4400 microns. In some embodiments, the height H of the waveguide 8700 is 400 microns. In some embodiments, one or more measured values of waveguide 8700 can be other values.
Referring now to fig. 88A-88D, an exemplary flow channel plate 8800 is shown. Specifically, fig. 88A shows an exemplary perspective view of a flow channel plate 8800. Fig. 88B illustrates an exemplary top view of a flow channel plate 8800. Fig. 88C shows an exemplary cross-sectional view of the flow channel plate 8800 cut from A-A' in fig. 88B and viewed from the direction of the arrows. Fig. 88D shows an exemplary side view of the flow channel plate 8800.
In some embodiments, the example flow channel plate 8800 can be manufactured by a PDMS molding process that provides a seal between the top surface of the waveguide cassette and the cassette body, forming a plurality of flow channels. In the example shown in fig. 88A-88D, an example flow channel plate 8800 includes a first flow channel 8802, a second flow channel 8804, and a third flow channel 8806.
In some implementations, each of the first, second, and third flow channels 8802, 8804, 8806 can correspond to one of the channels in the waveguide of the waveguide cassette. For example, referring to the waveguide 8700 shown in fig. 87A-87C, the first, second, and third flow channels 8802, 8804, 8806 of the example flow channel plate 8800 may be positioned on top of the first, second, and third channels 8701, 8703, 8705, respectively. In some embodiments, when waveguide 8700 is positioned within a waveguide box, the waveguide box provides optical access to the entrance and exit of waveguide 8700 such that a laser beam can be emitted through the waveguide, as described herein.
In some embodiments, each flow channel may receive a sample from an inlet opening and expel the sample through an outlet. In the example shown in fig. 88C, a sample may flow through the second flow channel 8804 from the inlet opening 8808 and exit from the second flow channel 8804 through the outlet opening 8810. In some implementations, each of the inlet opening 8808 and the outlet opening 8810 can be connected to an outlet port and an inlet port of the cartridge body, the details of which are described herein.
Referring now to fig. 89A-89E, an exemplary cartridge body 8900 is shown. Specifically, fig. 89A shows an exemplary perspective view of the cartridge body 8900 from the top. Fig. 89B shows an exemplary perspective view of the cartridge body 8900 from the bottom. Fig. 89C shows an exemplary top view of the cartridge body 8900. Fig. 89D shows an exemplary bottom view of the cartridge body 8900. Fig. 89E shows an exemplary view of the cartridge body 8900.
In some embodiments, the cartridge body 8900 can be manufactured by a Cyclic Olefin Copolymer (COC) injection molding process. In some embodiments, the box body 8900 can include a lower housing, a gasket disposed on the lower housing, and an upper housing disposed on the gasket. In some embodiments, cartridge body 8900 provides various fluids, buffer reservoir 8901, sample injection port 8921, sample circuit 8925, reference injection port 8905, reference circuit 8909, and vent chamber 8933. In some embodiments, the various circuits in cartridge body 8900 and the various channels in the flow channel plate are connected in series to form a flow path to ensure that the sample medium has exactly the same flow rate as the reference medium, the details of which are described herein. In some embodiments, the cartridge body 8900 can include a material such as ABS.
For example, referring now to fig. 89C (an exemplary top view) and 89D (an exemplary bottom view), port 8911 (which is an end port of reference circuit 8909) is connected and provides input fluid to a first flow channel in the flow channel plate. The first flow channel is also connected to port 8913 and outputs fluid to port 8913. As shown in fig. 89D, port 8913 is the end of buffer circuit 8915 and the other end of buffer circuit 8915 is port 8917 that is connected and provides input fluid to a second flow channel in the flow channel plate. A second flow channel is also connected to port 8919 and outputs fluid to port 8919. As shown in fig. 89D, port 8919 is the end of sample loop 8925 and the other end of sample loop 8925 is port 8927 that is connected and provides input fluid to a third flow channel in the flow channel plate. The third flow passage is also connected to port 8929 and outputs fluid to port 8929.
In some embodiments, buffer solution may be provided in a buffer reservoir 8901 connected to port 8903. In some embodiments, the buffer solution has been degassed and is free of bubbles. In some embodiments, the buffer solution in buffer reservoir 8901 may have a volume greater than 95 ml. In some embodiments, the buffer solution in buffer reservoir 8901 may have a volume of other values. As described above, port 8903 is connected to reference loop 8909. As described above, when the actuator pusher of the waveguide box is pushed downward, the actuator pusher in turn pushes the buffer solution in the buffer reservoir 8901 to move through the flow channel.
In some embodiments, a reference medium is provided to the reference injection port 8905 (e.g., by through injection) and travels to the reference circuit 8909 through a port 8907 connected to the reference injection port 8905 after the actuator push of the waveguide cassette is pushed down. As described above, the end of the reference circuit 8909 is the port 8911 connected to the first channel of the flow channel plate. Thus, the reference medium travels through the first channel of the flow channel plate.
As described above, the first channel of the flow channel plate is connected to port 8913. As the reference medium travels through the first channel, the reference medium pushes the buffer solution in the first channel through port 8913 to buffer circuit 8915. As described above, the end of the buffer circuit 8915 is the port 8917 connected to the second channel. Thus, the buffer solution travels through the second flow channel and exits at port 8919 connected to sample loop 8925.
In some embodiments, sample media is provided to sample injection port 8921 (e.g., by through injection) and travels to sample loop 8925 through port 8923 connected to sample injection port 8921 after the actuator push of the waveguide box is pushed down. As described above, the end 8927 of the sample loop 8925 is connected to the third channel of the flow channel plate. Thus, the sample medium travels through the third channel of the flow channel plate and exits at port 8929.
In some embodiments, port 8929 is connected to discharge chamber 8933 through port 8931. Thus, the sample can be discharged into the discharge chamber 8933.
In some embodiments, to meet the requirement of 75mL total flow with 30mL sample injection, buffer reservoir 8901 volume is greater than 95mL, vent chamber volume is greater than 110mL, and each of the sample loop and reference loop capacities is greater than 35mL. In some embodiments, a steady flow rate range between 5 and 15uL/min may be provided for 10 to 15 minutes. In some embodiments, one or more of the above requirements, flow rates, and/or volumes may be other values.
In some embodiments, the dimensions of the cartridge body may be designed based on system requirements. For example, the width W of the cartridge body 8900 shown in fig. 89C may be 7.4 millimeters. The height H of the cartridge body 8900 shown in fig. 89E may be 7.4 millimeters. The length L of the cartridge body 8900 shown in fig. 89E may be 31 millimeters. In some embodiments, the width W, height H, and/or length L of the cartridge body 8900 can be other values.
Referring now to fig. 90A-90E, an exemplary fluid cover 9000 is illustrated. Specifically, fig. 90A shows an exemplary perspective view of a fluid cover 9000 from the top. Fig. 90B shows an exemplary perspective view of the fluid cover 9000 from the bottom. Fig. 90C illustrates an exemplary top view of a fluid cover 9000. Fig. 90D shows an exemplary side view of the fluid cover 9000. Fig. 90E shows an exemplary bottom view of the fluid cover 9000.
In some embodiments, the fluid cap 9000 is deformable and may function as a pump with an actuator configured to push the buffer solution in the buffer reservoir downward under precise displacement control. For example, the fluid cover 9000 may comprise a silicone rubber formed by an injection molding process. In some embodiments, the fluid cover 9000 may comprise a material such as ABS.
In the example shown in fig. 90A-90E, the example fluid cover 9000 includes an actuator push 9006, a reference injection tube 9004, and a sample injection tube 9002, similar to the actuator push 8615, reference injection tube 8621, and sample injection tube 8627 described above in connection with fig. 86A-86F.
Referring now to fig. 91A-91C, an exemplary emissions filter 9100 is shown. Specifically, fig. 91A shows an exemplary perspective view of an emissions filter 9100. Fig. 91B illustrates an exemplary side view of the emissions filter 9100. Fig. 91C illustrates an exemplary bottom view of the emissions filter 9100.
In some embodiments, the emissions filter 9100 can comprise a gas permeable PTFE filter emissions that allows release of gaseous substances from the waveguide box without causing environmental risks.
Referring now to fig. 92A-92C, an exemplary lid 9200 is shown. Specifically, fig. 92A shows an exemplary perspective view of the box cover 9200. Fig. 92B shows an exemplary top view of the box cover 9200. Fig. 92C shows an exemplary side view of the box cover 9200.
In some embodiments, exemplary lid 9200 may comprise polycarbonate and be manufactured by an injection molding process. In some embodiments, the exemplary lid 9200 may comprise one or more additional or alternative materials and may be manufactured by one or more additional or alternative processes. In the example shown in fig. 92A-92C, the example lid 9200 includes an actuator opening 9202, a reference opening 9204, a sample opening 9206, and a drain opening 9208, similar to the actuator opening 8617, reference opening 8623, sample opening 8629, and drain opening 8633 described above in connection with fig. 86A-86F.
Many infectious diseases/pathogens are transmitted by aerosol droplets, and almost every bioassay capable of recognizing a specific pathogen (virus, bacteria, etc.) relies on-liquid based immunoassays. One of the technical challenges associated with virus detection is how to efficiently collect a sufficient amount of aerosol from a large air volume for subsequent immunoassays. Another technical challenge is to keep pathogens alive during the sampling process.
Many systems focus on implementing a sampler with a dedicated pump that samples a small percentage of the air in the space. Many of these samplers are also designed to recognize the RNA/DNA content of the pathogen and therefore are not designed to keep the pathogen alive (e.g., as a whole). Keeping the pathogen intact is critical to assess how infectious the aerosol particles are (e.g., a non-viable virus will not infect others, but still show positive in RNA analysis).
According to various embodiments of the present disclosure, the sample collection device is integrated into the condenser unit of an air conditioner. Referring to fig. 93A and 93B, an exemplary system 9300 in accordance with embodiments of the present disclosure is shown.
In the example shown in fig. 93A and 93B, an exemplary system 9300 includes an evaporator unit 9302 and a condenser unit 9304, which may be part of an air absorption unit. In some embodiments, evaporator unit 9302 includes an evaporator coil 9308 and a blower 9306. In some embodiments, condenser unit 9304 includes a compressor 9318 and a condenser coil 9320, which are connected to an evaporator coil 9308.
In some embodiments, the blower 9306 is configured to draw air into the evaporator unit 9302 and/or push air out of the evaporator unit 9302. In some embodiments, the air travels through the evaporator coil 9308. In some embodiments, a low temperature liquid refrigerant is circulated through the evaporator coil 9308. For example, condenser coil 9320 may release heat absorbed by liquid refrigerant that has circulated through evaporator coil 9308, and compressor 9318 may drive a cycle between condenser coil 9320 and evaporator coil 9308. In some embodiments, when the air drawn by blower 9306 reaches evaporator coil 9308, condensation may occur due to the temperature differential between the air and condenser coil 9320, and liquid may form on the outer surface of evaporator coil 9308. In some embodiments, the liquid formed on the surface may effectively collect aerosol particles from a large percentage of the air in the space that has been driven by the blower 9306 into the evaporator unit 9302.
In the example shown in fig. 93A, a condensate pan 9310 is positioned below the evaporator coil 9308 to collect condensed liquid 9312 dripping from the evaporator coil 9308. In some embodiments, sample collection device 9316 is connected to condensate tray 9310 through conduit 9314. In some embodiments, the sample collection device 9316 may include a buffer solution to keep pathogens in the condensed liquid 9312 alive prior to performing an immunoassay. For example, the sample collection device 9316 may include a container, storage device, and/or cartridge, similar to those described above.
Additionally or alternatively, a condensate pan 9310 may be positioned below the condenser coil 9320 in the condenser unit 9304 to collect the condensed liquid, and a sample collection device 9316 connected to the condensate pan 9310 (e.g., through a conduit) to receive the condensed liquid.
In some embodiments, the evaporator coil 9308 and/or the condenser coil 9320 are modified to collect condensed liquid more efficiently and/or more quickly. For example, various embodiments of the present disclosure may include coating the evaporator coil 9308 and/or the condenser coil 9320 with one or more hydrophobic layers to facilitate droplet formation and gravity-based collection of fluids.
In some embodiments, condensate tray 9310 may be directly enhanced to enable immunoassays. In some embodiments, condensate tray 9310 may include an optical surface, immobilized antibodies, a transduction mechanism, and/or other test components incorporated into the base of condensate tray 9310, such as, but not limited to, the sample test devices described herein. Additionally or alternatively, the condensate tray 9310 may include a separate liquid reservoir with a buffer solution that may be combined with the condensed aerosol liquid, and the condensed aerosol liquid with the buffer solution may be pumped into a channel of a sample testing device (such as a waveguide) described herein for performing immunoassays, similar to the various examples described herein.
As described above, an integrated waveguide viral sensor cartridge requires a precise amount of flow through the waveguide sensor along multiple (e.g., three) individual channels, all of which must flow at the same rate. There are a number of technical challenges and difficulties in designing an integrated waveguide viral sensor cartridge. For example, an integrated waveguide viral sensor cartridge cannot allow bubbles to flow through the waveguide, and must also allow multiple fluids to flow through the waveguide in a specified order.
Referring now to fig. 94A, 94B, 94C, 94D, 94E, an exemplary sample testing device 9400 is provided.
Referring now to fig. 94A, an exemplary sample testing device 9400 includes a waveguide box 9402. The waveguide box 9402 includes a waveguide 9404 having a first reference channel 9406, a second reference channel 9408, and a sample channel 9410. The waveguide box 9402 further includes a reservoir 9412 for storing a buffer solution and a waste collector 9418 for draining the solution from the waveguide box 9402. Specifically, the reservoir 9412 is connected to a first reference channel 9406. The first reference channel 9406 is connected to the second reference channel 9408. The second reference channel 9408 is connected to the sample channel 9410. The sample channel 9410 is connected to a waste collector 9418.
In some embodiments, buffer solution is injected into the first reference channel 9406, the second reference channel 9408, and the sample channel 9410 as part of assembling the waveguide box 9402. In some embodiments, all bubbles are removed from the waveguide box 9402 during assembly, and the waveguide box 9402 is a closed system except for a reference reservoir 9414 for receiving a reference solution and a sample reservoir 9416 for receiving a sample solution.
Fig. 94B illustrates an exemplary step/operation of connecting a pump 9420 to the reservoir 9412 that pushes buffer solution from the reservoir 9412 to flush the waveguide 9404. Specifically, the buffer solution travels from the reservoir 9412 to the first reference channel 9406, then to the second reference channel 9408, then to the sample channel 9410, and then to the waste collector 9418. As shown in fig. 94B, the first reference channel 9406 is connected to a second reference channel 9408, which in turn is connected to the sample channel 9410.
After the step/operation shown in fig. 94B, fig. 94C illustrates an exemplary step/operation of injecting the reference solution into the reference reservoir 9414 and injecting the sample solution into the sample reservoir 9416. The pump 9420 continues to push the buffer solution to the waste collector 9418.
After the step/operation shown in fig. 94C, fig. 94D illustrates an exemplary step/operation of having the pump 9420 push the reference solution from the reference reservoir 9414 to the first reference channel 9406 and push the sample solution from the sample reservoir 9416 to the sample channel 9410.
As shown in fig. 94D, the reference reservoir 9414 is connected between the reservoir 9412 and the first reference channel 9406, and the sample reservoir 9416 is connected between the second reference channel 9408 and the sample channel 9410, as shown in fig. 94D. As the pump 9420 continues to push the buffer solution from the reservoir 9412 to the waveguide box 9402, the buffer solution pushes the reference solution from the reference reservoir 9414 to the first reference channel 9406 and pushes the sample solution from the sample reservoir 9416 to the sample channel 9410.
As the sample solution and the reference solution travel over the waveguide 9404, the imaging component may capture signals, such as interference fringe patterns, from the waveguide 9404.
After the step/operation shown in fig. 94D, fig. 94E shows an exemplary step/operation of having the pump 9420 push buffer solution from the reservoir 9412 to the waveguide 9404 to move the reference solution and sample solution past 9404 and the buffer solution to the waste collector 9418. In some embodiments, after the imaging component captures the signal as described above, the waveguide box 9402 is discarded according to a biohazard safety procedure.
As described above, the sample testing device 9400 positions different fluids in a serial path, wherein a single pump pushes the fluids along a single channel. This design requires that precise amounts of fluid be injected into the waveguide box 9402 at multiple locations in order for the serial fluid flow path to position the fluid in the correct location during testing. This precise amount of fluid makes this operation technically challenging for unskilled operators to do so by hand. Thus, there is a need to simplify the sample testing device 9400.
Various embodiments of the present disclosure overcome these technical challenges and difficulties and satisfy these needs.
For example, various embodiments of the present disclosure use a single fluid source to change the flow path of fluid flowing through a waveguide to a parallel flow path to push fluid through the system. In some embodiments, the waveguide cassette contains a single on-board valve that alters the flow path of each type of fluid that needs to flow through the waveguide. Various embodiments of the present disclosure use a buffer solution reservoir that is separate from the waveguide and connected using a port. Various embodiments of the present disclosure also have a separate waste collector separate from the waveguide box to collect the fluid pushed through the waveguide box. In some embodiments, the waveguide box includes two internal large cavities (e.g., a sample reservoir and a reference reservoir) for injecting sample and reference solutions. As fluid is pushed through the system, the valve opens and closes to direct a precise amount of fluid from each of the lumens toward the channel in the waveguide, and the remainder of the fluid is stored within the lumen for disposal.
In some embodiments, the waveguide box has a single port connected to the buffer reservoir and a single port connected to the waste collector. The type of port may be any type of port, including a quick connect port, a threaded port, a pierceable membrane, and/or other types of ports. The sample reservoir and the reference reservoir are sealed with a pierceable membrane, which allows fluid to be injected into the waveguide box by an unskilled operator.
Referring to fig. 95A-95J, exemplary diagrams illustrating exemplary sample testing devices 9500 are provided. 96A-96C illustrate an example multiport valve 9600 that can be used in conjunction with the example sample testing device 9500 shown in FIGS. 95A-95J in accordance with various embodiments of the present disclosure.
Referring now to fig. 95A-95J, an exemplary sample testing device 9500 and an exemplary method for operating the sample testing device 9500 are provided.
Referring now to fig. 95A, a sample testing device 9500 includes a waveguide box 9501 and a multiport valve 9529. In some embodiments, the multiport valve 9529 is part of a waveguide box 9501.
In some embodiments, the waveguide box 9501 includes an inlet 9511 and an outlet 9515. In some embodiments, inlet 9511 is configured to receive buffer solution from reservoir 9513, the details of which are described herein. In some embodiments, outlet 9515 is configured to expel solution from waveguide box 9501 to waste collector 9517, the details of which are described herein.
In the example shown in fig. 95A, in some embodiments, an exemplary sample testing device 9500 includes a reservoir 9513 removably connected to an inlet 9511 of a waveguide cartridge 9501. In some embodiments, reservoir 9513 stores buffer solutions similar to those described herein. In some embodiments, sample testing device 9500 includes a pump 9523 connected to reservoir 9513. In some embodiments, pump 9523 is configured to push buffer solution stored in reservoir 9513 through reservoir port 9525. When the reservoir port 9525 is connected to the inlet 9511 of the waveguide box 9501, the pump 9523 is configured to inject a buffer solution from the reservoir 9513 into the waveguide box 9501 through the reservoir port 9525 and the inlet 9511 of the reservoir 9513.
In the example shown in fig. 95A, in some embodiments, the example sample testing device 9500 includes a waste collector 9517 removably connected to an outlet 9515 of the waveguide box 9501. For example, waste collector 9517 includes a waste collector port 9527 connectable to an outlet 9515 of waveguide box 9501.
In some embodiments, the waveguide box 9501 includes a waveguide 9503, which is similar to the various waveguides described herein. In some embodiments, the waveguide 9503 includes at least one reference channel and at least one sample channel. For example, the waveguide 9503 includes a first reference channel 9505, a second reference channel 9507, and a sample channel 9509.
In some embodiments, the first reference channel 9505, the second reference channel 9507, and the sample channel 9509 are filled with a buffer solution at an initial stage prior to the sample testing operation (e.g., when the waveguide box 9501 is assembled and/or delivered), and all bubbles are removed during assembly of the waveguide box 9501.
In some embodiments, when the sample testing device 9500 is used to perform a sample testing operation, the first reference channel 9505 is configured to receive a reference solution, the second reference channel 9507 is configured to receive a buffer solution, and the sample channel 9509 is configured to receive a sample solution comprising a sample to be tested. For example, in some embodiments, the waveguide box 9501 includes a reference reservoir 9519 connected to at least one reference channel (e.g., the first reference channel 9505). In some embodiments, the reference reservoir 9519 is configured to receive a reference solution. Additionally or alternatively, in some embodiments, the waveguide box 9501 includes a sample reservoir 9521 connected to the at least one sample channel (such as sample channel 9509). In some embodiments, sample reservoir 9521 is configured to receive a sample solution.
In some embodiments, the ports of the multiport valve 9529 are connected to the inlet 9511 of the waveguide box 9501. In some embodiments, the ports of multiport valve 9529 may be connected to one of the following options: (1) an outlet 9515 of the waveguide box 9501, (2) at least one reference channel and at least one sample channel of the waveguide 9503, or (3) a reference reservoir 9519 and a sample reservoir 9521 of the waveguide box 9501.
In some embodiments, multiport valve 9529 is configured to provide and/or switch between a plurality of configurations including at least:
(1) A first configuration, wherein the multiport valve 9529 connects an inlet 9511 of the waveguide cassette 9501 to an outlet 9515 of the waveguide cassette 9501,
(2) A second configuration in which the multiport valve 9529 connects the outlet 9515 of the waveguide cassette 9501 to at least one reference channel (e.g., the first reference channel 9505 and the second reference channel 9507) and at least one sample channel (e.g., the sample channel 9509) of the waveguide 9503, and/or
(3) A third configuration, wherein the multiport valve 9529 connects the inlet 9511 of the waveguide cassette 9501 to the reference reservoir 9519 and the sample reservoir 9521 of the waveguide cassette 9501, the details of which are described herein.
Referring now to fig. 95B, exemplary steps/operations of an exemplary method for operating sample testing device 9500 are shown. In the example shown in fig. 95B, exemplary steps/operations include connecting reservoir 9513 to inlet 9511 of waveguide box 9501 of sample testing device 9500. In some embodiments, the inlet 9511 of the waveguide box 9501 is connected to the reservoir 9513 via a reservoir port 9525, and the outlet 9515 of the waveguide box 9501 is connected to the waste collector 9517 via a waste collector port 9527.
As described above, in some embodiments, reservoir 9513 stores a buffer solution and is connected to pump 9523. In some embodiments, the sample testing device 9500 includes a multiport valve 9529.
Referring now to fig. 95C, exemplary steps/operations of an exemplary method for operating the sample testing device 9500 are shown after the steps/operations shown in fig. 95B. In the example shown in fig. 95C, an exemplary step/operation includes switching the multiport valve 9529 to a first configuration to connect the inlet 9511 of the waveguide cassette 9501 to the outlet 9515 of the waveguide cassette 9501.
In some embodiments, outlet 9515 is connected to waste collector 9517. In some embodiments, the exemplary method further comprises causing pump 9523 to inject buffer solution from reservoir 9513 to inlet 9511 of waveguide box 9501. Thus, multiport valve 9529 connects reservoir 9513 to waste collector 9517, and buffer solution is pushed through multiport valve 9529 by pump 9523 to expel any air from sample testing device 9500.
Referring now to fig. 95D, exemplary steps/operations of an exemplary method for operating the sample testing device 9500 are shown after the steps/operations shown in fig. 95C. In the example shown in fig. 95D, the exemplary steps/operations include switching the multiport valve 9529 to a second configuration to connect the inlet 9511 of the waveguide cassette 9501 to at least one reference channel (e.g., the first reference channel 9505 and the second reference channel 9507) and at least one sample channel (e.g., the sample channel 9509) of the waveguide 9503 of the waveguide cassette 9501.
As described above, pump 9523 is turned on to push buffer solution from reservoir 9513. Because the multiport valve 9529 is in the second configuration, buffer solution is pushed from the reservoir 9513 through the first reference channel 9505, the second reference channel 9507, and the sample channel 9509. In some embodiments, the first reference channel 9505, the second reference channel 9507, and the sample channel 9509 are each connected to the outlet 9515, and the buffer solution can flush through the first reference channel 9505, the second reference channel 9507, and the sample channel 9509 (e.g., to remove air from these channels) and drain from the first reference channel 9505, the second reference channel 9507, and the sample channel 9509 to the waste collector 9517 via the outlet 9515 and the waste collector port 9527.
Referring now to fig. 95E, exemplary steps/operations of an exemplary method for operating the sample testing device 9500 are shown after the steps/operations shown in fig. 95D. In the example shown in fig. 95E, exemplary steps/operations include releasing a reference solution through the reference reservoir 9519 of the waveguide cassette 9501 and the sample reservoir 9521 of the waveguide cassette 9501.
In some embodiments, sample reservoir 9521 stores a sample solution and is sealed with a pierceable membrane. When the membrane is pierced, the sample solution is released from the sample reservoir 9521. Similarly, reference reservoir 9519 stores a reference solution and is sealed with a pierceable membrane. When the membrane is pierced, the reference solution is released from the reference reservoir 9519.
In some embodiments, when the waveguide box 9501 is in use, a sample solution may be injected into the sample reservoir 9521. Similarly, when the waveguide box 9501 is in use, a reference solution may be injected into the reference reservoir 9519.
In some embodiments, the reference reservoir 9519 is connected to a first reference channel 9505. When in the first configuration, the multiport valve 9529 is also connected to the first reference channel 9505. In some embodiments, the connection point between the multiport valve 9529 and the first reference channel 9505 is positioned in the flow direction after the connection point between the reference reservoir 9519 and the first reference channel 9505 and before the waveguide 9503. In the example shown in fig. 95E, since pump 9523 pushes buffer solution through multiport valve 9529 to first reference channel 9505, when multiport valve 9529 is in the first configuration, reference solution released from or injected into reference reservoir 9519 does not travel to first reference channel 9505.
Similarly, in some embodiments, a sample reservoir 9521 is connected to the sample channel 9509. When in the first configuration, the multiport valve 9529 is also connected to the sample channel 9509. In some embodiments, the junction between the multiport valve 9529 and the sample channel 9509 is positioned downstream of the junction between the sample reservoir 9521 and the sample channel 9509 in the flow direction and before the waveguide 9503. In the example shown in fig. 95E, because pump 9523 pushes buffer solution through multiport valve 9529 to first sample channel 9509, sample solution released from or injected into sample reservoir 9521 does not travel to sample channel 9509 when multiport valve 9529 is in the first configuration.
Referring now to fig. 95F, exemplary steps/operations of an exemplary method for operating sample testing device 9500 after the steps/operations shown in fig. 95E are shown. In the example shown in fig. 95F, an exemplary step/operation includes switching the multiport valve 9529 from the second configuration to the third configuration to connect the inlet 9511 of the waveguide cassette 9501 to the reference reservoir 9519 and the sample reservoir 9521 of the waveguide cassette 9501.
As described above, the reference reservoir 9519 is connected to at least one reference channel (e.g., the first reference channel 9505), and the sample reservoir is connected to at least one sample channel (e.g., the sample channel 9509). Thus, by switching the multiport valve 9529 from the second configuration to the third configuration, the reservoir 9513 is connected to the multiport valve 9529, which in turn is connected to the reference reservoir 9519, which in turn is connected to the outlet 9515. At the same time, reservoir 9513 is connected to a multiport valve 9529, which in turn is connected to a second reference channel 9507, which in turn is connected to outlet 9515. Meanwhile, reservoir 9513 is connected to multiport valve 9529, which in turn is connected to sample reservoir 9521, which in turn is connected to sample channel 9509, which in turn is connected to outlet 9515.
Referring now to fig. 95G, exemplary steps/operations of an exemplary method for operating sample testing device 9500 after the steps/operations shown in fig. 95F are shown. In the example shown in fig. 95G, exemplary steps/operations include causing pump 9523 to simultaneously push reference solution from reference reservoir 9519 through first reference channel 9505, buffer solution from reservoir port 9525 through second reference channel 9507, and sample solution from sample reservoir 9521 through sample channel 9509.
Similar to the various embodiments described herein, the imaging component can capture a signal such as an interference fringe pattern from the waveguide 9503 as the sample solution travels through the sample channel 9509 of the waveguide 9503 (and the reference solution travels through the first reference channel 9505 of the waveguide 9503).
In some embodiments, the amount of reference solution and the amount of sample solution pushed into the sample channel 9509, respectively, may be controlled based on various means. For example, sample reservoir 9521 and reference reservoir 9519 each store a predetermined amount of sample solution and reference solution, respectively, and are each sealed with a pierceable membrane. When the membrane is pierced (e.g., in connection with fig. 95E), predetermined amounts of the sample solution and the reference solution are released.
Additionally or alternatively, the amount of reference solution and the amount of sample solution may be controlled based on the amount of time the multiport valve 9529 is in the third configuration. For example, the time period resulting from the point in time at which the multiport valve 9529 switches from the second configuration to the third configuration (as shown in fig. 95F) and the point in time at which the multiport valve 9529 switches from the third configuration to the second configuration (as will be described in connection with fig. 95H) is determined based on the amount of reference solution/sample solution required to perform the accurate test.
Referring now to fig. 95H, exemplary steps/operations of an exemplary method for operating sample testing device 9500 after the steps/operations shown in fig. 95G are shown. In the example shown in fig. 95H, the exemplary steps/operations include switching the multiport valve 9529 from the third configuration back to the second configuration to connect the inlet 9511 of the waveguide cassette 9501 to at least one reference channel (e.g., the first reference channel 9505 and the second reference channel 9507) and at least one sample channel (e.g., the sample channel 9509) of the waveguide 9503 of the waveguide cassette 9501.
In some embodiments, the multiport valve 9529 switches from the third configuration back to the second configuration after the imaging component captures a signal, such as an interference fringe pattern, from the waveguide 9503. In a third configuration, as shown in fig. 95H, multiport valve 9529 bypasses reference reservoir 9519 and sample reservoir 9521 and connects reservoir 9513 directly to first reference channel 9505 and sample channel 9509.
Referring now to fig. 95I, exemplary steps/operations of an exemplary method for operating sample testing device 9500 after the steps/operations shown in fig. 95H are shown. In the example shown in fig. 95I, exemplary steps/operations include causing pump 9523 to push buffer solution through first reference channel 9505 and sample channel 9509.
As described above, in the third configuration, the multiport valve 9529 bypasses the reference reservoir 9519 and the sample reservoir 9521. Thus, pump 9523 pushes buffer solution through first reference channel 9505 and sample channel 9509. When the first reference channel 9505 and the sample channel 9509 are connected to the outlet 9515 of the waveguide cassette 9501 (which is connected to the waste collector 9517), the pump 9523 flushes the reference solution in the first reference channel 9505 and the sample solution in the sample channel 9509 to the waste collector 9517.
Referring now to fig. 95J, exemplary steps/operations of an exemplary method for operating sample testing device 9500 after the steps/operations shown in fig. 95I are shown. In the example shown in fig. 95J, exemplary steps/operations include disconnecting the reservoir 9513 and the waste collector 9517 from the waveguide box 9501.
In some embodiments, after completion of sample test priming, the inlet 9511 of the waveguide cassette 9501 is disconnected from the inlet 9511 of the reservoir 9513, and the outlet 9515 of the waveguide cassette 9501 is disconnected from the outlet 9515 of the reservoir 9513. In some embodiments, the waveguide box 9501 may be discarded according to a biohazard safety treatment procedure.
Referring now to fig. 96A, 96B, and 96C, an exemplary multiport valve 9600 is shown that can be used in conjunction with the exemplary sample testing device 9500 shown in fig. 95A-95J in accordance with various embodiments of the present disclosure.
As described above, the example multiport valve 9529 of the example sample testing device 9500 may provide three different configurations. Thus, fig. 96A illustrates a first configuration of an example multi-port valve 9600, fig. 96B illustrates a second configuration of an example multi-port valve 9600, and fig. 96C illustrates a third configuration of an example multi-port valve 9600.
In the example shown in fig. 96A-96C, an exemplary multi-port valve 9600 includes a valve housing 9602 and a movable piston 9604.
In some embodiments, a plurality of channels are connected to the valve housing 9602, including a plurality of inlet channels and a plurality of outlet channels. In the example shown in fig. 96A to 96C, the first inlet flow path 9612, the second inlet passage 9614, the third inlet passage 9616, and the fourth inlet passage 9618 are connected to the valve housing 9602. Specifically, a first end of each of the first, second, third, and fourth inlet channels 9612, 9614, 9616, and 9618 is connected to a different opening on the valve housing 9602, while a second end of each of the first, second, third, and fourth inlet channels 9612, 9614, 9616, and 9618 is connected to the same inlet port 9620. In operation, the inlet port 9620 is connected to a pump.
In addition, a first outlet passage 9624, a second outlet passage 9626, a third outlet passage 9628, a fourth outlet passage 9630, a fifth outlet passage 9632, and a sixth outlet passage 9634 are connected to the valve housing 9602. Specifically, the first ends of the first, second, third, fourth, fifth, and sixth outlet passages 9624, 9626, 9628, 9620, 9632, and 9634 are connected to different openings on the valve housing 9602. The second end of the first outlet channel 9624 is connected to a first outlet port 9636 that is connected to a waste collector (e.g., to an outlet of a waveguide cartridge, which in turn is connected to the waste collector). The second ends of the second, third, and fourth outlet channels 9626, 9628, 9630 are connected to a second outlet port 9638 that is connected to the waveguide (e.g., each of them is connected to a different channel on the waveguide). The second ends of the fifth and sixth outlet channels 9632, 9634 are connected to a third outlet port 9640 that is connected to a reservoir (e.g., one of them is connected to a sample reservoir and the other is connected to a reference reservoir).
In some embodiments, the movable piston 9604 is positioned within the valve housing 9602 and is movable. For example, a plurality of rolling balls (such as rolling balls 9606) may be positioned between an inner surface of the valve housing 9602 and an outer surface of the movable piston 9604.
In some embodiments, movement of the movable piston 9604 may be controlled by an actuator within or outside of the example multiport valve 9600. For example, the movable piston 9604 may be directly connected to a motor that enables the movable piston 9604 to move in two different directions. Additionally or alternatively, the actuator may press the movable piston 9604 in one direction, and the spring (e.g., positioned inside the waveguide box) may press the movable piston 9604 in the opposite direction. Additionally or alternatively, actuators are positioned on each side of the example multiport valve 9600, and each actuator moves the movable piston 9604 in opposite directions (e.g., one actuator moves the movable piston 9604 in a left direction and another actuator moves the movable piston 9604 in a right direction). While the above description provides some exemplary ways of controlling the movement of the movable piston 9604, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, movement of the movable piston 9604 may be controlled in other ways.
In some embodiments, the movable piston 9604 includes various portions, including a connecting portion (e.g., connecting portion 9608) and a blocking portion (e.g., blocking portion 9610). In some embodiments, the connecting portion is configured to connect two openings on the valve housing 9602 such that liquid can flow from one opening to the other. In some embodiments, the blocking portion is configured to break or block two openings on the valve housing 9602 such that liquid cannot flow from one opening to the other.
As described above, the example multiport valve 9600 is in the first configuration in fig. 96A. In particular, when in the first configuration, the movable piston 9604 is within the valve housing 9602 such that the fourth inlet passage 9618 is connected to the first outlet passage 9624 by a connecting portion of the movable piston 9604, while the first, second, and third inlet passages 9612, 9614, 9616 are not connected to any of the outlet passages due to a blocking portion of the movable piston 9604.
In some embodiments, the fourth inlet channel 9618 is connected to an inlet port 9620, which in turn is connected to a pump and a reservoir for storing a buffer solution. The first outlet channel 9624 is connected to a first outlet port 9636 which in turn is connected to a waste collector. Thus, when in the first configuration, the example multi-port valve 9600 causes the pump to push buffer solution from the reservoir to the waste collector while the direct path from the pump to the waveguide and to the reservoir is closed.
As described above, the example multiport valve 9600 is in the second configuration in fig. 96B. Specifically, when in the second configuration, the movable piston 9604 moves within the valve housing 9602 such that the third inlet passage 9616 is connected to the second outlet passage 9626 via a connecting portion of the movable piston 9604, the second inlet passage 9614 is connected to the third outlet passage 9628 via a connecting portion of the movable piston 9604, and the first inlet passage 9612 is connected to the fourth outlet passage 9630 via a connecting portion of the movable piston 9604. The fourth inlet channel 9618 is not connected to any of the outlet channels.
In some embodiments, the first inlet channel 9612, the second inlet channel 9614, and the third inlet channel 9616 are connected to an inlet port 9620, which in turn is connected to a pump and a reservoir for storing a buffer solution. The second, third, and fourth outlet channels 9626, 9628, 9630 are connected to a waveguide (e.g., each of them is connected to a channel of the waveguide). Thus, when in the second configuration, the example multi-port valve 9600 causes the pump to push buffer solution from the reservoir to channels on the waveguide (e.g., at least one sample channel and at least one reference channel, such as the first reference channel 9505, the second reference channel 9507, and the sample channel 9509, shown in connection with fig. 95A-95J), while the direct path from the pump to the waste collector and to the reservoir is closed.
As described above, the example multi-port valve 9600 is in the third configuration in fig. 96C. Specifically, when in the third configuration, the movable piston 9604 moves within the valve housing 9602 such that the first inlet passage 9612 is connected to the fifth outlet passage 9632 via a connecting portion of the movable piston 9604, the second inlet passage 9614 is connected to the third outlet passage 9628 via a connecting portion of the movable piston 9604, and the third inlet passage 9616 is connected to the sixth outlet passage 9634 via a connecting portion of the movable piston 9604. The fourth inlet channel 9618 is not connected to any of the outlet channels.
In some embodiments, the first inlet channel 9612, the second inlet channel 9614, and the third inlet channel 9616 are connected to an inlet port 9620, which in turn is connected to a pump and a reservoir for storing a buffer solution. The fifth and sixth outlet channels 9632, 9634 may be connected to one of the sample reservoir or the reference reservoir, while the third outlet channel 9628 may be connected to one of the reference channels on the waveguide (e.g., the second reference channel 9507 shown above in connection with fig. 95A-95J). ). Thus, when in the third configuration, the example multi-port valve 9600 allows the pump to push the buffer solution through the sample reservoir and the reference reservoir while the direct path from the pump to the waste collector is closed.
Referring now to fig. 97A and 97B, an exemplary diagram of an exemplary sample testing device 9700 is provided. Fig. 98A, 98B, and 98C illustrate an example multiport valve 9800 that can be used in connection with the example sample testing device 9700 shown in fig. 97A and 97B, according to various embodiments of the present disclosure. Fig. 99A and 99B illustrate an example valve 9900 that can be used in conjunction with the example sample testing device 9700 shown in fig. 97A and 97B, according to various embodiments of the disclosure.
Referring now to fig. 97A and 97B, an exemplary sample testing device 9700 includes a waveguide 9701 and a multiport valve 9709.
In some embodiments, waveguide 9701 includes at least one reference channel and at least one sample channel. In the example shown in fig. 97A and 97B, the waveguide 9701 includes a buffer channel 9703, a reference channel 9705, and a sample channel 9707, similar to those described above.
In some embodiments, the multi-port valve 9709 includes at least one buffer solution port (e.g., a first buffer solution port 9719, a second buffer solution port 9721, and a third buffer solution port 9723), at least one reference solution port (e.g., a first reference solution port 9711 and a second reference solution port 9731), and at least one sample solution port (e.g., a first sample solution port 9715 and a second sample solution port 9733).
In some embodiments, the buffer reservoir 9717 stores buffer solution and is connected to a first buffer solution port 9719, a second buffer solution port 9721, and a third buffer solution port 9723 of the multi-port valve 9709. In some embodiments, the reference reservoir 9710 stores a reference solution and is connected to a first reference solution port 9711 and a second reference solution port 9731 of the multi-port valve 9709. In some embodiments, sample reservoir 9713 stores a sample solution and is connected to first sample solution port 9715 and second sample solution port 9733. In some embodiments, the waste collector 9753 is connected to a first waste port 9735 and a second waste port 9737 of the multiport valve 9709. In some embodiments, the buffer channel 9703 of the waveguide 9701 is connected to a buffer channel port 9725. In some embodiments, the reference channel 9705 is connected to a first reference channel port 9727 and a second reference channel port 9739. In some embodiments, the sample channel 9707 is connected to a first sample channel port 9729 and a second sample channel port 9741.
In some embodiments, the multiport valve 9709 includes a plurality of connectors, and the multiport valve 9709 is configured to provide a plurality of configurations, wherein the connectors connect different ports in different configurations. Specifically, fig. 97A shows a first configuration, and fig. 97B shows a second configuration.
Referring now to fig. 97A, in a first configuration, a multiport valve 9709 connects at least one buffer solution port to at least one reference channel and at least one sample channel. For example, the connector 9743 of the multiport valve 9709 connects the first buffer solution port 9719 to the buffer channel port 9725. The connector 9745 of the multiport valve 9709 connects the second buffer solution port 9721 to the first reference channel port 9727, and the connector 9747 of the multiport valve 9709 connects the third buffer solution port 9723 to the first sample channel port 9729.
In operation, a pump is connected to the buffer reservoir 9717 to push buffer solution from the buffer reservoir 9717 to the buffer channel 9703, the reference channel 9705, and the sample channel 9707. The buffer solution travels through these channels and is discharged to a waste collector 9753.
In the first configuration, the connector 9749 of the multi-port valve 9709 connects the first waste port 9735 to the first reference solution port 9711, and the connector 9751 of the multi-port valve 9709 connects the second waste port 9737 to the first sample solution port 9715. Thus, the reference solution from the reference reservoir 9710 flows to the waste collector 9753 without passing through any of the channels of the waveguide 9701, and the sample solution from the sample reservoir 9713 flows to the waste collector 9753 without passing through any of the channels of the waveguide 9701.
Referring now to fig. 97B, in a second configuration, the multi-port valve 9709 connects the reference solution port to at least one reference channel and the sample solution port to at least one sample channel. For example, the connector 9743 of the multi-port valve 9709 connects the first buffer solution port 9719 to the buffer channel port 9725, the connector 9749 of the multi-port valve 9709 connects the first reference solution port 9711 to the second reference channel port 9739, and the connector 9751 of the multi-port valve 9709 connects the first sample solution port 9715 to the second sample channel port 9741.
Further, in the second configuration, the connector 9745 of the multi-port valve 9709 connects the second buffer solution port 9721 to the second reference solution port 9731, and the connector 9747 of the multi-port valve 9709 connects the third buffer solution port 9723 to the second sample solution port 9733. In operation, a pump is connected to the buffer reservoir 9717 to push buffer solution from the buffer reservoir 9717 to the buffer channel 9703 and then to the waste collector 9753. The pump pushes liquid from the buffer reservoir 9717 to the reference reservoir 9710 (which stores the reference solution), which in turn pushes the reference solution from the reference reservoir 9710 to the reference channel 9705 via the first reference solution port 9711 and the second reference channel port 9739. Similarly, a pump pushes liquid from buffer reservoir 9717 to sample reservoir 9713 (which stores the sample solution), which in turn pushes sample solution from sample reservoir 9713 to sample channel 9707 via first sample solution port 9715 and second sample channel port 9741. Subsequently, the reference solution and the sample solution are pushed to a waste collector 9753.
Referring now to fig. 98A, 98B, and 98C, an exemplary multiport valve 9800 is shown that can be used in conjunction with the exemplary sample testing device 9700 shown in fig. 97A and 97B in accordance with various embodiments of the present disclosure.
As described above, the example multiport valve 9709 of the example sample testing device 9700 may provide two different configurations. Thus, fig. 98B illustrates a second configuration of the example multi-port valve 9800, and fig. 96C illustrates a first configuration of the example multi-port valve 9800. FIG. 98A illustrates exemplary components associated with a multiport valve 9800.
In some embodiments, the multiport valve 9800 includes a valve base 9804 and a flexible membrane 9806 defining a flow channel. Specifically, the flow channel is configured to receive buffer solution from buffer inlet 9802 (e.g., when pushed from the reservoir by a pump).
In some embodiments, the plurality of outlet channels connect to channels defined by the valve base 9804 and the flexible membrane 9806. Specifically, the first outlet channel 9808, the second outlet channel 9810, the third outlet channel 9812, the fourth outlet channel 9814, the fifth outlet channel 9816, and the sixth outlet channel 9818 are connected to a flow channel defined by the valve base 9804 and the flexible membrane 9806 (e.g., to a bottom surface of the valve base 9804).
Specifically, the first ends of the first, second, third, fourth, fifth, and sixth outlet passages 9808, 9810, 9812, 9814, 9816, 9818 are connected to different openings on the valve base 9804. In some embodiments, the second end of the fourth outlet channel 9814 is connected to a waste collector via an outlet port 9820 (e.g., to the outlet of a waveguide box, which in turn is connected to the waste collector). In some implementations, the second ends of the first, second, and third outlet channels 9808, 9810, 9812 are connected to the waveguide via an oral port 9822 (e.g., each of them is connected to a different channel on the waveguide). In some embodiments, the second ends of the fifth and sixth outlet channels 9816, 9818 are connected to a reservoir via an outlet port 9824 (e.g., one of them is connected to a sample reservoir and the other is connected to a reference reservoir).
In some embodiments, the example multiport valve 9800 includes a rigid block 9826 and a rigid block 9828. Rigid block 9826 includes two rigid rods and rigid block 9828 includes three rigid rods. The actuator may exert a vertical force on the rigid block 9826 and/or on the rigid block 9826 on the flexible membrane 9806, and the rigid block 9826 and/or the rigid block 9826 close different portions of the flow channel defined by the flexible membrane 9806 and the valve base 9804. In some embodiments, the one or more actuators may be a plurality of solenoids, and each of them pushes the rigid block 9826 or one of the rigid blocks 9826 to open/close the flow channel defined by the valve base 9804 and the flexible membrane 9806. In some embodiments, the actuator can press both the rigid block 9826 and the rigid block 9826 by a pressing or rotating action.
As shown in fig. 98B, when the multiport valve 9800 is in the second configuration, the actuator may push the rigid block 9828 onto the flexible membrane 9806, and three rods of the rigid block 9828 may block three different portions of the flow channel defined by the flexible membrane 9806 and the valve base 9804.
Specifically, after the rigid block 9828 is pressed onto the flexible membrane 9806, the three rods of the rigid block 9828 are positioned between the opening of the first outlet channel 9808 and the opening of the fifth outlet channel 9816, between the opening of the second outlet channel 9810 and the opening of the third outlet channel 9812, and between the opening of the sixth outlet channel 9818 and the opening of the fourth outlet channel 9814, respectively. Thus, the actuator presses the flexible membrane 9806 against the bottom surface of the valve base 9804 to close the path to the waveguide (e.g., block buffer solution from traveling through the first, second, and third outlet channels 9808, 9810, 9812) and open the path to the reservoir (e.g., enable buffer solution to travel from the buffer inlet 9802 to the fifth and sixth outlet channels 9816, 9818).
As shown in fig. 98C, when the multiport valve 9800 is in the first configuration, the actuator may push the rigid block 9826 onto the flexible membrane 9806, and the two rods of the rigid block 9826 may block two different portions of the flow channel defined by the flexible membrane 9806 and the valve base 9804.
Specifically, after the rigid block 9826 is pushed onto the flexible membrane 9806, the two rods of the rigid block 9826 are positioned between the opening of the fifth outlet channel 9816 and the opening of the second outlet channel 9810 and between the opening of the third outlet channel 9812 and the opening of the sixth outlet channel 9818, respectively. Thus, the actuator presses the flexible membrane 9806 against the bottom surface of the valve base 9804 to close the path to the reservoir (e.g., block buffer solution from traveling through the fifth outlet channel 9816 and to the sixth outlet channel 9818) and open the path to the waveguide (e.g., enable buffer solution to travel from the third outlet channel 9812 to the first, second, and third outlet channels 9808, 9810, 9812).
Referring now to fig. 99A and 99B, an exemplary valve 9900 is shown. In particular, the example valve 9900 can be used in conjunction with the example sample testing device 9700 shown in fig. 97A-97B and/or to provide the multi-port valve 9800 shown in fig. 98A-98C according to various embodiments of the present disclosure.
In some embodiments, the example valve 9900 includes a flexible member 9904 positioned on a fixed member 9902. In some embodiments, the flexible member 9904 includes a blocking member 9906. In some embodiments, the example valve 9900 is configured to provide different configurations based on the position of the blocking member 9906.
In some embodiments, the securing member 9902 defines a first opening 9908 and a second opening 9910. In the example shown in fig. 99A, the example valve 9900 is in a first configuration when an upward force is exerted on the flexible member 9904 (e.g., via an actuator). In the first configuration, when the blocking member 9906 of the flexible member 9904 does not block the flow of solution, the solution may flow in from one of the first opening 9908 or the second opening 9910 and exit from the other opening.
In the example shown in fig. 99B, the example valve 9900 is in the second configuration when a downward force is exerted on the flexible member 9904 (e.g., via an actuator). In the second configuration, the blocking member 9906 blocks one of the first opening 9908 or the second opening 9910, which blocks the flow of solution in the example valve 9900.
Sample testing devices such as waveguide virus sensors use antibodies to immobilize a particular virus on a waveguide sensing surface to detect a target virus. Sample channels in many waveguides have an effective width of 4 microns (e.g., the width of the effective sensing region) and a spacing of 250 microns (e.g., the inter-channel distance). Thus, for many waveguides implementing a uniform coating of antibodies, only 4/250=1.6% of the immobilized viral particles can be sensed by these narrow waveguides. For example, because areas that are not active areas (e.g., areas outside of the sample channel) may be coated with antibodies, viruses in the sample may be immobilized in these inactive sensing areas. Immobilization may occur on the entire antibody coated surface, but only viruses on a narrow effective sensing area may be detected. Thus, the virus detection capability of many waveguides is limited to detecting samples with high concentration virus levels.
In order to solve the problem of low detection efficiency of immobilized viral particles due to narrow waveguides at wider waveguide spacing, narrow antibody coating is required to closely match the width of the waveguide sensing width. Thus, accurate narrow antibody coating is required to increase the detection limit.
Various embodiments of the present disclosure overcome these technical challenges and difficulties and satisfy these needs.
For example, various embodiments of the present disclosure provide for precise narrow antibody coating that can increase the detection limit of a waveguide sensor by a factor of 60 compared to a uniformly coated antibody. In some embodiments, after dicing, the antibody is first uniformly coated over the entire sensing surface of the die on the wafer ring. In some embodiments, the antibody coating is then partially deactivated, and only the matched waveguide region remains active. In some embodiments, a photolithographic-like process may achieve semiconductor process accuracy to have a matching narrow pattern of antibodies to obtain optimal detection efficiency.
In some embodiments, the optically inactivating light source may be UV, VIS, or near IR. In some embodiments, a process like photolithography survives the antibody on the unexposed areas for immobilized virus sensing. Additionally or alternatively, the narrow antibody pattern may be printed directly with an inkjet-like process. Additionally or alternatively, the precise antibody coating methods provided according to various embodiments of the present disclosure may be applied to sensor types other than waveguides, such as lateral flow immunoassays, to increase sensitivity.
Accordingly, various embodiments of the present disclosure may provide technical improvements. For example, various embodiments of the present disclosure may provide accurate narrow antibody coating and increase detection limits. As another example, narrow antibody coating allows for wide fluid channels to be difficult due to the narrow fluid channels during manufacturing and operation. Additionally or alternatively, non-parallel flow directions need to be implemented in the fluid to achieve high immobilization efficiency of all viral particles.
Referring now to fig. 100A, 100B, and 100C, exemplary methods for manufacturing a sample testing device are provided. Specifically, fig. 100A, 100B, and 100C illustrate examples of precise antibody coating.
As shown in fig. 100A, an exemplary method includes providing at least one Ultraviolet (UV) shadow mask (such as UV shadow mask 10000A and UV shadow mask 10000B). In some embodiments, the UV shadow mask includes a material that blocks UV light. In some embodiments, the UV shadow mask has the same dimensions as the sampling area of the waveguide. For example, the width W of the UV shadow mask 10000A is 4um. In some embodiments, the width W may be other values.
Referring now to fig. 100B, an exemplary method includes uniformly coating an antibody on a surface of a waveguide layer 10004 of a sample testing device 10002, covering a sampling region of the waveguide layer with at least one UV shadow mask (e.g., UV shadow mask 10000A and UV shadow mask 10000B).
In some embodiments, the waveguide layer 10004 may be part of the sense die. In some embodiments, after dicing the sense die, the antibody may be uniformly covered over the entire sensing surface with the die on the wafer ring.
In some embodiments, UV shadow mask 10000A and UV shadow mask 10000B are attached to a region of the surface of waveguide layer 10004 corresponding to the sensing region. For example, the length L between the UV shadow mask 10000A and the UV shadow mask 10000B may be 250um. In some embodiments, the length L may be other values.
Referring now to fig. 100C, an exemplary method includes projecting UV light onto a surface of the waveguide layer 10004, and after projecting UV light onto the surface of the waveguide layer 10004, removing UV shadow masks (e.g., UV shadow masks 10000A and 10000B) from the waveguide layer 10004.
In some embodiments, when UV light is projected onto the surface of the waveguide layer 10004, the UV light deactivates antibodies on the surface of the waveguide layer 10004 that is not covered by any UV shadow mask, such as the region 10006 that is not covered by UV shadow mask 10000A or UV shadow mask 10000B. In some embodiments, UV light does not deactivate antibodies on surfaces of waveguide layer 10004, such as region 10008A and region 10008B, that are covered by a UV shadow mask (which includes UV blocking material).
Thus, the surface of the waveguide layer 10004 contains a sampling region including a region 10008A and a region 10008B and a non-sampling region including a region 10006.
In some embodiments, after removing the UV shadow mask from the waveguide layer 10004, an exemplary method includes attaching a flow channel plate to a surface of the waveguide layer. In some embodiments, the flow channel plate defines a plurality of flow channels, and the example method further includes aligning the plurality of flow channels of the flow channel plate with sampling regions (e.g., region 10008A and region 10008B) on the surface of the waveguide layer 10004. The flow channel may receive a sample solution that may contain viruses. The waveguide layer 10004 of the sample testing device allows immobilization of the virus to occur only in the matching narrow regions (e.g., region 10008A and region 10008B) where all bound virus particles can be detected because antibodies on other regions (such as region 10006) have been inactivated by UV light.
Although the above description provides an example of inactivating an antibody on the surface of the waveguide layer using UV light, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary method may use other types of optical inactivating light sources (such as, but not limited to, VIS or near IR) to inactivate antibodies on the surface of the waveguide layer. In these embodiments, exemplary methods may implement shadow masks comprising materials for blocking light from respective optically inactive light sources.
Referring now to fig. 101, an exemplary sample testing device 10100 is shown. In the example shown in fig. 101, the example sample testing device 10100 includes multiple layers, such as, but not limited to, a substrate layer 10101, an intermediate layer 10103, multiple waveguide layers 10105, 10107, 10109, and an interface layer 10111, similar to those described above.
Referring now to fig. 102A-102E, an exemplary waveguide 10200 is shown.
In the example shown in fig. 102A, the example waveguide 10200 may include a plurality of channels/windows for receiving a solution (e.g., sample solution, buffer solution, reference solution, etc.), such as, but not limited to, channels 10202, 10204, and 10206. In some embodiments, exemplary waveguide 10200 may include a total of six channels/windows. In some embodiments, exemplary waveguide 10200 may include fewer or more than six channels/windows. In some embodiments, exemplary waveguide 10200 may include an input region 10222.
In some embodiments, each channel may have a length L1 of 15mm and a width W1 of 50um. In some embodiments, the pitch P1 (e.g., the distance between the channels) may be 250um. In some embodiments, L1, W1, and/or P1 may be other values.
In some embodiments, the distance L2 between the edge of the waveguide 10200 and the edge of the channel may be 8mm. In some embodiments, L2 may be other values.
Referring now to fig. 102B, 102C, and 102D, additional views of the waveguide 10200 are shown. Specifically, fig. 102B shows an exemplary cross-sectional view of waveguide 10200 from section line A-A' and viewed in the direction indicated by the arrow. Fig. 102C shows an exemplary cross-sectional view of waveguide 10200 from section line B-B' and viewed in the direction indicated by the arrow. Fig. 102D shows an exemplary cross-sectional view of waveguide 10200 from section line C-C' and viewed in the direction indicated by the arrow.
As shown in fig. 102B, the waveguide 10200 may include multiple layers. For example, layer 10208 may include etched windows and materials (such as SiO 2). Layer 10208 is positioned on top of layer 10210, layer 10210 may include etched slots and material (such as polysilicon). Layer 10210 is positioned on top of layer 10212, and layer 10212 may include etched slots and material (such as SiO 2). Layer 10212 is positioned on top of layer 10214, and layer 10214 may include etched ribs and material (such as Si3N 4). Layer 10214 is positioned on top of layer 10216, and layer 10216 may comprise a material such as SiO 2. Layer 10216 is positioned on top of layer 10218, and layer 10218 may comprise a material such as silicon.
In the example shown in fig. 102B, the waveguide 10200 may have a total length L4 of 310 mm. In some embodiments, the total length L4 may be other values.
In the example shown in fig. 102B, layer 10214 may include recessed portions 10220 recessed from the edges of waveguide 10200. In some embodiments, the distance L3 between the edge of the waveguide 10200 and the edge of the recessed portion may be 75mm. In some embodiments, the distance L3 may be other values.
Referring now to fig. 102C, the width W2 of the waveguide 10200 may be 4.4mm. In some embodiments, the width W2 may be other values.
Referring now to fig. 102D, the width W3 of the input area 10222 may be 3.9mm. In some embodiments, the width W3 may be other values.
Fig. 102E shows an enlarged view of the area circled in fig. 102D. As shown in fig. 102E, the waveguide 10200 may include a total of six non-buried channels, and may additionally include two buried channels.
Referring now to fig. 103A-103D, an exemplary waveguide 10300 is shown.
As shown in fig. 103A, an exemplary top view of an exemplary waveguide 10300 is shown. In some embodiments, the total top length L1 of the exemplary waveguide 10300 may be 31mm and the width W1 of the exemplary waveguide 10300 may be 4.46mm. In some embodiments, L1 and/or W1 may be other values.
In some embodiments, the exemplary waveguide 10300 may include a plurality of channels. In some embodiments, the length L2 of the channel may be 15mm. In some embodiments, the distance L3 between the edge of the channel and the edge of the waveguide 10300 may be 8mm. In some embodiments, L2 and/or L3 may be other values.
In some embodiments, the width W2 of the recessed portion within the exemplary waveguide 10300 (e.g., similar to those described above in connection with at least fig. 102B) may be 44mm. In some embodiments, W2 may be other values.
Referring now to fig. 103B, an exemplary side view of an exemplary waveguide 10300 is shown. In the example shown in fig. 103B, the example waveguide 10300 may have a total bottom length L4 of 31.06 mm. In some embodiments, L4 may be other values.
Referring now to fig. 103C, an enlarged view of the encircled portion of fig. 103A is shown. Specifically, fig. 103C illustrates an input edge 10303 and an input region 10301 of an exemplary waveguide 10300. In some embodiments, the exemplary waveguide 10300 may include non-buried channels and buried channels, such as buried channels 10305 and buried channels 10307. In some embodiments, each channel may have a width W3 of 50um, and the distance W4 between two channels is 250um. In some embodiments, W3 and W4 may be other values.
Fig. 103D provides a perspective view of an exemplary interposer waveguide 10300.
In many cases, difficulties due to on-chip beam splitter fabrication can limit the application of multichannel waveguides, and direct waveguide edge coupling faces problems of low efficiency and high scattering.
Various embodiments of the present disclosure overcome these problems. For example, various embodiments of the present disclosure provide a microlens fiber array edge-emitting waveguide sensor that can achieve high efficiency direct edge coupling using fiber arrays with matched microlens arrays added. Direct array edge-emission enables a multi-channel waveguide sensor to be applied to multi-virus detection, where multiple test samples and references pass through different channels.
In some embodiments, the single mode laser diode is coupled to the 1 x 8 microlens fiber array through a 1 x 8 fiber coupler. Thus, the focused laser beam array is directly coupled into the plurality of channels of the waveguide at the input edge of the waveguide. In some embodiments, the array beam passes through a waveguide, with the top sensing surface exposed to the sample and reference. The resulting fringe pattern is captured directly by an imaging component, such as an image sensor, without the need for an imaging lens. In some embodiments, the direct edge coupling and edge imaging implementation in the waveguide sensor requires minimal components and is easy to implement in low cost mass production applications.
Referring now to fig. 104A, 104B and 104C, a sample testing device 10400 is provided. Specifically, fig. 104A shows an exemplary perspective view of sample testing device 10400, fig. 104B shows an exemplary top view of sample testing device 10400, and fig. 104C shows an exemplary side view of sample testing device 10400.
In some embodiments, sample testing device 10400 is a micro-lens fiber array edge-emitting waveguide sensor comprising light source coupler 10402, waveguide 10404, and imaging component 10406.
In some embodiments, the light source coupler 10402 includes a fiber array 10408 and a fiber holder 10410. In some embodiments, the fiber array 10408 is secured within a fiber holder 10410.
In some embodiments, fiber array 10408 includes eight fibers. In some embodiments, fiber array 10408 can include fewer or more than eight fibers. In some embodiments, the ends of each optical fiber are connected to the same laser source (such as a laser diode), and the optical fibers are configured to transmit laser light from the laser source.
In some embodiments, the waveguide 10404 includes at least one optical channel 10412. In some embodiments, at least one optical channel 10412 is aligned with the light source coupler 10402. For example, referring now to fig. 104B, each fiber in the fiber array 10408 of the light source coupler 10402 is directly aligned with an input edge of one of the at least one optical channels 10412 of the waveguide 10404 by direct edge coupling. Thus, when guided by the optical fibers in the fiber array 10408, the laser light may travel onto at least one optical channel 10412 of the waveguide 10404.
In some embodiments, the light source coupler 10402 includes a microlens array 10414 disposed on a first edge surface of the fiber holder 10410. In some embodiments, each optical fiber in the fiber array 10408 is aligned with a microlens of the microlens array 10414, and each microlens of the microlens array 10414 is aligned with one of the at least one optical channels 10412 of the waveguide 10404. Thus, laser light emitted by the laser light source may travel through the optical fibers in the fiber array 10408 and the microlenses of the microlens array 10414 and reach the at least one optical channel 10412 of the waveguide 10404.
Referring now to fig. 104C, in some embodiments, an imaging component 10406 (such as an image sensor) captures a multichannel fringe image directly from at least one optical channel 10412 of the waveguide 10404 without the use of an imaging lens.
Referring now to fig. 105A-105D, an exemplary light source coupler 10500 is shown in accordance with various embodiments of the present disclosure. Specifically, fig. 105A shows an exemplary perspective view of an exemplary light source coupler 10500. Fig. 105B illustrates an example top view of an example light source coupler 10500. Fig. 105C illustrates an example side view of an example light source coupler 10500. Fig. 105D illustrates an exemplary end view of an exemplary light source coupler 10500.
As shown in fig. 105A, 105B, 105C, and 105D, in some embodiments, the fiber holder 10502 includes a top holder member 10505 and a bottom holder member 10503. In some embodiments, the fiber array 10501 is secured between the top holder member 10505 and the bottom holder member 10503.
In some embodiments, the bottom retainer member 10503 includes an array of v-grooves. In some embodiments, the fiber array 10501 is secured to a v-groove array of bottom retainer members 10503, additional details of which are illustrated and described in connection with at least fig. 106A and 106B. Additionally or alternatively, the fiber array 10501 may be attached to the bottom retainer member 10503 by chemical glue. For example, the fiber array 10501 may be attached to the surface of the bottom retainer member 10503 that is not covered by the top retainer member 10505 by a chemical glue.
In some embodiments, the edge surface of the top retainer member 10505 and the edge surface of the bottom retainer member 10503 together form a first edge surface of the fiber retainer 10502, and the end of each fiber in the array of fibers 10501 extends onto the first edge surface of the fiber retainer 10502. In some embodiments, the microlens array 10507 is disposed on a first edge surface of the fiber holder 10502, and the optical fibers in the fiber array 10501 are aligned with the microlenses in the microlens array 10507. In some embodiments, the fiber array 10501 is configured to redirect light from a laser source through the microlens array 10507 into at least one optical channel of the waveguide.
Referring now to fig. 106A and 106B, an exemplary fiber holder 10600 of an exemplary light source coupler is shown, according to various embodiments of the present disclosure. Specifically, fig. 106A shows an exemplary first end view of an exemplary fiber holder 10600, and fig. 106B shows an exemplary second end view of an exemplary fiber holder 10600.
In fig. 106A, an exemplary fiber holder 10600 is viewed from an edge surface provided with a microlens array 10602.
As described above, microlens array 10602 includes at least one microlens 10601. In some embodiments, the radius R1 of the at least one microlens 10601 is 0.24mm. In some embodiments, the distance D1 between the microlenses in microlens array 10602 is 0.25mm. In some embodiments, the radius R1 and/or the distance D1 may be other values.
In fig. 106B, an exemplary fiber holder 10600 is viewed from the edge surface that receives fibers from the fiber array.
As described above, the optical fibers are secured between the top and bottom retainer members 10604, 10606 of the example fiber retainer 10600. In some embodiments, bottom retainer component 10606 includes a v-groove array 10608, and the fiber array is placed on v-groove array 10608.
In some embodiments, the distance D2 between two v-grooves of v-groove array 10608 is 0.25mm. In some embodiments, the distance D2 may be other values.
As shown in fig. 106B, in some embodiments, the v-groove array is aligned with the microlens array 10602. For example, the distance between v-grooves in v-groove array 10608 is the same as the distance between microlenses in microlens array 10602. Thus, when the fiber array is placed on v-groove array 10608, the fiber array is aligned with microlens array 10602.
In some embodiments, the number of optical fibers in the optical fiber array, the number of v-grooves in the v-groove array, and the number of microlenses in the microlens array are the same.
Referring now to fig. 107, an exemplary wave plate 10700 from an optical fiber of an exemplary fiber array that transmits laser light is shown, according to various embodiments of the present disclosure. In particular, the fibers are oriented such that the connector key 10701 of the fibers is aligned with the slow axis of the wave plate 10700 and the fast axis of the wave plate 10700 is aligned with the plane of the v-groove array.
Referring now to fig. 108, an exemplary view of an exemplary light source coupler 10800 is shown, according to various embodiments of the present disclosure.
Specifically, fig. 108 shows that bottom retainer member 10802 of example light source coupler 10800 has a length L1. In some embodiments, the length L1 may be 10mm. In some embodiments, length L1 may be other values. In some embodiments, the light source coupler 10800 can be fabricated with a0 degree D0 polish such that the fast axis of the optical fiber is aligned with the plane of the v-groove array, as described above in connection with at least fig. 107.
Referring now to fig. 109A-109C, an exemplary microlens array 10900 is shown in accordance with various embodiments of the present disclosure. Specifically, fig. 109A shows an exemplary perspective view of an exemplary microlens array 10900. Fig. 109B illustrates an example front side view of an example microlens array 10900. Fig. 109C illustrates an exemplary front view of an exemplary microlens array 10900.
As shown in fig. 109A, an exemplary microlens array 10900 can include at least one microlens 10903. As shown in fig. 109B, at least one microlens 10903 may have a depth D1 of 0.07mm, and a microlens array 10900 may have a depth D2 of 1 mm. In some embodiments, depth D1 and/or depth D2 may be other values.
As shown in fig. 109C, an exemplary microlens array 10900 can have a length L1 of 2.4mm and a height H1 of 1.8 mm. In some embodiments, the length L1 and/or the height H1 may be other values. At least one microlens 10903 may have a radius R1 of 0.24mm, and a distance D3 between the two microlenses may be 0.25mm. In some embodiments, R1 and/or D3 may be other values.
There are a number of technical challenges and difficulties associated with simultaneous quantitative sensing of multiple substances. For example, many sample testing devices can only determine whether an unknown sample contains one particular virus type (and variant). If it is determined that the unknown sample does not contain this particular virus type (and variant), another test may be required to determine if the unknown sample contains another virus type (and variant). For example, viruses may have multiple variants, and it may be desirable to test unknown samples for all variants. Since these sample detection devices detect samples only against one variant of the virus, they hamper the process of sample detection and lead to delays in virus detection.
Various embodiments of the present disclosure overcome these technical challenges and difficulties and satisfy these needs. For example, various embodiments of the present disclosure may combine multiple biometrics and multi-path calibrations using standard linear algebra methods, such as, but not limited to Principal Component Analysis (PCA), and may implement multi-path testing for discrete biometrics using multiple optical channels within a waveguide. For example, various embodiments of the present disclosure may determine that an unknown sample is associated with a particular virus type (e.g., SARS-CoV 2), but is associated with an unknown variant.
Referring now to fig. 110, a computer-implemented method 11000 for calibrating a sample testing device is provided. In some embodiments, the sample testing device includes a plurality of sample channels (e.g., a plurality of sample channels from a waveguide according to various examples described herein).
The exemplary method 11000 begins at step/operation 11002 and proceeds to step/operation 11004. At step/operation 11004, an example method 11000 includes causing a known sample associated with a sample type to be provided to a plurality of sample channels. In this example, the known sample is associated with a known sample type and variant (e.g., a known virus type and variant) and/or a known sample concentration level (e.g., a known virus concentration level).
In some embodiments, each of the plurality of sample channels is coated with a plurality of antibodies for detecting a plurality of sample types. For example, referring now to fig. 112A and 112B, exemplary diagrams illustrating exemplary waveguides 11200 are provided.
Similar to the various examples provided above, the exemplary waveguide 11200 includes a plurality of sample channels, and each channel may be coated with a plurality of antibodies 11202. In some embodiments, a sample (e.g., a sample comprising virus 11206' as shown in fig. 112A or virus 11206 as shown in fig. 112B) is provided through a sample channel, the sample flowing through the sample channel in a direction as shown by arrow 11204, similar to the various examples described above.
In some embodiments, when a known sample associated with a sample type is provided to a plurality of sample channels, the interference fringe pattern from the plurality of sample channels may change.
For example, if a sample contains a particular virus type and variant, and the surface of the sample channel of the waveguide is coated with antibodies to that particular virus type and variant, the antibodies bind strongly to the virus as the sample travels through the sample channel, holding the virus at the surface. An increase in the number of virus particles at the surface (due to chemical and/or biological reactions between the antibodies and the virus particles) may cause a change in the evanescent wave of the waveguide, which may in turn alter the interference fringe pattern from the waveguide.
Referring now to fig. 112B, when a sample containing virus 11206 is provided to a sample channel of waveguide 11200 coated with antibody 11202 to virus 11206, antibody 11202 attracts virus 11206 to the surface of the sample channel, causing a change in the refractive index of the sample channel. When laser source 11208 emits laser light into the sample channel of waveguide 11200, as shown, the interaction between virus 11206 and antibody 11202 causes a change in the interference fringe pattern from waveguide 11200, as detected by imaging component 11210.
Referring now to fig. 113A, an exemplary graph showing exemplary signal amplitudes of signals from a sample channel (labeled "measurement") and two control/reference channels (labeled "negative control" and "positive control") is shown. As shown in fig. 113A, the signal amplitude from the sample channel is not at the bottom of the signal amplitude range (e.g., due to a change in the interference fringe pattern), which indicates that the sample is a sample type and variant (e.g., virus type and variant) for which the sample channel is configured to detect.
As further shown in fig. 114A, exemplary signal amplitudes from a sample channel for testing SARS-Cov2 (labeled "SARS-Cov2 test channel") and two control/reference channels (negative control labeled "(-) control channel" and positive control labeled "(+) control channel") are shown. As shown in fig. 114A, the signal amplitude from the SARS-Cov2 test channel is not at the bottom of the signal amplitude range (e.g., within the positive signal range of the corresponding test channel), indicating that the sample contains SARS-Cov2 virus (or variant thereof) for which the SARS-Cov2 test channel is configured to detect.
In some examples, if the sample contains a particular virus type and variant, and the surface of the sample channel of the waveguide is coated with antibodies to that particular virus type, but not a particular virus variant, there may still be some chemical and/or biological reaction that alters the interference fringe pattern from the waveguide, although such a change may not be as pronounced as a change in which the surface of the sample channel of the waveguide is coated with antibodies to that particular variant.
In some examples, if the sample contains specific virus types and variants, and the surface of the sample channel of the waveguide is coated with antibodies to different virus types, there may be no chemical and/or biological reaction that alters the interference fringe pattern from the waveguide. For example, in the sample shown in fig. 112A, the antibody 11202 coated on the sample channel of the waveguide 11200 is not directed against the virus type 11206' flowing through the sample channel, and the variation in the interference fringe pattern from the waveguide 11200 as detected by the imaging component 11210 is minimal or non-existent.
Referring now to fig. 113B, an exemplary graph showing exemplary signal amplitudes from a sample channel (labeled "measurement") and two control/reference channels (labeled "negative control" and "positive control") is shown. As shown in fig. 113B, the signal amplitude from the sample channel is at the bottom of the signal amplitude range, indicating that the sample is not the type of sample for which the sample channel is configured to detect.
As further shown in fig. 114B, exemplary signal amplitudes from a sample channel for testing SARS-Cov2 (labeled "SARS-Cov2 test channel") and two control/reference channels (negative control labeled "(-) control channel" and positive control "(+) control channel") are shown. As shown in fig. 114B, the signal amplitude from the SARS-Cov2 test channel is at the bottom of the signal amplitude range (e.g., outside of the positive signal range associated with the corresponding test channel), indicating that the sample does not contain SARS-Cov2 virus (or variants thereof) for which the SARS-Cov2 test channel is configured to detect.
In some embodiments, each of the plurality of sample channels is coated with an antibody that is different from an antibody of another of the plurality of sample channels. For example, a first sample channel is coated with antibody A1 for detecting a particular viral variant T1, a second sample channel is coated with antibody A2 for detecting a particular viral variant T2, and a third sample channel is coated with antibody A3 for detecting a particular viral variant T3. In some embodiments, virus T1, virus T2, and virus T3 are variants of the same virus type T.
In some embodiments, only one of the plurality of sample channels is coated with antibodies for detecting sample types and variants associated with known samples. For example, if the sample is known to be associated with a particular virus type and variant T1, only one of the plurality of sample channels is coated with antibody A1 for detecting the particular virus type and variant T1.
Additionally, in accordance with fig. 110 again, in some embodiments, the steps/operations 11002 of the exemplary method 11000 can include causing at least one control substance to be provided to at least one control channel (or reference channel).
As described above, in some embodiments, at least one control channel (or reference channel) may be coated with a known substance associated with a known and/or determinable refractive index of one or more wavelengths and/or operating temperatures. In some embodiments, at least one control channel (or reference channel) may not be coated with any substance.
In some embodiments, each time a sample (whether a known sample or an unknown sample) is provided to a sample channel in the waveguide, at least one control substance is also provided to a control channel (or reference channel) of the waveguide. The at least one control substance may comprise a known substance and the change in refractive index caused by the interaction of the known substance with the known substance coated in the control/reference channel is known and/or determinable.
Referring back to fig. 110, after step/operation 11004, the exemplary method 11000 proceeds to step/operation 11006. At step/operation 11006, an example method 11000 includes recording a plurality of calibration signals received from a plurality of sample channels and detected by an imaging component. For example, signal amplitudes associated with a plurality of calibration signals may be recorded.
As described above, when a known sample travels through a plurality of sample channels, the interference fringe pattern from the plurality of sample channels may change, which may be detected and recorded by an imaging component (such as an image sensor). The interference fringe pattern can be used as a calibration signal associated with the particular type of virus, presence of variants, and concentration levels. For example, the signal amplitude of each calibration signal is recorded.
Continuing the above example, the known sample comprises a virus type T1, and the waveguide comprises a first sample channel coated with an antibody A1 for detecting a specific virus variant T1, a second sample channel coated with an antibody A2 for detecting a specific virus variant T2, and a third sample channel coated with an antibody A3 for detecting a specific virus variant T3. In this example, the imaging sensor records calibration signals (e.g., interference fringe patterns) from the first, second, and third sample channels. Since the first sample channel is coated with antibodies to a particular viral variant in a known sample, the variation in interference fringe pattern from the first sample channel may be more pronounced than the variation in interference fringe pattern from the second and third sample channels.
Referring now to fig. 116, 117, 118, 119, and 120, exemplary graphs are provided that illustrate exemplary signal magnitudes of calibration signals from exemplary waveguides.
In the examples shown in fig. 116, 117, 118, 119, and 120, an exemplary waveguide channel may include two control/reference channels, including a (-) control channel and a (+) control channel. Exemplary waveguide channels may also include four sample channels, including a SARS-CoV2 variant 1 test channel, a SARS-CoV2 variant 2 test channel, a SARS-CoV2 variant 3 test channel, and a SARS-CoV2 variant 4 test channel.
For example, the SARS-CoV2 variant 1 test channel can be coated with an antibody for detecting SARS-CoV2 variant type 1. The SARS-CoV2 variant 2 test channel can be coated with an antibody for detecting SARS-CoV2 variant type 2. The SARS-CoV2 variant 3 test channel can be coated with an antibody for detecting SARS-CoV2 variant type 3. The SARS-CoV2 variant 4 test channel can be coated with an antibody for detecting SARS-CoV2 variant type 4.
Referring now to fig. 116 and 117, exemplary graphs are provided that illustrate exemplary signal magnitudes of calibration signals associated with known samples. Specifically, FIGS. 116 and 117 show different signal amplitudes due to samples containing SARS-CoV2 variant type 1 but at different concentration levels.
In the example shown in fig. 116, the sample contains a first concentration level of SARS-CoV2 variant type 1 such that the signal amplitude of the calibration signal from the SARS-CoV2 variant 1 test channel is in the middle portion of the amplitude range of the calibration signal from the SARS-CoV2 variant 1 test channel (e.g., within the positive signal range of the test channel). In the example shown in fig. 117, the sample contains a second concentration level of SARS-CoV2 variant type 1 such that the signal amplitude of the calibration signal from the SARS-CoV2 variant 1 test channel is near the higher end of the amplitude range of the calibration signal from the SARS-CoV2 variant 1 test channel (e.g., within the positive signal range of the test channel). In some embodiments, the first concentration level is lower than the second concentration level. In addition, because the sample does not contain SARS-CoV2 variant type 2, SARS-CoV2 variant type 3 and SARS-CoV2 variant type 4, the signal amplitude of the calibration signals from the SARS-CoV2 variant 2 test channel, SARS-CoV2 variant 3 test channel and SARS-CoV2 variant 4 are at or near the bottom end of their corresponding signal amplitude ranges.
Similarly, FIG. 118 shows the signal amplitude associated with a known sample containing SARS-CoV2 variant type 2 at a particular concentration level. In the example shown in fig. 118, the sample is such that the signal amplitude of the calibration signal from the SARS-CoV2 variant 2 test channel is in the middle portion of the amplitude range of the calibration signal from the SARS-CoV2 variant 2 test channel (e.g., within the positive signal range of the test channel). Because the sample does not contain SARS-CoV2 variant type 1, SARS-CoV2 variant type 3, and SARS-CoV2 variant type 4, the signal amplitude of the calibration signals from the SARS-CoV2 variant 1 test channel, SARS-CoV2 variant 3 test channel, and SARS-CoV2 variant 4 test channel are at or near the bottom end of their corresponding signal ranges (e.g., outside the positive signal range of the test channel).
Similarly, FIG. 119 shows the signal amplitude associated with a known sample containing SARS-CoV2 variant type 3 at a particular concentration level. In the example shown in fig. 119, the sample is such that the signal amplitude of the calibration signal from the SARS-CoV2 variant 3 test channel is in the middle portion of the amplitude range of the calibration signal from the SARS-CoV2 variant 3 test channel (e.g., within the positive signal range of the test channel). Because the sample does not contain SARS-CoV2 variant type 1, SARS-CoV2 variant type 2, and SARS-CoV2 variant type 4, the signal amplitude of the calibration signals from the SARS-CoV2 variant 1 test channel, SARS-CoV2 variant 2 test channel, and SARS-CoV2 variant 4 test channel are at or near the bottom end of their corresponding signal ranges (e.g., outside the positive signal range of the test channel).
Similarly, graph 120 shows the signal amplitude associated with a known sample containing SARS-CoV2 variant type 4 at a particular concentration level. In the example shown in fig. 120, the sample is such that the signal amplitude of the calibration signal from the SARS-CoV2 variant 4 test channel is in the middle portion of the amplitude range of the calibration signal from the SARS-CoV2 variant 4 test channel (e.g., within the positive signal range of the test channel). Because the sample does not contain SARS-CoV2 variant type 1, SARS-CoV2 variant type 2, and SARS-CoV2 variant type 3, the signal amplitude of the calibration signals from the SARS-CoV2 variant 1 test channel, the SARS-CoV2 variant 2 test channel, and the SARS-CoV2 variant 3 test channel are at or near the bottom end of their corresponding signal ranges (e.g., outside the positive signal range of the test channel).
Additionally, in some embodiments, step/operation 11004 of exemplary method 11000 can include recording at least one control signal received from at least one control channel. For example, at least one signal amplitude associated with at least one control signal may be recorded after at least one control substance is provided to at least one control channel. In the examples shown in fig. 116 to 120, the signal amplitude of the control signal from the negative control channel ("(-) control channel") and the signal amplitude of the control signal from the positive control channel ("(+) control channel") are recorded.
Referring back to fig. 110, after step/operation 11006, the exemplary method 11000 proceeds to step/operation 11008. At step/operation 11008, the example method 11000 includes determining whether at least one control signal is within a control signal range. For example, the example method 11000 may determine whether the signal amplitude of the at least one control signal is within a signal amplitude range of the control signal. In some embodiments, the control signal range may be determined based on the environment in which the waveguide is placed (e.g., the temperature of the environment).
Referring now to fig. 115A-115C, exemplary graphs showing exemplary signal amplitudes of signals from a sample channel (labeled "SARS-CoV2 test channel") and two control/reference channels (labeled "(-) control channel" and "(+) control channel") are shown.
In the example shown in fig. 115A, the signal amplitude of the control signal from "(-) control channel" is higher than the signal amplitude range of the control signal range of "(-) control channel", and thus is not within the signal amplitude range. The signal amplitude of the control signal from "(+) control channel" is lower than the control signal range of "(+) control channel" and therefore is not within the signal amplitude range.
In the example shown in fig. 115B, the signal amplitude of the control signal from "(-) control channel" is within the signal amplitude range of "(-) control channel". The signal amplitude of the control signal from the "(+) control channel" is lower than the signal amplitude range of the "(+) control channel" and is therefore not within the signal amplitude range.
In the example shown in fig. 115C, the signal amplitude of the control signal from "(-) control channel" is higher than the signal amplitude range of "(-) control channel" and is not within the signal amplitude range of "(-) control channel". The signal amplitude of the control signal from the "(+) control channel" is within the signal amplitude range of the "(+) control channel".
Referring back to fig. 110, at step/operation 11008, if the example method 11000 determines that at least one control signal is not within the signal amplitude range of the control signal, the example method 11000 proceeds to step/operation 11012. At step/operation 11012, an exemplary method 11000 includes generating an error message.
For example, if any of the signal amplitudes of the control signals are not within the signal amplitude range of the corresponding control signal (e.g., as shown in fig. 115A-115C), then the example method 11000 may include generating an error message indicating that the calibration is invalid and may transmit the error message to the client device.
At step/operation 11008, if the example method 11000 determines that at least one control signal is within the signal amplitude range of the control signal, the example method 11000 proceeds to step/operation 11010. At step/operation 11010, the example method 11000 includes generating a data set indicative of a data relationship between a sample type, variant, and/or concentration level and a plurality of calibration signals.
In some embodiments, the processor may generate a data set based on the calibration signal recorded at step/operation 11006, and may establish a data relationship between the sample type, variation, and/or concentration level of the sample provided to the plurality of sample channels at step/operation 11004 and the calibration signal. For example, the processor may generate a data set that correlates signal amplitude from a calibration signal of a sample channel with (1) a sample type/variant and (2) a concentration level associated with a sample provided to the sample channel.
Continuing with the example above, the processor may generate a data set comprising signal amplitudes of calibration signals received from the first, second, and third sample channels and indicate a data association between the virus type/variant A1 (and concentration levels of the virus type/variant A1) and these calibration signals.
Referring back to fig. 110, after step/operation 11010, the exemplary method 11000 proceeds to step/operation 11014 and ends.
In some embodiments, to calibrate the waveguide, the example method 11000 may be repeated by providing a plurality of sample channels with different known samples associated with different sample variants of the same virus type.
Continuing with the above example, a known sample comprising a viral variant T2 may be provided to a first sample channel coated with antibody A1 for detecting a specific viral variant T1, a second sample channel coated with antibody A2 for detecting a specific viral variant T2, and a third sample channel coated with antibody A3 for detecting a specific viral variant T3. A plurality of calibration signals received from a plurality of sample channels are recorded and a dataset indicative of a data relationship between the sample variant T2 and the plurality of calibration signals is generated. In addition, a known sample comprising the virus variant T3 may be provided to a first sample channel coated with antibody A1 for detecting the specific virus variant T1, a second sample channel coated with antibody A2 for detecting the specific virus variant T2, and a third sample channel coated with antibody A3 for detecting the specific virus variant T3. A plurality of calibration signals received from a plurality of sample channels are recorded and a dataset indicative of a data relationship between the sample variant T3 and the plurality of calibration signals is generated.
In some embodiments, the exemplary method 11000 may be repeated. In each repetition, a known sample is provided that is associated with a different sample type or variant, and one of the sample channels is coated with an antibody directed against that sample type or variant. The repeated stopping is performed when all sample types and variants detectable by the plurality of antibodies coated on the plurality of sample channels have been provided to the plurality of sample channels. Through this iterative process, the processor can generate a complete database of data indicative of the links between different sets of calibration signals from different channels, different sample types/variants/concentration levels.
For example, referring now to fig. 116, the processor may generate a data set that correlates the signal amplitude of the calibration signal received from the SARS-CoV2 variant 1 test channel, the signal amplitude of the calibration signal received from the SARS-CoV2 variant 2 test channel, the signal amplitude of the calibration signal received from the SARS-CoV2 variant 3 test channel, and the signal amplitude of the calibration signal received from the SARS-CoV2 variant 4 test channel with the sample type of SARS-CoV2 variant 1 and the concentration level based on the known samples provided to these channels. Referring now to fig. 118, the processor may generate a data set that correlates the signal amplitude of the calibration signal received from the SARS-CoV2 variant 1 test channel, the signal amplitude of the calibration signal received from the SARS-CoV2 variant 2 test channel, the signal amplitude of the calibration signal received from the SARS-CoV2 variant 3 test channel, and the signal amplitude of the calibration signal received from the SARS-CoV2 variant 4 test channel with the sample type of SARS-CoV2 variant 2 and the concentration level based on the known samples provided to these channels. Referring now to fig. 119, the processor may generate a data set that correlates the signal amplitude of the calibration signal received from the SARS-CoV2 variant 1 test channel, the signal amplitude of the calibration signal received from the SARS-CoV2 variant 2 test channel, the signal amplitude of the calibration signal received from the SARS-CoV2 variant 3 test channel, and the signal amplitude of the calibration signal received from the SARS-CoV2 variant 4 test channel with the sample type of the SARS-CoV2 variant 3 and the concentration level based on the known samples provided to these channels. Referring now to fig. 120, the processor may generate a data set that correlates the signal amplitude of the calibration signal received from the SARS-CoV2 variant 1 test channel, the signal amplitude of the calibration signal received from the SARS-CoV2 variant 2 test channel, the signal amplitude of the calibration signal received from the SARS-CoV2 variant 3 test channel, and the signal amplitude of the calibration signal received from the SARS-CoV2 variant 4 test channel with the sample type of the SARS-CoV2 variant 4 and the concentration level based on the known samples provided to these channels.
Referring now to FIG. 111, a computer-implemented method 11100 for operating a sample testing device is provided. In some embodiments, the sample testing device includes a plurality of sample channels (e.g., a plurality of sample channels from a waveguide according to various examples described herein). In some embodiments, the sample testing device includes at least one control channel (or reference channel), similar to those described above.
The example method 11100 begins at step/operation 11101 and proceeds to step/operation 11103. At step/operation 11103, the example method 11100 includes causing an unknown sample to be provided to a plurality of sample channels. In this example, the unknown sample is associated with an unknown sample type and/or an unknown sample concentration level.
Similar to those described above, the plurality of sample channels are coated with a plurality of antibodies for detecting a plurality of sample types, variants, and/or concentration levels, similar to those described above in connection with at least step/operation 11004 of fig. 110. For example, a first sample channel is coated with antibody A1 for detecting a specific virus type/variant T1, a second sample channel is coated with antibody A2 for detecting a specific virus type/variant T2, and a third sample channel is coated with antibody A3 for detecting a specific virus type/variant T3. In some embodiments, virus T1, virus T2, and virus T3 are variants of the same virus T.
In some embodiments, each sample type of the plurality of sample types is associated with a set of calibration signals from the plurality of calibration signals. For example, the set of calibration signals associated with each of the plurality of sample types may be recorded based at least in part on the exemplary method 11000 described above in connection with fig. 110.
Continuing with the above example, the virus type/variant T1 (and its concentration level) may be associated with a first set of calibration signals from the first, second, and third sample channels. The virus type/variant T2 (and its concentration level) may be associated with a second set of calibration signals from the first, second and third sample channels. The virus type/variant T3 (and its concentration level) may be associated with a third set of calibration signals from the first, second and third sample channels.
In some embodiments, when an unknown sample is provided to a plurality of sample channels, the interference fringe pattern from the plurality of sample channels may change, similar to those described above in connection with at least fig. 110.
Additionally, in some embodiments, the steps/operations 11103 of the exemplary method 11100 can include causing a control substance to be provided to at least one control channel, similar to those described above in connection with at least fig. 110.
Referring back to fig. 111, after step/operation 11103, the example method 11100 proceeds to step/operation 11105. At step/operation 11105, the example method 11100 includes recording a plurality of sample signals received from a plurality of sample channels and detected by an imaging component. In some embodiments, exemplary method 11100 can include recording signal amplitudes of these sample signals, similar to those described above.
Additionally, in some embodiments, the steps/operations 11105 of the exemplary method 11100 may include recording at least one control signal received from at least one control channel, similar to those described above. In some embodiments, the exemplary method 11100 can include recording signal amplitudes of these control signals, similar to those described above.
As described above, as an unknown sample travels through multiple sample channels, sample signals (e.g., interference fringe patterns) from the multiple sample channels may change, which may be detected and recorded by an imaging component (such as an image sensor).
Continuing with the example above, the unknown sample travels through a first sample channel coated with antibody A1 for detecting a particular virus type/variant T1, a second sample channel coated with antibody A2 for detecting a particular virus type/variant T2, and a third sample channel coated with antibody A3 for detecting a particular virus type/variant T3. In this example, the imaging sensor records sample signals (e.g., interference fringe patterns) from the first, second, and third sample channels.
Referring back to fig. 111, after step/operation 11105, the example method 11100 proceeds to step/operation 11107. At step/operation 11107, the example method 11100 includes determining whether at least one control signal is within a control signal range.
In some embodiments, the example method 11100 may determine whether at least one control signal is within a control signal range similar to those described above in connection with at least step/operation 11008 of fig. 110.
Referring back to fig. 110, at step/operation 11107, if the example method 11100 determines that at least one control signal is not within the signal amplitude range of the control signal, the example method 11100 proceeds to step/operation 11123. At step/operation 11123, the example method 11100 includes generating an error message.
For example, the exemplary method 11100 may include generating an error message indicating that the test is invalid, and may transmit the error message to the client device, similar to step/operation 11012 of the graph 110 described above.
Referring back to fig. 111, at step/operation 11107, if the example method 11100 determines that at least one control signal is within the signal amplitude range of the control signal, the example method 11100 proceeds to step/operation 11109. At step/operation 11109, the example method 11100 includes retrieving a plurality of data sets indicative of a plurality of data linkages between a plurality of sample types/variants/concentration levels and a plurality of calibration signals.
For example, multiple data sets may be retrieved from a database of data sets indicating the relationship between different sets of calibration signals from different channels in the waveguide and different sample types/variants/concentration levels. In some embodiments, the database may be generated based at least in part on the exemplary method 11000 described above in connection with at least fig. 110.
Continuing with the above example, the processor may retrieve a plurality of data sets indicative of data links between the virus type/variant/concentration level of virus T1 and the calibration signals from the first, second, and third sample channels, the data links between the virus type/variant/concentration level of virus T2 and the calibration signals from the first, second, and third sample channels, and the data links between the virus type/variant/concentration level of virus T3 and the calibration signals from the first, second, and third sample channels.
Referring back to fig. 111, after step/operation 11109, the example method 11100 proceeds to step/operation 11111. At step/operation 11111, the example method 11100 includes determining whether the sample signal recorded at step/operation 11105 corresponds to a calibration signal from the plurality of data sets retrieved at step/operation 11109.
In some embodiments, the processor may determine whether the plurality of sample signals recorded at step/operation 11105 match a set of calibration signals associated with each sample type/variant from the plurality of data sets retrieved at step/operation 11109.
Referring back to fig. 111, if the processor determines that the sample signal recorded at step/operation 11105 corresponds to a calibration signal from the plurality of data sets retrieved at step/operation 11109, then the example method 11100 proceeds to step/operation 11115. At step/operation 11115, the example method 11100 includes reporting test positives for known/calibrated variants of the unknown sample corresponding to the variants associated with the matching calibration signal.
Continuing with the above example, the processing element determines whether the plurality of sample signals (e.g., from the first sample channel, from the second sample channel, and from the third sample channel) match the set of calibration signals associated with virus type A1 (e.g., from the first sample channel, from the second sample channel, and from the third sample channel). If so, the processor determines that the unknown virus is associated with virus type A1. If not, the processor determines that the unknown virus is not associated with virus type A1.
In other words, when an unknown sample is provided to the channels, the processor may compare the signal amplitudes from the channels and may determine whether the signal amplitudes match those recorded in the dataset. For example, as described above in connection with fig. 116-120, an exemplary waveguide may include a SARS-CoV2 variant 1 test channel, a SARS-CoV2 variant 2 test channel, a SARS-CoV2 variant 3 test channel, and a SARS-CoV2 variant 4 test channel. The processor can generate and store a data set that correlates sample type/variant (SARS-CoV 2 variant 1, SARS-CoV2 variant 2, SARS-CoV2 variant 3, or SARS-CoV2 variant 4) and concentration levels with the signal amplitudes from these channels. In some embodiments, the processor may compare the sample signals to the calibration signals when determining whether the sample signals match different sets of calibration signals.
If there is a match, the processor determines that the unknown sample is associated with the sample type and concentration level recorded in the dataset. For example, if the signal amplitudes of the sample signals from the SARS-CoV2 variant 1 test channel, the SARS-CoV2 variant 2 test channel, the SARS-CoV2 variant 3 test channel, and the SARS-CoV2 variant 4 test channel match those shown in FIG. 116, the processor determines that an unknown sample is associated with SARS-CoV2 variant 1 and concentration level based on the provided known sample in conjunction with FIG. 116.
As described above, the sample channel of the waveguide may be coated with different antibodies to different variants associated with the same virus type, and a data set may be generated that correlates the signal amplitude of the calibration signal with each variant type/variant and concentration level, similar to those described above in connection with at least fig. 110.
In some embodiments, in response to determining that the plurality of sample signals do not match any of the set of calibration signals at step/operation 11111, the example method 11100 proceeds to step/operation 11113. At step/operation 11113, the example method 11100 determines whether at least one signal amplitude of at least one of the sample signals received from the test channel and recorded at step/operation 11105 is within a signal-positive range of the test channel.
As shown, the signal amplitude from each test channel may indicate whether the sample is associated or correlated with at least the variant corresponding to the test channel. For example, if the signal amplitude of the sample signal received from the test channel is at the bottom portion of the amplitude signal range (e.g., a value of 0), then the sample is not associated or correlated with the virus (and variants) that the corresponding test channel is configured to detect. If the signal amplitude of the sample signal received from the test channel is at the middle or top portion (e.g., positive value) of the amplitude signal range, the sample is at least slightly correlated or associated with the virus (and variants) that the respective test channel is configured to detect.
Referring back to fig. 111, if the example method 11100 determines that at least one signal amplitude of the sample signal from the test channel is within the positive signal range for that channel, the example method 11100 proceeds to step/operation 11117. At step/operation 11117, the example method 11100 reports positive test results for unknown variants. For example, the example method 11100 reports that an unknown sample is associated with an unknown variant of a virus (e.g., the unknown sample includes an unknown variant of a virus).
In some embodiments, when an unknown sample is provided to the waveguide, an exemplary method may include determining that at least one signal amplitude of a sample signal from at least one sample channel is not at a bottom portion of the sample range (e.g., there is a change in refractive index of the channel), which is indicative of at least the presence of a virus. However, the exemplary method may further include determining that the set of signal amplitudes of the sample signal does not match any of those associated with the data set. For example, the sample signal from at least one of the channels does not match the calibration signal from a corresponding at least one of the channels as recorded in the dataset. In such examples, the exemplary method may further include determining that the unknown sample is associated with the same virus type as the antibody coated on the waveguide, but is associated with unknown viral variants that are different than those variants detectable by the antibody coated on the waveguide.
Referring to fig. 121, for example, an unknown sample is provided to a waveguide comprising a SARS-CoV2 variant 1 test channel (coated with an antibody to SARS-CoV2 variant 1), a SARS-CoV2 variant 2 test channel (coated with an antibody to SARS-CoV2 variant 2), a SARS-CoV2 variant 3 test channel (coated with an antibody to SARS-CoV2 variant 3), and a SARS-CoV2 variant 4 test channel (coated with an antibody to SARS-CoV2 variant 4). As shown in fig. 121, the signal amplitudes of the sample signals from the SARS-CoV2 variant 1 test channel, the SARS-CoV2 variant 3 test channel, and the SARS-CoV2 variant 4 test channel are not in the bottom portion of their corresponding signal ranges, indicating the presence of SARS-CoV2 virus. However, the set of signal amplitudes of the sampled signals from the four channels does not exactly match the signal amplitudes of the calibration signals from the four channels shown in any one of fig. 116 to 119. Thus, the exemplary method determines that the sample comprises SARS-CoV type 2 virus, but not variant 1, variant 2, variant 3, or variant 4.
Referring back to fig. 111, if the example method 11100 determines that none of the signal amplitudes of the sample signals from the test channels are within the positive signal range of those channels, the example method 11100 proceeds to step/operation 11119. At step/operation 11119, the example method 11100 reports negative test results for unknown samples not associated with viruses (e.g., not including viruses).
For example, if all sample signals received from the test channel are 0 (e.g., not within a positive signal range), the example method 11100 determines that the unknown sample does not contain a virus.
Referring back to FIG. 111, after step/operation 11123, step/operation 11115, step/operation 11117, and/or step/operation 11119, the example method 11100 proceeds to step/operation 11121 and ends.
Many sample testing devices utilize antibody immobilization assays to detect target viruses in pathogen detection. The limitation is that the detection can only detect one specific pathogen in one test, whereas it is necessary to detect more than one pathogen in a single test. A typical example is a test to detect different SARS-CoV2 variants.
According to various embodiments of the present disclosure, an instant multi-pathogen test is provided. Immediate multiple pathogen testing uses a multichannel viral sensor to detect many different types of pathogens with a single drop of sample in a single test. In some embodiments, the on-the-fly test eliminates multiple tests, reducing test time and test samples. Thus, various embodiments of the present disclosure provide for efficient, highly specific multi-pathogen assays that can replace multiple independent assays.
In some embodiments, for a waveguide comprising n sample channels (also referred to as test channels), the waveguide may be configured to detect a total of (2 n -1) types of viruses. For example, an eight-channel waveguide sensor may include six (6) active test channels and two (2) reference channels. The number of virus types that can be detected simultaneously by the six activity test channels can be calculated as:
26-1＝63
in other words, six active test channels can detect a total of 63 types of viruses, which is sufficient to cover the most interesting virus types in the sample test.
Referring now to fig. 122, an exemplary method 12200 for sample testing using a waveguide and multiple antibody sets for detecting multiple sample types is provided. In some embodiments, the waveguide comprises a plurality of sample channels.
The exemplary method 12200 begins at step/operation 12202 and proceeds to step/operation 12204. At step/operation 12204, the exemplary method 12200 includes generating a plurality of antibody mixtures using the plurality of antibody sets.
In some embodiments, each of the plurality of antibody sets comprises antibodies for detecting a particular virus type/variant. In some embodiments, each of the plurality of antibody mixtures comprises at least two different antibodies from the plurality of antibody sets.
In some embodiments, when producing a plurality of antibody mixtures, the method further comprises determining a total number of the plurality of sample channels of the waveguide, and selecting a total number of antibody sets from the plurality of antibody sets based at least in part on the total number of the plurality of sample channels.
In some embodiments, the total number of the plurality of antibody mixtures produced at step/operation 12204 is the same as the total number of the plurality of sample channels. In these embodiments, a unique antibody mixture is generated for each of a plurality of sample channels in the waveguide.
In some embodiments, when the total number of sample channels is n, a total number of sets of antibodies of m=2 n -1 is required to produce an antibody mixture. For example, if there are two sample channels, three antibody sets are required to produce an antibody mixture. If there are three sample channels, seven antibody sets are required to produce an antibody mixture. If there are four sample channels, ten antibody sets are selected to produce an antibody mixture.
In some embodiments, to generate a total of n antibody mixtures to be coated on a total of n sample channels from a total of m different antibody sets, step/operation 12204 may include implementing a combination selection algorithm to add antibodies from the different antibody sets to different antibody mixture combinations to be coated on different sample channels. For example, antibodies from each of the m different antibody sets may be added to one of the n antibody mixtures, two of the n antibody mixtures … …, or n of the n antibody mixtures. Specifically, antibodies from each antibody collection were added to a different combination of antibody mixtures than the combination of antibody mixtures to which other antibodies from the other antibody collections were added. In other words, antibodies from different antibody sets are added to different antibody mixture combinations such that no two antibody sets are added to the same antibody mixture combination.
For example, to generate a total of three (3) antibody mixtures for three (3) sample channels (e.g., channel 1, channel 2, and channel 3), step/operation 12204 may determine that a total of 3 2 -1 = 7 antibody sets (e.g., antibody sets A, B, C, D, E, F and G) are required. In such an example, antibodies from antibody set a may be added to the antibody mixture for only channel 1, antibodies from antibody set B may be added to the antibody mixture for only channel 2, antibodies from antibody set C may be added to the antibody mixture for only channel 3, antibodies from antibody set D may be added to the antibody mixture for channels 1 and 2, antibodies from antibody set E may be added to the antibody mixture for channels 1 and 3, antibodies from antibody set F may be added to the antibody mixture for channels 2 and 3, and antibodies from antibody set G may be added to the antibody mixture for channels 1,2, and 3.
In some embodiments, step/operation 12204 may include adding antibodies from the antibody collection to only one of the plurality of antibody mixtures. Additionally or alternatively, step/operation 12204 may include adding antibodies from the antibody collection to all of the plurality of antibody mixtures. Additionally or alternatively, step/operation 12204 may include adding antibodies from the antibody collection to all but one of the plurality of antibody mixtures.
For example, if the waveguide comprises two sample channels, the following two antibody mixtures may be produced:
in the above examples, the first antibody mixture comprises antibodies from antibody set a and antibody set C, and the second antibody mixture comprises antibodies from antibody set B and antibody set C.
As another example, if the waveguide includes three sample channels, the following three antibody mixtures may be produced:
As another example, if the waveguide includes four sample channels, the following four antibody mixtures may be produced:
Referring back to fig. 122, after step/operation 12204, the exemplary method 12200 proceeds to step/operation 12206. At step/operation 12206, the exemplary method 12200 includes coating a plurality of sample channels with a plurality of antibody mixtures. In some embodiments, each of the plurality of sample channels is coated with a different antibody mixture.
As described above, each of the plurality of sample channels is coated with a unique antibody mixture, and no two sample channels are coated with the same antibody mixture.
Continuing the 3-channel implementation example above, a total (2 3 -1=7) type of antibody mixture was generated and arranged in a binary sequence, with each channel coated with conjugated antibody mixture:
Referring back to fig. 122, after step/operation 12206, the exemplary method 12200 proceeds to step/operation 12208. At step/operation 12208, the example method 12200 includes providing samples to a plurality of sample channels such that the plurality of sample channels generate a plurality of test signals.
As described above, if the sample contains a virus and the surface of the sample channel of the waveguide is coated with antibodies to that virus type/variant, the antibodies attract the virus to the surface as the sample travels through the sample channel. Chemical and/or biological reactions between antibodies and viruses can cause changes in the evanescent wave of the waveguide, which in turn can alter the interference fringe pattern from the waveguide. In some examples, if the sample contains a virus and the surface of the sample channel of the waveguide is coated with antibodies to that virus type but different variants, there may still be some chemical and/or biological reaction that alters the interference fringe pattern from the waveguide, although such a change may not be as pronounced as a change in which the surface of the sample channel of the waveguide is coated with antibodies to that virus. In some examples, if the sample contains viruses and the surface of the sample channel of the waveguide is coated with antibodies to different virus types, there may be no chemical and/or biological reaction and the interference fringe pattern from the waveguide does not change.
In some embodiments, multiple test signals (e.g., interference fringe patterns) may be detected by the imaging component, similar to those described above.
Referring back to fig. 122, after step/operation 12208, the exemplary method 12200 proceeds to step/operation 12210. At step/operation 12210, the example method 12200 includes determining a sample type/variant from a plurality of sample types/variants corresponding to the sample based at least in part on the plurality of test signals.
In some embodiments, the test signal from the sample channel is indicative of any one of the following: (1) One of the antibodies from the antibody mixture coated on the sample channel targets a virus within the sample, or (2) none of the antibodies from the antibody mixture coated on the sample channel targets a virus (if any) within the sample. In some embodiments, the processor may analyze the test signals from different sample channels to determine the sample type/variant of the sample, details of which are described in connection with at least fig. 123.
Referring back to fig. 122, after step/operation 12210, the exemplary method 12200 proceeds to step/operation 12212 and ends.
Referring now to fig. 123, a computer-implemented method 12300 for determining a sample type associated with a sample is provided.
The example method 12300 begins at step/operation 12301 and proceeds to step/operation 12303. At step/operation 12303, the example method 12300 includes receiving a plurality of test signals from a plurality of sample channels associated with a sample.
In some embodiments, each of the plurality of sample channels is coated with an antibody mixture for detecting a plurality of sample types/variants, similar to those described above in connection with at least fig. 122.
In some embodiments, each test signal of the plurality of test signals is an interference fringe pattern from a sample channel of the waveguide that indicates whether there is a change in the evanescent wave of the waveguide due to a chemical and/or biological reaction between the antibody mixture and the sample, similar to those described above. In some embodiments, the processor may receive a plurality of test signals from the imaging component.
Referring back to fig. 123, after step/operation 12305, the exemplary method 12300 proceeds to step/operation 12305. At step/operation 12305, the example method 12300 includes determining, for a sample channel of a plurality of sample channels, whether a test signal of a plurality of test signals from the sample channel indicates that the sample is associated with at least one sample type of a plurality of sample types associated with an antibody mixture coated on the sample channel.
In some embodiments, the processor may compare the test signal to a threshold signal to determine whether the test signal indicates that the antibody mixture coated on the sample channel attracts viruses in the sample. If the test signal meets the threshold signal, the processor determines that the antibody mixture coated on the sample channel attracts viruses in the sample and the sample is associated with at least one sample type/variant of the plurality of sample types/variants associated with the antibody mixture coated on the sample channel. If the test signal does not meet the threshold signal, the processor determines that the antibody mixture coated on the sample channel does not attract viruses, if any, in the sample and the sample is not associated with any of the plurality of sample types/variants associated with the antibody mixture coated on the sample channel.
Referring back to fig. 123, at step/operation 12305, if the example method 12300 determines that the test signal is associated with at least one of the plurality of sample types, the example method 12300 proceeds to step/operation 12307. At step/operation 12307, the example method 12300 includes adding the plurality of sample types/variants as sample type/variant candidates for the sample type/variant associated with the sample in response to determining that the test signal indicates that the sample is associated with at least one of the plurality of sample types.
Continuing the 3-channel implementation example above, three channels may be coated with an antibody mixture according to the following table:
For example, the sample signal from channel 2 may indicate that the sample is associated with at least one sample type/variant of the plurality of sample types/variants associated with the antibody coated on channel 2. In such an example, the processor may add sample types/variants B, C, F and G to the pool of sample types/variant candidates associated with the sample. In other words, the processor determines that the sample type/variant is one of B, C, F and G.
In some embodiments, the exemplary method includes determining overlapping sample type/variant candidates based on different test signals. For example, if channel 1, channel 2, and channel 3 all indicate that the sample is associated with at least one of the plurality of sample types associated with antibodies coated on channel 1, channel 2, and channel 3, the processor adds sample type/variant A, C, E, G to the pool of sample type/variant candidates based on the test signal from channel 1, adds sample type/variant B, C, F, G to the pool of sample type/variant candidates based on the test signal from channel 2, and adds sample type/variant D, E, F, G to the pool of sample type/variant candidates based on the test signal from channel 3. The processor may determine that sample type G is an overlapping one of these sample type/variant candidates and may determine the sample type/variant of the sample as sample type/variant G.
Referring back to fig. 123, at step/operation 12305, if the example method 12300 determines that the test signal is not associated with at least one of the plurality of sample types, the example method 12300 proceeds to step/operation 12309. At step/operation 12309, the example method 12300 includes excluding the plurality of sample types/variants as sample type/variant candidates for the sample type/variant associated with the sample in response to determining that the test signal does not indicate that the sample is associated with at least one of the plurality of sample types/variants.
Continuing with the 3-channel implementation example above, the sample signal from channel 2 may indicate that the sample is not associated with any of the plurality of sample types/variants associated with the antibody coated on channel 2. In such an example, the processor may exclude sample types/variants B, C, F and G from the pool of sample type/variant candidates associated with the sample. In other words, the processor determines that the sample type/variant is not either of B, C, F and G.
In some embodiments, the processor may analyze each test signal from each sample channel according to the exemplary method 12300 to add and/or exclude sample types/variants from sample type/variant candidates until only one sample type remains.
Continuing with the 3-channel implementation example described above, one drop of sample is passed through all channels simultaneously during the test. The 3-channel sensor output signal provides the status of the test sample with various antibody combinations immobilized on the three channels. The test results are then derived by decoding the virus type A, B, C, D, E, F, G, as summarized in the following table ("0" indicates that the sample is not associated with any of the plurality of sample types associated with the antibody coated on the channel and "1" indicates that the sample is associated with at least one of the plurality of sample types associated with the antibody coated on the channel):
Alternatively, the 3-channel tests may be arranged in three groups to test seven virus types. In this example, each group utilizes two channels. In this implementation, each group has two side-by-side channels coated with the same antigen mixture. Redundancy of both increases the accuracy and confidence level of the test. For example, in the first group, both channels are coated with antibodies from the same antibody set combination (e.g., antibodies from antibody sets A, C, E and G). In the second group, both channels are coated with antibodies from the same antibody set combination (e.g., antibodies from antibody set B, C, F, G). In the third group, both channels are coated with antibodies from the same antibody set combination (e.g., antibodies from antibody set D, E, F, G). A side-to-side variation between channels may provide an indication of the test accuracy/confidence level of the test results.
As shown in the above example, fewer channels are required for a higher number of types of virus detection. For example, 12 active test channels can detect as many as (2≡12-1) =4095 types of viruses in a single test with a single drop of sample, sufficient to cover SARS-CoV2 variants.
In some embodiments, different antibody cocktail encodings and resulting decoding may be arranged to meet some special requirements and complications, for example when certain antibody cocktail combinations may not be allowed.
In some embodiments, the coded hybrid assay may also be applied to detection methods other than multichannel waveguide sensors, such as lateral flow immunoassays, to achieve the goal of having a single test to test different types/variants with a single drop of sample.
In some embodiments, other special arrangements may be added to the mixture list to introduce specific characteristic signals for sensor calibration and error correction, such as positive and negative controls/references, and redundancy for increasing accuracy and confidence levels.
Referring back to fig. 123, after step/operation 12307 and/or step/operation 12309, the example method 12300 proceeds to step/operation 12311 and ends.
In various embodiments of the present disclosure, the multichannel interferometer fringe pattern can be captured directly with a single-area imaging sensor without the need for an imaging lens. To prevent optical crosstalk between channels, various embodiments of the present disclosure provide imager baffle components.
In particular, crosstalk may exist between channels of a multi-channel interferometer. For example, when an optical signal exits from a waveguide, the optical signal from one channel (such as but not limited to an interferometer fringe pattern) may overlap with the optical signal from another optical channel (such as but not limited to an interferometer fringe pattern). In particular, the multi-channel output from the waveguide is actually a projection of light from a multi-slit grating or diffraction grating, which may introduce unwanted interference patterns.
In some embodiments, to limit and/or avoid crosstalk and unwanted interference between channels of the waveguide, an imager baffle component (such as a multi-fin baffle and/or a baffle with multiple optical slots) may be added between the interferometer output edge of the waveguide and the imaging component.
In some embodiments, the imaging component may include a sensor cover glass and/or a protective window that may prevent and/or limit the imager baffle component from reducing unwanted crosstalk between channels of the waveguide. In these embodiments, the imager baffle means may be in the form of an integrated baffle integrated with the imaging means and having direct mask pattern indicia on both surfaces of the protection window. In this disclosure, the term "imager baffle assembly" and the term "integrated baffle" are interchangeable.
Referring now to fig. 124A, 124B and 124C, a sample testing device 12400 is provided. Specifically, fig. 124A shows an exemplary top view of sample testing device 12400, fig. 124B shows an exemplary perspective view of sample testing device 12400, and fig. 124C shows an exemplary enlarged view of at least a portion of sample testing device 12400.
In the example shown in fig. 124A and 124B, sample testing device 12400 includes a light source coupler 12403, a waveguide 12408, and an imaging component 12412, similar to sample testing device 10400 illustrated and described above in connection with at least fig. 104A and 104B.
For example, the light source coupler 12403 includes a fiber holder 12404, and the fiber array 12402 is secured within the fiber holder 12404. In some embodiments, the ends of each optical fiber are connected to the same laser source (such as a laser diode), and the optical fibers are configured to transmit laser light from the laser source, similar to sample testing device 10400 illustrated and described above in connection with at least fig. 104A and 104B.
In addition, in the example shown in fig. 124A, the light source coupler 12403 includes a microlens array 12406 provided on the first edge surface of the optical fiber holder 12404. In some embodiments, each optical fiber in optical fiber array 12402 is aligned with one microlens of microlens array 12406, and each microlens of microlens array 12406 is aligned with one of at least one optical channel of waveguide 12408 (such as, but not limited to, optical channel 12410). Thus, laser light emitted by the laser light source may travel through the optical fibers in the optical fiber array 12402 and the microlenses of the microlens array 12406 and reach at least one optical channel of the waveguide 12408.
In some embodiments, as the laser light travels through at least one optical channel of the waveguide 12408, an interference fringe pattern may be the output from the at least one optical channel, and such interference fringe pattern may reach the imaging component 12412, as shown in the examples shown in fig. 124A and 124B.
Referring now to fig. 124C, an enlarged view of a portion of the waveguide 12408 and a portion of the imaging assembly 12412 is shown.
In the example shown in fig. 124C, the waveguide 12408 includes a plurality of optical channels, including a first optical channel 12410A and a second optical channel 12410B. For example, the first optical channel 12410A may be adjacent to the second optical channel 12410B, as shown in fig. 124C. In some embodiments, interference fringe patterns may be generated and exit from the first optical channel 12410A and the second optical channel 12410B, respectively, as the laser light travels through the first optical channel 12410A and the second optical channel 12410B. For example, the first interference fringe pattern 12416A may be the output from the first optical channel 12410A as the laser light travels through the first optical channel 12410A. Similarly, the second interference fringe pattern 12416B may be the output from the second optical channel 12410B as the laser light travels through the second optical channel 12410B.
In some embodiments, imaging components 12412 are positioned at the output end of the optical channels of waveguide 12408. For example, imaging component 12412 can include a sensing region 12414 that detects and/or receives interference fringe patterns, similar to those described above.
In the example shown in fig. 124C, the interference fringe pattern received by the sensing region 12414 of the imaging component 12412 can include noise and/or crosstalk between and/or among different optical channels of the waveguide 12408. For example, the first and second interference fringe patterns 12416A, 12416B may at least specifically overlap and/or interfere with each other before reaching the sensing region 12414, resulting in crosstalk between the first and second interference fringe patterns 12416A, 12416B. As shown in fig. 124C, the sensing region 12414 may receive crosstalk (e.g., an optical signal in the case where interference fringe patterns from different optical channels overlap each other). Thus, the accuracy of the test results may be affected.
As described above, various embodiments of the present disclosure overcome the above-described challenges. For example, various embodiments of the present disclosure may provide an imager baffle assembly that reduces and/or eliminates crosstalk of interference fringe patterns between different channels.
Referring now to fig. 125A and 125B, an imager baffle assembly 12500 is shown. Specifically, fig. 125A shows an exemplary perspective view of an imager baffle assembly 12500, and fig. 125B shows an exemplary top view of the imager baffle assembly 12500.
In the example shown in fig. 125A, the imager baffle assembly 12500 may be a shape resembling a cube shape. As further described herein, the imager baffle component 12500 can be positioned between the output end of the waveguide and the sensing region of the imaging component. For example, the imager baffle assembly 12500 may be disposed on a sensing region of an imaging assembly, the details of which are described herein.
Although the above description describes examples of a cube-shaped imager baffle member, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, an exemplary imager baffle assembly may include one or more additional and/or alternative elements. For example, the imager baffle members may be cube-shaped, sphere-shaped, etc.
In some embodiments, the imager baffle component 12500 can comprise one or more optical slots 12501. Referring now to fig. 125B, each of the optical slots 12501 may be in the form of an opening that allows an optical signal, such as an interference fringe pattern, to travel through. For example, each of the optical slots 12501 may be rectangular in shape. In some embodiments, one or more of the optical slots 12501 may be a shape other than a rectangular shape.
In some embodiments, each of the optical slots 12501 is aligned with an output end of one of the optical channels from the waveguide. For example, when an optical signal (such as an interference fringe pattern) travels from the output end of the optical channel, the optical signal may travel through the optical slot of the imager baffle member. At least because the optical signals (e.g., interference fringe patterns) from each optical channel travel through a respective corresponding slot of the imager baffle member, the imager baffle member avoids overlapping or crosstalk of the optical signals from the different optical channels with each other and thus improves the accuracy of the test results.
In the example shown in fig. 125A and 125B, an optical slot 12501 may be positioned on a central portion of the imager baffle component 12500. In some embodiments, the optical slots may be positioned in different portions of the imager baffle component 12500.
Referring now to fig. 126A, 126B and 126C, an imager baffle member 12600 is shown. Specifically, fig. 126A shows an exemplary top view of an imager baffle member 12600, fig. 126B shows an exemplary perspective view of the imager baffle member 12600, and fig. 126C shows an exemplary cross-sectional view of the imager baffle member 12600.
As shown in fig. 126A, the imager baffle member 12600 may have a width W1 and a length L1. In some embodiments, the length L1 is in a range between 9 millimeters and 13 millimeters. In some embodiments, the length L1 may be 11 millimeters. In some embodiments, the width W1 is in a range between 4.6 millimeters and 8.6 millimeters. In some embodiments, the width W1 may be 6.6 millimeters. In some embodiments, the length of the optical slot 12602 may be between one fifth and one third of the length L1 of the imager baffle member 12600. For example, the length of optical slot 12602 may be 4 millimeters.
While the above description provides some exemplary dimensions and dimensional ranges for the imager baffle member 12600 and the optical slot 12602, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the dimensions of exemplary imager baffle member 12600 and/or the dimensions of optical slot 12602 may be other values and/or within other dimensional ranges.
Referring now to fig. 126C, an exemplary cross-sectional view of an imager baffle member 12600 is shown. Specifically, FIG. 126C shows an exemplary cross-sectional view of the imager baffle member 12600 as cut through the A-A' line and as viewed from the direction indicated by the arrow.
In the example shown in fig. 126C, the imager baffle member 12600 may comprise one or more elements, layers, and/or coatings.
For example, the imager baffle assembly 12600 may comprise a glass base 12604. In some embodiments, the glass substrate 12604 can have a first surface and a second surface opposite the first surface. For example, the first surface may be a rectangular surface of a cube and the second surface may be a rectangular surface located on an opposite side of the cube.
In some embodiments, the imager baffle component includes a first optical coating 12606A and a second optical coating 12606B. For example, a first optical coating 12606A is disposed on a first surface of the glass substrate 12604 and a second optical coating 12606B is disposed on a second surface of the glass substrate 12604.
In some embodiments, at least one of first optical coating 12606A and/or second optical coating 12606B comprises one or more neutral density filters. In some embodiments, the neutral density filter may equally attenuate or alter the intensity of light and/or the color of light at all wavelengths so as not to cause a change in the hue of the color reproduction of light. In some embodiments, the neutral density filter may prevent or reduce the amount of unwanted optical signals (e.g., interference fringe patterns) from entering the imaging component. In some embodiments, the neutral density filter may be implemented within either optical coating (e.g., first optical coating 12606A and/or second optical coating 12606B) and/or within glass substrate 12604.
In some embodiments, at least one of the first optical coating 12606A and/or the second optical coating 12606B comprises one or more narrow bandpass filters and/or one or more anti-reflection (AR) filters. For example, a narrow band pass filter may isolate a narrow region of the infrared spectrum.
In some embodiments, imager baffle member 12600 comprises a first mask pattern 12608A disposed on first optical coating 12606A and/or a second mask pattern 12608B disposed on second optical coating 12606B.
For example, in some embodiments, a first mask pattern 12608A is printed on the first optical coating 12606A. Additionally or alternatively, a second mask pattern 12608B is printed on the second optical coating 12606B. For example, after/on the optical coating, mask reticle patterns can be added directly onto both surfaces of the glass substrate 12604 (e.g., the first optical coating 12606A and/or the second optical coating 12606B) by utilizing screen printing.
Additionally or alternatively, in some embodiments, a first mask pattern 12608A is etched on the first optical coating 12606A. Additionally or alternatively, in some embodiments, a second mask pattern 12608B is etched on the second optical coating 12606B. For example, photochemical etching may enable fine mask pattern features (e.g., for multi-channel waveguides having optical channels with fine pitch control). In some embodiments, the photochemical etching may be applied prior to optical coating (e.g., on the glass substrate) and/or after optical coating (e.g., on the optical coating) to form the first mask pattern and/or the second mask pattern.
In some embodiments, the first mask pattern 12608A and the second mask pattern 12608B form a plurality of optical slots 12602 of the imager baffle member 12600. For example, by printing and/or etching as described above, the optical slots 12602 may be formed to allow optical signals (such as interference fringe patterns) to each travel through a corresponding optical slot without overlapping one another, similar to those described above.
As shown in fig. 126C, the imager baffle member 12600 may have a thickness T1 of between 0.5 millimeters and 1.5 millimeters. In some embodiments, the imager baffle member 12600 may have a thickness T1 of 1 millimeter. In some embodiments, the imager baffle member 12600 may have a thickness T1 within other size ranges and/or other dimensions.
Referring now to fig. 127, a sample testing device 12700 is provided. As shown in the example of fig. 127, the sample testing device 12700 includes a waveguide 12707 and an imager baffle component 12711.
In the example shown in fig. 127, sample testing device 12700 includes a light source coupler 12703, similar to sample testing device 12400 illustrated and described above in connection with at least fig. 124A. For example, the light source coupler 12703 includes a fiber holder 12704, and the fiber array 12701 is fixed inside the fiber holder 12704. In some embodiments, the ends of each optical fiber are connected to the same laser source (such as a laser diode), and the optical fibers are configured to transmit laser light from the laser source, similar to sample testing device 12400 illustrated and described above in connection with at least fig. 124A.
In addition, in the example shown in fig. 127, the light source coupler 12703 includes a microlens array 12705 provided on a first edge surface of the optical fiber holder 12704. In some embodiments, each optical fiber in the optical fiber array 12701 is aligned with one microlens of the microlens array 12705, and each microlens of the microlens array 12705 is aligned with one of the at least one optical channel of the waveguide 12707 (such as, but not limited to, optical channel 12709). Thus, laser light emitted by the laser light source may travel through the optical fibers in the fiber array 12701 and the microlenses of the microlens array 12705 and reach at least one optical channel of the waveguide 12707.
In some embodiments, the interference fringe pattern may exit from at least one optical channel of the waveguide 12707 as the laser light travels through the at least one optical channel. For example, in some embodiments, the waveguide 12707 includes a plurality of optical channels, such as optical channel 12709. In this example, the interference fringe pattern may be the output from the optical channel 12709.
In some embodiments, the imager baffle assembly 12711 is disposed on the imaging assembly 12713. For example, the imager baffle assembly 12711 may be attached to the imaging assembly 12713 and/or replace a protective window of the imager baffle assembly 12711.
In some embodiments, the imager baffle member 12711 includes a plurality of optical slots, such as, but not limited to, optical slots 12717 as shown in fig. 127. In some embodiments, each of the plurality of optical slots of the imager baffle member 12711 is aligned with one of the plurality of optical channels of the waveguide 12707. In the example shown in fig. 127, the channel output 12715 of the optical channel 12709 of the waveguide 12707 is aligned with the optical slot 12717 of the imager baffle component 12711. In such an example, as the laser light travels through the fiber array 12701 and through the optical channel 12709, an interference fringe pattern may be generated and travel through the channel output 12715 of the optical channel 12709. The interference fringe pattern may travel through the optical slot 12717 of the imager baffle member 12711 and reach the imaging member 12713. When each interference fringe pattern travels through a single optical slot that is different from the optical slots through which other interference fringe patterns from other optical channels travel, overlapping interference fringe patterns and crosstalk of optical signals from different optical channels may be reduced and/or eliminated.
As described above, the imager baffle assembly 12711 may be in the form of a single element integrated imager baffle that may replace the protective window and/or optical filter of the imaging assembly 12713 and may function as an imager baffle, thus improving the accuracy of the test results and reducing the size of the sample testing device 12700.
There are many technical challenges in manufacturing and using sample testing devices. For example, to generate accurate test results, operation of the exemplary sample testing device requires a smooth flow of fluid (e.g., at a constant or target speed) through one or more fluid channels of the sample testing device.
By way of example, as described above, fig. 97A shows an exemplary sample testing device 9700 that includes a waveguide 9701 and a multiport valve 9709. In the example shown in fig. 97A, the waveguide 9701 includes at least a buffer channel 9703, a reference channel 9705, and a sample channel 9707. As described above, during operation, the pump/actuator is operably connected to the buffer reservoir 9717 to push (e.g., transport) buffer solution from the buffer reservoir 9717 to the buffer channel 9703, the reference channel 9705, and the sample channel 9707. The buffer solution travels through these channels and is discharged into a waste collector 9753.
Thus, it should be appreciated that an exemplary sample testing device may include one or more fluid channels configured to transport fluid therethrough and into a waste collector. Each fluid of the plurality of fluid channels is operably coupled to a pump or piston actuator that operates to facilitate fluid flow through the example sample testing device at a near constant velocity in order to ensure that measurements generated by the example testing device are accurate.
In various embodiments, the sample testing device needs to be configured to withstand variations in friction or force, including back pressure generated by the sample testing device during operation. Additionally, in some examples, one or more of the fluid channels may become blocked or clogged (e.g., due to remaining patient sample, contaminants, or microscopic particles being trapped in the exemplary fluid channel during operation). In these examples, if clogging of one or more fluid channels is not detected, the exemplary sample testing device may generate inaccurate test results (e.g., false negative or false positive results) during use.
Systems and methods for determining a fault condition with respect to at least one fluid channel of a sample testing device in accordance with various embodiments of the present disclosure are provided. In some examples, the method may include monitoring a current measurement signal of a pump or actuator of the sample testing device operably coupled to the at least one fluid channel. In some examples, the method may include providing an indication of a fault condition in response to detecting a current measurement signal above a threshold current value or above or below a target current range. In some examples, the current value above the threshold is 120mA. In some examples, the nominal current measurement signal is between 60-80 mA. In some examples, the sample testing device pump or actuator includes a motion controller and a voice coil actuator. In some examples, monitoring the current output includes obtaining a current measurement from within a motion controller of the sample testing device via the ammeter. In some examples, the target current range is determined based at least in part on a machine learning technique. In some examples, a temporal increase in force or pressure from a real occlusion is identified based at least in part on a time weighted analysis using machine learning techniques. In some examples, providing an indication of the fault condition includes generating an alert for presentation via a user interface of a user computing entity in electronic communication with the sample testing device.
In some embodiments, to maintain proper flow of fluid through the example sample testing device based at least in part on one or more detected parameters (e.g., detected load, pressure, or force), a motion controller operably coupled to the pump/actuator may cause an increase or decrease in current output of the pump/actuator to drive the pump/actuator to inject fluid (e.g., test liquid) into one or more flow channels of the example sample testing device at a target speed. By way of example, the example motion controller may provide control instructions to cause the example pump/actuator to supply a greater amount of current in response to detecting a significant amount of force or back pressure (e.g., greater than 1 pound) associated with the sample testing device. Similarly, the example motion controller may provide control instructions to cause the example pump/actuator to supply a smaller amount of current in response to detecting a small amount of force or back pressure (e.g., between 0.3 pounds and 0.4 pounds) associated with the sample testing apparatus.
Referring now to fig. 128, an exemplary system 12800 according to various embodiments of the disclosure is provided. As depicted in fig. 128, the exemplary system 12800 includes a controller component 12801, one or more sensing elements 12802, a pump/actuator 12803, and a current monitoring circuit 12805. The exemplary system 12800 can be or include at least a portion of a sample testing device.
As depicted in fig. 128, the exemplary system 12800 includes a controller component 12801 (e.g., a motion controller). In various examples, as depicted, the example controller component 12801 is operably coupled to and in electronic communication with one or more sensing elements 12802 and pump/actuators 12803 such that they can exchange data/information with one another. In some embodiments, based at least in part on one or more detected parameters, the controller component 12801 can operate (e.g., provide control instructions) to control one or more operations of the pump/actuator 12803. For example, the controller component 12801 may provide control instructions to adjust the current output of the pump/actuator 12803. Accordingly, the controller component 12801 can determine an amount of force or pressure associated with the sample testing device and provide control instructions to cause the pump/actuator 12803 to generate a particular current output to inject fluid into one or more flow channels of the example sample testing device at a target speed.
As depicted in fig. 128, the system 12800 includes one or more sensing elements 12802. In various embodiments, the one or more sensing elements 12802 may be or include a pressure sensor, load sensor, force sensor, or the like configured to determine one or more parameters (e.g., detected load, pressure, or force) with respect to the sample testing device. Thus, the one or more sensing elements 12802 may provide additional information/data regarding the current state of the system/sample testing device for use in controlling the operation of the controller component 12801 (e.g., motion controller and/or pump or actuator).
As further depicted in fig. 128, the exemplary system includes a current monitoring circuit 12805. In various examples, the current monitoring circuit 12805 is operably coupled to the controller component 12801 and/or the pump/actuator 12803 and is configured to monitor a current output of the pump/actuator 12803. In some examples, the current monitoring circuit 12805 may be configured to obtain current measurements via an electrical meter with respect to an exemplary controller component (e.g., a motion controller), as discussed below.
Referring now to fig. 129, another exemplary system 12900 is provided in accordance with various embodiments of the present disclosure. Exemplary system 12900 can be similar or identical to system 12800 discussed above in connection with fig. 128. In various embodiments, as depicted, the exemplary system 12900 includes at least a motion controller 12902 and a voice coil actuator 12904. In various embodiments, the example motion controller 12902 and voice coil actuator 12904 are operably coupled to and in electronic communication with each other such that they can exchange data/information with each other. In various aspects, the motion controller 12902 is configured to control one or more operations of a sample testing device (e.g., the pump or voice coil actuator 12904 of an exemplary sample testing device).
As depicted in fig. 129, the exemplary system 12900 includes a motion controller 12902. The motion controller 12902 may be operative to control one or more operations of the sample testing device and, in particular, the voice coil actuator 12904 of the sample testing device. As depicted in fig. 129, motion controller 12902 includes one or more circuits (e.g., processing elements, logic, etc.). The motion controller 12902 may determine an amount of force or pressure associated with one or more flow channels of the example sample testing device and provide control instructions to cause the voice coil actuator 12904 to generate a particular current output to inject fluid into one or more flow channels of the example sample testing device at a target speed. As shown, motion controller 12902 includes a target position and/or velocity determination circuit 12902A, a position control circuit 12902B, a velocity control circuit 12902C, and a current control circuit 12902D. In addition, as depicted, the motion controller 12902 includes stall/stall logic/circuitry 12902E configured to obtain current measurements (e.g., via an electric meter) from within the motion controller 12902 of the sample testing device.
As described above, and as depicted in fig. 12900, the exemplary system 12900 includes a voice coil actuator 12904 operably coupled to a motion controller 12902. In various implementations, voice coil actuator 12904 includes one or more circuits (e.g., processing elements, logic, etc.). As shown, voice coil actuator 12904 includes linear motor output circuitry 12904A and encoder 12904B. In various examples, voice coil actuator 12904 is configured to generate a force to push buffer solution through one or more channels of the sample testing device. The amount of force generated may be proportional to the amount of current provided by the motion controller 12902 (e.g., via the current control circuit 12902D). Thus, the voice coil actuator 12904 may be operable to push (e.g., transport) the buffer solution through one or more channels of the sample testing device at a target speed based at least in part on one or more control instructions provided by the motion controller 12902. In addition, as depicted, voice coil actuator 12904 may provide feedback to motion controller 12902 (e.g., via linear motor output circuit 12904A and encoder 12904B), based on which motion controller 12902 may change various operating parameters (e.g., position and/or speed control via position control circuit 12902B and speed control circuit 12902C).
Referring now to fig. 130, an exemplary flowchart 13000 illustrating exemplary operations according to various examples of the present disclosure is provided. It should be appreciated that the various operations form a process that may be performed via one or more computing devices and/or modules (e.g., computer-implemented methods) embodied in hardware, software, and/or firmware. In some embodiments, process 13000 is performed by one or more apparatuses (e.g., a sample testing device as described herein). In this regard, the apparatus may comprise or otherwise be configured with one or more memory devices having computer-encoded instructions stored thereon, and/or one or more processors (e.g., processing modules) configured to execute the computer-encoded instructions and perform the depicted operations. Additionally or alternatively, in some embodiments, computer program code for performing the operations depicted and described with respect to process 13000 can be stored on one or more non-transitory computer-readable storage media of a computer program product, e.g., for execution via one or more processors associated with or otherwise executing with the non-transitory computer-readable storage media of the computer program product.
Process 13000 begins at block 13002. At block 13002, the process 13000 comprises monitoring the current output of the sample test device pump/actuator via a current monitoring circuit (such as, but not limited to, current monitoring circuit 12805 discussed above in connection with fig. 128 or stall/block logic/circuit 12902E discussed above in connection with fig. 129).
At block 13004, the process comprises determining whether the detected current is within a target current range. In some embodiments, the target current range may be or include an operating current range associated with the sample testing device pump/actuator (e.g., a nominal range of 60-80mA with a current measurement threshold/limit of 120mA, indicating an abnormally high voltage). In some embodiments, machine learning techniques may be utilized to determine target parameters associated with the sample testing device pump/actuator (e.g., nominal current range and upper and lower control limits) in order to improve the accuracy of the fault detection operation. In some embodiments, temporal weighted analysis may be used to identify temporary increases in force (e.g., friction) from a real occlusion using machine learning techniques.
In some embodiments, where the detected current is within the target current range, the process 13000 returns to block 13002 where the current output of the sample testing device pump/actuator is continually monitored.
In some embodiments, where the detected current is not within the target current range, the process 13000 proceeds to block 13006.
At block 13006, the process 13000 comprises providing an indication of a fault condition. In some examples, providing an indication of the failure includes generating an alert for presentation via a user interface of a user computing entity in electronic communication with the sample testing device.
Referring now to fig. 131, a graph 13100 depicting exemplary measurements of an exemplary device (e.g., a pump or voice coil actuator, such as voice coil actuator 12904 operably coupled to motion controller 12902) is provided in accordance with various embodiments of the present disclosure.
As depicted in fig. 131, the x-axis represents a plurality of time instances. As depicted, the y-axis represents a detected current measurement signal (e.g., maximum current) associated with an exemplary device (e.g., pump or voice coil actuator).
As depicted in fig. 131, the current measurement signal is within a nominal current range (e.g., about 60 mA) between 0 seconds and 200 seconds. In various examples, the nominal current may range between 60-80 mA. Additionally, the example apparatus may be associated with a target current measurement range or a current measurement threshold. For example, as depicted, the exemplary device is associated with a current measurement threshold 13102 of 120 mA. As further shown, at about 200 seconds, a peak (indicative of a fault or abnormal condition) occurs. Then, between 200 seconds and 600 seconds, the current measurement signal depicted by line 13101 is above current measurement threshold 13102 (i.e., 120 mA). In various examples, peaks and/or current measurement signals/values above a threshold may be indicative of abnormally high pressure conditions, faults or blockages, etc. of one or more flow channels of the example sample testing device. In response to detecting a current measurement signal/value above a threshold, the example sample testing device may provide an indication of a fault (e.g., via a user interface of a user computing entity in electronic communication with the sample testing device).
Thus, fig. 131 illustrates that a detected current measurement signal associated with an exemplary device (e.g., a pump or voice coil actuator) may be monitored in order to identify an operational failure (e.g., due to a blockage in one or more flow channels of a sample testing apparatus).
Substance/liquid delivery systems are a class of systems configured to deliver substances and/or liquids from one location to another. For example, the substance/liquid delivery system may be in the form of one or more sample channels (as described above) in the waveguide that may deliver the buffer solution and/or the sample solution. As another example, the substance/liquid delivery system may be in the form of a conduit, duct, tube, or the like, such as, but not limited to, a tube configured to deliver a substance and/or liquid from one location to another.
There are many technical challenges and difficulties associated with substance/liquid delivery systems. For example, many substance/liquid delivery systems require different types of substances/liquids to be delivered at different points in time and/or according to the order of delivery. For example, a substance/liquid delivery system may receive a first type of substance/liquid at the beginning of a delivery sequence. Once the first type of liquid has passed completely through the delivery system, the substance/liquid delivery system can receive and deliver a second type of substance/liquid.
However, it is difficult to accurately predict whether a substance/liquid has passed completely through the substance/liquid delivery system. For example, referring now to fig. 132, an exemplary method 13200 associated with a waveguide is illustrated. Specifically, fig. 132 illustrates an exemplary delivery sequence associated with a sample channel of a waveguide (i.e., a substance/liquid delivery system).
The exemplary method 13200 illustrated in FIG. 132 begins at step/operation 13202. After and/or in response to step/operation 13202, exemplary method 13200 proceeds to step/operation 13204. At step/operation 13204, the exemplary method 13200 causes a buffer solution to be injected for a first time into a sample channel of a waveguide.
As described above, the surface of the sample channel of the waveguide may be coated with antibodies against the virus. For example, according to various embodiments of the present disclosure, the waveguide may be part of a sample testing device configured to detect and/or determine the presence of viruses in a sample solution (e.g., a liquid solution that captures aerosols from a user's breath). In the presence of viral molecules in the sample solution, antibodies coated on the surface of the sample channel may pull the molecules towards the surface of the sample channel.
In some embodiments, one or more preservative chemicals (such as, but not limited to, sugar) may be coated on the surface of the sample channel to protect antibodies on the surface of the sample channel before the user uses the waveguide. For example, there is a time interval between the time the sample testing device (and waveguide) is manufactured and the time the sample testing device is used by the user. In the absence of one or more preservative chemicals, antibodies coated on the surface of the sample channel may become inactive during this time interval when exposed to air. One or more preservative chemicals can cover antibodies on the surface of the sample channel, preserve these antibodies and extend the shelf life of the sample testing device.
In some embodiments, when a user begins to use the sample testing device, the user may inject or cause to be injected a buffer solution into the sample channel. Examples of buffer solutions include, but are not limited to, water. As the buffer solution travels along the sample channel, the buffer solution may clear, remove, and/or wash out one or more preservative chemicals from the surface of the sample channel (and from the antibodies) without removing the antibodies from the surface of the sample channel.
In some embodiments, according to various embodiments described herein, the sample channel of the waveguide may be connected to a pump configured to inject a buffer solution into the sample channel. In these embodiments, the pump may be in electronic communication with a processor and/or controller (as described above) such that the processor and/or controller may transmit instructions to the sample channel that will pump and cause the buffer solution to be injected into the waveguide for the first time.
Referring back to fig. 132, after and/or in response to step/operation 13204, exemplary method 13200 proceeds to step/operation 13206. At step/operation 13206, the example method 13200 causes a second injection of the sample solution to the sample channel of the waveguide.
In some embodiments, after a sufficient amount of buffer solution is injected into the sample channel of the waveguide, all of the preservative chemicals are cleared, removed, and/or washed away from the surface of the sample channel, thereby exposing the antibodies. In some embodiments, the exemplary method 13200 causes a second injection of the sample solution after the buffer solution injected at step/operation 13204 has traveled completely through the sample channel.
In some embodiments, a user may inject a sample solution into the sample channel, and the sample testing device may begin detecting whether the sample solution contains an antibody-targeted virus. In some embodiments, the processor and/or controller may cause the sample solution to be injected into the sample channel a second time by the pump according to various embodiments described herein.
Referring back to fig. 132, after and/or in response to step/operation 13206, exemplary method 13200 proceeds to step/operation 13208 and ends.
As shown in the above examples, it is important to determine when one or more preservative chemicals have been completely washed off or cleared from the surface of the sample channel, and/or when the buffer solution has traveled completely through the sample channel so that the sample solution can be injected into the sample channel. If the sample solution is injected into the sample channel before the one or more preservative chemicals have been completely washed or cleared from the surface and/or before the buffer solution has completely traveled through the sample channel, the one or more preservative chemicals and/or buffer solution may result in inaccurate results generated by the sample testing device (e.g., the one or more preservative chemicals may prevent the virus from binding to antibodies on the surface of the sample channel).
In addition, if a particular concentration of a substance/liquid (e.g., without limitation, a particular concentration of buffer solution in a sample channel) must be reached in order for a subsequent operation to begin (e.g., without limitation, injection of sample solution into the sample channel), it may be desirable to directly measure the substance/liquid under consideration (e.g., to measure the current concentration level of the substance/liquid).
As noted above, many systems and methods do not accurately predict whether a substance/liquid will pass completely through a substance/liquid delivery system. Thus, a more appropriate solution is needed to reliably identify that a fluid transition has been completed.
Various embodiments of the present disclosure overcome these technical challenges and difficulties and provide various technical benefits and advantages. Referring now to fig. 133A, 133B, and 133C, an exemplary method 13300 is shown according to various embodiments of the present disclosure.
In particular, the exemplary method 13300 illustrates an example of identifying a "clean-out" condition of a sample channel based on a change in refractive index as one or more preservative chemicals are washed out of the sample channel and antibody. For example, the exemplary method 13300 shows determining a change in refractive index using a laser beam that passes through a fluid-carrying channel (such as a sample channel of a waveguide) and impinges on an imaging sensor. Based on the refractive index, substances in the fluid may be identified. If two or more substances are expected to occur in the observation region at different times, the completion of the fluid transition may be identified. Thus, various embodiments of the present disclosure can optimize cycle time and fluid requirements and measure changes in the wash process. In some embodiments, the buffer and the solution of dissolved preservative have different refractive indices than the buffer solution alone. Thus, the time at which the channel transitions from the preservative covered state to the "clear to complete" state can be observed based on the change in refractive index. Similarly, the refractive index is different when the channels are dry and when the channels are wet. Thus, the dry-to-wet transition in the channel can also be observed based on the refractive index change.
The exemplary method 13300 illustrated in fig. 133A begins at step/operation 13302. After and/or in response to step/operation 13302, the example method 13300 proceeds to step/operation 13304. At step/operation 13304, the example method 13300 causes a laser source to emit a laser beam through a sample channel of a waveguide.
In some embodiments, the laser source may be configured to generate, and/or emit a laser beam. Examples of laser sources may include, but are not limited to, laser diodes (e.g., violet laser diodes, visible laser diodes, edge-emitting laser diodes, surface-emitting laser diodes, etc.).
Referring now to fig. 134A, an exemplary sample testing device 13400A is shown according to various embodiments of the present disclosure. In particular, the exemplary sample testing device 13400A includes a laser source 13401A, a waveguide with a sample channel 13403A (e.g., a substance/liquid delivery system), and an imaging sensor 13405A.
As shown in the example shown in fig. 134A, a laser source 13401A is positioned adjacent to the input end of the sample channel 13403A, and an imaging sensor 13405A is positioned adjacent to the output end of the sample channel 13403A. In some embodiments, the buffer solution and/or the sample solution may be injected into the sample channel through an opening at the input end of the sample channel and exit the sample channel through an opening at the output end of the sample channel.
In some embodiments, the user may turn on the laser source and cause the laser source to emit a laser beam through the sample channel. In some embodiments, the processor and/or controller may cause the laser source to emit a final beam. For example, the laser source may be aligned with the input end of the sample channel and in electronic communication with the processor and/or controller. The processor and/or controller may transmit instructions to an actuator of the laser source to cause the laser source to emit a laser beam.
As the laser source emits a laser beam through the sample channel of the waveguide, the laser beam may travel through the sample channel (e.g., through air in the sample channel) and reach the imaging sensor 13405A. In some embodiments, imaging sensor 13405A is an imaging component according to various examples provided herein. For example, imaging sensor 13405A may include, but is not limited to, a photodetector, a Contact Image Sensor (CIS), a Charge Coupled Device (CCD), a Complementary Metal Oxide Semiconductor (CMOS) sensor, and the like. As shown in fig. 134A, after the laser beam emitted by the laser source 13401A travels through the sample channel 13403A (e.g., through air in the sample channel), the laser beam reaches the first sensing region 13407a of the imaging sensor 13405A (e.g., the laser beam activates the first sensing region 13407a of the imaging sensor 13405A).
Referring back to fig. 133A, after and/or in response to step/operation 13304, the example method 13300 proceeds to step/operation 13306. At step/operation 13306, the example method 13300 receives first imaging data from an imaging sensor.
For example, as shown in fig. 134A, after the laser beam reaches the first sensing region 13407a of the imaging sensor 13405A, the imaging sensor 13405A can generate first imaging data. In some embodiments, the first imaging data may indicate the location of the first sensing region 13407a where the laser beam reaches/activates on the imaging sensor 13405A.
In some embodiments, imaging sensor 13405A may transmit the first imaging data to a processor and/or controller.
Referring back to fig. 133A, after and/or in response to step/operation 13306, exemplary method 13300 proceeds to step/operation 13310. At step/operation 13310, the example method 13300 causes a buffer solution to be first injected into a sample channel of a waveguide.
For example, a user may inject or cause to be injected a buffer solution into a sample channel (e.g., through an input opening at an input end of the sample channel). Examples of buffer solutions include, but are not limited to, water. As described above, one or more preservative chemicals (e.g., without limitation, sugar) may be coated on the surface of the sample channel and/or on the antibodies to protect those antibodies before the user uses the waveguide. As the buffer solution travels along the sample channel, the buffer solution may clear, remove, and/or wash out one or more preservative chemicals from the surface of the sample channel as well as from the antibodies.
In some embodiments, the waveguide may be connected to a pump configured to inject a buffer solution into a sample channel of the waveguide, similar to those described above. In these embodiments, the pump may be in electronic communication with the processor and/or controller as described above, such that the processor and/or controller may transmit instructions to the sample channel that will pump and cause the buffer solution to be injected into the waveguide for the first time.
Referring back to fig. 133A, after and/or in response to step/operation 13310, exemplary method 13300 proceeds to block a, which connects fig. 133A to fig. 133B. Referring back to fig. 133B, after block a and/or in response to block a (i.e., after step/operation 13310 and/or in response to step/operation), exemplary method 13300 proceeds to step/operation 13314. At step/operation 13314, the example method 13300 receives second imaging data from an imaging sensor. In some embodiments, after the first injection of the buffer solution at step/operation 13310, second imaging data is received from the imaging sensor.
For example, referring now to fig. 134B, an exemplary sample testing device 13400B is shown, similar to the exemplary sample testing device 13400A shown above in connection with fig. 134A, according to various embodiments of the present disclosure. In particular, the exemplary sample testing device 13400B includes a laser source 13401B, a waveguide with a sample channel 13403B (e.g., a substance/liquid delivery system), and an imaging sensor 13405B.
Similar to the exemplary sample testing device 13400A shown above in connection with fig. 134A, the laser source 13401B is positioned adjacent to the input end of the sample channel 13403B, and the imaging sensor 13405B is positioned adjacent to the output end of the sample channel 13403B.
In the example shown in fig. 134B, the laser source continues to emit a laser beam through the sample channel of the waveguide, and a buffer solution is injected into the sample channel. The laser beam may travel through the sample channel (e.g., through a buffer solution that has been injected into the sample channel) and reach the imaging sensor 13405B. In some embodiments, imaging sensor 13405B is an imaging component similar to imaging sensor 13405a described above in connection with fig. 134A. As shown in fig. 134B, after the laser beam emitted by the laser source 13401B travels through the sample channel 13403B (e.g., through a buffer solution that has been injected into the sample channel), the laser beam reaches the second sensing region 13407B of the imaging sensor 13405B (e.g., the laser beam activates the second sensing region 13407B of the imaging sensor 13405B).
After the laser beam reaches the second sensing region 13407B of the imaging sensor 13405B, the imaging sensor 13405B can generate second imaging data. In some embodiments, the second imaging data may indicate the location of the laser beam reaching/activating second sensing region 13407B on imaging sensor 13405B.
In some embodiments, imaging sensor 13405B may transmit the second imaging data to the processor and/or controller.
Referring back to fig. 133B, after and/or in response to step/operation 13314, the example method 13300 proceeds to step/operation 13318. At step/operation 13318, the example method 13300 calculates a refractive index change value associated with a sample channel based on the first imaging data and the second imaging data.
For example, comparing fig. 134A with fig. 134B, the first sensing region 13407a in fig. 134A is a different sensing region on the imaging sensor than the second sensing region 13407B in fig. 134B. In some embodiments, the difference is due to a change in refractive index of the sample channel.
In some embodiments, the change in refractive index of the sample channel may be caused by injection of a buffer solution. For example, when the laser beam first travels through the sample channel, there may not be any buffer solution in the sample channel. As the laser beam is continuously emitted and continuously travels through the sample channel, a buffer solution is injected into the sample channel, causing a change in the refractive index of the sample channel, which is reflected as a change in the sensing region activated by the laser beam.
Additionally or alternatively, the change in refractive index of the sample channel may be caused by the removal/stripping of one or more preservative chemicals on the surface of the sample channel. As described above, the buffer solution may clean and/or remove one or more preservative chemicals from the surface of the sample channel as the buffer solution travels through the sample channel. As the laser beam continuously emits and travels through the sample channel, the buffer solution continuously washes away the one or more preservative chemicals from the surface of the sample channel, and a decrease in the amount of the one or more preservative chemicals on the surface of the sample channel causes a change in the refractive index of the sample channel, which is reflected as a change in the sensing area activated by the laser beam.
In some embodiments, changes in the activation sensing area of the sensor may be measured and changes in the refractive index may be calculated. Continuing with the example described in connection with fig. 134A and 134B, a refractive index change value may be calculated based on a distance between the first sensing region 13407a and the second sensing region 13407B. For example, the refractive index change value (i.e., the change in refractive index of the sample channel) may be equal to the distance between the first sensing region 13407a and the second sensing region 13407B.
For example, based on the first imaging data received at step/operation 13306 and the second imaging data received at step/operation 13314, the processor and/or controller may calculate a distance between the first sensing region and the second sensing region and may designate the distance as the refractive index change value.
Referring back to fig. 133B, after and/or in response to step/operation 13318, exemplary method 13300 proceeds to block B, which connects fig. 133B to fig. 133C. Referring back to fig. 133C, after block B and/or in response to block B (i.e., after step/operation 13318 and/or in response to step/operation), exemplary method 13300 proceeds to step/operation 13320. At step/operation 13320, the example method 13300 determines whether a refractive index change value corresponds to a predetermined refractive index change value.
In some embodiments, the predetermined refractive index change value is a refractive index change value of the sample channel when one or more preservative chemicals have been completely washed off or cleared from the surface of the sample channel and/or when the buffer solution has traveled completely through the sample channel.
For example, various embodiments of the present disclosure may calculate a predetermined refractive index variation value through experimentation. For example, various embodiments of the present disclosure may cause a laser source to emit a laser beam through a sample channel. The laser source may activate a first experimental sensing region of the imaging sensor when there is no buffer solution in the sample channel. The laser source may activate the second experimental sensing region of the imaging sensor when the sample channel is in a defined state in which one or more preservative chemicals have been completely washed out or cleared from the surface of the sample channel and/or when the buffer solution has traveled completely through the sample channel. In some embodiments, the predetermined refractive index change value is calculated corresponding to a distance between the first experimental sensing region and the second experimental sensing region.
Although the above description provides an example of calculating a predetermined refractive index change value, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary predetermined refractive index change value may correspond to a refractive index value of the buffer solution.
As described above, various embodiments of the present disclosure may determine a change in a substance/liquid/solution in a sample channel based on determining that there is a change in the refractive index of the sample channel. Additionally or alternatively, the substance/liquid/solution in the sample channel (and/or the concentration level of the substance/liquid/solution in the sample channel) may be identifiable based on the refractive index change value and/or the change in the refractive index of the sample channel.
For example, exemplary embodiments of the present disclosure may compare the refractive index change value calculated at step/operation 13318 to a known refractive index change value associated with a known substance/liquid. If there is a match between the refractive index change value calculated at step/operation 13318 and the known refractive index change value, exemplary embodiments of the present disclosure may determine that the substance/liquid in the sample channel is a known substance/liquid corresponding to the known refractive index change value.
Additionally or alternatively, exemplary embodiments of the present disclosure may compare the refractive index change value calculated at step/operation 13318 to a known refractive index change value associated with a known concentration level of a substance/liquid. If there is a match between the refractive index change value calculated at step/operation 13318 and the known refractive index change value, exemplary embodiments of the present disclosure may determine that the substance/liquid in the sample channel has a concentration level that corresponds to the known concentration level associated with the known refractive index change value.
Referring back to fig. 133C, if at step/operation 13320 the example method 13300 determines that the refractive index change value corresponds to the predetermined refractive index change value, the example method 13300 proceeds to step/operation 13322. At step/operation 13322, the example method 13300 causes a second injection of a sample solution into a sample channel of a waveguide.
In some embodiments, if the refractive index change value matches the predetermined refractive index change value, the example method 13300 determines that one or more preservative chemicals have been completely washed away or cleared from the surface of the sample channel and/or that the buffer solution has traveled completely through the sample channel. Thus, the exemplary method 13300 allows for a second injection of the sample solution.
For example, the processor and/or controller may determine whether the refractive index change value calculated at step/operation 13318 matches a predetermined refractive index change value and, if so, transmit instructions to the pump and cause a second injection of the sample solution into the sample channel by the pump.
If at step/operation 13320, the example method 13300 determines that the refractive index change value does not correspond to the predetermined refractive index change value, the example method 13300 proceeds to step/operation 13324. At step/operation 13324, the example method 13300 causes a buffer solution to continue to be injected into a sample channel of a waveguide.
In some embodiments, if the refractive index change value does not match the predetermined refractive index change value, the example method 13300 determines that one or more preservative chemicals have not been completely washed out or cleared from the surface of the sample channel and/or that the buffer solution has not traveled completely through the sample channel. Thus, the example method 13300 enables the buffer solution to continue to be injected into the sample channel of the waveguide such that one or more preservative chemicals may continue to be washed off or cleared from the surface of the sample channel and/or the buffer solution may continue to travel through the sample channel.
For example, the processor and/or controller may determine whether the refractive index change value calculated at step/operation 13318 matches a predetermined refractive index change value and if not, transmit instructions to the pump and cause the buffer solution to continue to be injected into the sample channel by the pump.
In some embodiments, after and/or in response to step/operation 13324, the example method 13300 may return to step/operation 13314. In these embodiments, as the buffer solution continues to wash out the one or more preservative chemicals from the surface of the sample channel, the example method 13300 may receive additional imaging data from the imaging sensor, calculate a refractive index change value associated with the sample channel based on the first imaging data and the additional imaging data, and determine whether the refractive index change value corresponds to a predetermined refractive index change value. In some embodiments, this process may be repeated until the refractive index change value corresponds to a predetermined refractive index change value. In other words, exemplary embodiments of the present disclosure may continue to inject buffer solution into the sample channel of the waveguide until the index change value indicates that one or more preservative chemicals have been completely washed off or cleared from the surface of the sample channel and/or the buffer solution has traveled completely through the sample channel.
Referring back to fig. 133C, after and/or in response to step/operation 13322 and/or step/operation 13324, exemplary method 13300 proceeds to step/operation 13326 and ends.
As shown in the above-described exemplary methods, various embodiments of the present disclosure overcome various technical challenges and difficulties and provide various technical improvements, including but not limited to accurately determining whether a substance/liquid has traveled completely through a liquid delivery system (such as but not limited to a sample channel of a waveguide). For example, various embodiments of the present disclosure may arrange a light source (such as, but not limited to, a laser source that emits a laser beam) or other refractive index capture technique such that one or more light beams (in the case of a laser source) pass through a fluid-carrying channel (such as, but not limited to, a sample channel of a waveguide) and impinge on a suitable sensor (such as, but not limited to, an optical imaging sensor). The one or more light beams will activate one or more known areas of the sensor as the one or more light beams travel in air. After the substance/liquid is injected into the fluid-carrying channel, one or more light beams pass through the substance/liquid in the fluid-carrying channel and activate different areas of the sensor. In some embodiments, such changes in the activation sensing region of the sensor may be measured, and changes in the refractive index may be calculated. In some embodiments, the substance/liquid in the fluid bearing channel may be identifiable based on the refractive index value and/or the change in refractive index. If unidentifiable, various embodiments of the present disclosure may identify a change in a substance. In some examples, if two or more substances are expected to occur in the observation region at different times, various embodiments of the present disclosure can reliably identify that the transition has been completed (e.g., that the substance/fluid has traveled completely through the liquid/substance delivery system).
While the above description provides an exemplary structure associated with a waveguide, it is noted that the scope of the present disclosure is not limited to waveguides alone. The various embodiments associated with fig. 133A-134B may provide a wide range of applications in fluid condition monitoring, and may provide accurate results in applications ranging from nanometers to centimeters and in various fluids. For example, the various embodiments associated with fig. 133A-134B may be implemented in the medical field to differentiate between blood, saline, and glycerol. As another example, various embodiments associated with fig. 133A-134B may be implemented in an automobile to indicate fluid conditions (cooling, lubrication, etc.). As another example, various implementations associated with fig. 133A-134B may be implemented in a pipeline application to indicate the beginning and end of a petroleum product run.
As described above, sample testing devices according to various embodiments of the present disclosure may include a multi-channel waveguide defining a plurality of sample channels. In some embodiments, the laser beam may be provided to an input end of the sample channel and may exit from an output end of the sample channel. In some embodiments, an imaging component (e.g., an image sensor) may capture the laser beam exiting from the output and generate a test signal. In some embodiments, the test signal may be generated or indicative of an interference fringe pattern from the sample channel as the laser beam travels through the sample channel.
In some embodiments, when a sample solution is provided to a plurality of sample channels, the interference fringe pattern may change, which may be indicated or reflected by a change in the test signal. For example, the sample solution may contain an aerosol from the patient's expired breath. The sample solution may be injected into a plurality of sample channels of a sample testing device. In some embodiments, the surface of each sample channel may be coated with antibodies to one or more specific virus types. If the sample solution (e.g., aerosol) contains a particular virus type and the surface of the sample channel is coated with antibodies to that particular virus type, the antibodies bind to the virus, holding the virus at the surface. An increase in the number of virions at the surface (due to chemical and/or biological reactions between the antibodies and the virions) can cause a change in the evanescent wave of the waveguide, which in turn can cause a change in the interference fringe pattern from the sample channel and a change in the test signal generated by the imaging component. Thus, based on the variation of the test signal, the virus type can be determined. For example, if a particular test signal from a particular sample channel indicates a change in the interference fringe pattern, the sample solution may contain a virus corresponding to an antibody coated on the surface of the sample channel. For example, if the surface of the sample channel is coated with antibodies to SARS-CoV-2 virus and the test signal from the sample channel is indicative of a change in the interference fringe pattern, the sample solution contains SARS-CoV-2 virus.
However, there are a number of technical challenges and difficulties in implementing a multi-channel waveguide for sample testing. For example, different sample channels in a multi-channel waveguide may have thermal and/or structural differences. These differences may affect the wavelength of the laser beam in the different sample channels, resulting in variations in the test signal from the different channels.
For example, different sample channels may have differences or deviations in their ambient temperatures. As the laser beam travels through these sample channels, different ambient temperatures may affect the wavelength of the laser beam differently and may cause variations in the interference fringe pattern and test signal. As another example, different sample channels may have differences or deviations in their optical structures. As the laser beam travels through these sample channels, different optical structures may affect the wavelength of the laser beam differently and may cause variations in the interference fringe pattern and test signal. The sample testing device may erroneously determine that such a change in the test signal (caused by thermal and/or structural differences) is an indication that the sample solution contains a virus corresponding to the antibody coated on the surface of the sample channel.
Thus, thermal and/or structural differences in the sample channels in the multi-channel waveguide may result in different responses (e.g., test signals) from different sample channels, while it is important in quantitative sensing to have all channels in the multi-channel waveguide produce the same baseline response (e.g., prior to injection of sample solution into the sample channels) in order to perform a comparison process (e.g., to detect whether the sample solution includes one or more substances that would result in a difference in the test signals, and/or to detect a difference between the sample solution from different channels and a reference solution).
Various embodiments of the present disclosure overcome these technical challenges and difficulties and provide various technical advances and improvements. For example, since the interferometric waveguide sensor output signal depends on the wavelength of the input laser beam, various embodiments of the present disclosure can change the wavelength of the input laser beam to change the test signal and compensate for wavelength changes due to structural and thermal differences between different sample channels.
In some embodiments, to change the wavelength of the input laser beam, various embodiments of the present disclosure may (1) change the operating temperature of a laser diode that emits the laser beam into a sample channel of the multichannel waveguide, (2) change the drive current of the laser diode that causes the laser diode to emit the laser beam into a channel of the multichannel waveguide, or (3) add a wavelength adjustment device that provides a deformable grating to an optical fiber through which the laser beam travels to the input end of the multichannel waveguide.
In some implementations, a laser diode may be implemented to emit a laser beam into a sample channel of a waveguide. In some embodiments, the operating temperature of the laser diode may have an effect on the wavelength of the laser beam. For example, an increase in the operating temperature of the laser diode may result in an increase in the wavelength of the laser light emitted by the laser diode, while a decrease in the operating temperature of the laser diode may result in a decrease in the wavelength of the laser light emitted by the laser diode. Accordingly, an exemplary method may include adjusting an operating temperature of a laser diode based on a wavelength of a laser beam emitted by the laser diode. For example, in response to determining that the wavelength of the laser beam is below the desired wavelength, the example method may increase the operating temperature of the laser diode (e.g., by increasing the current of the laser diode). In response to determining that the wavelength of the laser beam is higher than the desired wavelength, the example method may reduce the operating temperature of the laser diode (e.g., by reducing the current of the laser diode).
In some embodiments, the laser diode may include a laser diode driver that provides a current to the laser diode that causes the laser diode to emit a laser beam. For example, a laser diode driver may provide a constant current source that delivers a driving current to a laser diode and causes the laser diode to emit a laser beam. As the drive current increases, the intensity of the laser beam generated by the laser diode increases, which in turn increases the wavelength of the laser beam. As the drive current decreases, the intensity of the laser beam generated by the laser diode decreases, which in turn decreases the wavelength of the laser beam. Accordingly, an exemplary method may include adjusting a drive current of a laser diode based on a wavelength of a laser beam emitted by the laser diode. For example, in response to determining that the wavelength of the laser beam is below a desired wavelength, the example method may increase the drive current of the laser diode. In response to determining that the wavelength of the laser beam is higher than the desired wavelength, the example method may reduce a drive current of the laser diode.
However, there are technical challenges in adjusting the wavelength of the laser light by adjusting the operating temperature and/or the drive current of the laser diode. For example, the driver current is related to the operating temperature of the laser diode. The higher the drive current, the higher the operating temperature of the laser diode. Because both the operating temperature and the drive current of the laser diode can affect the wavelength of the laser beam, it may be difficult to determine the proper operating temperature and drive current to achieve the proper wavelength of the laser beam.
According to various embodiments of the present disclosure, wavelength tuning devices may be provided that may overcome these technical challenges and difficulties. The wavelength tuning device may comprise a piezoelectric material that may exert/impose an adjustable pressure on the optical fiber of the waveguide based on a voltage applied to the piezoelectric material. As described above, the laser beam may travel through an optical fiber to the input end of the waveguide. When the voltage changes, the piezoelectric material may expand or contract, and thus may increase or decrease the pressure exerted or imposed on the optical fiber. As the pressure increases, the length of the optical fiber expands, which in turn increases the wavelength of the laser beam traveling through the optical fiber. As the pressure is reduced, the length of the optical fiber is reduced, which in turn reduces the wavelength of the laser beam traveling through the optical fiber. Accordingly, various embodiments of the present disclosure may provide a variable wavelength waveguide that may enable quantitative sensing using multichannel samples and references.
Referring now to fig. 135A and 135B, a sample testing device 13500 is shown according to some embodiments of the present disclosure. Sample testing device 13500 includes an exemplary wavelength adjustment device 13501. In particular, fig. 135A shows an exemplary side view of an exemplary sample testing device 13500 having an exemplary wavelength adjustment device 13501 in accordance with various embodiments of the present disclosure. Fig. 135B illustrates an exemplary cross-sectional view of an exemplary wavelength adjustment device 13501 in accordance with various embodiments of the present disclosure.
Referring now to fig. 135A, a sample testing device 13500 includes a laser source 13503, a wavelength adjustment device 13501, a light source coupler 13509, a waveguide 13515, and an imaging component 13517.
In some embodiments, light source coupler 13509 includes an array of optical fibers 13507 and an optical fiber holder 13511. In some embodiments, the fiber array 13507 is secured within a fiber holder 13511.
In some embodiments, the end of each optical fiber is connected to a laser source 13503 (such as a laser diode) and each optical fiber conveys a laser beam from the laser source 13503 toward the input end of the sample channel of the waveguide 13515. In some embodiments, the sample channel of waveguide 13515 is aligned with light source coupler 13509. For example, each of the optical fibers in the fiber array 13507 of the light source coupler 13509 is directly aligned with the input edge of one of the sample channels of the waveguide 13515 by direct edge coupling. Thus, the laser beam may travel onto the sample channel of the waveguide 13515 when directed by the optical fibers in the optical fiber array 13507.
In some embodiments, light source coupler 13509 includes microlens array 13513 disposed on a first edge surface of fiber holder 13511. In some embodiments, each optical fiber in fiber array 13507 is aligned with one microlens of microlens array 13513, and each microlens of microlens array 13513 is aligned with one of the sample channels of waveguide 13515. Thus, the laser beam emitted by the laser source 13503 may travel through the optical fibers in the optical fiber array 13507 and the microlenses of the microlens array 13513 and reach the input end of the sample channel of the waveguide 13515.
As described above, the sample testing device 13500 includes a wavelength adjustment device 13501. In the example shown in fig. 135A, a wavelength-adjusting device 13501 is positioned between the laser source 13503 and the light source coupler 13509. Specifically, an array of optical fibers 13507 of a light source coupler 13509 (which is connected to a laser source 13503) passes through a wavelength adjustment device 13501.
In some embodiments, the laser source 13503 may be in the form of a semiconductor laser that provides a small range of variable wavelength laser beams and without any complex tunable structures. For example, laser source 13503 may comprise a single-mode narrow bandwidth diode laser. The wavelength of the diode laser output (e.g., laser beam) varies over a small range, such as +/-0.1nm. The change in wavelength of the diode laser output may change the output (e.g., the test signal) from the waveguide in more than two cycles of phase change.
As described above, the laser source 13503 may be connected to one or more optical fibers in the optical fiber array 13507, and the one or more optical fibers in the optical fiber array 13507 may transmit a laser beam from the laser source 13503 to one or more input ends of one or more sample channels in the waveguide 13515. In some embodiments, the wavelength adjustment device 13501 may adjust the wavelength of the laser beam in each sample channel as desired. For example, the exemplary wavelength-conditioning device 13501 includes one or more compressors, and each of the one or more compressors applies pressure on one of the optical fibers from the optical fiber array 13507 such that the channel-by-channel output can be modified and the output phase from the waveguides can be synchronized, the details of which are described herein.
Specifically, referring now to fig. 135B, an exemplary cross-sectional view of a wavelength adjustment device 13501 is shown. In the example shown in fig. 135B, the wavelength-adjusting device 13501 includes a housing 13521, a fiber support base 13527 fixed within the housing 13521, and a compressor 13523 positioned within the housing 13521 and above the fiber support base 13527.
In some embodiments, the housing 13521 provides a shell or housing within which one or more compressors (such as compressor 13523) and the fiber support base 13527 can be positioned. In some embodiments, the housing 13521 may provide openings on a first side of the housing 13521 and a second side of the housing 13521 opposite the first side. In some embodiments, the optical fibers of the array of optical fibers 13507 can enter the housing 13521 through an opening on a first side of the housing 13521, pass through the housing 13521, and exit the housing 13521 through an opening on a second side of the housing 13521.
As described above, the wavelength-conditioning device 13501 may include one or more compressors. In some embodiments, each optical fiber from the optical fiber array 13507 is positioned between the optical fiber support base 13527 and one of the compressors such that the wavelength adjustment device 13501 can exert different pressures on different optical fibers from the optical fiber array 13507 by the compressor. In the example shown in fig. 135B, the optical fiber 13507A is positioned between the compressor 13523 and the optical fiber support base 13527.
In some embodiments, the compressor 13523 may comprise a piezoelectric material. In the present disclosure, the term "piezoelectric material" or "piezoelectric body" refers to a material that expands or contracts when a voltage is applied across the piezoelectric material or body. Examples of piezoelectric materials may include, but are not limited to, piezoelectric crystals, ceramics, quartz, and the like.
For example, the compressor 13523 may include a piezoelectric crystal. In some embodiments, the wavelength-regulating device 13501 may include a variable power source 13525 that applies a voltage across the compressor 13523. For example, the variable power supply 13525 may include a first electrode 13529A connected to a first side of the piezoelectric crystal of the compressor 13523 and a second electrode 13529B connected to a second side of the piezoelectric crystal of the compressor 13523. The first side is in a polarization direction relative to the second side. Thus, the variable power supply 13525 may provide electrical conduction across the electrode 13529A and the electrode 13529B in the direction of polarization of the compressor 13523.
In this example, the compressor 13523 may exhibit an inverse piezoelectric effect when the variable power source 13525 applies a voltage between the electrode 13529A and the electrode 13529B. Specifically, the voltage applied in the polarization direction of the piezoelectric crystal may deform or expand the compressor 13523. In some embodiments, the amount of deformation or expansion of the compressor 13523 is related to the amount of voltage applied to the piezoelectric crystal. For example, the higher the voltage applied in the polarization direction of the piezoelectric crystal, the more the piezoelectric crystal expands.
As described above, the optical fiber 13507A is positioned between the compressor 13523 and the optical fiber support base 13527. When a voltage is applied to the piezoelectric crystal of the compressor 13523, the piezoelectric crystal expands in response to the voltage and exerts a pressure on the optical fiber 13507A. In some embodiments, the fiber support base 13527 is secured to the bottom surface of the housing 13521. In some embodiments, the amount of pressure exerted by the compressor 13523 on the optical fiber 13507A is related to the amount of deformation or expansion of the piezoelectric crystal of the compressor 13523.
When the piezoelectric crystal of the compressor 13523 exerts pressure on the optical fiber 13507A, it causes the optical fiber 13507A to elongate or stretch. In some embodiments, the amount by which the optical fiber 13507A stretches or stretches is related to the amount of pressure applied by the compressor 13523 to the optical fiber 13507A, which in turn is related to the amount of deformation or expansion of the compressor 13523, which in turn is related to the amount of voltage applied to the piezoelectric crystal. Accordingly, the higher the voltage applied to the piezoelectric crystal, the more the optical fiber 13507A stretches. The lower the voltage applied to the piezoelectric crystal, the less elongation of the optical fiber 13507A.
In some embodiments, elongation of optical fiber 13507A causes a change in the thickness of optical fiber 13507A. As the laser beam travels through the optical fiber 13507A, a change in the thickness of the optical fiber 13507A may cause a change in the wavelength of the laser beam reflected within the optical fiber 13507A. For example, the more the optical fiber 13507A is elongated or stretched, the finer the optical fiber 13507A becomes, and the higher the wavelength of the laser beam reflected in the optical fiber 13507A. As described above, the elongation of the optical fiber 13507A is correlated with the amount of voltage applied to the compressor 13523. Thus, the wavelength of the laser beam in the optical fiber 13507A can be adjusted by changing the voltage applied to the compressor 13523.
As shown in the example shown in fig. 135B, the wavelength-adjusting device 13501 may produce a tunable grating on the optical fiber 13507A that can adjust the wavelength of the laser beam traveling through the optical fiber 13507A. In some embodiments, wavelength-regulating device 13501 may include a compressor for each individual optical fiber, and different voltages may be applied across the different compressors. When each of the plurality of optical fibers supplies a laser beam to one of the input ends of one of the sample channels of the waveguide, the wavelength adjustment device 13501 can adjust the wavelength of the laser beam to the sample channel of the waveguide by adjusting the voltage applied to the compressor so that all the laser beams can have the same wavelength or be within a narrow wavelength band. Accordingly, various embodiments of the present disclosure overcome technical challenges and difficulties due to thermal and/or structural differences between sample channels of waveguides, and may provide technical benefits and improvements.
Referring now to fig. 136, an exemplary block diagram 13600 is shown in accordance with some embodiments of the present disclosure. In particular, the example block diagram 13600 illustrates example components associated with the wavelength-adjusting device 13602 and the imaging component 13620, as well as example data communications between the example wavelength-adjusting device 13602 and the example imaging component 13620.
In the example shown in fig. 136, the wavelength tuning device 13602 may include a variable power supply 13608, input/output circuitry 13616, a data storage medium 13610, processing circuitry 13604, and communication circuitry 13612. While these components 13608, 13616, 13610, 13604, and 13612 are described with respect to functional limitations, it should be understood that a particular implementation necessarily involves the use of particular hardware.
In some embodiments, the variable power source 13608 may provide an adjustable voltage on the compressor of the wavelength tuning device 13602. In some embodiments, variable power supply 13608 may be in the form of a Direct Current (DC) voltage regulator (such as, but not limited to, LM 317T) coupled to a DC voltage source. In such an example, the DC voltage regulator may apply an adjustable amount of DC voltage from the DC voltage source to the compressor. Additionally or alternatively, the variable power supply 13608 may take other forms. In some implementations, the variable power supply 13608 may provide a maximum voltage that may be applied to the compressor of the wavelength-adjusting device and a minimum voltage (e.g., zero) that may be applied to the compressor of the wavelength-adjusting device.
In some embodiments, the variable power supply 13608 may be in electronic communication with the processing circuitry 13604. In some embodiments, the processing circuit 13604 may provide a voltage control signal to the variable power supply 13608 that indicates the amount of voltage to be applied to the compressor.
In some implementations, the processing circuitry 13604 (and/or coprocessors or any other processing circuitry that assists or is otherwise associated with the processor) may communicate with the memory via a bus. The memory is non-transitory and may include, for example, one or more volatile and/or non-volatile memories. In other words, the memory may be an electronic storage device (e.g., a computer-readable storage medium). The memory may be configured to store information, data, content, applications, instructions, and the like for enabling the apparatus to carry out various functions in accordance with exemplary embodiments of the present disclosure.
In some embodiments, the wavelength adjustment device 13602 may include input/output circuitry 13616, which may in turn communicate with the processing circuitry 13604 to provide output to a user, and in some embodiments, receive an indication of user input. Input/output circuitry 13616 may include user interface circuitry and may include a display, which may include a web page user interface, mobile application, client device, kiosk, and the like. In some embodiments, input/output circuitry 13616 may also include a keyboard, mouse, joystick, touch screen, touch area, soft keys, microphone, speaker, or other input/output mechanisms. The processor and/or user interface circuitry comprising the processor may be configured to control one or more functions of one or more user interface elements via computer program instructions (e.g., software and/or firmware) stored on a memory accessible to the processor.
In some implementations, the processing circuit 13604 may be in electronic communication with a data storage medium 13610. In some embodiments, the data storage medium 13610 may be embodied as one or more data storage devices, one or more separate database servers, or a combination of data storage devices and separate database servers. Further, in some embodiments, the data storage medium 13610 may be embodied as a distributed repository such that some of the stored information/data is centrally stored in a location within the system and other information/data is stored in one or more remote locations. Alternatively, in some embodiments, the distributed repository may be distributed only across a plurality of remote storage locations. More specifically, the data storage medium 13610 may contain one or more data storage areas configured to store information/data usable in certain embodiments.
In some embodiments, the communication circuit 13612 may include any means, such as a device or circuit embodied in hardware or a combination of hardware and software, that is configured to receive and/or transmit data from/to a network and/or any other device, circuit or module in communication with the wavelength-regulating device 13602. In this regard, the communication circuit 13612 may include, for example, a network interface for enabling communication with a wired or wireless communication network. For example, the communication circuitry 13612 may include one or more network interface cards, antennas, buses, switches, routers, modems and supporting hardware and/or software, or any other device suitable for enabling communications via a network. Additionally or alternatively, the communication circuit 13612 may include circuitry for interacting with an antenna to cause transmission of signals via the antenna or to process reception of signals received via the antenna.
As described above, the communication circuit 13612 of the wavelength tuning device 13602 may be in electronic communication with the imaging component 13620. In particular, imaging component 13620 may include image sensing circuitry 13618 and communication circuitry 13622. Although these components 13618 and 13616 are described with respect to functional limitations, it should be understood that a particular implementation necessarily involves the use of particular hardware.
In some implementations, the image sensing circuit 13618 may include circuitry that may detect an interference fringe pattern from an output of the sample channel of the waveguide and may generate a test signal based on the detected interference fringe pattern. For example, the image sensing circuit 13618 may include an image sensor (CIS), a Charge Coupled Device (CCD), or a Complementary Metal Oxide Semiconductor (CMOS) sensor, or the like.
In some embodiments, the image sensing circuit 13618 may be in electronic communication with the communication circuit 13622. In some embodiments, the image sensing circuit 13618 may generate a test signal and provide the test signal to the communication circuit 13622. In some embodiments, the communication circuitry 13622 of the imaging component 13620 is similar to the communication circuitry 13612 of the wavelength tuning device 13602 described above.
In some embodiments, the exemplary wavelength-adjusting device may provide different modes, such as, but not limited to, a continuous wavelength scanning mode and a direct wavelength setting mode. Referring now to fig. 137A-138, exemplary methods according to various embodiments of the present disclosure are shown. Specifically, fig. 137A and 137B illustrate an exemplary method 13700 in which the exemplary wavelength-adjusting device operates in a continuous wavelength scanning mode. Fig. 138 illustrates an exemplary method 13800 in which the exemplary wavelength-adjusting device operates in a direct wavelength-setting mode.
It is noted that each block of the flowchart, and combinations of blocks in the flowchart, can be implemented by various means, such as hardware, firmware, circuitry and/or other devices associated with execution of software including one or more computer program instructions. For example, one or more of the programs described in fig. 137A-138 may be embodied by computer program instructions that may be stored by a non-transitory memory of an apparatus employing embodiments of the present disclosure and executed by a processor of the apparatus. These computer program instructions may direct a computer or other programmable apparatus to function in a particular manner, such that the instructions stored in the computer-readable memory produce an article of manufacture the execution of which implement the function specified in the flowchart block or blocks. Thus, embodiments may comprise various means including entirely hardware, or any combination of software and hardware. Furthermore, embodiments may take the form of a computer program product on at least one non-transitory computer-readable storage medium having computer-readable program instructions (e.g., computer software) embodied in the storage medium. Similarly, embodiments may take the form of computer program code stored on at least one non-transitory computer-readable storage medium. Any suitable computer readable storage medium may be utilized including non-transitory hard disks, CD-ROMs, flash memory, optical storage devices, or magnetic storage devices.
Referring now to fig. 137A and 137B, an exemplary method 13700 is shown. As described above, the example method 13700 illustrates an example of the example wavelength adjustment device operating in a continuous wavelength scanning mode. In the continuous wavelength scanning mode, the voltage applied to the compressor is continuously adjusted so that the laser beams are continuously scanned over a range of wavelength variations as they enter the input end of the sample channel through the optical fiber. In some embodiments, the output laser beam from the output end of the sample channel in the waveguide may be continuously detected by the imaging component and the test signal recorded. In some embodiments, based on the recorded test signals, the example method 13700 may generate a voltage-dependent data object for the sample channel indicating a data correlation between a voltage applied to the compressor and a wavelength of the laser beam, details of which are described herein.
Referring now to fig. 137A, an exemplary method 13700 begins at step/operation 13702. In some embodiments, after step/operation 13702, exemplary method 13700 proceeds to step/operation 13704. At step/operation 13704, processing circuitry (such as, but not limited to, processing circuitry 13604 of wavelength-adjusting device 13602 described above in connection with fig. 136) may receive user input triggering a continuous wavelength scanning mode.
For example, a user may provide user input through the input/output circuitry 13616 of the wavelength-regulating device 13602 described above in connection with fig. 136. In some embodiments, the user input may indicate a request from a user to trigger the wavelength-regulating device to operate in the continuous wavelength scanning mode.
Referring back to fig. 137A, after and/or in response to step/operation 13704, exemplary method 13700 proceeds to step/operation 13706. At step/operation 13706, processing circuitry (such as, but not limited to, processing circuitry 13604 of wavelength tuning device 13602 described above in connection with fig. 136) may cause an increase in voltage applied to the compressor.
For example, the processing circuit 13604 may transmit a control signal to the variable power source 13608 after receiving a user input triggering the wavelength-adjustment device to operate in the continuous wavelength scanning mode and/or in response to receiving a user input triggering the wavelength-adjustment device to operate in the continuous wavelength scanning mode. In some embodiments, the control signal may trigger the variable power supply 13608 to increase the voltage applied to one of the compressors of the wavelength-regulating device (e.g., increase the voltage applied to the piezoelectric material). In some embodiments, the control signal may specify a voltage to be applied to a compressor of the wavelength adjustment device.
In some embodiments, after receiving the control signal from the processing circuit 13604, the variable power source 13608 may increase the voltage applied to the compressor of the wavelength-adjusting device. As described above, each compressor may exert pressure on one of the optical fibers that deliver the laser beam to the sample channel of the waveguide. In some embodiments, an increase in voltage causes the piezoelectric material in the compressor to expand, which in turn causes an increase in the pressure exerted on the optical fiber. Thus, the optical fiber becomes more elongated, which causes the optical fiber to deliver a laser beam having a higher wavelength to one of the sample channels of the waveguide.
Referring back to fig. 137A, after and/or in response to step/operation 13706, exemplary method 13700 proceeds to step/operation 13708. At step/operation 13708, processing circuitry (e.g., without limitation, processing circuitry 13604 of wavelength-adjusting device 13602 described above in connection with fig. 136) may extract an interference fringe pattern from the test signal received from the imaging component.
As described above in connection with fig. 136, the imaging component 13620 may include an image sensing circuit 13618 that detects an interference fringe pattern from an output of the sample channel and generates a test signal based on the detected interference fringe pattern. As described above in connection with step/operation 13706 of fig. 137A, the compressor of the wavelength-regulating device may increase the pressure exerted on the optical fiber delivering the laser beam to the sample channel of the waveguide. In some embodiments, the imaging component can detect interference fringe patterns from a sample channel associated with an optical fiber to which increased pressure is applied.
In some embodiments, the imaging component may generate a test signal indicative of the detected interference fringe pattern, and may transmit the test signal to the wavelength-adjusting device. For example, the communication circuit 13622 of the imaging component 13620 may transmit the test signal to the communication circuit 13612 of the wavelength tuning device 13602.
In some embodiments, the processing circuitry 13604 of the wavelength tuning device 13602 may extract the interference fringe pattern from the test signal. As described above, the wavelength of the laser beam may affect the interference fringe pattern. Thus, the interference fringe pattern extracted from the test signal is an indication of the wavelength of the laser beam.
In some embodiments, the processing circuit 13604 may also calculate the wavelength of the laser beam exiting from the output end of the sample channel. For example, the processing circuit 13604 may calculate wavelengths based on the extracted interference fringe pattern, similar to those described above in connection with at least fig. 1.
Although the above description provides an example of calculating the wavelength of the laser beam output from the sample channel, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary method according to embodiments of the present disclosure may calculate an exemplary wavelength of the laser beam output by one or more additional and/or alternative methods.
Referring back to fig. 137A, after and/or in response to step/operation 13708, exemplary method 13700 proceeds to step/operation 13710. At step/operation 13710, processing circuitry (such as, but not limited to, processing circuitry 13604 of wavelength tuning device 13602 described above in connection with fig. 136) may update the voltage dependency data object to indicate a data dependency between the voltage and the interference fringe pattern.
As described above, the data storage medium 13610 of the wavelength tuning device 13602 may store data and/or information. For example, the data storage medium 13610 may store a plurality of voltage dependency data objects. Each of the plurality of voltage-dependent data objects may correspond to or be associated with one of the sample channels of the waveguide. In particular, the voltage dependence data object may be indicative of a plurality of data dependencies between a voltage applied to a compressor of a wavelength-regulating device associated with a sample channel of the waveguide and an interference fringe pattern from an output of the sample channel of the waveguide.
As described above, when the voltage applied to the compressor of the wavelength adjustment device increases, the pressure applied to the optical fiber increases, which in turn causes the optical fiber to elongate and the wavelength of the laser beam passing through the optical fiber to increase. Because the interference fringe pattern is an indication of the wavelength of the laser beam, the processing circuitry may determine a data correlation between the voltage applied to the compressor at step/operation 13706 and the interference fringe pattern extracted at step/operation 13708.
In some embodiments, the processing circuitry may update the voltage dependency data object stored in the data storage medium 13610 by: adding voltage value data according to a voltage applied to the compressor at step/operation 13706; adding interference fringe pattern data according to the extracted interference fringe pattern at step/operation 13708; and adding a data correlation indicating a correlation between the voltage value data and the interference fringe pattern data.
As described above, the processing circuitry may calculate the wavelength of the laser beam exiting from the sample channel. In some embodiments, the processing circuitry may update the voltage dependency data object stored in the data storage medium 13610 by: adding voltage value data according to a voltage applied to the compressor at step/operation 13706; adding wavelength value data calculated based on the extracted interference fringe pattern at step/operation 13708; and adding a data correlation indicating an association between the voltage value data and the wavelength data.
Referring now to fig. 139, an exemplary graph 13900 is provided showing voltage value data, wavelength value data, and data correlation between voltage value data and wavelength value data for an exemplary voltage correlation data object. In particular, exemplary plot 13900 shows a data correlation between voltage value data (x-axis) and wavelength value data (y-axis). As shown in the exemplary plot 13900, the higher the voltage, the higher the wavelength.
Referring back to fig. 137A, after and/or in response to step/operation 13710, exemplary method 13700 proceeds to step/operation 13712. At step/operation 13712, a processing circuit (such as, but not limited to, the processing circuit 13604 of the wavelength-regulating device 13602 described above in connection with fig. 136) may determine whether the voltage applied to the compressor of the wavelength-regulating device reaches a maximum voltage.
As described above, the variable power source 13608 of the wavelength tuning device 13602 may provide a range of voltages to the compressor of the wavelength tuning device. In some implementations, the processing circuit 13604 of the wavelength-regulating device may determine whether the voltage applied to the compressor at step/operation 13706 reaches a maximum voltage.
If, at step/operation 13712, the processing circuitry determines that the applied voltage does not reach the maximum voltage, then the example method 13700 returns to step/operation 13706. At step/operation 13706, the processing circuitry causes an increase in voltage applied to the compressor of the wavelength adjustment device, similar to those described above.
If, at step/operation 13712, the processing circuit determines that the applied voltage reaches the maximum voltage, then the example method 13700 proceeds to block a, which connects fig. 137A to fig. 137B.
Referring now to fig. 137B, in some embodiments, after block a and/or in response to block a (e.g., after and/or in response to determining that the applied voltage reaches the maximum voltage), the example method 13700 proceeds to step/operation 13714. At step/operation 13714, processing circuitry (such as, but not limited to, processing circuitry 13604 of wavelength tuning device 13602 described above in connection with fig. 136) may cause a voltage applied to the compressor to decrease.
For example, the processing circuit 13604 may transmit control signals to the variable power supply 13608. In some implementations, the control signal can trigger the variable power source 13608 to decrease the voltage applied to the compressor of the wavelength adjustment device (e.g., increase the voltage applied to the piezoelectric material) described above in connection with step/operation 13706. In some embodiments, the control signal may specify a voltage to be applied to a compressor of the wavelength adjustment device.
In some embodiments, after receiving the control signal from the processing circuit 13604, the variable power source 13608 may reduce the voltage applied to the compressor of the wavelength-regulating device. As described above, each compressor may exert pressure on one of the optical fibers that deliver the laser beam to the sample channel of the waveguide. In some embodiments, the decrease in voltage causes the piezoelectric material in the compressor to contract, which in turn causes a decrease in the pressure exerted on the optical fiber. Thus, the optical fiber becomes less elongated, which causes the optical fiber to deliver a laser beam having a lower wavelength to one of the sample channels of the waveguide.
Referring back to fig. 137B, after and/or in response to step/operation 13714, exemplary method 13700 proceeds to step/operation 13716. At step/operation 13716, processing circuitry (such as, but not limited to, processing circuitry 13604 of wavelength tuning device 13602 described above in connection with fig. 136) may extract an interference fringe pattern from the received test signal.
As described above in connection with fig. 136, the imaging component 13620 may include an image sensing circuit 13618 that detects an interference fringe pattern from an output of the sample channel and generates a test signal based on the detected interference fringe pattern. As described above in connection with step/operation 13714 of fig. 137B, the compressor of the wavelength-adjusting device may reduce the pressure exerted on the optical fiber delivering the laser beam to the sample channel of the waveguide. At step/operation 13716, the imaging component may detect an interference fringe pattern from a sample channel associated with the optical fiber with the reduced pressure applied.
In some embodiments, the imaging component may generate a test signal indicative of the detected interference fringe pattern, and may transmit the test signal to the wavelength-adjusting device. For example, the communication circuit 13622 of the imaging component 13620 may transmit the test signal to the communication circuit 13612 of the wavelength tuning device 13602.
In some embodiments, the processing circuitry 13604 of the wavelength tuning device 13602 may extract the interference fringe pattern from the test signal. As described above, the wavelength of the laser beam may affect the interference fringe pattern. Thus, the interference fringe pattern extracted from the test signal is an indication of the wavelength of the laser beam.
In some embodiments, the processing circuit 13604 may also calculate the wavelength of the laser beam exiting from the output end of the sample channel. For example, the processing circuit 13604 may calculate wavelengths based on the extracted interference fringes, similar to those described above in connection with step/operation 13708.
Referring back to fig. 137B, after and/or in response to step/operation 13716, exemplary method 13700 proceeds to step/operation 13718. At step/operation 13718, processing circuitry (such as, but not limited to, processing circuitry 13604 of wavelength-adjusting device 13602 described above in connection with fig. 136) may update the voltage-dependent data object to indicate a data-dependency between the voltage and the interference fringe pattern.
As described above, the data storage medium 13610 of the wavelength tuning device 13602 may store data and/or information. For example, the data storage medium 13610 may store a voltage dependence data object that indicates a plurality of data dependencies between a voltage applied to a compressor of the wavelength-regulating device and an interference fringe pattern from an output end of a sample channel of the waveguide. As described above, when the voltage applied to the compressor of the wavelength adjustment device is reduced, the pressure applied to the optical fiber is reduced, which in turn causes the optical fiber to shorten and the wavelength of the laser beam passing through the optical fiber to be reduced. Because the interference fringe pattern is an indication of the wavelength of the laser beam, the processing circuitry may determine a data correlation between the voltage applied to the compressor at step/operation 13714 and the interference fringe pattern extracted at step/operation 13716.
In some embodiments, the processing circuitry may update the voltage dependency data object stored in the data storage medium 13610 by: adding voltage value data according to the voltage applied to the compressor at step/operation 13714; adding interference fringe pattern data according to the extracted interference fringe pattern at step/operation 13716; and adding a data correlation indicating a correlation between the voltage value data and the interference fringe pattern data.
As described above, the processing circuitry may calculate the wavelength of the laser beam exiting from the sample channel. In some embodiments, the processing circuitry may update the voltage dependency data object stored in the data storage medium 13610 by: adding voltage value data according to the voltage applied to the compressor at step/operation 13714; adding wavelength value data calculated based on the extracted interference fringe pattern at step/operation 13716; and adding a data correlation indicating an association between the voltage value data and the wavelength data.
Referring back to fig. 137B, after and/or in response to step/operation 13718, exemplary method 13700 proceeds to step/operation 13720. At step/operation 13720, processing circuitry (such as, but not limited to, processing circuitry 13604 of wavelength-regulating device 13602 described above in connection with fig. 136) may determine whether a voltage applied to a compressor of the wavelength-regulating device reaches a minimum voltage.
As described above, the variable power source 13608 of the wavelength tuning device 13602 may provide a range of voltages to the compressor of the wavelength tuning device. In some implementations, the processing circuit 13604 of the wavelength-regulating device may determine whether the voltage applied to the compressor at step/operation 13706 reaches a minimum voltage.
If at step/operation 13720, the processing circuitry determines that the applied voltage does not reach the minimum voltage, then the example method 13700 returns to step/operation 13714. At step/operation 13714, the processing circuitry causes a reduction in the voltage applied to the compressor of the wavelength adjustment device, similar to those described above.
If at step/operation 13720, the processing circuitry determines that the applied voltage reaches a minimum voltage, then the example method 13700 proceeds to step/operation 13722 and ends.
In some embodiments, the exemplary method 13700 illustrated in fig. 137A and 137B may be repeated to generate/update voltage-dependent data objects for all sample channels of the waveguide.
For example, if at step/operation 13720, the processing circuitry determines that the applied voltage reaches a minimum voltage, the example method 13700 may continue to determine voltage-dependent data objects for all sample channels for which waveguides have been generated/updated. If the processing circuitry determines that one of the sample channels is not associated with any of the voltage-dependent data objects stored in the data storage medium 13610, the example method 13700 may continue to generate/update the voltage-dependent data object for that sample channel, similar to those described above.
For example, if the voltage-dependent data object does not include a data dependence associated with a sample channel of the waveguide, the processing circuitry may cause an increase or decrease in a voltage applied to a compressor of a wavelength-regulating device in contact with an optical fiber delivering a laser beam to the sample channel (e.g., based on step/operation 13706 and step/operation 13714), which in turn causes the optical fiber to elongate or contract. In some embodiments, the processing circuitry may extract an interference fringe pattern from a corresponding sample channel and generate/update a voltage-dependent data object for that sample channel based on the voltage applied to the compressor and the interference fringe pattern (e.g., based on step/operation 13710 and step/operation 13718). Additionally or alternatively, the processing circuitry may calculate a wavelength of the laser beam based on the interference fringe pattern and generate/update a voltage-dependent data object for the sample channel based on the voltage applied to the compressor and the wavelength of the laser beam.
In some embodiments, the processing circuit may repeat the example method 13700 for different sample channels of the waveguide by adjusting the voltages applied to the different compressors of the wavelength-adjustment device and generating/updating voltage correlation data objects for all sample channels of the waveguide. Thus, when the wavelength-regulating device is operating in the continuous wavelength scanning mode, the wavelength-regulating device may generate/update voltage-dependent data objects of the sample channels, and each voltage-dependent data object indicates a data correlation between (1) a voltage applied to each compressor for delivering a laser beam to each optical fiber of a corresponding sample channel and (2) corresponding interference fringe pattern data from the sample channel or corresponding wavelength data of the laser beam exiting from the sample channel. In some embodiments, based on the voltage-dependent data object, the wavelength-regulating device may operate in a direct wavelength-setting mode that sets a wavelength for the laser beam in each sample channel, the details of which are described herein.
Referring now to fig. 138, an exemplary method 13800 is illustrated. As described above, the example method 13800 illustrates an example of an example wavelength-tuning device operating in a direct wavelength-setting mode. In the wavelength setting mode, each channel is characterized by finding a desired wavelength triggered by a voltage applied across the compressor of the wavelength adjusting device. Thus, the laser may then be set to have a matched wavelength or a matched interference fringe pattern output for each wavelength of each sample channel. In some embodiments, the example method 13800 may be performed prior to the sample solution being injected into any of the sample channels in order to ensure that the baseline output from the sample channels is the same. In some embodiments, the synchronized baseline output may be used directly for further analysis (e.g., after injection of the sample solution into the sample channel).
In the example shown in fig. 138, an exemplary method 13800 begins at step/operation 13802. In some embodiments, after step/operation 13802, the example method 13800 proceeds to step/operation 13804. At step/operation 13804, processing circuitry (e.g., without limitation, processing circuitry 13604 of wavelength-adjusting device 13602 described above in connection with fig. 136) may receive user input triggering a direct wavelength setting mode.
For example, a user may provide user input through the input/output circuitry 13616 of the wavelength-regulating device 13602 described above in connection with fig. 136. In some embodiments, the user input may indicate a request from a user to trigger the wavelength-regulating device to operate in the direct wavelength-setting mode.
Referring back to fig. 138, after and/or in response to step/operation 13804, exemplary method 13800 proceeds to step/operation 13806. At step/operation 13806, processing circuitry (e.g., without limitation, processing circuitry 13604 of wavelength-tuning device 13602 described above in connection with fig. 136) may retrieve voltage-dependence data objects associated with a sample channel of a waveguide.
As described above, the data storage medium 13610 of the wavelength tuning device 13602 may store a plurality of voltage dependent data objects. For example, the processing circuit 13604 of the wavelength tuning device 13602 may generate/update the plurality of voltage dependency data objects based at least in part on the exemplary method 13700 described above in connection with fig. 137A and 137B and may store the plurality of voltage dependency data objects in the data storage medium 13610 of the wavelength tuning device 13602.
Referring back to fig. 138, after and/or in response to step/operation 13806, exemplary method 13800 returns to step/operation 13808. At step/operation 13808, processing circuitry (e.g., without limitation, processing circuitry 13604 of wavelength-tuning device 13602 described above in connection with fig. 136) may determine overlapping interference fringe pattern data between voltage-dependent data objects.
As described above, each of the voltage-dependent data objects is associated with a sample channel of the waveguide and indicates interference fringe pattern data associated with the sample channel (e.g., triggered by a different voltage applied to a corresponding compressor). In some implementations, the processing circuit may traverse the interference fringe pattern data from different voltage-dependent data objects associated with different sample channels and select at least a portion of the interference fringe pattern data as the same overlapping interference fringe pattern data in the different voltage-dependent data objects associated with the different sample channels. For example, the processing circuitry may select an interference fringe pattern shared between the voltage-dependent data objects that may be correlated to different voltage data in different voltage-dependent data objects.
Although the above examples show examples of determining overlapping interference fringe pattern data, it is noted that the scope of the present disclosure is not limited to the above examples. As described above, each of the voltage-dependent data objects may be indicative of wavelength data associated with a sample channel (e.g., triggered by different voltages applied to the corresponding compressors). In some embodiments, the processing circuit may traverse wavelength data from different voltage-dependent data objects associated with different sample channels and select at least a portion of the wavelength data as the same overlapping wavelength data in the different voltage-dependent data objects associated with the different sample channels. For example, the processing circuitry may select wavelengths that are shared between the voltage-dependent data objects, which may be associated with different voltage data in different voltage-dependent data objects.
Referring back to fig. 138, after and/or in response to step/operation 13808, the example method 13800 returns to step/operation 13810. At step/operation 13810, processing circuitry (such as, but not limited to, processing circuitry 13604 of wavelength-adjusting device 13602 described above in connection with fig. 136) may determine voltages corresponding to overlapping interference fringe pattern data.
As described above, each of the voltage-dependent data objects includes a plurality of data dependencies between the voltage data of the sample channel and the interference fringe pattern data. In some embodiments, based on the data correlation, the processing circuitry may determine voltages or voltage data corresponding to overlapping interference fringe pattern data of the sample channel. For example, the processing circuitry may determine a voltage applied to a compressor of the wavelength-regulating device that triggers the interference fringe pattern from the sample channel to match an interference fringe pattern according to the overlapping interference fringe pattern data. The processing circuit may repeat this process for all sample channels of the waveguide and determine the voltage applied to each compressor such that the interference fringe pattern from all sample channels matches the interference fringe pattern according to the overlapping interference fringe pattern data.
Although the above examples illustrate examples of determining voltages corresponding to overlapping interference fringe pattern data, it is noted that the scope of the present disclosure is not limited to the above examples. As described above, exemplary methods according to various embodiments of the present disclosure may additionally or alternatively determine overlapping wavelength data. In some embodiments, based on the data correlation of the voltage correlation data object associated with the sample channel, the processing circuitry may determine a voltage or voltage data corresponding to overlapping wavelength data for the sample channel. For example, the processing circuitry may determine a voltage applied to a compressor of the wavelength adjustment device that triggers the wavelength of the laser beam from the sample channel to match the wavelength according to the overlapping wavelength data. The processing circuit may repeat this process for all sample channels of the waveguide and determine the voltage applied to each compressor such that the wavelengths from all sample channels match the wavelengths according to the overlapping wavelength data.
Referring back to fig. 138, after and/or in response to step/operation 13810, exemplary method 13800 returns to step/operation 13812. At step/operation 13812, processing circuitry (such as, but not limited to, processing circuitry 13604 of wavelength-regulating device 13602 described above in connection with fig. 136) may cause the voltage determined at step/operation 13810 to be applied to a compressor of the wavelength-regulating device.
As described above, the voltages determined at step/operation 13810 cause the interference fringe patterns from the different sample channels to be the same and/or cause the wavelengths of the laser beams from the different sample channels to be the same. Thus, in the direct wavelength setting mode, the exemplary wavelength tuning device enables a sample channel in a waveguide to provide quantitative sensing with highest sensitivity by removing common mode noise and drift caused by sensor thermal, structural, optical and electrical uncertainties, thereby minimizing errors in sensed data and maximizing sensor speed.
Referring back to fig. 138, after and/or in response to step/operation 13812, the example method 13800 proceeds to step/operation 13814 and ends.
Many virus detection assays use specific antibodies that target a particular virus to perform virus detection. Such virus detection assays suffer from a number of technical difficulties and challenges. For example, to detect multiple virus types or virus variants, multiple sample collections and multiple antigen checks are required, which can limit the speed of multiple virus detection in clinical applications.
Various embodiments of the present disclosure overcome these technical challenges and difficulties and may provide various technical advances and improvements. For example, various embodiments of the present disclosure provide a test method for multiple virus detection by utilizing biochemical fusions prepared with multiple samples and by utilizing multiple antigens coated on a sample channel. The test method can be performed with a virus sensor that requires only a reduced number of channels, and virus types/virus variants can be detected in a single test with a single sample collection.
Referring now to fig. 140, an exemplary method 14000 is shown according to various embodiments of the present disclosure. In particular, the exemplary method 14000 determines a sample type of a sample in a sample mixture according to various embodiments of the present disclosure.
In the example shown in fig. 140, an exemplary method 14000 begins at step/operation 14002. After and/or in response to step/operation 14002, the example method 14000 proceeds to step/operation 14004. At step/operation 14004, the exemplary method 14000 can include using the plurality of sample antibody sets to generate a plurality of antibody mixtures.
According to various embodiments of the present disclosure, a mixture of antibodies (also referred to as an antigen fusion) may be achieved by mixing several or many selected antibodies (also referred to as antigens) from multiple sample antibody sets. In some embodiments, each sample antibody set of the plurality of sample antibody sets may include antibodies to a particular type/variant of virus for which the exemplary method 14000 is implemented for detection. For example, if the exemplary method 14000 is implemented to detect virus type a, virus type B, and virus type C, the exemplary method 14000 may include generating a first set of sample antibodies including antibodies for detecting virus type a, a second set of sample antibodies including antibodies for detecting virus type B, and a third set of sample antibodies including antibodies for detecting virus type C.
In some embodiments, the exemplary method 14000 can determine the total number n of antibody mixtures to be produced at step/operation 14004. In some embodiments, the total number n of antibody mixtures is the same as the total number n of sample channels. For example, if the exemplary waveguide includes four sample channels, the exemplary method 14000 produces four antibody mixtures.
In some embodiments, the exemplary method 14000 can determine the total number m of sample antibody sets used to generate the antibody mixture. For example, when the total number of sample channels (or total number of antibody mixtures) is n, the total number of sample antibody sets, m, is determined based on m=2 n -1. For example, if there are two sample channels, three antibody sets are required to produce an antibody mixture. If there are three sample channels, seven antibody sets are required to produce an antibody mixture. If there are four sample channels, fifteen antibody sets are required to produce an antibody mixture.
In some embodiments, to generate a total of n antibody mixtures to be coated on a total of n sample channels from a total of m different antibody sets, the exemplary method 14000 can determine different combinations of antibody mixtures (in other words, different combinations of sample channels) and add antibodies from each of the antibody sets to one of the combinations of antibody mixtures. For example, antibodies from each of the m different antibody sets may be added to one of the n antibody mixtures, two of the n antibody mixtures … …, or n of the n antibody mixtures. In this embodiment, antibodies from each antibody collection are added to a different combination of antibody mixtures than combinations of antibody mixtures to which other antibodies from other antibody collections are added. In other words, antibodies from different antibody sets are added to different combinations of antibody mixtures, such that no two antibody sets are added to a combination of the same antibody mixture, similar to the various examples described herein in connection with fig. 122.
For example, if the sample testing device includes four sample channels (e.g., sample channel 1, sample channel 2, sample channel 3, and sample channel 4), a total of 15 antibody sets are required to produce an antibody mixture (e.g., antibody set A, B, C, D, E, F, G, H, I, J, K, L, M, N, O) to produce an antibody mixture for the four sample channels (e.g., antibody mixture 1, antibody mixture 2, antibody mixture 3, and antibody mixture 4). The following table shows examples of antibodies from different antibody pools in each antibody mixture:
Referring back to fig. 140, after and/or in response to step/operation 14004, the example method 14000 proceeds to step/operation 14006. At step/operation 14006, the exemplary method 14000 can include coating the plurality of sample channels with the plurality of antibody mixtures.
In some embodiments, the sample testing device may include a waveguide that includes a plurality of sample channels, similar to the various examples described herein. The sample channels of the waveguide are coated with an antibody mixture (also referred to as an antigen mixture) in a predetermined order prior to testing using the sample testing device. In some embodiments, each of the plurality of sample channels is coated with a unique antibody mixture, and no two sample channels are coated with the same antibody mixture.
In some embodiments, to apply the antibody mixture to the sample channel, the exemplary method 14000 can include applying the antibody mixture to a surface of the sample channel (e.g., on a bottom surface of the sample channel). Continuing with the example above, the exemplary method 14000 may coat antibody mixture 1 on the surface of sample channel 1, coat antibody mixture 2 on the surface of sample channel 2, coat antibody mixture 3 on the surface of sample channel 3, and coat antibody mixture 4 on the surface of sample channel 4.
Referring back to fig. 140, after and/or in response to step/operation 14006, the example method 14000 proceeds to step/operation 14008. At step/operation 14008, the example method 14000 can include coating at least one positive reference channel with at least one reference binding substance.
In some embodiments, the at least one reference binding substance can include a substance that binds the reference substance to the at least one reference binding substance. For example, the at least one reference binding substance can attract and adsorb the reference substance to the at least one reference binding substance. For example, the reference substance may be in the form of a virus of one type or variant of virus, and the at least one reference binding substance may comprise an antibody to the virus of that particular type or variant.
Although the above description provides examples using viruses as reference substances and virus antibodies as reference binding substances, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, exemplary reference substances and/or reference binding substances may include other molecules, chemicals, substances.
In some embodiments, the waveguide of the sample testing device may include at least one positive reference channel in addition to the sample channel, and the at least one reference binding substance may be coated on a surface of the at least one positive reference channel. For example, the waveguide of the sample testing device may include two positive reference channels, and each of the two positive reference channels may be coated with the same or different reference binding substances.
Referring back to fig. 140, after and/or in response to step/operation 14008, the exemplary method 14000 proceeds to step/operation 14010. At step/operation 14010, the exemplary method 14000 can include preparing a sample mixture using the reference substance and the sample substance.
As described above, the reference substance may be bound to a reference binding substance coated on the positive reference channel. For example, the reference substance may comprise a known virus or a good control virus surrogate, and the surface of the positive reference channel may be coated with an antibody to the known virus or the good control virus surrogate.
In some embodiments, the sample material may include a sample whose sample type is determined by the exemplary method 14000. For example, the sample material may include an unknown virus or unknown specimen, and the example method 14000 may determine a type of the unknown virus or unknown specimen.
Thus, at step/operation 14010, the exemplary method 14000 can form a sample mixture (e.g., a sample fusion) by mixing a sample substance (e.g., a test sample) with one or more reference substances (e.g., a well-controlled viral surrogate) as a binding reference in a test, the details of which are described herein.
Referring back to fig. 140, after and/or in response to step/operation 14010, the example method 14000 proceeds to step/operation 14012. At step/operation 14012, the example method 14000 can include injecting a sample mixture into the plurality of sample channels and the at least one positive reference channel of the waveguide.
In some embodiments, the sample mixture prepared at step/operation 14010 is injected simultaneously into all channels of the waveguide. For example, the sample mixture is injected into the sample channel of the waveguide (which has been coated with the plurality of antibody mixtures at step/operation 14006) and into the at least one positive reference channel (which has been coated with the at least one reference binding substance at step/operation 14008).
Referring back to fig. 140, after and/or in response to step/operation 14012, the example method 14000 proceeds to step/operation 14014. At step/operation 14014, the example method 14000 can include receiving a plurality of test signals from the plurality of sample channels and at least one reference signal from the at least one positive reference channel.
In some embodiments, the laser beam may be emitted through the plurality of sample channels and the at least one positive reference channel of the waveguide to generate a test signal, similar to those described above. For example, the waveguide may be in the form of a bimodal waveguide that forms an interference fringe pattern as the laser beam travels through a passage of the waveguide, and the imaging component may detect the interference fringe pattern. In some embodiments, after injecting the sample mixture into the plurality of sample channels and the at least one positive reference channel, the interference fringe pattern from one or more of the channels may change, and the imaging component may generate the test signal based on the detected interference fringe pattern.
Referring back to fig. 140, after step/operation 14014, the exemplary method 14000 proceeds to step/operation 14016. At step/operation 14016, the example method 14000 can include determining a sample type from a plurality of sample types associated with the sample substance.
In some embodiments, the test signal from the sample channel may be normalized based on the at least one reference signal from the at least one positive reference channel. As described above, the sample mixture includes a reference substance, and the at least one positive reference channel is coated with at least one reference binding substance that binds to the reference substance. Thus, the at least one reference signal from the at least one positive reference channel provides a baseline signal that indicates when the sample mixture includes a sample type targeted by one of the antibodies coated on the channel. In some embodiments, each of the test signals from the sample channel may be compared to the at least one reference signal to determine whether it provides a positive indication, the details of which are described herein in connection with at least fig. 142A-142B.
Referring back to step/operation 14016, the exemplary method 14000 proceeds to step/operation 14018 and ends.
According to some embodiments of the present disclosure, an exemplary method for determining a sample type of a sample may be performed by an exemplary sample type determining device including one or more computing systems, such as sample type determining device 14100 shown in fig. 141. Sample type determining device 14100 can include a processor 14101, a memory 14103, a communication circuit 14105, an input/output circuit 14107, and/or a display 14109. The sample type determination device 14100 can be configured to perform the operations described herein. Although the components are described with respect to functional limitations, it should be appreciated that a particular implementation necessarily involves the use of particular hardware. It should also be understood that certain components described herein may include similar or common hardware. For example, both sets of circuitry may use the same processor, network interface, storage medium, etc. to perform their associated functions such that no duplicate hardware is required for each set of circuitry. Thus, it should be understood that the use of the term "circuitry" as used herein with respect to a component of an apparatus includes particular hardware configured to perform the functions associated with the particular circuitry described herein.
As described above, the term "circuitry" should be construed broadly to include hardware, and in some embodiments, software for configuring the hardware. For example, in some implementations, a "circuit" may include processing circuitry, storage medium, network interface, input/output devices, etc. In some embodiments, other elements of sample type determining device 14100 can provide or supplement the functionality of specific circuits. For example, the processor 14101 may provide processing functionality, the memory 14103 may provide storage functionality, the communication circuit 14105 may provide network interface functionality, and the like.
In some implementations, the processor 14101 (and/or a coprocessor or any other processing circuitry that assists or is otherwise associated with the processor) may communicate with the memory 14103 via a bus for communicating information between components of the apparatus. The memory 14103 may be non-transitory and may include, for example, one or more volatile and/or non-volatile memories. In other words, for example, the memory 14103 can be an electronic storage device (e.g., a computer-readable storage medium). The memory 14103 can be configured to store information, data, content, applications, instructions, and the like for enabling the sample type determining device 14100 to perform various functions in accordance with exemplary embodiments of the present disclosure.
The processor 14101 can be embodied in a number of different ways and can, for example, include one or more processing devices configured to execute independently. Additionally or alternatively, processor 14101 may include one or more processors configured in series via a bus to enable independent execution of instructions, pipelines, and/or multiple threads. The use of the term "processing circuitry" may be understood to include a single-core processor, a multi-core processor, multiple processors within a device, and/or a remote or "cloud" processor.
In an exemplary embodiment, the processor 14101 may be configured to execute instructions stored in the memory 14103 or otherwise accessible to the processor. Alternatively or additionally, the processor 14101 may be configured to perform hard-coded functions. Thus, whether configured by hardware methods or software methods, or by a combination thereof, a processor may represent an entity (e.g., physically embodied in circuitry) capable of performing operations according to embodiments of the disclosure while configured accordingly. Alternatively, as another example, when the processor 14101 is embodied as an executor of software instructions, the instructions may specially configure the processor to perform the algorithms and/or operations described herein when the instructions are executed.
In some embodiments, sample type determining device 14100 can include input/output circuitry 14107 which can in turn communicate with processor 14101 to provide output to a user and, in some embodiments, receive an indication of user input. Input/output circuitry 14107 can include interfaces, mobile applications, kiosks, and the like. In some implementations, the input/output circuitry 14107 may also include a keyboard, a mouse, a joystick, a touch screen, a touch area, soft keys, a microphone, a speaker, or other input/output mechanisms. The processor and/or user interface circuitry comprising the processor may be configured to control one or more functions of one or more user interface elements by computer program instructions (e.g., software and/or firmware) stored on a memory accessible to the processor (e.g., memory 14103, etc.).
In some embodiments, the sample type determination device 14100 can include a display 14109, which in turn can be in communication with the processor 14101 to display user interface renderings. In various examples of the present disclosure, the display 14109 can include a Liquid Crystal Display (LCD), a Light Emitting Diode (LED) display, a plasma (PDP) display, a quantum dot (QLED) display, and the like.
The communication circuit 14105 may be any means, such as a device or circuit embodied in hardware or a combination of hardware and software, configured to receive and/or transmit data from/to a network and/or any other device, circuit or module in communication with the sample type determining device 14100. In this regard, the communication circuit 14105 may include, for example, a network interface for enabling communication with a wired or wireless communication network. For example, communication circuitry 14105 may include one or more network interface cards, antennas, buses, switches, routers, modems and supporting hardware and/or software, or any other device suitable for enabling communications over a network. Additionally or alternatively, the communication interface may include circuitry for interacting with one or more antennas to cause transmission of signals via the one or more antennas or to process reception of signals received via the one or more antennas.
It is also noted that all or some of the information discussed herein may be based on data received, generated, and/or maintained by one or more components of the sample type determination device 14100. In some embodiments, one or more external systems (such as remote cloud computing and/or data storage systems) may also be utilized to provide at least some of the functionality discussed herein.
Various methods described herein (including, for example, the exemplary method 14200 shown in fig. 142A-142B) may determine a sample type associated with a sample from among a plurality of sample types.
It is noted that each block of the flowchart, and combinations of blocks in the flowchart, can be implemented by various means, such as hardware, firmware, circuitry and/or other devices associated with execution of software including one or more computer program instructions. For example, one or more of the programs described in fig. 142A-142B may be embodied by computer program instructions that may be stored by a non-transitory memory of an apparatus employing embodiments of the present disclosure and executed by a processor of the apparatus. These computer program instructions may direct a computer or other programmable apparatus to function in a particular manner, such that the instructions stored in the computer-readable memory produce an article of manufacture the execution of which implement the function specified in the flowchart block or blocks.
As described above and as will be appreciated based on the present disclosure, embodiments of the present disclosure may be configured as methods, mobile devices, backend network devices, and the like. Thus, embodiments may comprise various means including entirely hardware, or any combination of software and hardware. Furthermore, embodiments may take the form of a computer program product on at least one non-transitory computer-readable storage medium having computer-readable program instructions (e.g., computer software) embodied in the storage medium. Similarly, embodiments may take the form of computer program code stored on at least one non-transitory computer-readable storage medium. Any suitable computer readable storage medium may be utilized including non-transitory hard disks, CD-ROMs, flash memory, optical storage devices, or magnetic storage devices.
Fig. 142A and 142B illustrate exemplary methods of determining a sample type of a sample in a sample mixture according to various embodiments of the present disclosure.
Referring now to fig. 142A, an exemplary method 14200 begins with step/operation 14202. After and/or in response to step/operation 14202, the example method 14200 proceeds to step/operation 14204. At step/operation 14204, a processing circuit (such as, but not limited to, processor 14101 of sample type determining device 14100 described above in connection with fig. 141) may receive a plurality of test signals associated with a plurality of sample channels and at least one reference signal from at least one reference channel.
For example, similar to those described above, the imaging component may generate a plurality of test signals based on the interference fringe pattern detected from the output of the sample channel of the waveguide and generate the at least one reference signal from the output of the at least one reference channel of the waveguide.
As described above, if the surface of a channel is coated with an antibody against a particular type/variant of virus, and the sample substance includes the particular type/variant of virus, the antibody causes the virus in the sample substance to bind to the surface of the channel, which causes a change in the interference fringe pattern from the channel. For example, the amplitude of the interference fringe pattern may increase (e.g., the interference fringe pattern may be shifted upward). In some embodiments, the imaging component may detect the interference fringe pattern. In some embodiments, if the interference fringe pattern is from the sample channel, the imaging component may generate the test signal based on the interference fringe pattern. In some embodiments, if the interference fringe pattern is from a positive reference channel, the imaging component may generate a reference signal based on the interference fringe pattern. For example, the signal amplitude of the test signal or the reference signal may correspond to the amplitude of the interference fringe pattern from the sample channel or the positive reference channel, respectively.
In some embodiments, the imaging component may generate a plurality of test signals based on interference fringe patterns from a plurality of sample channels and at least one reference signal based on at least one interference fringe pattern from at least one reference channel. In some embodiments, the imaging component may transmit the plurality of test signals and the at least one reference signal to a sample type determining device.
Referring back to fig. 142A, after and/or in response to step/operation 14204, the example method 14200 proceeds to step/operation 14206. At step/operation 14206, processing circuitry (e.g., without limitation, processor 14101 of sample type determining device 14100 described above in connection with fig. 141) may record the at least one reference signal as at least one positive indication datum.
As described above, the sample mixture includes at least one reference substance, and the at least one positive reference channel is coated with at least one reference binding substance that binds to or attracts the at least one reference substance. For example, the reference substance in the sample mixture may be in the form of a virus of one type or variant of virus, and the at least one reference binding substance may comprise an antibody to the virus of that particular type or variant. Thus, the reference signal from the at least one positive reference channel corresponds to a signal indicating that the surface of the channel is coated with antibodies to the virus of the type or variant contained in the sample mixture.
In some embodiments, the processing circuit may record the at least one reference signal as at least one positive indication datum. For example, the processing circuit may record the amplitude of the at least one reference signal as a positive baseline amplitude. In such an example, if the amplitude of the test signal from the other sample channel is the same as or greater than the amplitude of the at least one reference signal, the test signal indicates that the sample channel is coated with antibodies to the type/variant of virus contained in the sample mixture.
Referring back to fig. 142A, after and/or in response to step/operation 14204, the example method 14200 proceeds to block a, which connects fig. 124A-142B. As shown in fig. 142B, after block a and/or in response to block a (e.g., after and/or in response to step/operation 14206), exemplary method 14200 proceeds to step/operation 14208. At step/operation 14208, processing circuitry (e.g., without limitation, processor 14101 of sample type determining device 14100 described above in connection with fig. 141) may determine whether a test signal from a sample channel provides a positive indication based on a positive indication reference.
As described above, the example method 14200 may record the at least one reference signal from a positive reference channel as at least one positive indication baseline. For example, the at least one reference signal may be associated with a signal amplitude corresponding to the amplitude of the interference fringe pattern.
In some embodiments, to determine whether the test signal from the sample channel provides a positive indication, the processing circuit may compare the test signal to the at least one reference signal. For example, the processing circuit may compare the signal amplitude of the test signal with the at least one reference signal.
The processing circuitry may determine that the test signal provides a positive indication if the signal amplitude of the test signal from the sample channel reaches or is higher than the signal amplitude of the at least one reference signal from the at least one positive reference channel. In such an example, the test signal indicates that the sample channel is coated with antibodies that bind to viruses in the sample substance in the sample mixture. The higher the signal amplitude of the test signal compared to the signal amplitude of the reference signal, the higher the confidence that the test signal provides a positive indication.
If the signal amplitude is lower than the signal amplitude of the at least one reference signal from the at least one positive reference channel, the processing circuitry may determine that the test signal does not provide a positive indication. In such an example, the test signal indicates that the sample channel is not coated with antibodies that will bind to viruses in the sample substance in the sample mixture. The lower the signal amplitude of the test signal compared to the signal amplitude of the reference signal, the higher the confidence that the test signal does not provide a positive indication.
Referring back to fig. 142B, if at step/operation 14208 the example method 14200 determines that the test signal provides a positive indication based on a positive reference, the example method 14200 proceeds to step/operation 14210. At step/operation 14210, processing circuitry (e.g., without limitation, processor 14101 of sample type determining device 14100 described above in connection with fig. 141) may generate a candidate data set comprising a sample type associated with an antibody mixture coated on a sample channel.
For example, the sample channel may be coated with an antibody mixture comprising antibodies to A, E, F, G, L, M, N and O-type viruses. If the test signal from the sample channel provides a positive indication, it indicates that the sample material in the sample mixture may include a type A virus, a type E virus, a type F virus, a type G virus, a type L virus, a type M virus, a type N virus, or a type O virus. In such examples, the processing circuitry may generate candidate data sets including a type a, type E, type F, type G, type L, type M, type N, and type O samples.
Referring back to fig. 142B, if at step/operation 14208, the example method 14200 determines that the test signal does not provide a positive indication based on a positive reference, the example method 14200 proceeds to step/operation 14212. At step/operation 14212, processing circuitry (e.g., without limitation, processor 14101 of sample type determining device 14100 described above in connection with fig. 141) may generate an exclusion data set comprising sample types associated with the antibody mixture coated on the sample channel.
For example, the sample channel may be coated with an antibody mixture comprising antibodies to A, E, F, G, L, M, N and O-type viruses. If the test signal from the sample channel does not provide a positive indication, it indicates that the sample material in the sample mixture does not include a type A virus, a type E virus, a type F virus, a type G virus, a type L virus, a type M virus, a type N virus, and a type O virus. In such examples, the processing circuitry may generate the exclusion data set comprising a type a, type E, type F, type G, type L, type M, type N, and type O samples.
Referring back to fig. 142B, after and/or in response to step/operation 14210 and/or step/operation 14212, the exemplary method 14200 proceeds to step/operation 14214. At step/operation 14214, processing circuitry (such as, but not limited to, processor 14101 of sample type determining device 14100 described above in connection with fig. 141) may determine whether to examine test signals from all sample channels.
For example, the processing circuitry may determine whether the test signal from each sample channel of the waveguide has been examined to determine whether it provides a positive indication, similar to those described above in connection with step/operation 14208.
If, at step/operation 14214, the processing circuit determines that at least one test signal from at least one sample channel has not been examined, then the example method 14200 proceeds to step/operation 14208. In such an example, the processing circuit may determine whether the at least one test signal provides a positive indication, similar to those described above.
If at step/operation 14214, the processing circuit determines that all test signals from all sample channels have been examined, then the exemplary method 14200 proceeds to step/operation 14216. At step/operation 14216, a processing circuit (such as, but not limited to, processor 14101 of sample type determining device 14100 described above in connection with fig. 141) may determine that a sample substance is associated with a sample type in each candidate dataset and not in any excluded dataset.
As described above, the processing circuitry may add a sample type to the candidate data set or exclude the data set based on whether the test signal provides a positive indication. For example, an exemplary waveguide may include four sample channels coated with different combinations of antibodies as shown in the following table:
| Sample channel | A | B | C | D | E | F | G | H | I | J | K | L | M | Whether or not | O |
| 1 | X | X | X | X | X | X | X | X | |||||||
| 2 | X | X | X | X | X | X | X | X | |||||||
| 3 | X | X | X | X | X | X | X | X | |||||||
| 4 | X | X | X | X | X | X | X | X |
For example, the processing circuitry may determine that the test signal from sample channel 1 provides a positive indication. In this example, the processing circuitry may generate a first candidate data set that includes a type a, E, F, G, L, M, N, and O.
Continuing with this example, the processing circuitry may determine that the test signal from sample channel 2 does not provide a positive indication. In this example, the processing circuit may generate a first exclusion data set that includes type B, type E, type H, type I, type K, type M, type N, and type O.
Continuing with this example, the processing circuitry may determine that the test signal from sample channel 3 does not provide a positive indication. In this example, the processing circuit may generate a second exclusion dataset comprising type C, F, H, type J, type K, type L, type N, and type O.
Continuing with this example, the processing circuitry may determine that the test signal from the sample channel 4 provides a positive indication. In this example, the processing circuitry may generate a second candidate data set comprising D-type, G-type, I-type, J-type, K-type, L-type, M-type, and O-type.
In some embodiments, the processing circuitry may compare sample types in the first candidate data set and the second candidate data set and determine one or more overlapping sample types in the first candidate data set and the second candidate data set. If the sample type is not in both the first candidate data set and the second candidate data set, the sample type is not associated with the sample substance because the sample type associated with the sample substance must be each candidate data set. In the above example, the first candidate data set includes a type a, E, F, G, L, M, N, and O, and the second candidate data set includes D, G, I, J, K, L, M, and O. The processing circuitry may determine that the types of overlapping samples between the first candidate data set and the second candidate data set include G-type, M-type, and O-type.
As mentioned above, the sample type associated with the sample material is not in any exclusion dataset. In some embodiments, the processing circuitry may compare the overlapping sample types in the candidate dataset with the sample types in the excluded dataset and remove any overlapping sample types that are also in the excluded dataset. Continuing with the example above, the example processing circuitry may determine that the M-type and the O-type are in the first exclusion dataset and may determine that the sample is not associated with the M-type or the O-type. Thus, the processing circuitry may determine that the sample type associated with the sample is type G.
Referring back to fig. 142B, after and/or in response to step/operation 14216, the example method 14200 proceeds to step/operation 14218 and ends.
Referring now to fig. 143A and 143B, various exemplary views associated with exemplary waveguide 14300 are shown. Specifically, fig. 143A illustrates an exemplary perspective view of an exemplary waveguide 14300 according to various embodiments of the present disclosure. Fig. 143B illustrates an exemplary enlarged view of at least a portion of an exemplary waveguide 14300 in accordance with various embodiments of the present disclosure.
In the example shown in fig. 143A, an example waveguide 14300 may define a plurality of channels 14301 on the waveguide 14303. In some embodiments, the plurality of channels 14301 may include a plurality of sample channels and one or more reference channels, the details of which are shown in fig. 143B.
Referring now to fig. 143B, an exemplary enlarged view of at least a portion of an exemplary waveguide 14300 is shown.
In some embodiments, the exemplary waveguide 14300 can include a total of eight channels, including two combined reference channels, four sample channels, and two buried reference channels. In the example shown in fig. 143B, the example waveguide 14300 may include channels arranged in the following order: binding reference channel 14305A, sample channel 14307A, embedded reference channel 14309a, sample channel 14307B, sample channel 14307C, embedded reference channel 14309B, sample channel 14307D, and binding reference channel 14305B.
In some embodiments, each of sample channel 14307A, sample channel 14307B, sample channel 14307C, and sample channel 14307D may be coated with a sample mixture, similar to those described above.
In some embodiments, the binding reference channel 14305A and the binding reference channel 14305B may comprise a positive reference channel and/or a negative reference channel. For example, one or both of the binding reference channel 14305A and the binding reference channel 14305B may be a positive reference channel coated with at least one reference binding substance, similar to those described above. Additionally or alternatively, one or both of the binding reference channel 14305A and the binding reference channel 14305B may be a negative reference channel.
In such an example, the negative reference channel may be coated with a substance that does not bind or attract any substance from the sample mixture. For example, the combined reference channel 14305A and the combined reference channel 14305B may be coated with water. Because the substance coated on the negative reference channel does not bind or attract any substance from the sample mixture, the reference signal from the negative reference channel corresponds to a signal indicating that the surface of the channel is not coated with any antibodies to the type or variant of virus contained in the sample mixture. In some embodiments, the processing circuit may record the amplitude of the reference signal from the negative reference channel as a negative base amplitude. In such an example, if the magnitude of the test signal from the other sample channel reaches or is lower than the magnitude of the at least one reference signal from the negative reference channel, the test signal indicates that the sample channel is not coated with antibodies to any viruses contained in the sample mixture. In some embodiments, the processing circuit may record the signal of the at least one reference signal from the negative reference channel as at least one negative indication datum.
In some embodiments, the reference signal from the negative reference channel may be used as a negative basis for the test signal from the sample channel. For example, processing circuitry may determine whether the test signal provides a negative indication based on a negative indication reference in addition to or in lieu of those described above in conjunction with step/operation 14208 of fig. 142B.
The processing circuitry may determine that the test signal provides a negative indication if the signal amplitude of the test signal from the sample channel is equal to or lower than the signal amplitude of the at least one reference signal from the negative reference channel. In such an example, the test signal indicates that the sample channel is not coated with antibodies that bind to viruses in the sample substance in the sample mixture, and the processing circuitry may generate an exclusion data set that includes sample types associated with the antibody mixture coated on the sample channel, similar to those described above in connection with at least step/operation 14212. The lower the signal amplitude of the test signal compared to the signal amplitude of the reference signal, the higher the confidence that the test signal provides a negative indication.
The processing circuitry may determine that the test signal provides a positive indication if the signal amplitude is higher than the signal amplitude of the at least one reference signal from the negative reference channel. In such an example, the test signal indicates that the sample channel is coated with antibodies that will bind to viruses in the sample substance in the sample mixture, and the processing circuitry may generate a candidate data set comprising sample types associated with the antibody mixture coated on the sample channel, similar to those described above in connection with step/operation 14210. The higher the signal amplitude of the test signal compared to the signal amplitude of the reference signal, the higher the confidence that the test signal provides a positive indication.
In some embodiments, the embedded reference channel 14309a and the embedded reference channel 14309B may be sealed and contain the same or different reference media, similar to those described above. In some implementations, buried reference channel 14309a and buried reference channel 14309B may provide a buried sensing region that may be added to provide an absolute reference to compensate for sensor signal variations with signals from the surrounding environment, similar to those described above.
Thus, in the example shown in fig. 143B, test signals from sample channel 14307A, sample channel 14307B, sample channel 14307C, and sample channel 14307D may be compensated based on signals from embedded reference channels to eliminate signal noise caused by the surrounding environment, and may be normalized according to a positive indication benchmark and/or a negative indication benchmark to determine whether the test signal provides a positive indication or a negative indication.
Accordingly, various embodiments of the present disclosure may overcome technical challenges and difficulties associated with waveguides. For example, various embodiments of the present disclosure provide a sample specimen with a control binding reference fusion, wherein a patient sample specimen is mixed with one or more good control viral substitutes for binding reference. Various embodiments of the present disclosure may provide antigen-combination fusion in which several or many antigen-type combinations are determined for multi-virus immobilization and sequentially applied to a sensing channel. Various embodiments of the present disclosure provide a multi-channel viral sensor in which as few as 8 channels can detect up to 15 types of viruses using test environment compensation and using combined quantification of noise cancellation. Thus, various embodiments of the present disclosure provide a multi-virus sensing mechanism that allows for multi-virus detection simultaneously in a single sample collection.
In various examples, the multichannel viral sensor requires uniform flow in all channels. However, many parallel channels do not provide uniform flow due to the differences between the channels.
Various embodiments of the present disclosure may provide a sample testing device that provides for continuous flow of sample solution through a single injection, which solves the flow uniformity problem. In some embodiments, single injection continuous flow can simplify the flow system in a sample testing device and provide various technical benefits and advances. For example, the reduced channel volume of the sample testing device may minimize detection delays between channels to allow real-time multi-channel detection and processing.
Referring now to fig. 144A, 144B, 144C, 144D, 144E, 144F, and 144G, exemplary views of an exemplary waveguide cassette 14400 according to various embodiments of the present disclosure are provided. The exemplary waveguide cartridge 14400 can provide continuous flow from a single injection to a multi-channel interferometric virus sensor.
Specifically, fig. 144A and 144B illustrate exemplary exploded views of an exemplary waveguide cassette 14400.
In the example shown in fig. 144A, the example waveguide cassette 14400 may include a fluid body 14414 defining a buffer reservoir 14408, an injection port 14410, and a waste reservoir 14412, similar to those described above in connection with fig. 86A-86F.
In some embodiments, buffer reservoir 14408 may be in the form of a recessed region on the top surface of fluid body 14414 in which buffer solution may be stored. For example, as part of assembling the exemplary waveguide cassette 14400, buffer solution is filled into buffer reservoir 14408. Examples of buffer solutions may include, but are not limited to, water.
In some embodiments, the waveguide cartridge 14400 includes a pump membrane 14406. In some embodiments, pump membrane 14406 is aligned to cover the top opening of buffer reservoir 14408. For example, pump membrane 14406 and buffer reservoir 14408 may define a space for storing a buffer solution.
In some embodiments, pump membrane 14406 may comprise a flexible material, such as, but not limited to, silicon. In some embodiments, the pump membrane 14406 may deform when a force is exerted on the pump membrane 14406. For example, as described in detail herein, buffer reservoir 14408 may define a buffer release tunnel on a bottom surface of buffer reservoir 14408. As described above, pump membrane 14406 may be aligned to cover the top opening of buffer reservoir 14408. When a downward force is applied on pump membrane 14406 and toward buffer reservoir 14408, pump membrane 14406 can deform, which pushes the buffer solution stored in buffer reservoir 14408 through a buffer release tunnel on the bottom surface of buffer reservoir 14408.
As described in further detail herein, the buffer release tunnel may be connected to a beginning of a continuous flow channel defined on a bottom surface of fluid body 14414. Thus, by pushing the pump membrane 14406, the buffer solution can be released into the continuous flow channel, the details of which are described herein.
In some embodiments, injection port 14410 may be in the form of a recessed region on the top surface of fluid body 14414. In some embodiments, the sample solution may be injected into the waveguide cartridge 14400 through injection port 14410.
For example, the waveguide box 14400 includes an injection septum 14404. In some embodiments, the injection septum 14404 is aligned to cover the top opening of the injection port 14410. In some embodiments, the injection septum 14404 may comprise a flexible material, such as, but not limited to, silicon.
In some embodiments, the injection septum 14404 may define a channel that connects to the space defined by the injection port 14410. In some embodiments, the outer opening of the central channel is covered by a cover. In some embodiments, a syringe device (or other suitable device) storing the sample solution may pierce the cap and inject the sample solution through the central channel into injection port 14410.
In some embodiments, injection port 14410 may define a sample release tunnel on a bottom surface of injection port 14410. In some embodiments, the channel defined by the injection septum 14404 is connected to a sample release tunnel. When sample solution is injected into injection port 14410 through injection septum 14404, the sample solution is released through a sample release tunnel on the bottom surface of buffer reservoir 14408.
As described in further detail herein, the sample release tunnel may be connected to a continuous flow channel defined on the bottom surface of fluid body 14414. Thus, the sample solution may be released into the continuous flow channel through a sample release tunnel of injection port 14410, the details of which are described herein.
In some embodiments, waste reservoir 14412 may be in the form of a recessed area on the top surface of fluid body 14414. In some embodiments, waste reservoir 14412 may define a waste release tunnel on a bottom surface of waste reservoir 14412. In some embodiments, the waste release tunnel is connected to an end of a continuous flow channel defined on a bottom surface of fluid body 14414 and can receive a waste solution (e.g., a solution after the buffer solution and/or sample solution travels through the continuous flow channel). In some embodiments, the waste solution may be stored in a waste reservoir 14412.
In some embodiments, the waveguide cartridge 14400 includes an emission filter 14402. In some embodiments, the emission filter 14402 is aligned to cover the top opening of the waste reservoir 14412. In some embodiments, the emission filter 14402 may include a filter material, such as, but not limited to, a HEPA air filter, that prevents the release of harmful particulates in the waste solution to the environment.
As shown in fig. 144A, fluid body 14414 is positioned on waveguide sensor 14416 that defines a plurality of channels (e.g., sample channels positioned between two reference channels). In some embodiments, portions of the continuous flow channel defined on the bottom surface of fluid body 14414 are aligned with channels on waveguide sensor 14416. For example, as shown in fig. 144B, an exemplary continuous flow channel 14418 is defined on a bottom surface of fluid body 14414.
In some embodiments, exemplary continuous flow channel 14418 may be in the form of a groove on the bottom surface of fluid body 14414. The channel may include a plurality of connection sections, including a sample section, a continuous flow channel section, and a pre-wash section, the details of which are described herein. In some implementations, the continuous flow channel section may define three parallel grooves that connect and align with three channels (e.g., a sample channel and two reference channels) on the waveguide sensor 14416, the details of which are described herein.
Referring now to fig. 144C, an exemplary top view of an exemplary waveguide cassette 14400 is shown. In some embodiments, exemplary waveguide box 14400 may have a width W of 10 millimeters. In some embodiments, exemplary waveguide box 14400 may have a length L of 32 millimeters.
Referring now to fig. 144C, an exemplary side view of an exemplary waveguide cassette 14400 is shown. In some embodiments, exemplary waveguide box 14400 may have a thickness T of 6 millimeters.
Referring now to fig. 144D, an exemplary top view of an exemplary waveguide cassette 14400 is shown. Specifically, fig. 144D shows waveguide sensor 14416 aligned with a continuous flow channel defined on a bottom surface of fluid body 14414.
Referring now to fig. 144F, an exemplary perspective view of an exemplary waveguide cassette 14400 is shown. Specifically, fig. 144F shows pump diaphragm 14406 aligned to cover buffer reservoir 14408, injection diaphragm 14404 aligned to cover injection port 14410, and vent filter 14402 aligned to cover waste reservoir 14412.
Referring now to fig. 144G, an exemplary left side view of an exemplary waveguide cassette 14400 is shown.
Referring now to fig. 145A, 145B, 145C, 145D, 145E, and 145F, exemplary views of an exemplary cartridge body 14500 according to various embodiments of the present disclosure are provided.
In particular, fig. 145A illustrates an exemplary top view of an exemplary cartridge body 14500. Fig. 145B illustrates an example bottom view of an example cartridge body 14500. Fig. 145C illustrates an example cross-sectional view of an example cartridge body 14500.
In the example shown in fig. 145A, an example cartridge body 14500 may include a buffer reservoir 14505, an injection port 14503, and a waste reservoir 14501, similar to buffer reservoir 14408, injection port 14410, and waste reservoir 14412 described above in connection with fig. 144A.
In some embodiments, the buffer reservoir 14505 may define an opening of the buffer release tunnel 14511 on a bottom surface of the buffer reservoir 14505. Similarly, injection port 14503 may define an opening of sample release tunnel 14509 on a bottom surface of injection port 14503. Similarly, the waste reservoir 14412 may define an opening to the waste release tunnel 14507 on a bottom surface of the waste reservoir 14412.
Referring now to fig. 145B, a continuous flow channel 14513 defined on a bottom surface of an exemplary cartridge body 14500 is shown. In the example shown in fig. 145B, a buffer release tunnel 14511, a sample release tunnel 14509, and a waste release tunnel 14507 are connected to the continuous flow channel 14513.
As described above, the continuous flow channel 14513 may include a plurality of sections. For example, the continuous flow channel 14513 can include a sample section 14515, a pre-wash section 14517, and a continuous flow section 14519. In some embodiments, sample section 14515 is connected to a pre-wash section 14517, which in turn is connected to a continuous flow section 14519. For example, fluid may flow from sample section 14515 to pre-wash section 14517 and then to continuous flow section 14519.
In some embodiments, the buffer release tunnel 14511 is connected to the beginning of the sample section 14515 of the continuous flow channel 14513. Thus, when buffer solution (such as water) is released from the buffer release tunnel 14511, the buffer solution can flow from the sample section 14515 to the pre-wash section 14517, to the continuous flow section 14519, and out of the continuous flow channel 14513 through the waste release tunnel 14507.
In some embodiments, the sample release tunnel 14509 is connected to the sample section 14515 of the continuous flow channel 14513. In particular, sample release tunnel 14509 is connected to a point in the flow direction that is after the start of sample section 14515 (at buffer release tunnel 14511). Thus, when the sample solution is released from the sample release tunnel 14509, the sample solution can flow from at least a portion of the sample section 14515 to the pre-wash section 14517, to the continuous flow section 14519, and out of the continuous flow channel 14513 through the waste release tunnel 14507.
In the example shown in fig. 145B, sample section 14515 is arranged parallel to pre-wash section 14517. For example, sample section 14515 and pre-wash section 14517 may each be disposed along a long side of the bottom surface of exemplary cartridge body 14500 and connected by a portion of continuous flow channel 14513 along a short side of the bottom surface of exemplary cartridge body 14500.
In some embodiments, the continuous flow section 14519 is positioned between the sample section 14515 and the pre-wash section 14517. Specifically, the continuous flow section 14519 includes three parallel grooves connected in series. As described above, the three parallel grooves of the continuous flow section 14519 may be aligned with the three channels on the waveguide sensor. For example, the top groove of the continuous flow section 14519 may be aligned with the reference channel of the waveguide sensor. The intermediate groove of the continuous flow section 14519 may be aligned with the sample channel of the waveguide sensor. The bottom groove of the continuous flow section 14519 may be aligned with another reference channel of the waveguide sensor.
In some embodiments, the ends of the continuous flow section 14519 are connected to a waste release tunnel 14507, similar to those described above.
According to various embodiments of the present disclosure, exemplary methods of performing sample testing by utilizing exemplary cartridge body 14500 are provided.
In some embodiments, an exemplary method may include causing buffer solution to be injected into the continuous flow channel 14513 through the buffer release tunnel 14511 (e.g., by pushing on a pump septum, as described above). In some embodiments, the buffer solution flows through the continuous flow channel 14513 and exits the continuous flow channel 14513 through the waste release tunnel 14507, similar to those described above. Thus, the buffer solution may clean the continuous flow channel 14513 and remove any dust, air, or particulates that may affect the sample testing.
In some embodiments, an exemplary method may include causing the sample solution to be injected into the continuous flow channel 14513 through the sample release tunnel 14509 (e.g., through an injection septum as described above). In some embodiments, after injecting the sample solution into the continuous flow channel 14513, the pump diaphragm continues to push the buffer solution through the continuous flow channel 14513. Because the sample release tunnel 14509 is connected to the continuous flow channel 14513 after connecting the location of the buffer release tunnel 14511, the pump diaphragm can push the sample solution through the continuous flow channel 14513.
For example, as the pump diaphragm continues to push the sample solution, the sample solution may travel through the pre-wash section 14517, the top groove of the continuous flow section 14519, and to the middle groove of the continuous flow section 14519. When the sample solution reaches the middle groove of continuous flow section 14519, both the top groove and the bottom groove of continuous flow section 14519 are filled with buffer solution (such as water). As described above, the top groove of the continuous flow section 14519 may be aligned with a reference channel of the waveguide sensor, the middle groove of the continuous flow section 14519 may be aligned with a sample channel of the waveguide sensor, and the bottom groove of the continuous flow section 14519 may be aligned with another reference channel of the waveguide sensor. Thus, according to various embodiments described herein, a waveguide sensor may detect a sample type of a sample solution.
In some embodiments, the amount of sample solution injected into the continuous flow channel 14513 may be based on the length of the intermediate groove in the continuous flow section 14519. For example, if the length of the intermediate groove in continuous flow section 14519 is one inch, then sample solution may be injected into continuous flow channel 14513 such that it fills the one inch length of the intermediate groove.
Although the above description provides an example of the volume of sample solution to be injected, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the volume of injected sample solution may be higher than the middle groove in the continuous flow section 14519, such that two or more sensing channels have overlapping sensing times. For example, the volume of sample solution may be higher than the continuous flow section 14519 so that all three channels in the waveguide sensor can be simultaneously detected and referenced for data comparison and noise cancellation.
Referring now to fig. 145C, an exemplary cross-sectional view of an exemplary cartridge body 14500 is shown. Specifically, fig. 145C shows a cross section of buffer reservoir 14505, injection port 14503, and waste reservoir 14501.
Fig. 145D and 145E illustrate exemplary perspective views of an exemplary cartridge body 14500. Fig. 145F illustrates an exemplary left side view of exemplary cartridge body 14500.
Accordingly, various embodiments of the present disclosure provide an exemplary waveguide box 14400 that overcomes various technical challenges and difficulties and provides technical advances and improvements. For example, various embodiments of the present disclosure provide a fluid body defining an injection port for receiving sample injection. The fluid body also provides a buffer reservoir positioned to the front end of the injection port and a waste reservoir positioned to the rear end of the injection port.
As described above, the buffer solution is pre-filled in the buffer reservoir and filled along the sample section, pre-wash section and continuous flow section of the continuous flow channel. In some embodiments, the sample solution is then injected with a syringe to fill the injection port and push a portion of the buffer solution into the pre-wash section of the continuous flow channel. In some embodiments, after injection of the sample solution, the pump membrane pushes the buffer solution and the sample solution through a continuous flow section of the continuous flow channel to complete the pre-wash, sample fixation, and post-wash.
Thus, an exemplary waveguide cartridge according to embodiments of the present disclosure may provide a continuous flow channel that may perform pre-wash, sample fluid testing, post-wash functions. Various embodiments of the present disclosure may reduce the volume of segments in a continuous flow channel that are arranged with minimal connection volume therebetween to minimize sensing delay between channels.
In various embodiments of the present disclosure, the exemplary sample testing device does not utilize an imaging lens because the exemplary sample testing device does not need to image the output, but rather directly detects the positional shift of the laser beam from the output end of the waveguide that may be caused by a change in the refractive index of the waveguide (e.g., as the sample travels through the sample channel of the sample testing device). Thus, the exemplary sample testing device may position the image sensor at a predetermined distance from the output end of the waveguide, and the image sensor may detect a positional shift of the laser beam from the output end of the waveguide.
However, when the position of the laser beam from the output end of the waveguide in the vertical direction changes, the incident angle between the laser beam and the detection surface of the image sensor may change. For example, when the laser beam from the output end of the waveguide is shifted upward, the incident angle between the laser beam and the detection surface of the image sensor may increase. When the laser beam from the output end of the waveguide is shifted downward, the incident angle between the laser beam and the detection surface of the image sensor may decrease. Variations in the angle of incidence between the laser beam and the detection surface of the image sensor can cause a number of technical challenges and difficulties.
For example, a change in the angle of incidence may affect the amplitude of the laser light detected by the image sensor. As the angle of incidence decreases (e.g., as the laser light is shifted toward the middle of the image sensor), the amplitude of the laser light increases (e.g., the laser light detected by the image sensor becomes brighter). As the angle of incidence increases (e.g., as the laser light is shifted toward the top or bottom of the image sensor), the amplitude of the laser light decreases (e.g., the laser light detected by the image sensor becomes darker). The variation in the amplitude of the laser light may cause a signal loss and generate a deviation when the position of the laser light is detected by the image sensor. For example, the signal loss may reflect the signal position detected by the image sensor. For example, as the laser light is shifted toward the top or bottom of the image sensor, the amplitude and light intensity of the laser light decrease, and the image sensor may not be able to detect the position of the highest/lowest laser beam, and may inaccurately detect how much the laser light has been shifted. Thus, image sensors in interferometric sensing have sensor angular response problems. The actual fringe pattern image may be distorted and the fringe offset detection is lower than the actual offset.
Various embodiments of the present disclosure may overcome the technical challenges and difficulties described above, and provide various technical improvements and advances. For example, various embodiments of the present disclosure may incorporate a field lens at the front of the image sensor. The image sensor may correct an incident angle of the laser light to the image sensor to a normal angle. The normal incidence angle to the image sensor ensures that the image sensor is able to provide the highest response with undistorted fringe pattern sensing across the image sensor area of the image sensor.
Referring now to fig. 146A, 146B, 146C, and 146D, exemplary views of a sample testing device 14600 according to various embodiments of the present disclosure are shown. Specifically, fig. 146A illustrates an exemplary perspective view of an exemplary sample testing device 14600. Fig. 146B illustrates an exemplary enlarged view of at least a portion of an exemplary sample testing device 14600. Fig. 146C illustrates an example side view of an example sample testing device 14600. Fig. 146D illustrates another example enlarged view of at least a portion of an example sample testing device 14600.
In the example shown in fig. 146A, an exemplary sample testing device 14600 may include a multi-channel waveguide 14602, similar to those described above.
In some embodiments, exemplary sample testing device 14600 can include fiber array 14604, similar to those described above. In some embodiments, fiber array 14604 may include optical fibers that may receive laser beams. In some embodiments, after the optical fiber array 14604 receives the laser beams, the laser beams may be provided to the multichannel waveguide 14602. For example, each of the fiber arrays 14604 may deliver a laser beam to one of the channels in the multi-channel waveguide 14602.
In some embodiments, after the laser beam travels through the channels in the multi-channel waveguide 14602, the laser beam may exit from the output end of the multi-channel waveguide 14602. In some embodiments, the position of the laser beam from the output of the multi-channel waveguide 14602 may be shifted based at least in part on the change in refractive index of the multi-channel waveguide 14602. For example, the change in refractive index of the multichannel waveguide 14602 may occur after the sample solution is injected into the multichannel waveguide 14602, and the amount of change in refractive index of the multichannel waveguide 14602 may be an indication of binding between the virus molecules in the sample solution and the antibodies coated on the surface of the multichannel waveguide 14602.
In some embodiments, the image sensor 14606 is positioned adjacent to the output end of the multichannel waveguide 14602. As described above, the image sensor 14606 can detect the shift in the vertical position of the output laser beam from the multi-channel waveguide 14602.
As described above, when the laser beam is shifted to a different position in the vertical direction, the incident angle of the laser beam may be changed, which may cause technical problems and difficulties. According to some embodiments of the present disclosure, exemplary sample testing device 14600 may comprise field lens 14608.
Referring now to fig. 146B, an exemplary enlarged view of an exemplary sample testing device 14600 is shown. In particular, fig. 146B illustrates an exemplary enlarged view of at least a portion of the exemplary sample testing device 14600 described above in connection with fig. 146A.
As described above, one of the technical problems faced by many sample testing devices is the incident angle between the lasers output from the multi-channel waveguide 14602. For example, the farther the image sensor is positioned from the output of the multi-channel waveguide 14602, the more offsets the image sensor can detect from the output of the multi-channel waveguide 14602. Another problem with the angle of incidence is the signal/energy loss caused by this angle. Only right angle positions will provide zero energy loss and zero positioning loss.
Various embodiments of the present disclosure overcome these technical challenges and difficulties and provide various technical improvements and advances. In the example shown in fig. 146B, an exemplary sample testing device 14600 can include a field lens 14608 secured to an imaging surface of an image sensor 14606. In some embodiments, the field lens 14608 may be positioned to receive a laser beam output from the multi-channel waveguide 14602.
In some implementations, the field lens 14608 can be positioned at or near an image field corresponding to the overall image sensing surface of the image sensor 14606 such that light can enter the image sensing surface of the image sensor 14606 without passing through any other imaging lenses. For example, field lens 14608 can be positioned in close proximity to a sensing area of image sensor 14606. Additionally or alternatively, field lens 14608 can be attached to a sensing region of image sensor 14606.
In some embodiments, the fixed distance between the output end of the multi-channel waveguide 14602 and the field lens 14608 may be determined based on the focal length of the field lens 14608. For example, the distance from the output end of the multi-channel waveguide 14602 to the field lens 14608 may be matched by the focal length of the field lens 14608. Thus, the field lens 14608 may correct the incident angle of the output from the multi-channel waveguide 14602 when it is positioned at such a fixed distance from the output of the multi-channel waveguide 14602. After correction, light enters the sensing surface of image sensor 14606 at a normal angle. Thus, various embodiments may normalize the angle of incidence to the sensor pixels over the entire field of view of the image sensor 14606 to generate an undistorted fringe pattern image, which may enhance the sensitivity of the image sensor 14606 to detect laser beams exiting the multichannel waveguide 14602.
Referring now to fig. 146C and 146D, an exemplary side view and an exemplary enlarged view of an exemplary sample testing device 14600 according to some embodiments of the present disclosure are shown.
With field lens 14608 in place, all light exiting the lens and entering the illustrated transmitting surface will be parallel to the lens optical axis, as shown in fig. 146C and 146D. Accordingly, various embodiments of the present disclosure can correct the angle of light incident to the image sensor to obtain uniform and efficient light, and correct the angle of light normally incident to the sensor pixels over the entire field of view to obtain a fringe pattern image without distortion.
Referring to fig. 147A and 147B, an exemplary field lens 14700 is shown in accordance with some embodiments of the present disclosure. In particular, fig. 147A shows an exemplary perspective view of an exemplary field lens 14700, and fig. 147B shows an exemplary side view of an exemplary field lens 14700.
In the example shown in fig. 147A and 147B, the exemplary field lens 14700 may be in the form of a plano-convex single lens. For example, exemplary field lens 14700 may include a curved surface that provides a positive focal length. The curvature of exemplary field lens 14700 may bend the angle of incidence of light such that light enters the sensing region of the image sensor at or near a right angle in order to reduce and/or eliminate signal loss caused by the angle difference.
Thus, the exemplary field lens 14700 shown in fig. 147A and 147B can correct the angle of incidence of light into the image sensor and can provide the various technical benefits and improvements described herein. For example, as described above, interferometric sensing may suffer from sensor angular response problems in which the actual fringe pattern image is distorted and fringe offset detection is lower than the actual offset. This requires a more appropriate solution. By attaching the exemplary field lens 14700 to the sensing surface of the image sensor, various embodiments of the present disclosure may use the exemplary field lens 14700 in front of the image sensor to correct the angle of light incident to the image sensor such that the light will be perpendicular to the image sensor. Here, the focal length of the field lens matches the distance from the exit pupil.
There are many technical challenges and difficulties associated with treating viruses. For example, a virus may have multiple variants, each of which may be associated with a particular mechanism of infection, and each of which may also be responsive to different antibodies and treatments (including therapeutic antibody mixtures). Spike proteins may be the primary mechanism by which viruses (e.g., coronaviruses such as but not limited to SARS-CoV-2 virus) enter host cells. Therapeutic antibodies have gained popularity as a treatment option for people with disease. In particular, SARS-CoV2 pandemic has increased the use of convalescent antibodies for the treatment of severe and prevention of death. In many examples, the therapeutic antibody mixture may include antibodies that are generally semi-specific for a particular variant. Exemplary therapeutic antibody mixtures may be ineffective because the injected antibodies do not have the correct binding coefficients for spike proteins on a particular variant (e.g., a variant of the SARS-CoV-2 virus). However, conventional techniques do not use analysis of spike proteins within a given virus sample as a basis for determining optimal treatment. In particular, therapeutic antibodies may primarily recognize/interact with spike proteins on the outer surface of the virus. However, spike proteins may not be retained when the virus is mutated, and thus antibodies directed against early variants may be ineffective against new variants. There is a need for a rapid way of diagnosing the type and/or extent of spike protein mutations within an infection-causing virus to facilitate rapid identification of optimal treatment.
Various embodiments of the present disclosure overcome these technical challenges and difficulties and satisfy these needs. For example, various embodiments of the present disclosure may facilitate the use of multiple optical channels within a waveguide as discrete test channels to identify optimal therapies (e.g., therapeutic antibody mixtures) for treating particular variants of a virus. For example, various embodiments of the present disclosure can determine that a confirmed/positive viral sample (e.g., a SARS-CoV2 viral sample of a particular patient) is associated with at least one known variant or unknown variant. In some embodiments, multiple channels of the waveguide may be treated or coated with different antibodies or nanobodies that are known to be highly selective for specific spike protein mutations (in the receptor binding Regions (RBDs)). The resulting signals obtained using these waveguides can be used to identify therapies (e.g., therapeutic antibodies or nanobodies) that can be used to treat a particular infection/individual.
In some embodiments, a computer-implemented method for determining an optimal treatment for a known virus sample using a sample testing device comprising a plurality of sample channels is provided. In some embodiments, the computer-implemented method causes a known virus sample to be provided to the plurality of sample channels, wherein each sample channel of the plurality of sample channels comprises an antibody or nanobody associated with a particular variant; recording a plurality of sample signals received from the plurality of sample channels using an imaging component of the sample testing device; and responsive to determining that the at least one sample signal amplitude meets a predetermined threshold, determining an optimal treatment based at least in part on the relative sample signal amplitude for each of the plurality of sample channels. In some examples, the known virus sample is SARS-CoV2. In some examples, each sample signal amplitude is associated with a concentration amount of a variant of a known virus sample. In some examples, each sample channel of the plurality of sample channels comprises an antibody or nanobody that is selective for a spike protein associated with each variant. In some examples, the optimal treatment comprises a therapeutic antibody mixture or a therapeutic nanobody mixture.
Referring now to fig. 148, an exemplary schematic diagram illustrating an exemplary waveguide 14800 according to various embodiments of the present disclosure is provided. The exemplary waveguide 14800 may be similar or identical to the exemplary waveguides discussed herein. Similarly, as depicted, the exemplary waveguide 14800 includes a plurality of sample channels (e.g., sample channels 14802). In various embodiments, each sample channel may be coated with a specific type of antibody or nanobody associated with a known variant of the virus. For example, a first sample channel may be coated with an antibody or nanobody associated with a first known variant of a virus (e.g., variant 1 of SARS-CoV2 virus), a second sample channel may be coated with an antibody or nanobody associated with a second known variant of a virus (e.g., variant 2 of SARS-CoV2 virus), and so on. In various embodiments, the sample (e.g., a validated sample of a particular virus, such as but not limited to SARS-CoV2 virus) is provided through each of the waveguide sample channels. In some embodiments, the sample is provided through a sample channel. For example, the sample depicted in fig. 148, including virus 14806, flows through sample channel 14802, similar to the various embodiments described herein.
In various embodiments, when a validated sample of a particular virus flows through a plurality of sample channels, the virus sample may interact differently with different antibodies or nanobodies coating each sample channel of the plurality of sample channels to generate a different signal amplitude for each respective sample channel. In some embodiments, the interferometrically modulated light beams of multiple optical modes (e.g., two modes) within an exemplary waveguide exit the waveguide at a particular deflection angle. In various examples, the relative magnitudes of deflection angles across the plurality of waveguide channels correspond to specific spike proteins/variants within the virus sample.
In some examples, the antibodies or nanobodies disposed within the sample channel may be particularly sensitive to certain spike proteins of the virus sample. For example, if a virus sample contains a particular type and variant of virus, and the surfaces of a plurality of sample channels are each coated with antibodies or nanobodies to a particular known variant, the virus may strongly bind and/or adhere to antibodies or nanobodies within at least one of the plurality of sample channels as the virus sample travels through the plurality of sample channels. Thus, an increase in the number of virions at the surface of at least one sample channel (due to chemical and/or biological reactions between antibodies/nanobodies and virions) can cause a change in the refractive index of the at least one sample channel, which is recorded as a change in the angle at which light leaves the waveguide. In various examples, when laser 14808 emits a laser beam within the plurality of sample channels, spike protein interactions between a virus (e.g., virus 14806) and antibodies or nanobodies coating at least one channel (e.g., first sample channel 14802) may generate a measurable signal/cause a change in the angle at which light exits waveguide 14800 as detected by imaging component 14801.
Referring now to fig. 149, an exemplary schematic diagram is provided showing exemplary signal amplitudes of signals from a plurality of sample channels obtained using an exemplary waveguide according to various embodiments of the present disclosure. As depicted in fig. 149, the channels include a negative control channel 14202, a positive control channel 14404, and a plurality of sample channels. The operation of the negative control channel 14202 and the positive control channel 14904 may be similar or identical to the operation of the negative control channel and the positive control channel described elsewhere herein (e.g., in connection with fig. 148, 111, 114A, 114B, 115A, 115B, and 115C).
Specifically, as shown, the plurality of sample channels includes a first sample channel 14106 ("variant 1"), a second sample channel 1408 ("variant 2"), a third sample channel 1491 ("variant 3"), and a fourth sample channel 14912 ("variant 4"). In some embodiments, an exemplary waveguide may include more than four sample channels (e.g., eight sample channels or twelve sample channels). As described above, each waveguide channel of the plurality of waveguide channels may be provided with a known virus sample (e.g., a positive sample is confirmed). In some embodiments, when a known viral sample travels through the plurality of sample channels, a measurable electrical signal may be generated with respect to each of the plurality of sample channels. In some examples, interference fringe patterns from the plurality of sample channels may change, which may be detected and recorded by an imaging component (such as an image sensor). The interference fringe pattern can be used as a calibration signal associated with the particular type of virus, presence of variants, and concentration levels. For example, the signal amplitude of each calibration signal may be recorded.
In various embodiments, each of the first, second, third, and fourth sample channels 14106, 1496, 14910, 14912 may be coated with antibodies or nanobodies associated with a particular variant of a virus (e.g., the first sample channel 14106 may be coated with antibodies or nanobodies sensitive to variant 1 of a virus). The virus sample may interact differently with antibodies or nanobodies within each of the plurality of waveguide sample channels. In various examples, the imaging sensor may record signal/interference fringe patterns from the first sample channel 14106, the second sample channel 14108, the third sample channel 14910, and the fourth sample channel 14912. In some examples, the virus may more fully interact/bind with antibodies or nanobodies disposed in at least one sample channel (e.g., first sample channel 14106, second sample channel 14108, third sample channel 14910, and/or fourth sample channel 14912) and thus generate a higher signal amplitude relative to the at least one sample channel.
In the example shown in fig. 149, the virus sample interacts more with the antibodies or nanobodies disposed in the first sample channel 14106 ("variant 1"), resulting in a stronger signal amplitude for the first sample channel 14106 as compared to the second, third, and fourth sample channels 1498, 1491, 14912. In various embodiments, the signal amplitude is further indicative of the concentration or value (e.g., approximation/amount of spike protein) of each variant within the virus sample and the binding coefficient of the variant to the antibody/nanobody coated on the sample channel. In various examples, the signal amplitude may be related to both the concentration of the variant/virus and the binding kinetics of the virus to the specific antibody.
As shown in fig. 149, in addition to the relatively high signal amplitude generated with respect to the first sample channel 1496, non-zero signal amplitudes are generated with respect to the second, third and fourth sample channels 1499, 14912. The variation in the interference fringe pattern from the first sample channel 14106 may be more pronounced than the variation in the interference fringe pattern from the second, third, and fourth sample channels 1499, 14912. Thus, the therapeutic antibody mixture may be designed/formulated to include antibodies or nanobodies to each variant (e.g., variant 1, variant 2, variant 3, and variant 4) present in the viral sample based at least in part on the determined concentration (e.g., approximation/amount of spike protein) associated with each variant in the viral sample.
Referring now to fig. 150, an exemplary schematic diagram illustrating exemplary signal magnitudes of a calibration signal from an exemplary waveguide is provided.
In the example shown in fig. 150, the exemplary waveguide channel includes two control/reference channels, including a (-) control channel 15002 and a (+) control channel 15004. The exemplary waveguide channel also includes four sample channels, including a first sample channel 15006 (e.g., a "variant 1" or SARS-CoV2 variant 1 test channel), a second sample channel 15008 (e.g., a "variant 2" or SARS-CoV2 variant 2 test channel), a third sample channel 1501480 (e.g., a "variant 3" or SARS-CoV2 variant 3 test channel), and a fourth sample channel 15012 (e.g., a "variant 4" or SARS-CoV2 variant 4 test channel). Each of the first sample channel 15006, the second sample channel 15008, the third sample channel 15010, and the fourth sample channel 15012 may be coated with antibodies or nanobodies that are specific (e.g., have affinity) for the variant with which they are associated.
In the example shown in fig. 150, the virus sample (in particular, the spike protein contained therein) interacts more with the antibodies or nanobodies disposed in the fourth sample channel 15012 ("variant 4"), resulting in a stronger signal amplitude for the fourth sample channel 15012 compared to the first sample channel 15006, the second sample channel 15008, and the third sample channel 15010. The signal amplitude generated within each channel is further indicative of the concentration (e.g., approximation/amount of spike protein) of each variant within the virus sample. As shown, in addition to generating a relatively high signal amplitude with respect to the fourth sample channel 15012, a non-zero signal amplitude is generated with respect to the first sample channel 15006 and the third sample channel 15010. However, the signal generated with respect to the second sample channel 15008 is approximately 0 in amplitude. In other words, the variation in the interference fringe pattern from the fourth sample channel 15012 is more remarkable than the variation in the interference fringe patterns from the first sample channel 15006, the second sample channel 15008, and the third sample channel 15010. Thus, the therapeutic antibody mixture may be designed to include antibodies or nanobodies against each variant (e.g., variant 1, variant 3, and variant 4) present in the viral sample based at least in part on the determined concentration (e.g., approximation/amount of spike protein) associated with each variant in the viral sample. For example, a therapeutic antibody mixture may include 70% antibody/nanobody against variant 4, 15% antibody/nanobody against variant 1, and 15% antibody/nanobody against variant 3.
In referring to fig. 151, an exemplary schematic diagram illustrating exemplary signal magnitudes of calibration signals from an exemplary waveguide is provided.
In the example shown in fig. 151, the exemplary waveguide channel includes two control/reference channels, including a (-) control channel 15102 and a (+) control channel 15104. The exemplary waveguide channel also includes four sample channels, including a first sample channel 15106 (e.g., a "variant 1" or SARS-CoV2 variant 1 test channel), a second sample channel 15108 (e.g., a "variant 2" or SARS-CoV2 variant 2 test channel), a third sample channel 15110 (e.g., a "variant 3" or SARS-CoV2 variant 3 test channel), and a fourth sample channel 15112 (e.g., a "variant 4" or SARS-CoV2 variant 4 test channel). Each of the first, second, third, and fourth sample channels 15106, 15108, 15110, 15112 may be coated with antibodies or nanobodies specific for the variant with which it is associated.
In the example shown in fig. 151, the virus sample (specifically, the spike protein contained therein) interacts more with the antibodies or nanobodies disposed in the first sample channel 15106 ("variant 1") and the fourth sample channel 15112 ("variant 4"), resulting in stronger signal amplitudes for the first sample channel 15106 and the fourth sample channel 15112 compared to the second sample channel 15108 and the third sample channel 15110. The signal amplitude generated within each channel is further indicative of the concentration of the viral variant (e.g., approximation/amount of spike protein) and the strength of the interaction of the variant with the antibody/nanobody on the waveguide channel (e.g., binding kinetics). As shown, in addition to the relatively high signal amplitudes generated with respect to the first and fourth sample channels 15106, 15112, a non-zero signal amplitude is generated with respect to the third sample channel 15110 and a signal amplitude approaching 0 is generated with respect to the second sample channel 15108. Therefore, the variation in the interference fringe pattern from the first sample channel 15106 and the fourth sample channel 15112 is more remarkable than the variation in the interference fringe pattern from the second sample channel 15108 and the third sample channel 15110. Thus, the therapeutic antibody mixture may be designed/formulated to include antibodies or nanobodies to each variant (e.g., variant 1, variant 4, and variant 3) present in the viral sample based at least in part on the determined concentration (e.g., approximation/amount of spike protein) associated with each variant in the viral sample. For example, a therapeutic antibody mixture may include 45% antibody/nanobody to variant 1, 45% antibody/nanobody to variant 4, and 10% antibody/nanobody to variant 3. It should be appreciated that in instances where all signal amplitudes of the plurality of waveguide channels are near 0 and/or each signal amplitude fails to meet a predetermined threshold, it may be inferred that there may be no viable therapeutic antibody mixture for the viral sample being tested based on known variants in the plurality of waveguide channels.
Referring now to fig. 152, a computer-implemented method 15200 for determining an optimal treatment (e.g., therapeutic antibody mixture) using a sample testing device is provided. In some embodiments, the sample testing device is a waveguide comprising a plurality of sample channels. In some embodiments, the sample testing device further comprises a positive control channel and a negative control channel.
In some examples, method 15200 may be performed by a processing circuit, such as, but not limited to, an Application Specific Integrated Circuit (ASIC) or a Central Processing Unit (CPU). In some examples, the processing circuitry may be electrically coupled to and/or in electronic communication with other circuitry of the example apparatus, such as, but not limited to, sensing elements, memory (such as, for example, random Access Memory (RAM) for storing computer program instructions), and/or display circuitry (for presenting readings on a display).
In some examples, one or more of the programs described in fig. 152 may be embodied by computer program instructions that may be stored by a memory (such as a non-transitory memory) of a system employing embodiments of the present disclosure and executed by a processing circuit (such as a processor) of the system. These computer program instructions may direct a system to function in a particular manner, such that the instructions stored in the memory circuit produce an article of manufacture including instructions which implement the function specified in the flowchart step/operation. In addition, the system may include one or more other circuits. The various circuits of the system may be electrically coupled to and/or in each other to transmit and/or receive energy, data, and/or information.
In some examples, the embodiments may take the form of a computer program product on a non-transitory computer-readable storage medium storing computer-readable program instructions (e.g., computer software). Any suitable computer readable storage medium may be utilized including non-transitory hard disks, CD-ROMs, flash memory, optical storage devices, or magnetic storage devices.
The exemplary method 15200 begins at step/operation 15202. At step/operation 15202, method 15200 includes causing a known virus sample (e.g., a confirmed/positive SARS-CoV2 sample) to be provided to the plurality of sample channels. In some embodiments, each sample channel of the plurality of sample channels is coated with an antibody or nanobody associated with (e.g., sensitive to) a different variant of the virus. For example, a first sample channel may be coated with antibody/nanobody A1 associated with variant 1, a second sample channel may be coated with antibody/nanobody A2 associated with variant 2, and a third sample channel may be coated with antibody/nanobody A3 associated with variant 3. In some embodiments, variant 1, variant 2, and variant 3 are variants of the same virus (e.g., SARS-CoV 2).
In some embodiments, when a known virus sample is provided to the plurality of sample channels, the interference fringe pattern from the plurality of sample channels may change. For example, spike proteins within the SARS-CoV-2 virus can more tightly bind/attach to antibodies or nanobodies in at least one sample channel of the waveguide, thereby causing a change in the evanescent wave of the waveguide, which in turn can alter the interference fringe pattern from the waveguide. In some examples, if the virus sample contains a particular variant and the surface of the sample channel of the waveguide is not coated with antibodies to that variant, there may still be minimal chemical and/or biological reactions (interactions between spike proteins and antibodies or nanobodies) that may cause detectable/measurable interference fringe pattern changes that may not be as significant as the changes observed when the surface of the sample channel is coated with antibodies or nanobodies to that variant.
After step/operation 15202, the method 15200 proceeds to step/operation 15204. At step/operation 15204, the example method 15200 includes recording (e.g., obtaining) a plurality of signals received from each of the plurality of sample channels (e.g., as detected by the imaging component). As described above, when a known virus sample travels through the plurality of sample channels, the interference fringe pattern from the plurality of sample channels may change based on the concentration (e.g., approximation/amount of spike protein) that can be detected and recorded by an imaging component, such as an image sensor.
After step/operation 15204, the method 15200 proceeds to step/operation 15206. At step/operation 15206, the method 15200 includes determining whether at least one signal amplitude meets a predetermined threshold (e.g., a value indicative of a concentration of a variant or an amount of spike protein). For example, the signal amplitude range may be between 0 and 1, and an exemplary predetermined threshold may be 0.5. Thus, if the recorded signal amplitude of the first sample channel is 0.7, the processor may determine that the signal amplitude of the sample channel meets a predetermined threshold. Conversely, if the recorded signal amplitude of the second sample channel is 0.2, the processor may determine that the signal amplitude of the second sample channel does not meet the predetermined threshold. In some examples, each sample channel (i.e., each variant) may be associated with a different predetermined threshold. In some embodiments, step/operation 15204 includes comparing the relative signal magnitudes received from the sample channel. As described above in connection with fig. 149, 150, and 151, the relative signal amplitude detected with respect to each sample channel may correspond to the concentration of the variant (e.g., an approximation or amount of spike protein) in the virus sample.
After step/operation 15206, the method 15200 proceeds to step/operation 15208. At step/operation 15208, the method 15200 comprises determining an optimal treatment (e.g., therapeutic antibody mixture) based at least in part on the relative signal magnitudes meeting a predetermined threshold. For example, a known virus sample may include variant 1 at a concentration of 70%, variant 2 at a concentration of 15%, and variant 3 at a concentration of 0% (based on the relative signal amplitude associated with/obtained from each sample channel). In the above examples, the optimal therapy/antibody mixture for the virus sample may be or include 70% antibodies or nanobodies against variant 1 and 15% antibodies or nanobodies against variant 2.
As another example, a known virus sample may include variant 1 of 0% concentration amount/value, variant 2 of 1% concentration amount/value, and variant 3 of 0% concentration amount/value. In the above example, each signal amplitude may also fail to meet a predetermined threshold. Thus, the processor may determine that no optimal therapy (e.g., a therapeutic antibody mixture) is available for the virus sample (i.e., the virus sample is associated with one or more unknown variants).
As another example, a known virus sample may include only variant 1 in a concentration amount/value of 70% (e.g., it may also be a value above a threshold). Thus, the processor may determine that the optimal therapy/antibody mixture for the virus sample may be 100% antibodies or nanobodies against variant 1.
As described above, a sample testing device according to an exemplary embodiment of the present disclosure may determine a type associated with a sample (e.g., a type of virus contained in the sample) based on interferometric sensing. For example, the sample testing device may include a waveguide having a plurality of channels, and a light source (such as, but not limited to, a laser diode) may emit a light beam through the plurality of channels, forming an interference fringe pattern as the light beam exits from the plurality of channels. In some embodiments, a sample may be injected into the plurality of channels, and one or more surfaces of the plurality of channels may be coated with one or more types of antibodies against one or more types of viruses. If the sample contains virus and the surface of the sample channel is coated with antibodies to the virus of that type/variant, the antibodies attract the virus to the surface as the sample travels through the channel. Chemical and/or biological reactions between antibodies and viruses can cause changes in the evanescent wave of the waveguide, which in turn can alter the interference fringe pattern from the waveguide.
In some embodiments, the sample testing device includes an imaging component (such as, but not limited to, an imager and/or an image sensor) that detects an interference fringe pattern from the waveguide and generates interferometric sensed data based on the detected interference fringe pattern. In some embodiments, the sample testing device is also referred to as an interferometric sensor.
As shown in the above example, interferometric sensing relies on a light source to generate an interference fringe pattern. In some embodiments, the light or light beam emitted by the light source may be represented or modeled as a light wave. In some embodiments, light waves may be described or modeled as electromagnetic waves. For example, an oscillating electric field generates an oscillating magnetic field, which in turn generates an oscillating electric field and generates light.
In some embodiments, the light source may be in the form of a laser source (such as, but not limited to, a laser diode) that emits a laser beam. In such an example, the laser beam may be represented or modeled as a sinusoidal form of light waves (also referred to as sinusoidal light waves). In this disclosure, the term "optical phase" refers to the phase of a positive-chord optical wave. In some embodiments, the optical phase is in the form of an angular measurement relative to a complete cycle of the sinusoidal optical wave. In such an example, two points in the sinusoidal wave may have the same phase when they represent the same angular measure over the complete cycle of the sinusoidal wave. In some embodiments, the phase of the sinusoidal light wave may be represented as an offset angle value that is offset from the initial phase of the sinusoidal light wave.
In some embodiments, a complete cycle of sinusoidal light corresponds to a single complete oscillation cycle of the electric field that generates the light. In this example, the optical phase refers to the phase of the oscillation cycle of the electric field.
As described above, interferometric sensing may detect small physical changes such as, but not limited to, length, material refractive index, and the like. The interferometric sensed output is in the form of a sinusoid. Referring now to fig. 153, an exemplary plot 15300 illustrates exemplary interferometric sensed data 15301. In some embodiments, the exemplary interferometric sensed data indicates a correlation between the optical phase (X-axis) of the light from the light source and the output (Y-axis) from the interferometric sensor.
For example, as described above, according to some embodiments of the present disclosure, the light source may be in the form of a laser source (such as, but not limited to, a laser diode) that emits a laser beam through a waveguide. In some embodiments, the waveguide includes a first waveguide portion and a second waveguide portion, similar to those described above. In some embodiments, the laser beam propagates through the waveguide and creates an interference fringe pattern.
As described above, the interferometric sensor may include an imaging component that detects the interference fringe pattern. In some embodiments, the interferometric sensor may generate an output (e.g., by the imaging component) indicative of the light intensity or fringe pattern displacement of the interference fringe pattern. In the example shown in fig. 153, the light intensity or fringe pattern displacement of the interference fringe pattern is highest when the output (Y axis) is 1, and the light intensity or fringe pattern displacement of the interference fringe pattern is lowest when the output (Y axis) is-1. For example, the interference fringe pattern includes a plurality of bright spots/bands and a plurality of dark spots/bands. The plurality of bright spots/bands of the interference fringe pattern are brightest and the plurality of dark spots/bands of the interference fringe pattern are darkest when the light intensity or fringe pattern displacement of the interference fringe pattern is highest (e.g., when the output on the Y-axis indicates 1). The plurality of bright spots/bands of the interference fringe pattern are darkest and the plurality of dark spots/bands of the interference fringe pattern are brightest when the light intensity or fringe pattern displacement of the interference fringe pattern is lowest (e.g., when the output on the Y-axis indicates-1). In other words, when the output of the Y-axis is changed from 1 to-1, the bright spots/bands of the interference fringe pattern become dark spots/bands and the dark spots/bands of the interference fringe pattern become bright spots/bands, or the bright fringe pattern position is moved to the dark fringe pattern position and the dark fringe pattern position is moved to the bright fringe pattern position.
The exemplary plot 15300 shown in fig. 153 shows that the correlation between the optical phase (X-axis) of the light from the light source and the output (Y-axis) from the interferometric sensor is sinusoidal in nature rather than linear. Therefore, the rate of change of the output (Y axis) fluctuates with the change of the optical phase (X axis).
For example, when the optical phase (X-axis) starts at 0 degrees, the output from the interferometric sensor may provide an approximately linear response. Specifically, the rate of change of the output (Y-axis) is at its peak value, as indicated by the slope of the output from the interferometric sensor being at the highest value. As the optical phase (X-axis) increases and approaches 90 degrees, the rate of change of the output (Y-axis) slows down as indicated by the decreasing slope of the output from the interferometric sensor.
When the optical phase (X-axis) reaches 90 degrees, the rate of change of the output (Y-axis) is at its lowest point, as indicated by the slope of the output from the interferometric sensor being at a minimum. As the optical phase (X-axis) continues to increase and approaches 180 degrees, the rate of change of the output (Y-axis) increases, as indicated by the increase in slope of the output from the interferometric sensor.
When the optical phase (X-axis) reaches 180 degrees, the output from the interferometric sensor may provide an approximately linear response. Specifically, the rate of change of the output (Y-axis) is at its peak value, as indicated by the slope of the output from the interferometric sensor being at the highest value. As the optical phase (X-axis) continues to increase and approaches 270 degrees, the rate of change of the output (Y-axis) decreases, as indicated by the decreasing slope of the output from the interferometric sensor.
When the optical phase (X-axis) reaches 270 degrees, the rate of change of the output (Y-axis) is at its lowest point, as indicated by the slope of the output from the interferometric sensor being at a minimum. As the optical phase (X-axis) continues to increase and approaches 360 degrees, the rate of change of the output (Y-axis) increases, as indicated by the increase in slope of the output from the interferometric sensor.
When the optical phase (X-axis) reaches 360 degrees, the slope of the output from the interferometric sensor (Y-axis) is again at its highest value.
As shown in the above example, exemplary interferometric sensed data 15301 includes outputs from interferometric sensors associated with the orthogonal points and outputs associated with the extreme points. At the intersection points (such as but not limited to 0 degrees, 180 degrees, 360 degrees), the result has a maximum and near linear responsivity. At extreme points (such as but not limited to 90 degrees, 270 degrees) the result has minimal responsivity due to sign changes.
In this disclosure, the term "orthogonal point" refers to a segment of interferometric sensed data or a point associated with interferometric sensed data, where the output response is linear or nearly linear with respect to the optical phase. In particular, when the output is linear or nearly linear with respect to the optical phase, the rate of change of the output is highest, and the output is most sensitive to optical phase changes (and thus provides a good response). For example, a change in the phase of light at or near the intersection point may cause a proportional change in the output from the interferometric sensor. In the example shown in fig. 153, the orthogonal points of exemplary interferometric sensed data 15301 include, but are not limited to, 0 degree optical phase, 180 degree optical phase, 360 degree optical phase, and 540 degree optical phase. For example, the output at 0 degrees may be considered linear or nearly linear, and the output at 180 degrees may also be considered linear (but with the opposite sign compared to the output at 0 degrees). Such points are good and usable points.
In this disclosure, the term "extremum point" refers to a segment of interferometric sensed data or a point associated with interferometric sensed data, where the output response is not linear with respect to the optical phase. In particular, when the output is not linear to the optical phase, the rate of change of the output is the slowest and the output is least sensitive to optical phase changes (and thus provides an adverse response). For example, a change in the phase of light at or near the extreme point may not cause a change in the output from the interferometric sensor. In the example shown in fig. 153, the orthogonal points of exemplary interferometric sensed data 15301 include, but are not limited to, 90 degrees optical phase, 270 degrees optical phase, 450 degrees optical phase, and 630 degrees optical phase.
As shown in the examples above, interferometric sensing based on sinusoidal response output faces a number of technical problems. While the portion of interferometric sensed data associated with the orthogonal point may provide good, usable data because the output response is linear to changes in optical phase, the portion of interferometric sensed data associated with the extreme point provides poor, unusable data because the output response is nonlinear to changes in optical phase. While the responsivity may peak at a linear point (e.g., at a positive intersection point), there is a loss of responsivity at a non-linear point (e.g., at an extreme point). For example, a change in optical phase that occurs near a positive intersection point (such as 0 degrees and 180 degrees) may cause a proportional change in output, but the same change in optical phase that occurs near an extreme point (such as 90 degrees and 270 degrees) may not cause the same amount of change. Thus, the output associated with the extreme point cannot be used to reflect the actual change detected by interferometric sensing.
Furthermore, non-linear points (such as extreme points) also present technical challenges, such as periodic blurring due to sign changes occurring at extreme points. For example, while the output from the interferometric sensor may increase before the optical phase reaches the extreme point, the output from the interferometric sensor may begin to decrease after the optical phase reaches the extreme point. Therefore, the amount of change in the output from the interferometric sensor when the optical phase passes through the extreme point cannot accurately reflect the change in the optical phase. For example, the output at the 45 degree optical phase is the same as the output at the 135 degree optical phase, but the change in the output response (i.e., 0) is not linear to the change in the optical phase (i.e., 90 degrees). Thus, the output data is only related to the nearest extreme point. For example, the value of the output data is changed in sign every 180 degrees to mirror the value of the output data, and the value of the output data is repeated every 360 degrees.
Referring now to fig. 154, 155, and 156, exemplary diagrams illustrating exemplary interferometric sensing data sets are provided. In particular, figures 154, 155, and 156 illustrate various exemplary technical challenges and difficulties associated with analyzing and processing output from interferometric sensors.
In the example shown in fig. 154, an exemplary plot 15400 illustrates ideal responsiveness of output from an interferometric sensor over a sampling period. In particular, exemplary plot 15400 illustrates an ideal case where the output from an interferometric sensor has a transient change when a physical change in the waveguide (e.g., a change in the refractive index of the material due to injection of a sample solution) is detected.
In some embodiments, only one liquid (e.g., buffer solution) is present in the waveguide prior to the sampling time segment 15402 shown in fig. 154. Thus, the output from the interferometric sensor may indicate 0.
In some embodiments, a sample solution may be injected into the sample channel at the beginning of the sampling time segment 15402, such that the output from the interferometric sensor increases (e.g., reflecting a change in the interference fringe pattern from the waveguide). In some embodiments, the sample solution may continue to flow in the sample channel of the waveguide during the sampling time segment 15402 such that the output from the interferometric sensor is maintained at a high level to indicate the presence of the sample solution in the waveguide.
In some embodiments, the injection of the sample solution stops at the end of the sampling time segment 15402. In some embodiments, only one liquid is present in the waveguide after the sampling time segment 15402, and the output from the interferometric sensor returns to 0.
As described above, the graph 154 depicts an ideal case where the output is perfectly responsive to the input. Because interferometric sensing relies on interference fringe patterns and light sources, the output from interferometric sensors in the real world is not perfectly responsive to injection of sample solution.
In the example shown in fig. 155, an example diagram 15500 illustrates linearized interferometric sensed data based on output from an interferometric sensor over a sampling period. In particular, exemplary diagram 15500 illustrates a case where the output from the interferometric sensor provides a delay but good response when a physical change in the waveguide (e.g., a change in the refractive index of the material due to injection of a sample solution) is detected.
In some embodiments, only one liquid (e.g., buffer solution) is present in the waveguide prior to the sampling time segment 15501 shown in fig. 155. Thus, the output from the interferometric sensor may indicate 0.
In some embodiments, the sample solution may be injected into the sample channel at the beginning of the sampling time segment 15501. As shown in fig. 155, there is a delay between the time of injection of the sample solution and the time of the output from the interferometric sensor increasing to a maximum value. Even with a time delay, the output from the interferometric sensor still provides good responsiveness to injection of the sample solution. For example, as shown in fig. 155, as the sample solution continues to be injected into the waveguide, the output value from the interferometric sensor continues to increase.
In some embodiments, the injection of the sample solution is stopped at the end of the sampling time segment 15501. In some embodiments, only one liquid is present in the waveguide after the sampling time segment 15501, and the output from the interferometric sensor returns to 0.
As described above, fig. 155 shows a case where an output provides good responsiveness to an input. While the example graph 15500 shown in fig. 155 does not provide for a transient change in output when a physical change in the waveguide is detected (as shown in the example graph 15400 shown in fig. 154), the example graph 15500 shows an increase in output from the interferometric sensor when sample solution is injected and a decrease in output from the interferometric sensor when injection of sample solution ceases. Thus, the linearized interferometric sensed data illustrated in fig. 155 may provide sufficient responsiveness for interferometric sensing.
In the example shown in fig. 156, exemplary diagram 15600 shows interferometric sensed data based on output from the interferometric sensor over a sampling period and the interferometric sensed data is not linearized. In particular, exemplary diagram 15600 illustrates output from interferometric sensors that may be affected by optical phase changes.
In some embodiments, only one liquid (e.g., buffer solution) is present in the waveguide prior to sampling time segment 15602 shown in fig. 156. Thus, the output from the interferometric sensor may indicate 0.
In some embodiments, sample solution may be injected into the sample channel at the beginning of sampling time segment 15602 such that the output from the interferometric sensor increases (e.g., reflecting a change in the interference fringe pattern from the waveguide). Similar to those described above in connection with fig. 155, there is a delay between the time of injection of the sample solution and the time of the output from the interferometric sensor increasing to a maximum value.
However, after the optical phase reaches an extreme point (such as 90 degrees), the output starts to decrease due to the sign change even if the sample solution is continuously injected into the waveguide. After the optical phase passes another extreme point (such as 270 degrees), the output starts to increase due to another sign change. Thus, the output from the interferometric sensor does not reflect the actual state of the waveguide.
In some embodiments, the concentration level of the sample solution in the waveguide may change as the sample solution is continuously injected into the sample channel of the waveguide. The change in concentration level of the sample solution may in turn affect the output from the interferometric sensor. For example, as shown in exemplary diagram 15600, a change in the concentration level of the sample solution may cause a change in the amplitude of the output from the interferometric sensor.
In some embodiments, injection of sample solution stops at the end of sampling time segment 15602. As shown in the exemplary graph 15600 of fig. 156, there is a delay between the time the injection of the sample solution is stopped and the time the output from the interferometric sensor returns to 0. For example, even if injection of the sample solution ceases, the output from the interferometric sensor may continue to increase due to the sign of the optical phase change.
Thus, the exemplary diagram 15600 shown in fig. 156 illustrates an example in which optical phase changes affect the output from an interferometric sensor. For example, after the injection of the sample solution begins, the sign change of the optical phase may cause the output from the interferometric sensor to decrease even though the sample solution is being injected into the waveguide. As another example, even if injection of the sample solution has stopped after the injection of the sample solution has stopped, another sign change in the optical phase may cause an increase in the output from the interferometry sensor.
Thus, it is desirable to optimize the output from the interferometric sensor in sinusoidal form to obtain continuous linear response results. Various examples of the present disclosure overcome these technical challenges and difficulties and provide various technical benefits and improvements. For example, various embodiments of the present disclosure utilize multi-wavelength sensing to capture results with different initial phases and combine the results with different initial phases to eliminate and replace data associated with near extremum points with data associated with near positive intersection points. In some embodiments, linearizing interferometric sensing data can ensure optimal sensing performance without requiring complex modifications to the sensors and instruments.
In particular, an exemplary multi-wavelength interferometric sensor may include a tunable laser source to provide input light at multiple wavelengths or initial optical phases and may sense physical changes in the waveguide, such as changes in length or refractive index. During operation, the tunable laser source may scan multiple wavelengths and sensor results are recorded in multiple data sets associated with different wavelengths. In some embodiments, different data sets having different wavelengths have different initial phases. In some implementations, the final output data is the result of classifying, searching, linearizing, and combining multiple interferometric sensing data sets from scanning multiple wavelengths, the details of which are described herein. For example, interferometric sensed data is reconstructed by piecewise search, linearization, and combining, the details of which are described herein.
In some embodiments, the tunable laser source may only provide certain limited wavelengths due to mode hopping and laser stability. In such an embodiment, interferometric sensed data may be classified and the range of data that may be actually used may be determined. For example, exemplary embodiments of the present disclosure may select a wavelength range (or initial optical phase) associated with a laser based on identifying interferometric sensed data sets having slopes that meet a predetermined threshold/range and selecting the wavelength range associated with these interferometric sensed data sets. In some embodiments, the overlap in the data ranges may be arranged to take full advantage of the usable range of data to reduce transitional errors. In some implementations, transition noise may be reduced by averaging and/or filtering the data. For example, when there are multiple interferometric sensed data sets with slopes that meet a predetermined threshold/range, exemplary embodiments of the present disclosure may average and/or filter the interferometric sensed data sets.
Referring now to fig. 157, an exemplary method 15700 is shown according to some embodiments of the present disclosure. In particular, the example method 15700 linearizes and recovers interferometric sensed data from the example interferometric sensor, wherein the interferometric sensed data is in a sinusoidal form.
In the example shown in fig. 157, the example method 15700 begins at step/operation 15701. In some embodiments, after and/or in response to step/operation 15701, the example method 15700 proceeds to step/operation 15703. At step/operation 15703, a processor (such as, but not limited to, processor 2702 described above in connection with fig. 45, processor 2802 described above in connection with fig. 46, etc.) receives a plurality of interferometric sensing data sets.
In some embodiments, the plurality of interferometric sensing data sets are received from a sample testing device (e.g., an exemplary interferometric sensor comprising a tunable laser source as described herein). In some embodiments, the plurality of interferometric sensing data sets includes output data captured by an exemplary interferometric sensor. For example, the plurality of interferometric sensing data sets may indicate light intensity magnitudes or fringe pattern displacement magnitudes of interference fringe patterns from the waveguide, similar to those described above.
In some embodiments, the plurality of interferometric sensing data sets are associated with a plurality of optical phases and sampling periods.
For example, the plurality of interferometric sensing data sets is based on output data collected over a sampling period. In some embodiments, the sample solution is injected into the waveguide during the sampling period. For example, the interferometric sensing dataset may comprise output data before, during, and after injection of the sample solution.
In some embodiments, the plurality of interferometric sensing data sets are associated with a plurality of light wavelength/initial light phases. For example, each of the plurality of interferometric sensing data sets is associated with one of the plurality of initial optical phases. As described above, the light source that produces the interference fringe pattern may be a tunable laser source that may produce laser light of different wavelengths and/or initial phases. In some embodiments, the tunable laser source may be continuously switched between/among different wavelengths and/or initial phases during the sampling period.
For example, the plurality of optical phases includes 0 degrees, 90 degrees, 180 degrees, and 270 degrees. In such an example, the tunable laser source may emit laser light with an initial phase of 0 degrees through the waveguide at the beginning of the sampling period. After 10 milliseconds of emitting the laser light having the initial phase of 0 degrees, the tunable laser light source stops emitting the laser light having the initial phase of 0 degrees and starts emitting the laser light having the initial phase of 90 degrees. After 10 milliseconds of emitting the laser light having the initial phase of 90 degrees, the tunable laser light source stops emitting the laser light having the initial phase of 90 degrees and starts emitting the laser light having the initial phase of 180 degrees. After 10 milliseconds of emitting the laser light having the 180 degree initial phase, the tunable laser light source stops emitting the laser light having the 180 degree initial phase and starts emitting the laser light having the 270 degree initial phase. After 10 milliseconds of emitting the laser light having the 270 degree initial phase, the tunable laser light source stops emitting the laser light having the 270 degree initial phase and starts emitting the laser light having the 0 degree initial phase. In this example, the plurality of interferometric sensing data sets includes an interferometric sensing data set associated with a laser having an initial phase of 0 degrees, an interferometric sensing data set associated with a laser having an initial phase of 90 degrees, an interferometric sensing data set associated with a laser having an initial phase of 180 degrees, and an interferometric sensing data set associated with a laser having an initial phase of 270 degrees.
Although the above description provides an example of switching the initial optical phase of the laser every 10 milliseconds, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the frequency of the initial optical phase of the switched tunable laser source may be determined based on the frequency at which different sample solutions are injected into the waveguide. In some embodiments, the switching frequency of the tunable laser source is 10 to 100 times the switching frequency of the sample solution to the waveguide. For example, if a waveguide first injects a sample solution into the waveguide for 10 seconds and then another sample solution, a tunable laser source may first emit laser light associated with one initial phase for 1 or 0.1 seconds and then emit laser light associated with another initial phase in order to provide technical benefits and advantages.
Although the above description provides an exemplary method of switching lasers having different initial phases, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary method may switch lasers having different wavelengths.
Referring now to fig. 158, an exemplary diagram illustrating a plurality of interferometric sensing datasets 15818 and an exemplary linearized interferometric sensing dataset 15816 in accordance with some embodiments of the present disclosure is provided.
In the example shown in fig. 158, an exemplary interferometric sensing dataset 15802 may be captured using a laser having an initial optical phase of 0 degrees. An exemplary interferometric sensing dataset 15804 may be captured based on using a laser with an initial optical phase of 90 degrees. An exemplary interferometric sensing dataset 15806 can be captured using a laser having an initial optical phase of 180 degrees. An exemplary interferometric sensing dataset 15808 can be captured using a laser with an initial optical phase of 270 degrees.
Referring back to fig. 157, after and/or in response to step/operation 15703, the example method 15700 proceeds to step/operation 15705. At step/operation 15705, a processor (such as, but not limited to, processor 2702 described above in connection with fig. 45, processor 2802 described above in connection with fig. 46, etc.) identifies interferometric sensed data segments from the plurality of interferometric sensed data sets.
In some embodiments, the sampling period described above in connection with step/operation 15703 is divided into a plurality of sampling time segments, and the processor may identify segments from each interferometric sensing dataset that correspond to each sampling time segment.
For example, the sampling period may be divided into 1 second sampling time segments (where each sampling time segment lasts 1 second). In some embodiments, the processor identifies interferometric sensed data segments from the plurality of interferometric sensed data sets for which data was captured in the 1 second.
As an example in connection with the graph 158, the processor may determine an interferometric sensed data segment from the interferometric sensed data set 15802 based on output data collected between 200 seconds and 201 seconds, an interferometric sensed data segment from the interferometric sensed data set 15804 based on output data collected between 200 seconds and 201 seconds, an interferometric sensed data segment from the interferometric sensed data set 15806 based on output data collected between 200 seconds and 201 seconds, and an interferometric sensed data segment from the interferometric sensed data set 15808 based on output data collected between 200 seconds and 201 seconds.
Although the above description provides an example of sampling time segments lasting 1 second, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, an exemplary sampling time segment may be less than or greater than 1 second.
Referring back to fig. 157, after and/or in response to step/operation 15705, the example method 15700 proceeds to step/operation 15707. At step/operation 15707, a processor (such as, but not limited to, processor 2702 described above in connection with fig. 45, processor 2802 described above in connection with fig. 46, etc.) calculates a slope associated with the plurality of interferometric sensed data segments identified in step/operation 15705.
In some embodiments, the plurality of interferometric sensed data segments are indicative of a plurality of light intensity magnitudes (or a plurality of fringe pattern displacement magnitudes) of an interference fringe pattern generated by the laser associated with different initial light phases/different wavelengths. For example, the plurality of light intensity magnitudes are associated with light emitted from a tunable laser source and passing through a channel of the waveguide, similar to those described above.
In some embodiments, the processor calculates a slope associated with the plurality of interferometric sensed data segments. In some implementations, the slope of the interferometric sense data segment indicates the degree of sensitivity/response of the interferometric sense data segment (e.g., light intensity magnitude) to a physical change of the waveguide.
Continuing from the example above in connection with the graph 158, the processor may calculate a slope of the interferometric sensed data segment from the interferometric sensed data set 15802 based on the output data collected between the 200 second time and the 201 second time. In such an example, the slope may indicate a degree of response of the interferometric sensed data segment from the interferometric sensed data set 15802 between 200 seconds and 201 seconds. Similarly, the processor may calculate a slope of the interferometric sense data segment from the interferometric sense dataset 15804 based on the output data collected between the 200 second time and the 201 second time. In such an example, the slope may indicate a degree of response of the interferometric sensed data segment from the interferometric sensed data set 15804 between 200 seconds and 201 seconds. Similarly, the processor may calculate a slope of the interferometric sensed data segment from the interferometric sensed data set 15806 based on the output data collected between the 200 second time and the 201 second time. In such an example, the slope may indicate a degree of response of the interferometric sensed data segment from the interferometric sensed data set 15806 between 200 seconds and 201 seconds. Similarly, the processor may calculate the slope of the interferometric sensed data segment from the interferometric sensed data set 15808 based on the output data collected between the 200 second time and the 201 second time. In such an example, the slope may indicate a degree of response of the interferometric sensed data segment from the interferometric sensed data set 15808 between 200 seconds and 201 seconds.
Referring back to fig. 157, after and/or in response to step/operation 15707, exemplary method 15700 proceeds to step/operation 15709. At step/operation 15709, a processor (such as, but not limited to, processor 2702 described above in connection with fig. 45, processor 2802 described above in connection with fig. 46, etc.) selects an interferometric sensed data segment based on the slope.
In some embodiments, the processor selects an interferometric sensed data segment from the plurality of interferometric sensed data segments identified at step/operation 15707 based on the interferometric sensed data segment associated with the highest slope of the plurality of slopes calculated at step/operation 15707.
As described above, the slope indicates the degree of response of the interferometric sensed data segment. If the slope is low, the interferometric sensed data segment is not responsive to a physical change in the waveguide (e.g., when the optical phase is at or near an extreme point as described above). As another example, if the slope is high, the interferometric sensed data segment is responsive to a physical change in the waveguide (e.g., when the optical phase is at or near the positive intersection point as described above). Thus, the processor selects an interferometric sensed data segment from the plurality of interferometric sensed data segments that is most sensitive to the physical change of the waveguide.
Continuing with the example described above in connection with fig. 158, the processor may select from the interferometric sense data set 15802 the interferometric sense data segment within the sample time segment 15810 because it has the highest slope during the sample time segment 15810. The processor may select the interferometric sensed data segment within sample time segment 15812 from interferometric sensed data set 15804 because it has the highest slope during sample time segment 15812. The processor may select the interferometric sensed data segment from the interferometric sensed data set 15806 that is within the sampling time segment 15814 because it has the highest slope during the sampling time segment 15814.
Referring back to fig. 157, after and/or in response to step/operation 15709, the example method 15700 proceeds to step/operation 15711. At step/operation 15711, a processor (such as, but not limited to, processor 2702 described above in connection with fig. 45, processor 2802 described above in connection with fig. 46, etc.) adds the interferometry sensing data segments to the linearized interferometry sensing data set.
In some implementations, the processor adds the interferometry sensing data segment selected at step/operation 15709 to have the highest slope during the sampling time segment to the linearized interferometry sensing data set.
Continuing with the example described above in connection with fig. 158, the processor may add interferometric sense data segments within the sample time segment 15810 from the interferometric sense data set 15802 to the linearized interferometric sense data set 15816. The processor may add the interferometric sense data segments within the sample time segment 15812 from the interferometric sense dataset 15804 to the linearized interferometric sense dataset 15816. The processor may add interferometric sense data segments within the sample time segment 15814 from the interferometric sense data set 15806 to the linearized interferometric sense data set 15816.
Referring back to fig. 157, after and/or in response to step/operation 15711, the example method 15700 proceeds to step/operation 15713. At step/operation 15713, a processor (such as, but not limited to, processor 2702 described above in connection with fig. 45, processor 2802 described above in connection with fig. 46, etc.) determines whether interferometric sensed data associated with each sampling time segment has been examined.
For example, at step/operation 15713, the processor determines whether the linearized interferometric sense dataset includes interferometric sense data segments from all sample time segments of the sample time period. If the interferometric sensed dataset does not include at least one interferometric sensed data segment from the at least one sampling time segment, the processor determines that not every sampling time segment has been examined. If the interferometric sensed dataset includes all interferometric sensed data segments from all sample time segments, the processor determines that each sample time segment has been examined.
If at step/operation 15713 the processor determines that interferometric sensed data associated with at least one sample time segment has not been examined, then the example method 15700 returns to step/operation 15705, wherein the example method repeats steps/operation 15705, step/operation 15707, step/operation 15709, and step/operation 15711 for segments of the plurality of interferometric sensed data sets associated with sample time segments that have not been examined.
At step/operation 15713, the processor determines that interferometric sensed data associated with each sampling time segment has been examined, and the example method 15700 proceeds to step/operation 15715. At step/operation 15715, a processor (such as, but not limited to, processor 2702 described above in connection with fig. 45, processor 2802 described above in connection with fig. 46, etc.) outputs a linearized interferometric sensed data set.
In some implementations, the processor can output a linearized interferometric sensed dataset on a user interface that is rendered on a display of the client device. For example, the processor may render the linearized interferometric sensed dataset 15816 shown in fig. 158 on a display of the client device.
Referring back to fig. 157, after and/or in response to step/operation 15715, the example method 15700 proceeds to step/operation 15717 and ends.
In the example shown in fig. 157, various embodiments of the present disclosure overcome various technical challenges and difficulties associated with processing output from interferometric sensors by capturing data having multiple initial phases, classifying, searching, linearizing, and combining the data to linearize and recover sinusoidal sensor output data.
In various embodiments of the present disclosure, a fluid channel (e.g., a sample channel) may be defined as a space between a top surface of a biosensor chip (e.g., a waveguide) and a bottom surface of a fluid cap. In some embodiments, the biosensing sensitivity of the biosensor chip may be affected or contributed by the flow dynamics of the fluid in the fluid channel.
For example, the fluid may flow in a laminar flow within the fluid channel. In such an example, particles in the fluid may move along a layered smooth path, where each layer moves smoothly through adjacent layers with little or no mixing. Thus, the fluid in the laminar flow may have low flow contact efficiency at the sensing surface of the biosensing chip.
In some examples, the fluid cap may include chevron pattern grooves on a bottom surface of the fluid cap to increase contact efficiency so that more particles in the fluid may contact a top surface of the biosensor chip. However, such fluid caps may face a number of technical challenges and difficulties.
Referring now to fig. 159A, 159B, and 159C, an exemplary fluid cap 15000 is shown. Specifically, fig. 159A illustrates an exemplary oblique view of an exemplary fluid cap 15000. Fig. 159B illustrates an example top view of an example fluid cap 15900. Fig. 159C illustrates an example cross-sectional view of an example fluid cap 15900.
In some embodiments, an exemplary fluid cap 15900 is disposed on the top surface of the biosensing chip to create the fluid channel. In particular, an example fluid cap 15900 may include an inlet opening 15901 in which fluid may enter a fluid channel between a bottom surface 15005 of the fluid cap 15900 and a top surface of the biosensing chip. Fluid may flow through the fluid channel and exit the fluid channel through the outlet opening 15903 of the fluid cap 15000.
In some embodiments, bottom surface 1505 of fluid cap 15900 may include a plurality of chevron pattern grooves 15907. For example, the plurality of chevron pattern grooves 15907 include a plurality of rows of parallel grooves, where each parallel groove includes two connected groove portions having ramps in opposite directions. As shown in fig. 159B, each of the plurality of chevron pattern grooves 15907 may be shaped like an arrow shape.
The exemplary chevron pattern trenches 15907 shown in fig. 159A-159C may pose a number of technical challenges and difficulties. For example, sharp edges and corners of chevron pattern grooves 15907 may cause manufacturing difficulties and defects. As another example, chevron pattern grooves 15907 may form discontinuous profile features and cause abrupt surface changes in flow voids and bubbles.
Thus, there is a need for an enhanced fluid channel that optimizes the sensing surface to improve the response sensitivity of the fluid while minimizing flow rate variations and bubble-related noise in biosensing by the biosensing chip. Various embodiments of the present disclosure overcome these technical challenges and difficulties and provide various technical improvements and advantages.
Referring now to fig. 160A-160C, an exemplary fluid cover 16000 is shown according to various embodiments of the present disclosure. Specifically, fig. 160A illustrates an exemplary oblique view of an exemplary fluid cover 16000. Fig. 160B illustrates an exemplary top view of an exemplary fluid cover 16000. Fig. 160C illustrates an exemplary cross-sectional view of an exemplary fluid cover 16000.
In some embodiments, an exemplary fluid cover 16000 is disposed on the top surface of the biosensing chip to create a fluid channel. In particular, the example fluid cover 16000 can include an inlet opening 16002 in which fluid can enter a fluid channel between a bottom surface 16008 of the fluid cover 16000 and a top surface of the biosensing chip. Fluid may flow through the fluid channel and exit the fluid channel through the outlet opening 16004 of the fluid cover 16000.
In some embodiments, the bottom surface 16008 of the fluid cover 16000 can include a plurality of polynomial-curve grooves 16006.
In particular, the plurality of polynomial curve grooves 16006 includes a series of 3D curve grooves that may deviate the laminar flow of fluid to improve the efficiency of sensing surface contact at the bottom of the fluid channel (e.g., between the fluid and the top surface of the biosensing chip). In some embodiments, the plurality of polynomial curve grooves 16006 comprise curved surfaces defined by polynomial forms whose coefficients are optimized to provide the highest contact surface bioreaction efficiency. In some embodiments, the plurality of polynomial-curve grooves 16006 may include free-form surfaces continuously connected with smoothly rounded transitions to prevent flow voids and bubbles.
For example, each of the plurality of chevron pattern grooves 15907 shown above in connection with fig. 159A, 159B, and 159C includes two groove portions connected at an acute angle. In contrast, each of the plurality of polynomial-curve grooves 16006 shown in fig. 160A, 160B, and 160C provides a plurality of rounded transitions between two connected groove portions.
Referring now to fig. 161A, 161B, and 161C, exemplary flow rates associated with an exemplary fluid cap 16100 are shown, according to some embodiments of the present disclosure. Specifically, fig. 161A illustrates an example flow rate from an example perspective view of an example fluid cap 16100. Fig. 161B illustrates an example flow rate from an example top view of an example fluid cap 16100. Fig. 161C illustrates an example flow rate from an example side view of an example fluid cap 16100.
In particular, the example fluid cover 16100 is similar to the example fluid cover 16000 described above in connection with fig. 160A-160C. For example, an exemplary fluid cap 16100 is disposed on the top surface of the biosensing chip to create the fluid channel. In particular, the example fluid cap 16100 can include an inlet opening 16101, wherein fluid can enter a fluid channel between a bottom surface of the fluid cap 16100 and a top surface of the biosensing chip. Fluid may flow through the fluid channel and exit the fluid channel through the outlet opening 16103 of the fluid cap 16100. In some embodiments, the bottom surface of the fluid cap 16100 may include a plurality of polynomial curved grooves 16105.
As shown in fig. 161A-161C, an exemplary fluid cap 16100 provides free-form fluid flow. The exemplary fluid cap 16100 is an alternative to the chevron-shaped fluid caps described above in connection with fig. 159A-159C and achieves high bio-reaction efficiency on the sensing surface while eliminating non-continuous flow and bubble-related sensing noise. The high signal-to-noise ratio improves the biosensor sensitivity and achieves the optimal limit for sample detection in a biosensing system. Thus, the example fluid cap 16100 is capable of biosensing with a free-form enhanced flow, which results in high sensitivity in many virus sensing/detection applications.
Referring now to fig. 162A-162F, exemplary components associated with exemplary sample testing device 16200 according to some embodiments of the present disclosure are shown.
Specifically, fig. 162A illustrates an example of an exploded view of an exemplary sample testing device 16200. In the example shown in fig. 162A, an exemplary sample testing device 16200 includes a fluid cover 16202 and a biosensing chip 16204. In some embodiments, a fluid cover 16202 is disposed over a top surface of the biosensing chip 16204, as shown in fig. 162B.
Referring now to fig. 162C, an exemplary cross-sectional view of an exemplary sample testing device 16200 is shown, according to some embodiments of the present disclosure. In some embodiments, the fluid cover 16202 defines an inlet opening 16206 and an outlet opening 16208. In some embodiments, a fluid (such as, but not limited to, a sample solution) is injected through inlet opening 16206. In some embodiments, the bottom surface of the fluid cover 16202 and the top surface of the biosensing chip 16204 define a fluid channel, and fluid flows through the fluid channel. In some embodiments, fluid is released from the fluid channel through the outlet opening 16208.
Referring now to fig. 162D-162E, fig. 162D shows an exemplary oblique view of the fluid cover 16202, fig. 162E shows an exemplary bottom view of the fluid cover 16202, and fig. 162F shows an exemplary cross-sectional view of the fluid cover 16202.
As shown in fig. 162D-162F, the bottom surface of the fluid cover 16202 may include a plurality of polynomial curved grooves 16210.
Similar to those described above in connection with fig. 160A-160C, the plurality of polynomial curve grooves 16210 includes a series of 3D curve grooves that may deflect a laminar flow of fluid to increase the efficiency of sensing surface contact at the bottom of the fluid channel (e.g., between the fluid and the top surface of the biosensing chip). In some embodiments, the plurality of polynomial curve grooves 16210 includes a curved surface defined by a polynomial form whose coefficients are optimized to provide the highest biological reaction efficiency of the contact surface. In some embodiments, the plurality of polynomial curved grooves 16210 may include free-form surfaces that are continuously connected in a smooth circular transition to prevent flow voids and bubbles.
The free-form fluid channel top fluid cap can be manufactured by an injection molding process with consistent quality and micron-scale surface accuracy compared to the chevron groove pattern. In some embodiments, the optimized flow design of the polynomial curved slots also ensures minimal flow friction and further improves flow rate accuracy. In some embodiments, the smooth continuous surface profile of the plurality of polynomial curve grooves 16210 prevents undesirable trapping of particles in the fluid and further improves biological particle detection.
There are many technical challenges and difficulties in fabricating waveguide devices (also referred to as "waveguides" or "waveguide cores"). For example, the waveguide device may be composed of silicon nitride (such as, but not limited to, in the form of a silicon nitride film). In many examples, the silicon nitride is formed by a Low Pressure Chemical Vapor Deposition (LPCVD) process. In many examples, one or more waveguide ridges are formed in LPCVD silicon nitride to define a waveguide device. For example, the one or more waveguide ridges may provide a component for an analysis window of the waveguide device.
However, many fabrication processes for LPCVD silicon nitride suffer from technical challenges and limitations that make them unsuitable for fabricating waveguide devices. For example, the silicon nitride film needs to be maintained at a certain thickness level in order to provide a useful analysis window for the waveguide device, but many LPCVD processes may create stresses in the silicon nitride film, resulting in cracking of the silicon nitride film. For example, standard LPCVD silicon nitride produced in many fabrication facilities has a stress high enough to cause cracking at the thickness of the silicon nitride film required for the waveguide device, resulting in a fabrication yield of the waveguide device at or below 50%.
Various embodiments of the present disclosure overcome the technical challenges and difficulties described above and provide various technical improvements and advantages.
For example, during the fabrication process of an exemplary waveguide device, various embodiments of the present disclosure may form one or more stress reduction patterns on the thermal silicon dioxide layer. In such an example, the stress reduction pattern may reduce stress in the silicon nitride film and prevent the silicon nitride film from cracking. By forming the stress-reducing pattern during the fabrication process of the waveguide device, various embodiments of the present disclosure may improve fabrication yield (e.g., near or up to 100%). In many examples, the waveguide fabrication process may produce large waveguide cores (e.g., 88 waveguide cores assembled on a 150 millimeter diameter wafer). In such an example, the increase in yield may significantly reduce the final cost of manufacturing the waveguide device.
Referring now to fig. 163, an exemplary waveguide 16300 is provided. In particular, the exemplary waveguide 16300 illustrated in fig. 163 does not include any stress reduction pattern according to some embodiments of the present disclosure.
In some embodiments, the exemplary waveguide 16300 includes an exemplary single mode region 16301 and an exemplary multimode region 16303.
In the example shown in fig. 163, the example single mode region 16301 is positioned at the light input edge 16307 of the example waveguide 16300. In some embodiments, the optical input edge 16307 of the exemplary waveguide 16300 receives laser light as an input to the exemplary waveguide 16300. Similar to the first waveguide portion 212 described above in connection with at least fig. 2, the exemplary single mode region 16301 may provide, support, and/or cause a single transverse mode of the laser light as the laser light travels through the exemplary single mode region 16301.
In the example shown in fig. 163, the example multimode region 16303 is positioned behind the example single mode region 16301 in the direction of travel of the laser light through the example waveguide 16300. For example, the laser light passes through an exemplary single mode region 16301 and then into an exemplary multimode region 16303. Similar to the second waveguide portion 216 described above in connection with at least fig. 2, the exemplary multimode region 16303 may allow the laser light to have more than one transverse mode as it passes through the exemplary multimode region 16303. For example, the exemplary waveguide 16300 may define one or more stepped portions between the exemplary single mode region 16301 and the exemplary multimode region 16303, similar to those described above in connection with at least fig. 2.
In some embodiments, the example multimode region 16303 of the example waveguide 16300 includes an example analysis window region 16305. In some embodiments, exemplary analysis window area 16305 includes one or more waveguide ridges. In the example shown in fig. 163 and 164, the exemplary analysis window area 16305 includes a total of eight waveguides including, but not limited to, at least waveguide ridge 16309A, waveguide ridge 16309B, and waveguide ridge 16309C. In some embodiments, each of the one or more waveguide ridges defines a sample channel, similar to those described above.
Although the example shown in fig. 163 illustrates an exemplary waveguide device, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary waveguide device may include fewer or greater numbers of channels than shown in the exemplary waveguide device of fig. 163.
In some implementations, each of waveguide ridge 16309A, waveguide ridge 16309B, and waveguide ridge 16309C is formed on a silicon nitride film. As described above, the silicon nitride film may be manufactured by an LPCVD process. In many examples, the LPCVD process may result in stress or pressure in the silicon nitride film that causes the silicon nitride film to crack. Thus, fabricating the exemplary waveguide 16300 shown in fig. 163 is technically challenging and difficult.
Various embodiments of the present disclosure overcome these technical challenges and difficulties and provide various technical advantages and improvements. Referring now to fig. 164, an exemplary waveguide 16400 is provided in accordance with some embodiments of the disclosure.
Similar to those described above in connection with at least fig. 164, the exemplary waveguide 16400 includes an exemplary single mode region 16402 and an exemplary multimode region 16404.
In the example shown in fig. 164, the example single mode region 16402 is positioned at the light input edge 16408 of the example waveguide 16400. In some embodiments, the light input edge 16408 of the exemplary waveguide 16400 receives laser light as input to the exemplary waveguide 16400. Similar to the first waveguide portion 212 described above in connection with at least fig. 2, the exemplary single mode region 16402 may provide, support, and/or cause a single transverse mode of the laser light as the laser light travels through the exemplary single mode region 16402.
In the example shown in fig. 164, the example multimode region 16404 is positioned after the example single mode region 16402 in the direction of travel of the laser light through the example waveguide 16400. For example, the laser light passes through an exemplary single mode region 16402 and then into an exemplary multimode region 16404. Similar to the second waveguide portion 216 described above in connection with at least fig. 2, the exemplary multimode region 16404 may allow the laser light to have more than one transverse mode as it passes through the exemplary multimode region 16404. For example, the exemplary waveguide 16400 may define one or more stepped portions between the exemplary single mode region 16402 and the exemplary multimode region 16404, similar to those described above in connection with at least fig. 2.
In some embodiments, the exemplary multimode region 16404 of the exemplary waveguide 16400 includes an exemplary analysis window region 16406. In some embodiments, the exemplary analysis window area 16406 includes one or more waveguide ridges (e.g., without limitation, waveguide ridge 16410A, waveguide ridge 16410B, and waveguide ridge 16410C). In some embodiments, each of the one or more waveguide ridges (such as, but not limited to, waveguide ridge 16410A, waveguide ridge 16410B, and waveguide ridge 16410C) define a sample channel, similar to those described above.
Although the example shown in fig. 164 illustrates an exemplary waveguide device including eight channels, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, an exemplary waveguide device may include fewer than eight or more than eight channels.
Similar to those described above, each of the waveguide ridge 16410A, the waveguide ridge 16410B, and the waveguide ridge 16410C is formed in a silicon nitride film. As described above, the silicon nitride film may be manufactured by an LPCVD process. While the LPCVD process may create stress or pressure in the silicon nitride film that causes the silicon nitride film to crack, the exemplary waveguide 16400 shown in fig. 164 includes a stress-reducing pattern 16412 formed on the waveguide 16400. In some embodiments, the stress-reducing pattern 16412 may reduce or eliminate stress on the silicon nitride film caused by the LPCVD process. Thus, the stress-reducing pattern 16412 may reduce the likelihood of cracking of the silicon nitride film, thereby overcoming the various technical challenges and difficulties described above and providing various technical improvements and advantages.
Referring now to fig. 165, an exemplary portion of an exemplary waveguide device 16500 according to some embodiments of the present disclosure is provided. In particular, fig. 165 highlights the exemplary structure of the exemplary stress reduction pattern 16503, as well as the exemplary positional relationship between the exemplary stress reduction pattern 16503 and other features of the waveguide device 16500, such as, but not limited to, the exemplary analysis window portion 16505 and the exemplary waveguide rib 16507.
In some embodiments, the example stress reduction pattern 16503 includes a plurality of polygonal pattern units (such as, but not limited to, polygonal pattern unit 16509A, polygonal pattern unit 16509B, polygonal pattern unit 16509C, etc.). In some embodiments, each of the plurality of polygonal pattern elements shows an etched portion on the thermal silicon dioxide layer of the silicon wafer, additional details of which are described herein (including, but not limited to, those described in connection with at least fig. 166A-166C). In some embodiments, the plurality of polygonal pattern elements in the example stress reduction pattern 16503 may provide technical benefits and advantages such as, but not limited to, reducing stress exerted on the silicon nitride film when formed by the example LPCVD process, details of which are described herein (including but not limited to those described in connection with at least fig. 166A-166C).
In some embodiments, each of the plurality of polygonal pattern elements may be square in shape, as shown in fig. 165. For example, the polygon pattern unit 16509A, the polygon pattern unit 16509B, and the polygon pattern unit 16509C are all square in shape. In some embodiments, square-shaped multiple polygonal pattern units may provide technical benefits and advantages, such as, but not limited to, reducing stress exerted on the silicon nitride film when formed by an exemplary LPCVD process.
In some embodiments, the plurality of polygonal pattern units are spaced apart by a distance that is about twice the size of each of the plurality of polygonal pattern units. For example, polygon pattern unit 16509A and polygon pattern unit 16509B are spaced apart by a distance that is approximately twice the size of polygon pattern unit 16509A and/or polygon pattern unit 16509B. In some embodiments, such an arrangement may provide technical benefits and advantages, such as, but not limited to, reducing stress exerted on the silicon nitride film when formed by an exemplary LPCVD process.
In some embodiments, the plurality of polygonal pattern units includes alternating rows of polygonal pattern units (e.g., in a square shape) that are spaced apart by a distance of about half the side length of the polygonal pattern units (e.g., square). For example, the example stress reduction pattern 16503 includes alternating rows of polygon pattern units, including a first row of polygon pattern units (including polygon pattern unit 16509A and polygon pattern unit 16509B) and a second row of polygon pattern units (including polygon pattern unit 16509C). In some implementations, the first row of polygon pattern units and the second row of polygon pattern units are spaced apart by a distance of approximately half a side length of the polygon pattern units (e.g., polygon pattern unit 16509A, polygon pattern unit 16509B, and/or polygon pattern unit 16509A and polygon pattern unit 16509C). In some embodiments, such an arrangement may provide technical benefits and advantages, such as, but not limited to, reducing stress exerted on the silicon nitride film when formed by an exemplary LPCVD process.
In some embodiments, each of the plurality of polygon pattern units is located at a center of a gap of a preceding row of polygon pattern units. For example, the polygon pattern unit 16509C is located at the center of the gap of the preceding row of polygon pattern units (including the polygon pattern unit 16509A and the polygon pattern unit 16509B). In some embodiments, such an arrangement may provide technical benefits and advantages such as, but not limited to, reducing the stress exerted on the silicon nitride film when formed by an exemplary LPCVD process.
Thus, fig. 165 shows an exemplary stress reduction pattern 16503 comprising squares spaced apart by approximately twice the size of a square, with alternating rows of squares spaced apart by a distance of approximately half the side length of the square and centered in the gaps of the previous row. In some embodiments, such an arrangement may provide technical benefits and advantages such as, but not limited to, reducing the stress exerted on the silicon nitride film when formed by an exemplary LPCVD process.
Although the above description provides a square as an example of the shape of the polygon pattern unit, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the example polygonal pattern elements of the example stress reduction pattern may be other shapes and/or other polygons (such as, but not limited to, triangles, rectangles, etc.).
Although the above description provides an exemplary arrangement of polygon pattern units, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the example polygonal pattern cells of the example stress reduction pattern may be arranged differently.
In some embodiments, the exemplary stress reduction pattern 16503 is remote from the analysis window portion 16505 and the waveguide rib 16507. In the example shown in fig. 165, the distance 16511 between the pattern edge 16513 of the stress-reducing pattern 16503 and the analysis window edge 16515 of the analysis window portion 16505 is at least 250 micrometers. In some embodiments, the pattern edge 16513 of the stress-reducing pattern 16503 refers to an edge of the stress-reducing pattern 16503 that is disposed parallel to the longitudinal axis of the waveguide device 16500 and closest to the analysis window portion 16505. In some embodiments, the analysis window edge 16515 of the analysis window portion 16505 refers to an edge of the analysis window portion 16505 that is disposed parallel to the longitudinal axis of the waveguide device 16500 and closest to the stress reduction pattern 16503.
Although the above description provides an exemplary distance between the stress reduction pattern and the analysis window portion, it is noted that the scope of the present disclosure is not limited to the above description.
Referring now to fig. 166A, 166B, and 166C, exemplary methods 16600 for fabricating exemplary waveguide devices according to some embodiments of the present disclosure are provided. In particular, exemplary method 16600 illustrates an example of fabricating an exemplary waveguide device including one or more stress-reducing patterns that provide technical benefits and advantages, such as, but not limited to, reducing stress exerted on a silicon nitride film when formed by an exemplary LPCVD process.
Referring to fig. 166A, an exemplary method 16600 begins with step/operation 16602. In some embodiments, after step/operation 16602, the exemplary method 16600 proceeds to step/operation 16606. In some embodiments, at step/operation 16606, the example method 16600 includes causing oxidation of silicon on the silicon wafer.
In some embodiments, the exemplary method 16600 utilizes silicon wafers to fabricate waveguide devices. In some embodiments, the exemplary method 16600 forms a thermal silicon dioxide layer on a silicon wafer. In some embodiments, the thermal silicon dioxide layer comprises a nominal thickness of 2 microns.
For example, the waveguide device is fabricated by first thermally oxidizing a silicon wafer to produce a thermal silicon dioxide layer. In such an example, when forming the thermal silicon dioxide layer, the exemplary method further includes thermally oxidizing the silicon wafer. In this specification, the term "thermal oxidation" refers to a microfabrication process that produces a thin layer of oxide (such as, but not limited to, silicon dioxide) on the surface of a wafer (such as, but not limited to, a silicon wafer). For example, an exemplary thermal oxidation process may force the oxidizing agent to diffuse into the wafer at high temperatures and cause reactions between the oxidizing agent and the wafer.
Referring back to fig. 166A, after step/operation 16606, the exemplary method 16600 proceeds to step/operation 16608. In some embodiments, at step/operation 16608, an exemplary method 16600 includes forming a stress relief pattern and etching the thermal silicon dioxide layer formed at step/operation 16606.
In some embodiments, an exemplary method 16600 for fabricating an exemplary waveguide includes forming a stress-reducing pattern on a thermal silicon dioxide layer. In some embodiments, when forming the stress-reducing pattern on the thermal silicon dioxide layer, the example method 16600 further comprises etching the thermal silicon dioxide layer according to the stress-reducing pattern.
In some embodiments, the stress relief pattern is similar to the examples described above in connection with at least fig. 164 and 165. In some embodiments, the stress relief pattern is formed on the thermal silicon dioxide layer by, for example, but not limited to, an exemplary etching process.
In some embodiments, the exemplary etching process for forming the stress relief pattern includes an exemplary wet etching process. For example, an exemplary etching process uses a fluorine-generating plasma etch to etch the pattern. Additionally or alternatively, the stress-reducing pattern may be formed by other processes.
In some embodiments, the etch depth associated with the stress reduction pattern is based at least in part on a film depth associated with a silicon nitride film to be formed by exemplary LPCVD. For example, the thermal silicon dioxide layer may be etched to a depth equal to or greater than the thickness of the silicon nitride film formed by exemplary LPCVD, details of which are described in connection with at least step/operation 16610.
Referring back to fig. 166A, after step/operation 16608, the exemplary method 16600 proceeds to step/operation 16610. In some embodiments, at step/operation 16610, an exemplary method 16600 comprises depositing LPCVD silicon nitride.
In some embodiments, the exemplary method 16600 includes forming a silicon nitride film on the stress-reducing pattern. In some embodiments, when forming the silicon nitride film, the example method 16600 further includes producing the silicon nitride film based at least in part on an LPCVD process.
In some embodiments, an exemplary LPCVD process refers to a chemical vapor deposition mechanism that utilizes heat to initiate a reaction of a precursor gas on a solid substrate. For example, the exemplary method 16600 may release nitride gas onto a silicon wafer (e.g., onto a stress reduction pattern that has been formed on a silicon oxide layer of the silicon wafer, as described above in connection with step/operation 16608). Therefore, after transferring the stress reduction pattern to the silicon oxide layer of the silicon wafer, LPCVD silicon nitride is deposited.
Referring back to fig. 166A, after step/operation 16610, the exemplary method 16600 proceeds to step/operation 16612. In some embodiments, at step/operation 16612, the exemplary method 16600 includes forming the single-mode region by patterning and/or etching.
For example, after forming a silicon nitride film on the stress-reducing pattern, the example method 16600 forms a single-mode region on the silicon nitride film by patterning and/or etching. For example, the exemplary method 16600 can utilize a mask having a shape corresponding to the single-mode region and etch the silicon nitride film to form the single-mode region.
Referring back to fig. 166A, after step/operation 16612, the exemplary method 16600 proceeds to block a, which connects fig. 166A to fig. 166B. Referring now to fig. 166B, in some embodiments, after block a, the exemplary method 16600 proceeds to step/operation 16614. In some embodiments, at step/operation 16614, the exemplary method 16600 includes forming the waveguide ribs by patterning and/or etching.
For example, after forming the single mode region on the silicon nitride film, the exemplary method 16600 includes forming at least one waveguide rib on the silicon nitride film. For example, the exemplary method 16600 may utilize a mask having a shape corresponding to at least one waveguide rib and etch a silicon nitride film to form the at least one waveguide rib.
As shown in the exemplary steps/operations, the silicon nitride film is not planarized during any step/operation of manufacturing the waveguide device, thereby providing technical benefits and advantages such as, but not limited to, reducing the likelihood of cracking of the silicon nitride film.
Referring back to fig. 166B, after step/operation 16614, the exemplary method 16600 proceeds to step/operation 16616. In some embodiments, at step/operation 16616, an exemplary method 16600 includes depositing silicon oxide.
In some embodiments, the exemplary method 16600 can deposit silicon oxide on top of the at least one waveguide rib and single mode region, as described above in connection with at least step/operation 16616.
Referring back to fig. 166B, after step/operation 16616, the exemplary method 16600 proceeds to step/operation 16618. In some embodiments, at step/operation 16618, an exemplary method 16600 includes depositing polysilicon.
In some embodiments, the exemplary method 16600 deposits polysilicon on top of the silicon oxide formed at step/operation 16616.
Referring back to fig. 166B, after step/operation 16618, the exemplary method 16600 proceeds to step/operation 16620. In some embodiments, at step/operation 16620, the exemplary method 16600 includes forming the slot by patterning and/or etching.
For example, the exemplary method 16600 forms a slot in a waveguide device that can guide laser light in a sub-wavelength level low refractive index region by total internal reflection.
Referring back to fig. 166B, after step/operation 16620, the exemplary method 16600 proceeds to step/operation 16622. In some embodiments, at step/operation 16622, an exemplary method 16600 includes depositing silicon oxide.
In some embodiments, the exemplary method 16600 deposits silicon oxide on top of the slots formed at step/operation 16620.
Referring back to fig. 166B, after step/operation 16622, the exemplary method 16600 proceeds to block B, which connects fig. 166B to fig. 166C. Referring now to fig. 166C, in some embodiments, after block B, the exemplary method 16600 proceeds to step/operation 16624. In some embodiments, at step/operation 16624, the exemplary method 16600 includes etching an analysis window portion.
For example, the exemplary method 16600 can utilize a mask having a shape corresponding to the analysis window portion and etch silicon oxide to form the analysis window portion of the waveguide device.
Referring back to fig. 166C, after step/operation 16624, the exemplary method 16600 proceeds to step/operation 16626. In some embodiments, at step/operation 16626, the exemplary method 16600 comprises causing reoxidation. For example, the exemplary method 16600 may reoxidize the surface of a silicon wafer.
Referring back to fig. 166C, after step/operation 16626, the exemplary method 16600 proceeds to step/operation 16628. In some embodiments, at step/operation 16628, the example method 16600 includes forming a street by patterning and/or etching.
Referring back to fig. 166C, after step/operation 16628, the exemplary method 16600 proceeds to step/operation 16630. In some embodiments, at step/operation 16630, the exemplary method 16600 comprises removing the waveguide device from the silicon wafer by sawing.
For example, an exemplary silicon wafer having a diameter dimension of 150 millimeters may be manufactured.
Referring back to fig. 166C, after step/operation 16630, the exemplary method 16600 proceeds to step/operation 16632 and ends.
As shown in the various examples above, the use of multi-channel waveguides for pathogen sensing may provide a number of technical benefits and advantages, such as, but not limited to, high sensitivity, high specificity, and high throughput. Various embodiments of the present disclosure provide a parallel flow multi-channel pathogen sensing system that further eliminates channel-to-channel variation and uncertainty to achieve optimal stability and repeatability.
In some embodiments, an exemplary parallel flow multi-channel pathogen sensing system may provide the same flow to multiple sensing channels. In some embodiments, a multichannel pump and a multichannel sample injection valve are introduced into a parallel flow multichannel pathogen sensing system to enable parallel buffer flow and sample injection through precise control. In some embodiments, an exemplary parallel flow multi-channel pathogen sensing system implements parallel flow microfluidics to ensure the same flow of sample and reference on the waveguide sensing channel.
Referring now to fig. 167, an exemplary parallel flow multichannel pathogen sensing system 16700 is shown, according to some embodiments of the present disclosure. In particular, the exemplary parallel flow multi-channel pathogen sensing system 16700 shown in fig. 167 may provide technical benefits and advantages such as, but not limited to, high sensitivity, high specificity, and high throughput, while also eliminating channel-to-channel variation and uncertainty to achieve optimal stability and repeatability.
In some embodiments, exemplary parallel flow multichannel pathogen sensing system 16700 includes multichannel peristaltic pump 16701, multichannel flow sensor array 16703, sample valve array 16705, tunable laser diode 16715, fiber coupler 16713, fiber array 16707, waveguide fluid assembly 16709, and imaging sensor 16711.
In some embodiments, the multichannel peristaltic pump 16701 of the exemplary parallel flow multichannel pathogen sensing system 16700 includes a plurality of pump flow channel tubes (e.g., without limitation, pump flow channel tube 16747a, pump flow channel tube 16747B, and pump flow channel tube 16747C).
In some embodiments, the number of pump flow channel tubes may be determined based on the number of optical sensing channels in waveguide fluid assembly 16709, the details of which are described herein.
In some embodiments, the buffer solution flows through the plurality of pump flow channel tubes (e.g., without limitation, pump flow channel tube 16747a, pump flow channel tube 16747B, and pump flow channel tube 16747C). In some embodiments, the buffer solution comprises PBS, phosphate buffered saline.
In some embodiments, multichannel peristaltic pump 16701 includes a pump frame and a pump wheel secured to the pump frame. In some embodiments, the plurality of pump flow channel tubes (e.g., without limitation, pump flow channel tube 16747a, pump flow channel tube 16747B, and pump flow channel tube 16747C) are disposed on a pump wheel, and the pump wheel can adjust the flow rate of the buffer solution in the plurality of pump flow channel tubes (e.g., without limitation, pump flow channel tube 16747a, pump flow channel tube 16747B, and pump flow channel tube 16747C). Additional details associated with multichannel peristaltic pump 16701 are described herein, including but not limited to at least fig. 168 and 169B.
In some embodiments, the multichannel flow sensor array 16703 of the exemplary parallel flow multichannel pathogen sensing system 16700 includes one or more flow sensors housed within an outer housing of the multichannel flow sensor array 16703. Examples of flow rate sensors include, but are not limited to, eddy current sensors, mechanical flow sensors, and the like. In some embodiments, the number of flow rate sensors may be determined based on the number of optical sensing channels in waveguide fluid assembly 16709, the details of which are described herein.
In some embodiments, multichannel flow sensor array 16703 includes a plurality of flow sensor input ports (such as, but not limited to, flow sensor input port 16743a, flow sensor input port 16743B, and flow sensor input port 16743C) disposed on the outer housing of multichannel flow sensor array 16703. In some embodiments, each of the plurality of flow sensor input ports (such as, but not limited to, flow sensor input port 16743a, flow sensor input port 16743B, and flow sensor input port 16743C) is connected to a flow sensor within the outer housing of the multi-channel flow sensor array 16703.
In some embodiments, the plurality of pump tubes are connected to the plurality of flow sensor input ports. For example, the plurality of pump flow channel tubes (such as but not limited to pump flow channel tube 16747a, pump flow channel tube 16747B, and pump flow channel tube 16747C) are each connected to one of the plurality of flow sensor input ports (such as but not limited to flow sensor input port 16743a, flow sensor input port 16743B, and flow sensor input port 16743C).
In some embodiments, each of the plurality of pump flow channel tubes (such as, but not limited to, pump flow channel tube 16747a, pump flow channel tube 16747B, and pump flow channel tube 16747C) provides buffer solution flow to the flow sensors of the multichannel flow sensor array 16703 through one of the plurality of flow sensor input ports (such as, but not limited to, flow sensor input port 16743a, flow sensor input port 16743B, and flow sensor input port 16743C). In some embodiments, each of the one or more flow sensors of the multi-channel flow sensor array 16703 generates a flow rate detection signal indicative of the flow rate of buffer solution from one of the plurality of pump flow channel tubes (e.g., without limitation, pump flow channel tube 16747a, pump flow channel tube 16747B, and pump flow channel tube 16747C).
In some embodiments, multichannel flow sensor array 16703 includes a plurality of flow sensor output ports (such as, but not limited to, flow sensor output port 16745a, flow sensor output port 16745B, and flow sensor output port 16745C) disposed on an outer housing of multichannel flow sensor array 16703. In some embodiments, each of the plurality of flow sensor output ports (such as, but not limited to, flow sensor output port 16745A, flow sensor output port 16745B, and flow sensor output port 16745C) is connected to a flow sensor within the outer housing of the multi-channel flow sensor array 16703. In some embodiments, the buffer solution exits the multichannel flow sensor array 16703 through the plurality of flow sensor output ports (such as, but not limited to, flow sensor output port 16745A, flow sensor output port 16745B, and flow sensor output port 16745C).
In some embodiments, sample valve array 16705 of exemplary parallel flow multichannel pathogen sensing system 16700 includes a plurality of sample valves (such as, but not limited to sample valve 16719a, sample valve 16719B, and sample valve 16719C). In some embodiments, the number of sample injection valves may be determined based on the number of optical sensing channels in waveguide fluid assembly 16709, the details of which are described herein.
In some embodiments, the plurality of injection valves are stacked together. In the example shown in fig. 167, the sample valve 16719a, the sample valve 16719B, and the sample valve 16719C are stacked together by a sample valve wheel 16721.
In some embodiments, each of the plurality of sample valves (such as, but not limited to, sample valve 16719a, sample valve 16719B, and sample valve 16719C) takes the form of a 6-port sample valve. For example, each of the plurality of sample valves includes a buffer solution injection port and a sensing channel connection port.
In some embodiments, each buffer injection port (e.g., buffer injection port 16723A of sample valve 16719a, buffer injection port 16723B of sample valve 16719B, and buffer injection port 16723C of sample valve 16719C) receives a buffer solution. For example, each of the plurality of flow sensor output ports (such as but not limited to flow sensor output port 16745a, flow sensor output port 16745B, and flow sensor output port 16745C) of multichannel flow sensor array 16703 is connected to one of the buffer solution injection ports (e.g., buffer solution injection port 16723A of sample valve 16719a, buffer solution injection port 16723B of sample valve 16719B, and buffer solution injection port 16723C of sample valve 16719C).
In some embodiments, each sense channel connection port (e.g., sense channel connection port 16725A of sample valve 16719a, sense channel connection port 16725B of sample valve 16719B, and sense channel connection port 16725C of sample valve 16719C) is connected to a sense channel input port on waveguide fluid assembly 16709. Details associated with the sense channel input port of waveguide fluid assembly 16709 are described herein.
Although the above description provides an exemplary port for sample valve array 16705, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the example sample valve array 16705 may include one or more additional or alternative ports, such as, but not limited to, a sample solution injection port (such as, but not limited to, sample solution injection port 16727A, sample solution injection port 16727B, sample solution injection port 16727C) for receiving a sample solution. Additional details associated with the example sample valve array 16705 are described herein, including but not limited to those described at least in connection with fig. 171A-172B.
In some embodiments, waveguide fluidic assembly 16709 also includes one or more components including, but not limited to, parallel flow microfluidic cover 16729, multichannel waveguide sensor 16731, and thermal control sensor base 16733.
In some embodiments, the parallel flow microfluidic cover 16729 provides multichannel microfluidics. For example, the parallel flow microfluidic cover 16729 defines a plurality of sense channel input ports. In this example, each of the plurality of sense channel input ports is connected to a sample channel of the multichannel waveguide sensor 16731.
In some embodiments, each sense channel connection port (e.g., sense channel connection port 16725A of sample valve 16719a, sense channel connection port 16725B of sample valve 16719B, and sense channel connection port 16725C of sample valve 16719C) is connected to a sense channel input port on waveguide fluid assembly 16709. Additional details associated with the parallel flow microfluidic cover 16729 are described herein, including but not limited to those described in connection with at least fig. 173A-173C.
In some embodiments, the multichannel waveguide sensor 16731 includes a multimode planar waveguide. For example, the multimode planar waveguide includes a plurality of sample channels. Additional details of the multichannel waveguide sensor 16731 are described herein.
In some embodiments, the thermal control sensor base 16733 provides thermal heating/cooling of the sensor mount. For example, the thermal control sensor base 16733 may include at least one of a heater component or a cooler component or a dual-function heater-cooler component secured to the thermal control sensor base. Additional details associated with the thermal control sensor base 16733 are described herein, including but not limited to those described in connection with at least fig. 173A-173C.
In some embodiments, exemplary parallel flow multichannel pathogen sensing system 16700 includes tunable laser diode 16715, fiber coupler 16713, and fiber array 16707.
Similar to the various examples described above, the tunable laser diode 16715 is configured to generate a wavelength tunable laser beam. For example, tunable laser diode 16715 may scan multiple wavelengths of laser light. Examples of tunable laser diodes 16715 may include, but are not limited to, violet laser diodes, visible laser diodes, edge-emitting laser diodes, surface-emitting laser diodes, and the like.
In some embodiments, tunable laser diode 16715 emits laser light through a single optical fiber 16739 to fiber optic coupler 16713. In some embodiments, a single optical fiber 16739 of the tunable laser diode 16715 is connected to the coupler input optical fiber 16741 of the fiber optical coupler 16713. Accordingly, the fiber optic coupler 16713 receives the laser light through a signal fiber (e.g., the coupler input fiber 16741).
In some embodiments, the fiber optical coupler 16713 includes a plurality of coupler output fibers 16735. In some embodiments, the fiber optic coupler 16713 splits the laser light received from the coupler input fiber 16741 into a plurality of laser lights and transmits the plurality of laser lights through the plurality of coupler output fibers 16735. For example, the fiber optical coupler 16713 may include a planar waveguide beam splitter that splits laser light from the coupler input fiber 16741. Additionally or alternatively, the fiber optic coupler 16713 may include other components used to split the laser light.
Similar to the various examples described above, the fiber array 16707 includes a plurality of array fibers 16737. In some embodiments, each of the coupler output fibers 16735 is connected to one of the array fibers 16737 of the fiber array 16707. Thus, each of the plurality of array fibers 16737 receives laser light from one of the coupler output fibers 16735. Similar to the various examples described above, the plurality of array fibers 16737 of the fiber array 16707 are aligned with the optical input ends of the multimode planar waveguides of the multi-channel waveguide sensor 16731 of the waveguide fluid assembly 16709.
In some embodiments, the laser light emitted from the tunable laser diode travels through the array optical fibers 16737 of the optical fiber array 16707 and is emitted through the optical input end of the multimode planar waveguide of the multi-channel waveguide sensor 16731 of the waveguide fluid assembly 16709. In some embodiments, the laser light exits the multimode planar waveguide of the multichannel waveguide sensor 16731 and reaches the imaging sensor 16711.
Similar to the various examples described above, the parallel flow multichannel pathogen sensing system 16700 also includes an imaging sensor 16711. In some embodiments, imaging sensor 16711 may include one or more imagers and/or image sensors (such as integrated 1D, 2D, or 3D image sensors). Various examples of image sensors may include, but are not limited to, CIS, CCD or CMOS sensors, photodetectors, one or more optical components (e.g., one or more lenses, filters, mirrors, beam splitters, polarizers, etc.), auto-focusing circuitry, motion tracking circuitry, computer vision circuitry, image processing circuitry (e.g., one or more digital signal processors configured to process images to improve image quality, reduce image size, increase image transmission bit rate, etc.), scanners, cameras, any other suitable imaging circuitry, or any combination thereof.
In some embodiments, imaging sensor 16711 is positioned at the output end of the multimode planar waveguide of multichannel waveguide sensor 16731. Similar to the various examples described above, the imaging sensor 16711 may generate one or more detection signals based on the laser light detected from the multimode planar waveguide of the multichannel waveguide sensor 16731.
In various embodiments of the present disclosure, exemplary parallel flow multichannel pathogen sensing system 16700 can provide various technical benefits and advantages.
For example, the exemplary parallel flow multi-channel pathogen sensing system 16700 provides parallel flows of buffer solution and sample solution. As described above, the multichannel peristaltic pump 16701 includes a plurality of pump flow channel tubes (e.g., without limitation, pump flow channel tube 16747a, pump flow channel tube 16747B, and pump flow channel tube 16747C). In some embodiments, multichannel flow sensor array 16703 includes a plurality of flow sensor input ports (such as, but not limited to, flow sensor input port 16743a, flow sensor input port 16743B, and flow sensor input port 16743C) and a plurality of flow sensor output ports (such as, but not limited to, flow sensor output port 16745a, flow sensor output port 16745B, and flow sensor output port 16745C). In some embodiments, the sample valve array 16705 includes a plurality of sample valves (such as, but not limited to, sample valve 16719a, sample valve 16719B, and sample valve 16719C).
In some embodiments, the number of the plurality of pump flow channel tubes, the number of the plurality of flow sensor input ports, the number of the plurality of flow sensor output ports, and/or the number of the plurality of sample valves may be determined based on the number of optical sensing channels in the waveguide sensor of waveguide fluid assembly 16709. Thus, the example parallel flow multi-channel pathogen sensing system 16700 can provide parallel flows of sample solution, buffer solution, and reference solution to sample channels in a waveguide sensor of the waveguide fluid assembly 16709.
In some embodiments, the parallel streams of the exemplary parallel flow multi-channel pathogen sensing system 16700 may have the same flow rate. As described above, the exemplary parallel flow multichannel pathogen sensing system 16700 includes a multichannel flow sensor array 16703. In some embodiments, multichannel flow sensor array 16703 generates a flow rate detection signal that indicates the flow rate associated with each parallel flow in the pump flow channel tube. In some embodiments, multichannel flow sensor array 16703 provides a flow rate detection signal to the processing component, and the processing component transmits a control signal that adjusts multichannel peristaltic pump 16701 based on the flow rate detection signal so that the flow rate is the same between pump flow channel tubes.
For example, a flow rate detection signal associated with one of the pump flow channel tubes may indicate that a flow rate in that pump flow channel tube is lower than one or more flow rates associated with one or more other flow channel tubes. In such an example, the processor may transmit a control signal to the multichannel peristaltic pump 16701 to increase the rotational speed of the pump wheel upon which the pump flow channel tube is disposed such that the flow rate associated with the pump flow channel tube may be increased.
Additionally or alternatively, a flow rate detection signal associated with a pump flow channel tube of the pump flow channel tubes may indicate that a flow rate in the pump flow channel tube is higher than one or more flow rates associated with one or more other flow channel tubes. In such an example, the processor may transmit a control signal to the multichannel peristaltic pump 16701 to reduce the rotational speed of the pump wheel upon which the pump flow channel tube is disposed such that the flow rate associated with the pump flow channel tube may be reduced.
Thus, the exemplary parallel flow multichannel pathogen sensing system 16700 provides a closed loop control system by implementing a multichannel peristaltic pump 16701 and a multichannel flow sensor array 16703.
In some embodiments, the exemplary parallel flow multichannel pathogen sensing system 16700 can achieve controlled timing of parallel injections of sample solution, reference solution, and buffer solution through the sample valve array 16705. As described above, the sample valve array 16705 may include a plurality of multi-channel 2-position 6-port valves. In some embodiments, by timing the switching of the configuration of sample valve array 16705, exemplary parallel flow multi-channel pathogen sensing system 16700 can allow for the simultaneous supply of sample solution to parallel sample channels of waveguides in waveguide fluidic assembly 16709, the simultaneous supply of reference solution to parallel sample channels of waveguides in waveguide fluidic assembly 16709, and the simultaneous supply of buffer solution to parallel sample channels of waveguides in waveguide fluidic assembly 16709. For example, buffer solution parallel to sample solution injection and/or reference solution injection may flow through parallel flow channels of the parallel flow microfluidic cover 16729, which are positioned over the multichannel waveguide sensor 16731 with shims. In some embodiments, the opening of the gasket restricts three flows of sample/reference solution to six optical sensing channels (such as, but not limited to, sample channels and/or reference channels) to detect refractive index changes in the flow of sample/reference solution.
In some embodiments, tunable laser diode 16715 generates a multi-wavelength laser beam and fiber optic coupler 16713 splits the multi-wavelength laser beam into two or more laser beams (such as, but not limited to, eight laser beams). In some embodiments, the laser beams from fiber coupler 16713 are all the same, and they illuminate the light input edge of the multichannel waveguide sensor through fiber array 16707 (e.g., an exemplary microlens fiber array according to some embodiments of the present disclosure). For example, these same laser beams travel under the sensing region (e.g., under the flow channel defined by the gasket and through the sample/reference channel of the waveguide sensor), forming eight interference patterns on the imaging sensor 16711.
In some embodiments, waveguide fluid assembly 16709 includes one or more temperature sensors (and/or one or more heater components and/or one or more cooler components) as part of a thermally controlled sensor base to provide thermal control of the waveguide sensor to eliminate temperature-related errors. In some embodiments, the waveguide sensor provides a total of eight optical channels, including two buried reference channels (detection signals from these buried reference channels can be used to correct for laser sources and environmental changes) and six sensing channels (e.g., two channels for each of the flow channels from the gasket as redundancy).
Referring now to fig. 168, an exemplary cross-sectional view 16800 of an exemplary multichannel peristaltic pump 16802 is shown, according to some embodiments of the present disclosure.
In some embodiments, multichannel peristaltic pump 16802 includes a pump frame 16806, a plurality of pump wheels (such as, but not limited to, pump wheels 16804), and one or more tube covers (such as, but not limited to, tube covers 16508).
In some embodiments, pump frame 16806 provides a base for securing pump wheel 16104 and tube cover 16508. For example, pump frame 16806 can include rigid materials such as, but not limited to, plastic, metal, and the like.
In some embodiments, the plurality of pump wheels (such as, but not limited to, pump wheel 16804) are secured to pump frame 16806. For example, pump frame 16806 can include a wheel frame portion, and the shaft of pump wheel 16804 is secured to the wheel frame portion. Additional details are described in connection with at least fig. 169A-170B.
As described above, a plurality of pump tubes are positioned on top of the pump wheel of the multi-channel peristaltic pump 16802. In some embodiments, each of the plurality of pump tubes is disposed on a separate pump wheel of the multichannel peristaltic pump 16802. In the example shown in fig. 168, pump tube 16810 is disposed on top of multi-channel peristaltic pump 16802.
In some embodiments, rotation of the pump wheel of the multichannel peristaltic pump 16802 causes a change in the flow rate of the solution in the corresponding pump tube disposed on top of the pump wheel. For example, the faster the impeller 16104 rotates, the higher the flow rate of the solution in the pump tube 16810. In some embodiments, each rotational speed of the pump wheel of the multi-channel peristaltic pump 16802 may be controlled separately such that the flow rate in the pump tube of the multi-channel peristaltic pump 16802 is the same.
In some embodiments, tube cover 16508 is pivotally secured to pump frame 16806. For example, the tube cover 16508 is rotatably secured to a pivot pin 16112 that is secured to the pump frame 16806. In such examples, tube cover 16508 may be rotated such that multichannel peristaltic pump 16802 may be in a different configuration. For example, the tube cover 16508 may be rotated away from the pump tube 16810 so that the pump tube 16810 may be released. Additionally or alternatively, the tube cover 16508 may be rotated onto the pump tube 16810 such that the pump tube 16810 may be secured to the pump frame 16806.
Referring now to fig. 169A and 169B, exemplary views associated with an exemplary multichannel peristaltic pump 16900 are shown, in accordance with some embodiments of the present disclosure. In particular, fig. 169A and 169B illustrate different configurations associated with the exemplary multichannel peristaltic pump 16900.
In the example shown in fig. 169A and 169B, the example multichannel peristaltic pump 16900 includes a pump frame 16901, a plurality of pump wheels (such as, but not limited to, pump wheels 16903A, pump wheels 16903B, and pump wheels 16903C), and a plurality of tube caps (such as, but not limited to, tube caps 16907A, tube caps 16907B, tube caps 16907C).
In the example shown in fig. 169A and 169B, a plurality of pump pipes are provided on the plurality of pump wheels. In some embodiments, the number of pump wheels and the number of tube caps are the same as the number of pump tubes of the example multichannel peristaltic pump 16900. In some embodiments, the number of pump wheels, the number of tube caps, and the number of pump tubes are the same as the flow channels of the waveguide fluid assembly, the details of which are described herein.
In some embodiments, pump frame 16901 includes wheel frame portion 16909. In some embodiments, the shaft of the pump impeller (such as but not limited to pump impeller 16903A, pump impeller 16903B, pump impeller 16903C) is secured to an impeller frame portion 16909 of pump frame 16901.
Similar to those described above, each of the plurality of tube caps (such as, but not limited to, tube cap 16907A, tube cap 16907B, and tube cap 16907C) is pivotally secured to pump frame 16901 such that the plurality of tube caps can be rotated to form different configurations for the example multichannel peristaltic pump 16900.
In fig. 169A, the exemplary multichannel peristaltic pump 16900 is in a closed configuration. In such an example, each of the plurality of tube caps rotates to push onto one of the plurality of pump tubes such that the plurality of pump tubes are secured to a corresponding pump wheel. For example, the tube cover 16907A is pushed onto the pump tube 16905A so that the pump tube 16905A is disposed on the pump wheel 16903A. As another example, tube cover 16907B is pushed onto pump tube 16905B such that pump tube 16905B is disposed on pump wheel 16903B. As another example, tube cover 16907C is pushed onto pump tube 16905C such that pump tube 16905C is disposed on pump wheel 16903C. When the example multichannel peristaltic pump 16900 is in a closed configuration, buffer solution may flow through the pump tube and the flow rate of the buffer solution may be adjusted based on the rotational speed of the pump wheel.
In fig. 169B, the plurality of tube caps are rotated away from the pump tube. In such an example, the example multichannel peristaltic pump 16900 is in an open configuration such that the pump tube may be placed on or removed from a corresponding pump wheel.
Referring now to fig. 170A and 170B, exemplary cross-sectional views associated with an exemplary multichannel peristaltic pump 17000 are provided in accordance with some embodiments of the present disclosure.
Similar to those described above, the example multichannel peristaltic pump 17000 includes a pump frame 17001, one or more pump wheels (such as, but not limited to, pump wheel 17003), one or more tube caps (such as, but not limited to, tube cap 17005). In some embodiments, one or more pump tubes (such as but not limited to pump tube 17007) are secured to one or more pump wheels (such as but not limited to pump wheel 17003) by one or more tube caps (such as but not limited to tube cap 17005).
Fig. 170A shows an exemplary multichannel peristaltic pump 17000 in a closed configuration similar to the example shown in fig. 169A. In such a configuration, buffer solution may flow through the one or more pump tubes (such as but not limited to pump tube 17007) and the flow rate is controlled based on the rotational speed of the one or more pump wheels (such as but not limited to pump wheel 17003).
Fig. 170B shows an exemplary multichannel peristaltic pump 17000 in an open configuration similar to the example shown in fig. 169B. In this configuration, the one or more pump tubes (such as but not limited to pump tube 17007) are accessible and removable from or placed on the corresponding pump wheel.
Referring now to fig. 171A and 171B, an exemplary view of an exemplary sample valve array 17100 according to some embodiments of the present disclosure is provided. Specifically, fig. 171A provides an exemplary perspective view of an exemplary sample valve array 17100. Fig. 171B provides an exemplary exploded view of an exemplary sample valve array 17100.
In some embodiments, the example sample valve array 17100 includes an array base 17101. In some embodiments, array base 17101 may include a rigid material such as, but not limited to, plastic, metal, and the like.
In some embodiments, a plurality of valve switches (such as, but not limited to, valve switch 17103a, valve switch 17103B, and valve switch 17103C) are affixed to array base 17101. In some embodiments, each of the plurality of valve switches (such as, but not limited to, valve switch 17103a, valve switch 17103B, and valve switch 17103C) includes one or more configuration switching channels (e.g., valve switch 17103B includes at least configuration switching channel 17105B) that can cause switching of a corresponding valve switch configuration. Additional details associated with the configuration of the diverter valve switch are described herein, including but not limited to those described in connection with at least fig. 172A and 172B.
Similar to those described above, the sample valve array 17100 includes a plurality of sample valves (e.g., without limitation, sample valve 17107a, sample valve 17107B, and sample valve 17107C). In some embodiments, each of the plurality of injection valves cooperates with one of the plurality of valve switches such that the valve switch can change the configuration of the corresponding injection valve.
For example, sample injection valve 17107a cooperates with valve switch 17103 a. In such an example, valve switch 17103a may be positioned through the central opening of sample valve 17107a such that the inner surface of sample valve 17107a surrounding the central opening is in contact with the outer surface of valve switch 17103 a. In some embodiments, sample valve 17107a may be rotated along valve switch 17103a, and valve switch 17103a may change the configuration of sample valve 17107a, details of which are described in connection with at least fig. 172A and 172B.
Similarly, sample valve 17107B cooperates with valve switch 17103B. In such an example, valve switch 17103B may be positioned through the central opening of sample valve 17107B such that the inner surface of sample valve 17107B surrounding the central opening is in contact with the outer surface of valve switch 17103B. In some embodiments, sample valve 17107B may be rotated along valve switch 17103B, and valve switch 17103B may change the configuration of sample valve 17107B, the details of which are described in connection with at least fig. 172A and 172B.
Similarly, sample valve 17107C cooperates with valve switch 17103C. In such an example, valve switch 17103C may be positioned through the central opening of sample valve 17107C such that the inner surface of sample valve 17107C surrounding the central opening is in contact with the outer surface of valve switch 17103C. In some embodiments, sample valve 17107C may be rotated along valve switch 17103C, and valve switch 17103C may change the configuration of sample valve 17107C, details of which are described in connection with at least fig. 172A and 172B.
Similar to those described above, each of the plurality of sample valves (e.g., without limitation, sample valve 17107a, sample valve 17107B, and sample valve 17107C) includes at least a buffer solution injection port that receives a buffer solution and a sensing channel connection that connects to a sensing channel input port of the waveguide fluidic assembly. In some embodiments, each of the plurality of sample valves further comprises a sample solution injection port that receives a sample solution, and a waste release port that is connected to a waste reservoir. In some embodiments, each of the plurality of sample injection valves further comprises two sample loop ports connected via a sample loop tube. Additional details associated with ports and configurations of the injection valves are described in connection with at least fig. 172A and 172B.
Referring now to fig. 172A and 172B, an exemplary block diagram of an exemplary sample valve array 17200 according to some embodiments of the present disclosure is provided. In particular, fig. 172A and 172B illustrate different configurations associated with an exemplary sample valve array 17200.
In some embodiments, the example sample valve array 17200 includes sample valves 17214 mated with valve switches 17216, similar to those described above.
In some embodiments, the sample valve 17214 includes six ports. For example, the sample valve 17214 includes a buffer solution injection port 17202 that receives buffer solution (e.g., from a multichannel peristaltic pump). In some embodiments, the sample valve 17214 includes a sample solution injection port 17206 that receives a sample solution. In some embodiments, the sample valve 17214 includes a sense channel connection port 17212 that connects to a sense channel input port on the waveguide fluidic component. In some embodiments, the sample valve 17214 includes a waste release port 17208 that is connected to a waste reservoir. In some embodiments, the sample valve 17214 includes a first sample loop port 17204 and a second sample loop port 17210 connected to each other. For example, the first sample loop port 17204 and the second sample loop port 17210 may be connected to each other by a sample loop tube.
In some embodiments, the buffer solution injection port 17202 is positioned between the first sample loop port 17204 and the sense channel connection port 17212. In some embodiments, the first sample loop port 17204 is positioned between the buffer solution injection port 17202 and the sample solution injection port 17206. In some embodiments, the sample solution injection port 17206 is positioned between the first sample loop port 17204 and the waste release port 17208. In some embodiments, waste release port 17208 is positioned between sample solution injection port 17206 and second sample loop port 17210. In some embodiments, the second sample loop port 17210 is positioned between the waste release port 17208 and the sensing channel connection port 17212. In some embodiments, the sensing channel connection port 17212 is positioned between the buffer solution injection port 17202 and the second sample loop port 17210.
In some embodiments, the sample valve 17214 may be switched to a different configuration to switch between a sensing channel input port that injects buffer solution onto the waveguide fluidic component and a sensing channel input port that injects sample solution onto the waveguide fluidic component, similar to those described above in connection with at least fig. 67A and 68.
For example, in the configuration shown in fig. 172A, the buffer solution injection port 17202 is connected to the sensing channel connection port 17212 through a configuration switching channel on the valve switch 17216. Thus, the buffer solution is injected into the sensing channel input port on the waveguide fluidic assembly. Continuing in this example, sample solution is injected into sample solution injection port 17206, which is connected to first sample loop port 17204 through a configuration switching channel on valve switch 17216. As described above, the first sample loop port 17204 is connected to the second sample loop port 17210 through the sample loop. In the example shown in fig. 172A, the second sample loop port 17210 is connected to the waste release port 17208 through a configuration switching channel on the valve switch 17216. Accordingly, the sample solution flows through the sample solution injection port 17206, the first sample loop port 17204, and the second sample loop port 17210 and is released from the waste release port 17208.
In some embodiments, rotation of the valve switch 17216 inside the sample valve 17214 may cause the configuration of the example sample valve array 17200 to switch from the configuration shown in fig. 172A to the configuration shown in fig. 172B.
In the example shown in fig. 172B, the sample solution injection port 17206 is connected to the waste release port 17208 through a configuration switching channel on the valve switch 17216. In addition, the buffer solution injection port 17202 is connected to the first sample loop port 17204 through a configuration switching channel on the valve switch 17216. As described above in connection with fig. 172A, the first sample loop port 17204 is connected to the second sample loop port 17210 through the sample loop, and the sample loop tube can store a sample solution due to the configuration shown in fig. 172A. Thus, when the buffer solution injection port 17202 is connected to the first sample loop port 17204, the buffer solution injected into the buffer solution injection port 17202 pushes the sample solution in the sample loop tube through the second sample loop port 17210.
In the example shown in fig. 172B, the second sample loop port 17210 is connected to the sense channel connection port 17212 through a configuration switching channel on the valve switch 17216. Thus, the buffer solution injected through buffer solution injection port 17202 may push sample solution from the sample loop through sensing channel connection port 17212 to the sensing channel input port on the waveguide fluidic assembly.
As described above, the example sample valve array 17200 may include multiple sample valves. In some embodiments, the switching of the configuration of the plurality of sample valves may be controlled separately such that the same amount of sample solution may be injected into the sensing channel input port on the waveguide fluidic component and/or sample solution may be injected simultaneously into the sensing channel input port on the waveguide fluidic component. Thus, the example sample valve array 17200 of the example parallel flow multichannel pathogen sensing system can provide technical benefits and advantages, such as, but not limited to, precise control of parallel flow.
Referring now to fig. 173A, 173B, and 173C, exemplary views associated with exemplary waveguide fluid assemblies 17300 according to some embodiments of the present disclosure are provided. Specifically, fig. 173A illustrates an exemplary exploded view of an exemplary waveguide fluid assembly 17300 according to some embodiments of the present disclosure. Fig. 173B illustrates an example top view of an example waveguide fluid assembly 17300 according to some embodiments of the present disclosure. Fig. 173C illustrates an exemplary perspective view of an exemplary waveguide fluid assembly 17300 according to some embodiments of the present disclosure.
In the example shown in fig. 173A, 173B, and 173C, the example waveguide fluidic assembly 17300 includes a thermal control sensor base 17301, a multichannel waveguide sensor 17303, and a parallel flow microfluidic cover 17305.
In some embodiments, the multichannel waveguide sensor 17303 is disposed on top of the thermal control sensor base 17301. In some embodiments, a parallel flow microfluidic cover 17305 is disposed on top of the multichannel waveguide sensor 17303.
In some embodiments, the thermal control sensor base 17301 includes one or more separable components. In the example shown in fig. 173A, 173B, and 173C, the thermal control sensor base 17301 includes a heat sink 17307, insulation 17309, heating and cooling plates 17311, sensor base 17317, and thermal sensor 17319.
In some embodiments, insulation 17309 is provided on top of heat sink 17307 and may include an insulating material (such as, but not limited to, fiberglass, polyurethane, etc.).
In some embodiments, heating and cooling plates 17311 are disposed on top of insulation 17309. In some embodiments, the heating and cooling plate 17311 may regulate the ambient temperature around the multichannel waveguide sensor 17303. For example, waveguide fluid assembly 17300 includes at least one of a dual function heater-cooler component having two wires (i.e., wire 17313 and wire 17315). The direction of the current through the wire determines whether the cooling or heating function. In the example shown in fig. 173A, the dual function heater-cooler component is secured to a heating and cooling plate 17311. Similar to the various examples described above, the dual function heater-cooler component may raise the ambient temperature around the multi-channel waveguide sensor 17303 or lower the ambient temperature around the multi-channel waveguide sensor 17303.
In some embodiments, the adjustment of the ambient temperature may be determined based on the temperature detected by the thermal sensor 17319. In some embodiments, the thermal sensor 17319 may include one or more temperature sensors (such as, but not limited to, thermocouples, resistive temperature detectors, etc.) that detect the ambient temperature around the multichannel waveguide sensor 17303.
For example, the multichannel waveguide sensor 17303 may be secured to a top surface of the sensor base 17317. In this example, a thermal sensor 17319 is also secured to the sensor base 17317.
In some embodiments, waveguide fluidic assembly 17300 includes a gasket 17321 affixed to a bottom surface of parallel flow microfluidic cover 17305. In some embodiments, the gasket 17321 is aligned with the multichannel waveguide sensor 17303 such that the sample solution and/or the reference solution may flow through the flow channel defined by the gasket 17321 and on top of one or more optical sensing channels of the multichannel waveguide sensor 17303.
Referring now to fig. 174, an exemplary top view of a shim 17402 and a multi-channel waveguide sensor 17404 according to some embodiments of the present disclosure is provided.
In some embodiments, a spacer 17402 is affixed to the bottom surface of the parallel flow microfluidic cover 17408, similar to those described above in connection with at least fig. 173A-173C.
In some embodiments, the multichannel waveguide sensor 17404 is disposed on top of the thermally-controlled sensor base 17410.
In some embodiments, the parallel flow microfluidic cover 17408 is positioned on top of the thermal control sensor mount 17410 such that the gasket 17402 is aligned with the multichannel waveguide sensor 17404.
For example, the shim 17402 may define one or more flow channels (such as, but not limited to, flow channel 17406a, flow channel 17406B, and flow channel 17406C). In some embodiments, the shim 17402 is aligned with the multi-channel waveguide sensor 17404 such that each of the one or more flow channels (such as, but not limited to, flow channel 17406a, flow channel 17406B, and flow channel 17406C) overlaps one or more optical sensing channels of the multi-channel waveguide sensor 17404.
Referring now to fig. 175A and 175B, exemplary views associated with an exemplary multi-channel waveguide sensor 17500 are provided in accordance with some embodiments of the present disclosure. Specifically, fig. 175A shows an exemplary perspective view of an exemplary multi-channel waveguide sensor 17500. Fig. 175B shows an exemplary top view of an exemplary multi-channel waveguide sensor 17500.
In some embodiments, the exemplary multi-channel waveguide sensor 17500 comprises multiple channels. In the example shown in fig. 175A and 175B, the example multi-channel waveguide sensor 17500 includes eight optical channels (e.g., optical channel 17501, optical channel 17503, optical channel 17505, optical channel 17507, optical channel 17509, optical channel 17511, optical channel 17513, and optical channel 17515).
In some embodiments, the eight optical channels include two buried reference channels (e.g., optical channel 17505 and optical channel 17511) to correct for laser sources and environmental changes, and six optical sensing channels (e.g., optical channel 17501, optical channel 17503, optical channel 17507, optical channel 17509, optical channel 17513, and optical channel 17515). In this example, the exemplary multi-channel waveguide sensor 17500 includes two channels for each flow channel from the shim as redundancy.
As described above, the number of the plurality of pump flow channel tubes, the number of the plurality of flow sensor input ports, the number of the plurality of flow sensor output ports, and/or the number of the plurality of sample valves may be determined based on the number of optical sensing channels in the waveguide sensor of the waveguide fluidic assembly. In the example shown in fig. 175A and 175B, the exemplary multi-channel waveguide sensor 17500 includes six optical sensing channels. In some embodiments, the ratio between the optical sensing channel and the flow channel of the gasket may be two to one. In some embodiments, the number of pump flow channel tubes, the number of flow sensor input ports, the number of flow sensor output ports, and/or the number of sample valves may be determined based on the number of optical sensing channels in the waveguide sensor and the ratio between the optical sensing channels and the flow channels. Continuing with the above example, the number of the plurality of pump flow channel tubes, the number of the plurality of flow sensor input ports, the number of the plurality of flow sensor output ports, and the number of the plurality of sample valves may be three.
Accordingly, various embodiments of the present disclosure provide a parallel flow multi-channel pathogen sensing system that provides technical benefits and advantages such as, but not limited to, eliminating channel-to-channel variation and uncertainty for optimal stability and repeatability.
Although the multi-channel waveguide sensor described in connection with fig. 175A and 175B includes eight optical channels, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, an exemplary multi-channel waveguide sensor may include fewer than eight optical channels or more than eight optical channels.
There are many technical challenges and difficulties associated with sample sensing and testing. For example, many viral particle sensing methods suffer from technical limitations, such as, but not limited to, non-specific detection of viruses, which can reduce the accuracy of the various assays. For example, viruses may be associated with different sizes (e.g., diameters). However, many virus sensing methods do not provide for specific virus detection of a specific virus associated with a specific diameter, thus reducing the specificity of the virus detection.
Various embodiments of the present disclosure overcome the technical challenges and difficulties described above and provide various technical benefits and advantages. For example, various embodiments of the present disclosure may prefilter the sample solution such that the resulting sample solution may only contain viruses associated with a particular diameter. In some embodiments, various embodiments of the present disclosure can reduce and improve the specificity of detecting viruses by prefiltering a sample.
For example, SARS-CoV2 virus particles have an average diameter of about 100 nanometers. In some embodiments, filtering the sample solution stream may remove particles that are not about 100 nanometers in diameter, thereby reducing or eliminating the possibility of non-specific detection. According to various embodiments of the present disclosure, a two-stage filter may be arranged to remove particles smaller or larger than SARS-CoV2 virus particles.
For example, various embodiments of the present disclosure provide an in-line flow particulate filter to filter both small and large particles through one pass of a sample solution. In some embodiments, the dual-flow viral particle filtration device has a circular shape and defines a circular flow path. In some embodiments, the circular flow path creates centrifugal forces that push the solution flow through both the blocking filter and through the filter. In some embodiments, both the blocking filter and the pass-through filter may have an annular shape to accommodate the circular shape of the dual-flow viral particle filtration device. In such an example, the blocking filter and the pass filter may also be referred to as a "blocking filter ring" and a "pass filter ring", respectively.
In some embodiments, the blocking filter may block particles having a diameter greater than 130 nanometers. In some embodiments, particles having a diameter of less than 70 nanometers may be filtered out by a filter. In some embodiments, particles having diameters less than 130 nanometers and greater than 70 nanometers may flow out of the dual flow viral particle filtration device for further detection (e.g., by one or more biochemical sensors).
Referring now to fig. 176A, 176B, and 176C, exemplary views associated with an exemplary dual-flow viral particle filtration device 17600 according to some embodiments of the present disclosure are provided.
In some embodiments, the exemplary dual-flow viral particle filtration apparatus 17600 includes a filter base 17602, a blocker filter ring 17604, a pass filter ring 17106, and a filter cap 17608.
In some embodiments, the filter base 17602 defines a circular flow channel 17610. In some embodiments, the circular flow channel 17610 may be in the form of a groove disposed on a surface of the filter base 17602. In some embodiments, the circular flow channel 17610 may be shaped like an incomplete circle. For example, the groove of the circular flow channel 17610 may include a first end and a second end.
In some embodiments, a filter ring 17106 is disposed over the circular flow channel 17610 of the filter base 17602. In some embodiments, the pass-through filter ring 17106 is shaped like a circle. For example, the pass filter ring 17106 may be an incompletely rounded shape comprising a first end and a second end.
In some embodiments, passing through the filter ring 17106 includes passing through a filter membrane. For example, the pass filter membrane may include one or more porous materials that prevent particles in the sample solution associated with a diameter greater than the pass filter threshold from flowing through the pass filter ring 17106. Examples of porous materials may include, but are not limited to, nanofilters (e.g., polyacrylic acid (PAA) nanofilters, etc.).
In some embodiments, the pass filter threshold is 70 nanometers. In such an example, if a particle (such as a viral molecule) has a diameter greater than 70 nanometers, the particle may be blocked by the filter ring 17106. In other words, only particles smaller than 70 nanometers in diameter may pass through the filter ring 17106.
Although the above description provides an example of a pass filter threshold of 70 nanometers, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary pass filter threshold may be less than or greater than 70 nanometers.
In some embodiments, a blocking filter ring 17604 is disposed over the circular flow channel 17610 of the filter base 17602. In some embodiments, the blocking filter ring 17604 is shaped like a circle. For example, the blocking filter ring 17604 may be an incompletely rounded shape comprising a first end and a second end.
In some embodiments, the blocking filter ring 17604 comprises a blocking filter membrane. For example, the blocker filter ring 17604 can include one or more porous materials that prevent particles in the sample solution associated with a diameter greater than a blocker filter threshold from flowing through the blocker filter ring 17604. Examples of porous materials may include, but are not limited to, nanofilters (e.g., PAA nanofilters, etc.).
In some embodiments, the blocking filter threshold is 130 nanometers. In such an example, if a particle (such as a viral molecule) has a diameter greater than 130 nanometers, the particle may be blocked by the blocking filter ring 17604. In other words, the blocking filter ring 17604 may pass only particles having a diameter of less than 130 nanometers.
Although the above description provides an example of a pass filter threshold of 130 nanometers, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary blocking filter threshold may be less than or greater than 130 nanometers.
As described above, both the blocker filter ring 17604 and the pass-through filter ring 17106 are positioned within the circular flow channel 17610 of the filter base 17602. In some embodiments, a blocking filter ring 17604 is positioned within the pass-through filter ring 17106.
For example, as shown in fig. 176A and 176C, a blocking filter ring 17604 is positioned within the pass-through filter ring 17106. In this example, the blocker filter ring 17604 is positioned closer to the center of the circular flow passage 17610 of the filter base 17602 than through the filter ring 17106.
In some embodiments, the circular flow channel 17610 of the filter base 17602 may be divided into multiple portions by the blocker filter ring 17604 and by the filter ring 17106. For example, as shown in fig. 176C, the circular flow channel 17610 includes a circular flow channel portion 17616 formed between the central wall of the circular flow channel 17610 and the blocking filter ring 17604. In some embodiments, the circular flow channel 17610 includes a circular flow channel portion 17178 formed between the blocker filter ring 17604 and the pass-through filter ring 17106. In some embodiments, the circular flow channel 17610 includes a circular flow channel portion 17620 formed between the pass-through filter ring 17106 and the circumferential wall of the circular flow channel 17610.
In some embodiments, a filter cover 17608 is disposed on top of the filter base 17602. In some embodiments, the filter cover 17608 covers the circular flow channel 17610 defined by the filter base 17602.
In some embodiments, the filter cap 17608 of the dual-flow viral particle filtration device 17600 defines a flow input opening 1766 and a flow output opening 17114. In some embodiments, the sample solution flows into the circular flow channel 17610 through the flow input opening 1766 and out of the circular flow channel through the flow output opening 17610.
Referring now to fig. 176C, in some embodiments, a flow input opening 1766 is positioned within the circular flow channel portion 17616. In some embodiments, the circular flow channel portion 17616 is within the pass-through filter ring 17106 and within the blocker filter ring 17604.
In some embodiments, the flow output opening 17610 is positioned within the circular flow channel portion 17218 of the circular flow channel 17610. In some embodiments, the flow output opening 1766 is positioned between the pass-through filter ring 17106 and the blocker filter ring 17604.
As shown in fig. 176C, the circular flow channel 17610 is shaped like an incomplete circle. In particular, the circular flow channel 17610 defines an incomplete circle including a first end 17622 and a second end 17624 that are not connected to each other. In some embodiments, the flow input opening 1766 is positioned adjacent to the first end 17622 such that the flow input opening 1766 injects solution into the first end 17622 of the circular flow channel 17610. In some embodiments, injecting the solution into the circular flow channel 17610 creates a centrifugal force that causes the solution to flow through the circular flow channel 17610 and to the second end 17624 of the circular flow channel 17610. In some embodiments, the flow output opening 17610 is positioned adjacent the second end 17624 of the circular flow channel 17610 and receives solution from the circular flow channel 17610.
In some embodiments, the positional relationship within the circular flow channel 17610 through the filter ring 17106 and the blocker filter ring 17604 may provide technical benefits and advantages, such as, but not limited to, ensuring that only particles having diameters within a particular range (e.g., particles having diameters between 70 nanometers and 130 nanometers) will be provided as an output of the flow output opening 17114. Referring now to fig. 177, an exemplary top view of at least an exemplary portion of an exemplary dual-flow viral particle filtration device 17700 is provided, according to some embodiments of the disclosure.
In the example shown in fig. 177, the example dual-flow virus particle filtration apparatus 17700 includes a filter base 17701, a blocking filter ring 17703, and a pass-through filter ring 17705.
Similar to those described above, the filter base 17701 defines a circular flow channel 17707. In some embodiments, the circular flow channel 17707 may be in the form of a groove disposed on a surface of the filter base 17701. In some embodiments, the circular flow channel 17707 may be shaped like an incomplete circle. For example, the groove of the circular flow channel 17707 may include a first end 17709 and a second end 17711. In some embodiments, the first end 17709 is not connected to the second end 17711.
In some embodiments, a filter ring 17705 is disposed over the circular flow channel 17707 of the filter base 17701. In some embodiments, the pass-through filter ring 17705 is shaped like a circle. For example, the pass filter ring 17705 can be an incompletely rounded shape comprising a first end and a second end.
Similar to the exemplary pass-through filter ring 17106 described in connection with fig. 176A-176C, pass-through filter ring 17705 includes a pass-through filter membrane. For example, the pass filter membrane may include one or more porous materials that prevent particles in the sample solution associated with a diameter greater than the pass filter threshold from flowing through the pass filter ring 17705. Examples of porous materials may include, but are not limited to, nanofilters (e.g., PAA nanofilters, etc.).
Similar to the exemplary pass filter ring 17106 described in connection with fig. 176A-176C, the pass filter threshold is 70 nanometers. In such an example, if a particle (such as a viral molecule) has a diameter greater than 70 nanometers, the particle may be blocked by passing through the filter ring 17705. In other words, only particles smaller than 70 nanometers in diameter may pass through the filter ring 17705.
Although the above description provides an example of a pass filter threshold of 70 nanometers, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary pass filter threshold may be less than or greater than 70 nanometers.
In some embodiments, a blocking filter ring 17703 is disposed over the circular flow channel 17707 of the filter base 17701. In some embodiments, the blocking filter ring 17703 is shaped like a circle. For example, the blocking filter ring 17703 may be an incompletely rounded shape comprising a first end and a second end.
Similar to the exemplary blocking filter ring 17604 described in connection with fig. 176A-176C, the blocking filter ring 17703 includes a blocking filter membrane. For example, the blocker filter ring 17703 can include one or more porous materials that prevent particles in the sample solution associated with a diameter greater than a blocker filter threshold from flowing through the blocker filter ring 17703. Examples of porous materials may include, but are not limited to, nanofilters (e.g., PAA nanofilters, etc.).
Similar to the exemplary blocking filter ring 17604 described in connection with fig. 176A-176C, the blocking filter threshold is 130 nanometers. In such an example, if a particle (such as a viral molecule) has a diameter greater than 130 nanometers, the particle may be blocked by the blocking filter ring 17703. In other words, the blocking filter ring 17703 may pass only particles having a diameter of less than 130 nanometers.
Although the above description provides an example of a pass filter threshold of 130 nanometers, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary blocking filter threshold may be less than or greater than 130 nanometers.
As described above, both the blocker filter ring 17703 and the pass filter ring 17705 are positioned within the circular flow channel 17707 of the filter base 17701. In some embodiments, a blocking filter ring 17703 is positioned within the pass-through filter ring 17705.
For example, as shown in fig. 177, a blocking filter ring 17703 is positioned within the pass-through filter ring 17705. In this example, the blocker filter ring 17703 is positioned closer to the center of the circular flow passage 17707 of the filter base 17701 than through the filter ring 17705.
In some embodiments, the circular flow channel 17707 of the filter base 17701 may be divided into multiple portions by the blocker filter ring 17703 and by the filter ring 17705.
For example, as shown in fig. 177, the circular flow channel 17707 includes a circular flow channel portion 17713 formed between the central wall of the circular flow channel 17707 and the blocking filter ring 17703. In some embodiments, the circular flow channel 17707 includes a circular flow channel portion 17715 formed between the blocker filter ring 17703 and the pass-through filter ring 17705. In some embodiments, the circular flow channel 17707 includes a circular flow channel portion 17717 formed between the pass-through filter ring 17705 and the circumferential wall of the circular flow channel 17707.
Similar to those described above in connection with at least fig. 176A-176C, a solution (such as, but not limited to, a sample solution) may be injected from a flow input opening of the filter cap into the circular flow channel 17707 at the first end 17709. In some embodiments, the first end 17709 is positioned in the circular flow channel portion 17713.
In some embodiments, after the solution is injected into the circular flow channel 17707, the force of the injection causes the solution to flow from the circular flow channel portion 17713 to the circular flow channel portion 17715 through the blocking filter ring 17703.
As described above, the blocking filter ring 17703 includes a blocking filter membrane that prevents particles in the sample solution associated with a diameter greater than the blocking filter threshold from flowing through the blocking filter ring 17703. In some embodiments, circular flow channel portion 17713 includes only particles associated with diameters greater than the barrier filtration threshold, and circular flow channel portion 17715 includes only particles associated with diameters less than the barrier filtration threshold.
In some embodiments, the blocking filter threshold is 130 nanometers. In this example, the blocking filter ring 17703 prevents the passage of particles greater than 130 nanometers in diameter such that the circular flow channel portion 17713 includes only particles associated with diameters greater than 130 nanometers and the circular flow channel portion 17715 includes only particles associated with diameters less than 130 nanometers.
Although the above description provides an example of a blocking filter threshold of 130 nanometers, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary blocking filter threshold may be less than 130 nanometers or greater than 130 nanometers.
In some embodiments, after the solution flows to the circular flow channel portion 17715, the force of injection causes the solution to flow from the circular flow channel portion 17715 to the circular flow channel portion 17717 by passing through the filter ring 17705.
As described above, passing through the filter ring 17705 includes passing through a filter membrane that prevents particles in the sample solution associated with a diameter greater than the pass through filter threshold from flowing through the filter ring 17705. In some embodiments, circular flow channel portion 17715 includes only particles associated with a diameter greater than the pass-through filtration threshold, and circular flow channel portion 17717 includes only particles associated with a diameter less than the pass-through filtration threshold.
In some embodiments, the pass filter threshold is 70 nanometers. In this example, particles having a diameter greater than 70 nanometers are prevented from passing through by the filter ring 17705 such that the circular flow channel portion 17715 includes only particles associated with diameters greater than 70 nanometers and the circular flow channel portion 17717 includes only particles associated with diameters less than 70 nanometers.
Although the above description provides an example of a pass filter threshold of 70 nanometers, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary pass filter threshold may be less than 70 nanometers or greater than 70 nanometers.
In some embodiments, the circular flow channel portion 17715 includes only particles associated with diameters less than the blocking filtration threshold due to the blocking filter ring 17703 and only particles associated with diameters greater than the passing filtration threshold due to the passing filter ring 17705. In some embodiments, the blocking filter threshold is 130 nanometers and the pass filter threshold is 70 nanometers. In this example, the solution released from the example dual flow viral particle filtration device 17700 through the flow output opening (which is located in the circular flow channel portion 17715) includes particles between 70 nanometers and 130 nanometers in diameter.
In some embodiments, the exemplary dual-flow viral particle filtration device may be integrated into an exemplary parallel flow multi-channel pathogen sensing system. Referring now to fig. 178A and 178B, exemplary views associated with exemplary portions of an exemplary parallel flow multi-channel pathogen sensing system 17800 are provided, according to some embodiments of the disclosure. Specifically, fig. 178A illustrates an example exploded view associated with an example parallel flow multi-channel pathogen sensing system 17800. Fig. 178B illustrates another example exploded view associated with an example parallel flow multi-channel pathogen sensing system 17800.
In the example shown in fig. 178A and 178B, an exemplary dual-flow viral particle filtration device may be added to the front or beginning of the sample injection path to improve virus sensing specificity.
For example, the exemplary parallel flow multi-channel pathogen sensing system 17800 includes a sample injector 17802, a dual flow viral particle filter device 17804, a sample valve array 17806, a waveguide fluid assembly 17808, an optical fiber array 17810, and an imaging sensor 17812. In some embodiments, sample valve array 17806, waveguide fluid assembly 17808, fiber optic array 17810, and imaging sensor 17812 are similar to the various examples described above in connection with at least fig. 167-175B. In some embodiments, the dual-flow viral particle filtration device 17804 is similar to the various examples described in connection with at least fig. 176A-177.
In the example shown in fig. 178A and 178B, a sample injector 17802 injects a sample solution into a dual flow virus particle filtration apparatus 17804. In some embodiments, the dual flow viral particle filtration device 17804 releases the sample solution having particles associated with a size between the pass filtration threshold and the block filtration threshold into the sample valve array 17806 (e.g., sample solution injection port of sample valve array 17806). In some embodiments, sample valve array 17806 injects a sample solution into waveguide fluid assembly 17808, similar to the various examples described above. In some embodiments, the fiber array 17810 emits laser light into a waveguide sensor in the waveguide fluid assembly 17808, similar to the various examples described above. In some embodiments, the imaging sensor 17812 generates a detection signal, similar to the various examples described above.
While the above description provides examples of integrating an exemplary dual-flow viral particle filtration device into an exemplary parallel flow multi-channel pathogen sensing system, it should be noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary dual-flow viral particle filtration device may be integrated into other systems and/or devices. For example, the exemplary dual-flow viral particle filtration device may be integrated into a lab-on-a-chip solution.
As shown in the various embodiments herein, various embodiments of the present disclosure provide a multichannel pathogen sensor that can effectively detect targeted viruses with sensitivity and specificity references. In some embodiments, exemplary multi-channel pathogen sensors may provide cross-binding pathogen sensing that may be arranged to detect multiple viruses with multiple references to further improve the sensitivity, specificity, and throughput of sample testing.
For example, various embodiments of the present disclosure provide a cross-coupled pathogen detection method that utilizes a multi-channel waveguide sensor with multi-channel microfluidics to achieve multiple virus detection with multiple references. In some embodiments, multiple types of antibodies are employed to allow multiple pairs of cross-binding between the viral particles and the antibodies. In some embodiments, the results of cross-binding can be analyzed to characterize specific viral particles against specific antibodies with high confidence.
Referring now to fig. 179A and 179B, exemplary views associated with exemplary multi-channel waveguide fluidic assemblies 17900 according to some embodiments of the present disclosure are provided. In the example shown in fig. 179A and 179B, the example multichannel waveguide fluid assembly 17900 includes a fluid cover 17901 and a thermally controlled sensor mount 17903.
In some embodiments, the fluid cap 17901 includes a plurality of fluid cap flow channel input openings and a plurality of fluid cap flow channel output openings. In the example shown in fig. 179A and 179B, the fluid cap 17901 includes a fluid cap flow channel input opening 17911A, a fluid cap flow channel input opening 17911B, and a fluid cap flow channel input opening 17911C, as well as a fluid cap flow channel output opening 17913a, a fluid cap flow channel output opening 17913B, and a fluid cap flow channel output opening 17913C.
In some embodiments, a gasket 17905 is secured to the bottom surface of the fluid cover 17901, similar to the various examples described above. In some embodiments, the shim 17905 includes a plurality of fluid grooves, the details of which are described herein. In some embodiments, each of the plurality of fluid cap flow channel input openings and each of the plurality of fluid cap flow channel output openings are connected to one of the plurality of fluid grooves. For example, each of the plurality of fluid cap flow channel input openings and each of the plurality of fluid cap flow channel output openings define a start point and an end point, respectively, of one of the plurality of fluid grooves.
Similar to the various examples described above, the multi-channel waveguide fluid assembly 17900 includes a multi-channel waveguide sensor 17907 disposed on top of a thermally controlled sensor mount 17903. In some embodiments, the thermally controlled sensor mount 17903 provides temperature control for the multichannel waveguide sensor 17907.
In some embodiments, the multi-channel waveguide sensor 17907 provides multiple waveguide fluid channels. In some embodiments, when the fluid cover 17901 is secured to the thermally-controlled sensor mount 17903, the gasket 17905 is aligned with the multi-channel waveguide sensor 17907 such that one or more sample solutions can be injected through one or more fluid cover flow channel input openings of the fluid cover 17901, flow on top of one or more of the plurality of waveguide flow channels of the multi-channel waveguide sensor 17907, and exit from one or more fluid cover flow channel output openings of the fluid cover 17901.
Referring now to fig. 180A and 180B, exemplary views associated with exemplary multi-channel waveguide fluid assemblies 18000 according to some embodiments of the present disclosure are provided. Specifically, fig. 180A illustrates an exemplary top view of an exemplary multi-channel waveguide fluid assembly 18000, and fig. 180B illustrates an exemplary bottom view of an exemplary multi-channel waveguide fluid assembly 18000.
Similar to the various examples described above, the exemplary multichannel waveguide fluid assembly 18000 includes a fluid cap 18002 and a thermal control sensor base 18004.
In some embodiments, the fluid cap 18002 includes a plurality of fluid cap flow channel openings. In the example shown in fig. 180A and 180B, the fluid cap 18002 includes three pairs of fluid cap flow channel openings. For example, the fluid cover 18002 includes: a first pair of fluid cap flow channel openings comprising a fluid cap flow channel input opening 18010A and a fluid cap flow channel output opening 18012A; a second pair of fluid cap flow channel openings comprising a fluid cap flow channel input opening 18010B and a fluid cap flow channel output opening 18012B; and a third pair of fluid cover flow channel openings comprising a fluid cover flow channel input opening 18010C and a fluid cover flow channel output opening 18012C.
In some embodiments, shim 18006 is affixed to the bottom surface of fluid cover 18002, while multichannel waveguide sensor 18008 is affixed to the top surface of thermal control sensor base 18004. In this example, shim 18006 is aligned with multichannel waveguide sensor 18008 when fluid cover 18002 is secured to thermal control sensor base 18004.
In some embodiments, shim 18006 and multi-channel waveguide sensor 18008 define a plurality of waveguide fluid channels, including waveguide fluid channel 18014A, waveguide fluid channel 18014B, and waveguide fluid channel 18014C. In some embodiments, waveguide fluid channel 18014A, waveguide fluid channel 18014B, and waveguide fluid channel 18014C are arranged parallel to one another. In some embodiments, each of waveguide fluid channel 18014A, waveguide fluid channel 18014B, and waveguide fluid channel 18014C includes two or more optical sensing channels as redundancy. In some embodiments, the multi-channel waveguide sensor 18008 includes two or more buried reference channels that receive laser light from a laser source and test environmental conditions to compensate for sensor results that drift due to temperature factors.
In some embodiments, each of the plurality of waveguide fluid channels is connected to a pair of fluid cap flow channel openings. For example, the waveguide fluid channel 18014A is connected to a first pair of fluid cap flow channel openings, including a fluid cap flow channel input opening 18010A and a fluid cap flow channel output opening 18012A. In this example, one or more solutions are injected into waveguide fluid channel 18014A through fluid cap flow channel input opening 18010A and discharged from waveguide fluid channel 18014A through fluid cap flow channel output opening 18012A. Additionally or alternatively, the waveguide fluid channel 18014B is connected to a second pair of fluid cap flow channel openings, including a fluid cap flow channel input opening 18010B and a fluid cap flow channel output opening 18012B. In this example, one or more solutions are injected into waveguide fluid channel 18014B through fluid cap flow channel input opening 18010B and discharged from waveguide fluid channel 18014B through fluid cap flow channel output opening 18012B. Additionally or alternatively, the waveguide fluid channel 18014C is connected to a third pair of fluid cap flow channel openings, including a fluid cap flow channel input opening 18010C and a fluid cap flow channel output opening 18012C. In this example, one or more solutions are injected into waveguide fluid channel 18014C through fluid cap flow channel input opening 18010C and discharged from waveguide fluid channel 18014C through fluid cap flow channel output opening 18012C.
Although the above description provides examples of three waveguide fluidic channels, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the exemplary multi-channel waveguide fluidic assembly may provide fewer than three or more than three waveguide fluidic channels.
As shown in the various examples described herein (including but not limited to those described in connection with at least fig. 179A-180B), an exemplary multi-channel waveguide fluidic assembly according to some embodiments of the present disclosure may provide three or more parallel flow channels to allow fluid sample to flow through the waveguide fluidic channels of a multi-channel waveguide sensor for pathogen detection. Various examples of the present disclosure provide exemplary sample testing methods utilizing exemplary multi-channel waveguide fluidic assemblies.
For example, a sample testing method according to some embodiments of the present disclosure may include: coating a plurality of sample channels with antibodies associated with one or more antibody types, inputting one or more sample solutions to the plurality of sample channels, and receiving a plurality of sample detection signals corresponding to the plurality of sample channels.
For example, the sample testing method in conjunction with fig. 179A-179B and/or fig. 180A-180B may include coating a plurality of sample channels (including waveguide fluid channel 18014A, waveguide fluid channel 18014B, and waveguide fluid channel 18014C) with antibodies associated with one or more antibody types. In some embodiments, the sample testing method may further comprise inputting one or more sample solutions into the plurality of sample channels. For example, the sample testing method may include injecting one or more sample solutions through the fluid lid flow channel input opening 18010A, the fluid lid flow channel input opening 18010B, and the fluid lid flow channel input opening 18010C. As described above, the fluid cap flow channel input opening 18010A, the fluid cap flow channel input opening 18010B, and the fluid cap flow channel input opening 18010C are connected to the waveguide flow channel 18014A, the waveguide flow channel 18014B, and the waveguide flow channel 18014C, respectively.
Similar to the examples described above, laser light from one or more laser sources is transmitted through each of waveguide fluid channel 18014A, waveguide fluid channel 18014B, and waveguide fluid channel 18014C. In some embodiments, one or more imaging sensors are aligned with the output end of each of waveguide fluid channel 18014A, waveguide fluid channel 18014B, and waveguide fluid channel 18014C. The one or more imaging sensors generate a plurality of sample detection signals based on the detected laser light from each of waveguide fluid channel 18014A, waveguide fluid channel 18014B, and waveguide fluid channel 18014C as one or more sample solutions flow through waveguide fluid channel 18014A, waveguide fluid channel 18014B, and waveguide fluid channel 18014C.
As described above, the parallel flow channels of the exemplary multichannel waveguide fluidic assemblies according to various embodiments of the present disclosure enable cross-binding of pairs of viral particles from one or more sample solutions and antibodies associated with one or more antibody types.
For example, an exemplary multichannel waveguide fluidic assembly according to some embodiments of the present disclosure may be implemented to detect whether one type of sample solution includes any viruses corresponding to any of a plurality of antibody types. In some embodiments, the number n of antibody types is the same as the number of waveguide fluidic channels provided by the exemplary multichannel waveguide fluid. In such an example, one type of virus sample may pass through a waveguide fluidic channel coated with different antibodies, and one of several target viruses in the sample solution may be identified in one pass through the exemplary multi-channel waveguide fluidic assembly.
Continuing with this example, the one or more sample solutions injected into the fluid cap flow channel input opening 18010A, the fluid cap flow channel input opening 18010B, and the fluid cap flow channel input opening 18010C are comprised of a single sample solution. In some embodiments, antibodies associated with multiple antibody types are coated on waveguide fluid channel 18014A, waveguide fluid channel 18014B, and waveguide fluid channel 18014C. For example, an antibody associated with a first antibody type is coated on waveguide fluid channel 18014A, an antibody associated with a second antibody type is coated on waveguide fluid channel 18014B, and an antibody associated with a third antibody type is coated on waveguide fluid channel 18014C. In such examples, the sample testing method may determine whether the sample solution is associated with one or more of a plurality of sample types corresponding to the plurality of antibody types based at least in part on the plurality of sample detection signals. For example, if the sample detection signal from waveguide fluid channel 18014A indicates that a virus from the sample solution binds to an antibody coated on waveguide fluid channel 18014A, the sample testing method determines that the sample solution includes a virus corresponding to the first antibody type. If the sample detection signal from waveguide fluid channel 18014B indicates that a virus from the sample solution binds to an antibody coated on waveguide fluid channel 18014B, the sample testing method determines that the sample solution includes a virus corresponding to a second antibody type. If the sample detection signal from waveguide fluid channel 18014C indicates that a virus from the sample solution binds to an antibody coated on waveguide fluid channel 18014C, the sample testing method determines that the sample solution includes a virus corresponding to a third antibody type.
Additionally or alternatively, an exemplary multi-channel waveguide fluidic assembly according to some embodiments of the present disclosure may be implemented to detect whether multiple types of sample solutions include viruses corresponding to one antibody type. In some embodiments, the number n of sample solution types is the same as the number of waveguide fluidic channels provided by the exemplary multi-channel waveguide fluidic assembly. In such an example, sample solutions associated with different sample solution types may pass through a waveguide fluid channel coated with the same antibody.
Continuing with this example, the one or more sample solutions injected into the fluid cap flow channel input opening 18010A, the fluid cap flow channel input opening 18010B, and the fluid cap flow channel input opening 18010C include a plurality of sample solutions associated with a plurality of types. For example, a sample solution associated with a first sample solution type is injected into the fluid lid flow channel input opening 18010A, a sample solution associated with a second sample solution type is injected into the fluid lid flow channel input opening 18010B, and a sample solution associated with a third sample solution type is injected into the fluid lid flow channel input opening 18010C. In some embodiments, antibodies associated with the same antibody type are coated on waveguide fluid channel 18014A, waveguide fluid channel 18014B, and waveguide fluid channel 18014C. In such examples, the sample testing method may determine whether any of the plurality of sample solutions are associated with a sample type corresponding to the antibody type based at least in part on the plurality of sample detection signals. For example, if the sample detection signal from waveguide fluid channel 18014A indicates that a virus from the first sample solution binds to an antibody coated on waveguide fluid channel 18014A, the sample testing method determines that the first sample solution includes a virus corresponding to the antibody type. If the sample detection signal from waveguide fluid channel 18014B indicates that the virus from the second sample solution binds to the antibody coated on waveguide fluid channel 18014B, the sample testing method determines that the second sample solution includes a virus corresponding to the antibody type. If the sample detection signal from waveguide fluid channel 18014C indicates that the virus from the third sample solution binds to the antibody coated on waveguide fluid channel 18014C, the sample testing method determines that the third sample solution includes a virus corresponding to the antibody type.
Additionally or alternatively, an exemplary multi-channel waveguide fluidic assembly according to some embodiments of the present disclosure may be implemented to detect whether multiple types of sample solutions include viruses corresponding to multiple antibody types. In some embodiments, the number of sample solution types and the number of antibody types are the same as the number n of waveguide fluidic channels provided by the exemplary multi-channel waveguide fluidic assembly. In such an example, sample solutions associated with different sample solution types may pass through waveguide fluid channels coated with different antibodies. In such an example, a combination of sample virus-antibody binding results can be obtained for specific detection of the targeted virus with non-specific detection eliminated.
Continuing with this example, the one or more sample solutions injected into the fluid cap flow channel input opening 18010A, the fluid cap flow channel input opening 18010B, and the fluid cap flow channel input opening 18010C comprise a plurality of sample solutions. For example, a sample solution associated with a first sample solution type is injected into the fluid lid flow channel input opening 18010A, a sample solution associated with a second sample solution type is injected into the fluid lid flow channel input opening 18010B, and a sample solution associated with a third sample solution type is injected into the fluid lid flow channel input opening 18010C. In some embodiments, an antibody associated with a first antibody type is coated on waveguide fluid channel 18014A, an antibody associated with a second antibody type is coated on waveguide fluid channel 18014B, and an antibody associated with a third antibody type is coated on waveguide fluid channel 18014C. In such an example, the sample testing method may determine whether any of the n sample solutions are associated with one or more sample types corresponding to any of the n antibody types based at least in part on the plurality of sample detection signals. For example, if the sample detection signal from waveguide fluid channel 18014A indicates that a virus from the first sample solution binds to an antibody of the first antibody type coated on waveguide fluid channel 18014A, the sample testing method determines that the first sample solution includes a virus corresponding to the first antibody type. If the sample detection signal from waveguide fluid channel 18014B indicates that the virus from the second sample solution binds to an antibody of the second antibody type coated on waveguide fluid channel 18014B, the sample testing method determines that the second sample solution includes a virus corresponding to the second antibody type. If the sample detection signal from waveguide fluid channel 18014C indicates that the virus from the third sample solution binds to an antibody of the third antibody type coated on waveguide fluid channel 18014C, the sample testing method determines that the third sample solution includes a virus corresponding to the third antibody type. In some embodiments, the sample testing method may further comprise: if the sample detection signal indicates no binding between the sample solution and the antibody, injection of the sample solution is switched. For example, if the sample detection signal from waveguide fluid channel 18014A indicates that virus from the first sample solution does not bind to the antibody of the first antibody type coated on waveguide fluid channel 18014A, the sample testing method includes injecting the first sample solution into fluid cap flow channel input opening 18010B and/or fluid cap flow channel input opening 18010C.
Additionally or alternatively, an exemplary multi-channel waveguide fluidic assembly according to some embodiments of the present disclosure may be implemented to detect whether n types of sample solutions include viruses corresponding to 2 n antibody types. In some embodiments, n is the number of waveguide fluidic channels provided by the exemplary multi-channel waveguide fluidic assembly. In such an example, the sample solution associated with the n types of sample solutions may be passed through a waveguide fluidic channel coated with different antibody mixtures, and a combination of sample virus fusion binding results may be obtained by signal transmission of the sample solution.
Continuing with this example, the one or more sample solutions injected into the fluid cap flow channel input opening 18010A, the fluid cap flow channel input opening 18010B, and the fluid cap flow channel input opening 18010C comprise a plurality of sample solutions. For example, a sample solution associated with a first sample solution type is injected into the fluid lid flow channel input opening 18010A, a sample solution associated with a second sample solution type is injected into the fluid lid flow channel input opening 18010B, and a sample solution associated with a third sample solution type is injected into the fluid lid flow channel input opening 18010C. In some embodiments, an antibody mixture comprising antibodies associated with a first antibody type and a second antibody type is coated on waveguide fluid channel 18014A, an antibody mixture comprising antibodies associated with a third antibody type and a fourth antibody type is coated on waveguide fluid channel 18014B, and an antibody mixture comprising antibodies associated with a fifth antibody type and a sixth antibody type is coated on waveguide fluid channel 18014C. In such an example, the sample testing method may determine whether any of the n sample solutions are associated with one or more sample types corresponding to any of the 2 n antibody types based at least in part on the plurality of sample detection signals. For example, if the sample detection signal from waveguide fluid channel 18014A indicates that a virus from the first sample solution binds to an antibody coated on waveguide fluid channel 18014A, the sample testing method determines that the first sample solution includes a virus corresponding to the first antibody type or the second antibody type. If the sample detection signal from waveguide fluid channel 18014A indicates that virus from the first sample solution does not bind to the antibody coated on waveguide fluid channel 18014A, the sample testing method determines that the first sample solution does not include a virus corresponding to the first antibody type or the second antibody type, and may inject the first sample solution into fluid cap flow channel input opening 18010B to determine whether the first sample solution includes a virus corresponding to the third antibody type or the fourth antibody type, and/or inject the first sample solution into fluid cap flow channel input opening 18010C to determine whether the first sample solution includes a virus corresponding to the fifth antibody type or the sixth antibody type.
Additionally or alternatively, an exemplary multi-channel waveguide fluidic assembly according to some embodiments of the present disclosure may be implemented to detect whether a2 n type of sample solution includes viruses corresponding to n antibody types. In some embodiments, n is the number of waveguide fluidic channels provided by the exemplary multi-channel waveguide fluidic assembly. In such an example, the sample solution mixture associated with the 2 n types of sample solutions may pass through a waveguide fluid channel coated with different antibodies. In such an example, a combination of fusion virus results may be obtained by signaling of the sample solution mixture.
Continuing with this example, the one or more sample solutions injected into the fluid cap flow channel input opening 18010A, the fluid cap flow channel input opening 18010B, and the fluid cap flow channel input opening 18010C comprise different mixtures of sample solutions. For example, a sample mixture associated with a first sample solution type and a second sample solution type is injected into the fluid lid flow channel input opening 18010A, a sample solution associated with a third sample solution type and a fourth sample solution type is injected into the fluid lid flow channel input opening 18010B, and a sample solution associated with a fifth sample solution type and a sixth sample solution type is injected into the fluid lid flow channel input opening 18010C. In some embodiments, an antibody associated with a first antibody type is coated on waveguide fluid channel 18014A, an antibody associated with a second antibody type is coated on waveguide fluid channel 18014B, and an antibody associated with a third antibody type is coated on waveguide fluid channel 18014C. In such an example, the sample testing method may determine whether any of the 2 n sample solutions are associated with one or more sample types corresponding to any of the n antibody types based at least in part on the plurality of sample detection signals. For example, if the sample detection signal from waveguide fluid channel 18014A indicates that a virus from the sample mixture associated with the first sample solution type and the second sample solution type binds to an antibody coated on waveguide fluid channel 18014A, the sample testing method determines that the sample solution associated with the first sample solution type or the second sample solution type includes a virus corresponding to the first antibody type. If the sample detection signal from waveguide fluid channel 18014A indicates that a virus from the sample mixture associated with the first sample solution type and the second sample solution type does not bind to an antibody coated on waveguide fluid channel 18014A, the sample testing method determines that the sample solution associated with the first sample solution type and the second sample solution type does not include a virus corresponding to the first antibody type or the second antibody type.
Additionally or alternatively, an exemplary multichannel waveguide fluidic assembly according to some embodiments of the present disclosure may be implemented to detect whether a2 n type of sample solution includes viruses corresponding to 2 n antibody types. In some embodiments, n is the number of waveguide fluidic channels provided by the exemplary multi-channel waveguide fluidic assembly. In such an example, the sample solution mixture associated with the 2 n types of sample solutions may pass through a waveguide fluid channel mixture coated with different antibody mixtures. In such an example, a combination of fusion virus-fusion antibody binding results can be obtained by signaling of the sample solution mixture.
Continuing with this example, the one or more sample solutions injected into the fluid cap flow channel input opening 18010A, the fluid cap flow channel input opening 18010B, and the fluid cap flow channel input opening 18010C comprise different mixtures of sample solutions. For example, a sample mixture associated with a first sample solution type and a second sample solution type is injected into the fluid lid flow channel input opening 18010A, a sample solution associated with a third sample solution type and a fourth sample solution type is injected into the fluid lid flow channel input opening 18010B, and a sample solution associated with a fifth sample solution type and a sixth sample solution type is injected into the fluid lid flow channel input opening 18010C. In some embodiments, an antibody mixture comprising antibodies associated with a first antibody type and a second antibody type is coated on waveguide fluid channel 18014A, an antibody mixture comprising antibodies associated with a third antibody type and a fourth antibody type is coated on waveguide fluid channel 18014B, and an antibody mixture comprising antibodies associated with a fifth antibody type and a sixth antibody type is coated on waveguide fluid channel 18014C.
In such an example, the sample testing method may determine whether any of the 2 n sample solutions are associated with one or more sample types corresponding to any of the 2 n antibody types based at least in part on the plurality of sample detection signals. For example, if the sample detection signal from waveguide fluid channel 18014A indicates that a virus from the sample mixture associated with the first sample solution type and the second sample solution type binds to the antibody mixture associated with the first antibody type and the second antibody type coated on waveguide fluid channel 18014A, the sample testing method determines that the sample solution associated with the first sample solution type or the second sample solution type includes a virus corresponding to the first antibody type or the second antibody type. If the sample detection signal from waveguide fluid channel 18014A indicates that a virus from the sample mixture associated with the first sample solution type and the second sample solution type does not bind to the antibody mixture associated with the first antibody type and the second antibody type coated on waveguide fluid channel 18014A, the sample testing method determines that the sample solution associated with the first sample solution type and the second sample solution type does not include a virus corresponding to the first antibody type or the second antibody type.
As shown in the various examples above, an exemplary multi-channel waveguide fluidic assembly including n waveguide fluidic channels according to some embodiments of the present disclosure may provide 2 n×2n＝22n different test results based on a combination of sample solutions and/or a combination of antibodies, thereby providing technical benefits and advantages in fields such as, but not limited to, pharmaceutical research activities including new drug development for characterizing effectiveness and side effects.
As shown in the various examples above, the multichannel waveguide pathogen sensor may utilize microfluidics to direct sample fluid and reference fluid through sensing channels on top of the waveguide by a gasket to detect a pathogen of interest. However, there are a number of technical challenges and difficulties associated with implementing shims to define a sensing channel on a waveguide. For example, proper alignment of the gasket in the microfluidic can be technically challenging and difficult due to the elastic properties of the gasket material. Alignment difficulties limit channel-to-channel spacing and limit the number of channels that a waveguide can provide. Thus, for a large number of channels in multi-channel fluid sensing for multi-sample pathogen detection, a precision shim with better alignment features is needed.
Various embodiments of the present disclosure overcome these technical challenges and difficulties and provide various technical advantages and improvements.
For example, various embodiments of the present disclosure provide a precision shim that includes fluid features for improved performance and alignment features for precise alignment with a parallel flow microfluidic cover. In some embodiments, the parallel flow microfluidic cover may be precisely aligned with a waveguide fluidic assembly comprising a multichannel waveguide sensor. When secured to the bottom surface of the parallel flow microfluidic cover, the precision shim can be precisely aligned with the waveguide on the waveguide fluidic assembly, creating a flow channel that was previously aligned on top of one or more sensing channels of the waveguide.
Referring now to fig. 181A, 181B, and 181C, exemplary views associated with exemplary spacer 18100 are shown. Specifically, fig. 181A illustrates an exemplary perspective view of an exemplary spacer 18100. Fig. 181B illustrates an exemplary top view of an exemplary spacer 18100. Fig. 181C illustrates an exemplary cross-sectional view of an exemplary spacer 18100.
In the example shown in fig. 181A, 181B, and 181C, the example spacer 18100 can define a plurality of fluid grooves such as, but not limited to, fluid grooves 18101, 18103, and 18105. In such an example, when the example spacer 18100 is positioned on top of the waveguide, the solution can flow in the fluid grooves 18101, 18103, and 18105. In order for the waveguide to detect a target sample in solution, it is important that the fluidic grooves 18101, 18103, and 18105 be aligned on top of one or more sensing channels of the waveguide. However, as noted above, the resilient nature of the example spacer 18100 makes ensuring proper alignment technically challenging and difficult.
Various embodiments of the present disclosure overcome these technical challenges and difficulties and provide various technical improvements and advantages. Referring now to fig. 182A, 182B, and 182C, exemplary views associated with an exemplary precision shim 18200 according to some embodiments of the present disclosure are provided. Specifically, fig. 182A illustrates an exemplary perspective view of an exemplary precision shim 18200. Fig. 181B illustrates an exemplary top view of an exemplary precision shim 18200. Fig. 181C illustrates an exemplary cross-sectional view of an exemplary precision shim 18200.
In the example shown in fig. 182A-182C, an example precision shim 18200 may include a silicone component. In some embodiments, the example precision shim 18200 may be in the form of a single piece silicone part that may be mass produced using a liquid injection molding process.
In some embodiments, the example precision shim 18200 may include a hard plastic cover in addition to the silicone material. In some embodiments, the hard plastic cover of the example precision shim 18200 may be manufactured by an injection molding process to provide support to the silicone portion of the example precision shim 18200 and an interface to the fluid fitting and waveguide base.
In some embodiments, the example precision shim 18200 includes a plurality of alignment ribs. In the example shown in fig. 182A to 182C, the plurality of alignment ribs includes an alignment rib 18202A, an alignment rib 18202B, an alignment rib 18202C, and an alignment rib 18202D.
Although the above description provides an example of four alignment ribs, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the example precision shim 18200 may include fewer than four or more than four alignment ribs.
In some embodiments, the plurality of alignment ribs are disposed on an outer surface of the precision shim 18200. In the example shown in fig. 182A-182C, alignment ribs 18202A, 18202B, 18202C, and 18202D are provided on and protrude from an outer surface 18208 of the example precision shim 18200.
In some embodiments, the example precision shim 18200 includes a plurality of channel cover portions between a plurality of alignment ribs. In some embodiments, each of the plurality of access cover portions is defined between two of the plurality of alignment ribs.
In the example shown in fig. 182A to 182C, the plurality of passage cover portions includes a passage cover portion 18204a, a passage cover portion 18204B, and a passage cover portion 18204C.
For example, the channel cover portion 18204a is defined between the alignment rib 18202A and the alignment rib 18202B. In some embodiments, the channel cover portion 18204B is defined between the alignment rib 18202B and the alignment rib 18202C. In some embodiments, the channel cover portion 18204C is defined between the alignment rib 18202C and the alignment rib 18202D.
In some embodiments, the plurality of alignment ribs are positioned based on a plurality of alignment grooves on the exemplary parallel flow microfluidic cover. For example, the example precision gasket 18200 may be attached to the example parallel flow microfluidic cover by engagement between a plurality of alignment ribs of the example precision gasket 18200 and a plurality of alignment grooves of the example parallel flow microfluidic cover. Additional details are described herein, including but not limited to those described in connection with at least fig. 184A and 184B.
In some embodiments, the plurality of channel cover portions define a plurality of chevron patterns on an inner surface 18210 of the example precision shim 18200. In some embodiments, the inner surface 18210 of the example precision shim 18200 is opposite the outer surface 18208 of the example precision shim 18200.
For example, a plurality of chevron patterns are formed on the inner surface of the channel cover portion 18204A of the example precision gasket 18200 such that the inner surface of the channel cover portion 18204A and the top surface waveguide sensor define a flow channel in which the sample solution can flow. Similarly, a plurality of chevron patterns are formed on the inner surface of the channel cover portion 18204B of the example precision gasket 18200 such that the inner surface of the channel cover portion 18204B and the top surface waveguide sensor define a flow channel in which the sample solution can flow. Similarly, a plurality of chevron patterns are formed on the inner surface of the channel cover portion 18204C of the example precision gasket 18200 such that the inner surface of the channel cover portion 18204C and the top surface waveguide sensor define a flow channel in which the sample solution can flow.
In some embodiments, each of the plurality of channel cover portions defines a flow channel input opening and a flow channel output opening. In some embodiments, a flow channel input opening and a flow channel output opening are positioned at an end of each of the plurality of channel cover portions. In some embodiments, the sample solution may flow into the flow channel from the flow channel input opening and may flow out of the flow channel from the flow channel output opening.
In the example shown in fig. 182B, the channel cover portion 18204A includes a flow channel input opening 18206a and a flow channel output opening 18208A. The channel cover portion 18204B includes a flow channel input opening 18206B and a flow channel output opening 18208B. The channel cover portion 18204C includes a flow channel input opening 18206C and a flow channel output opening 18208C.
Referring now to fig. 183A and 183B, an exemplary perspective view of an exemplary precision shim 18300 according to some embodiments of the disclosure is provided.
Fig. 183A illustrates an exemplary top perspective view of an exemplary precision shim 18300 according to some embodiments of the present disclosure. In the example shown in fig. 183A, the example precision shim 18300 includes a plurality of alignment ribs (including, but not limited to, alignment rib 18301a, alignment rib 18301B, alignment rib 18301C, and alignment rib 18301D) on an outer surface of the example precision shim 18300.
Fig. 183B illustrates an example bottom perspective view of an example precision shim 18300, according to some embodiments of the disclosure. In the example shown in fig. 183B, the example precision shim 18300 includes a plurality of channel cover portions positioned between a plurality of alignment ribs of the example precision shim 18300. For example, the example precision shim 18300 includes a channel cover portion 18303A, a channel cover portion 18303B, and a channel cover portion 18303C.
In some embodiments, the plurality of channel cover portions define a plurality of chevron patterns on an inner surface of the example precision shim 18300. For example, each of the plurality of channel cover portions (including channel cover portion 18303A, channel cover portion 18303B, and channel cover portion 18303C) defines a plurality of chevron patterns on an inner surface of the example precision pad 18300.
Fig. 183C illustrates an example top view of an example precision shim 18300, according to some embodiments of the disclosure. In the example shown in fig. 183C, an example length L1 of the alignment rib of the example precision shim 18300 is 15.36 millimeters and an example width W1 of the alignment rib of the example precision shim 18300 is 0.36 millimeters.
Fig. 183D illustrates an example side view of an example precision shim 18300, according to some embodiments of the disclosure. In the example shown in fig. 183D, an exemplary thickness T1 associated with the alignment rib is 0.4 millimeters. An exemplary thickness T2 associated with the chevron pattern is 0.05 millimeters. An exemplary distance D1 between the top of the chevron pattern and the inner surface of the exemplary precision shim 18300 is 0.3 millimeters. An exemplary depth D2 of the recessed portion of the inner surface of the exemplary precision shim 18300 is 0.1 millimeters. An exemplary thickness T3 of the exemplary precision shim 18300 without alignment ribs is 0.4 millimeters.
Fig. 183E illustrates an exemplary bottom view of an exemplary precision shim 18300 according to some embodiments of the present disclosure. In the example shown in fig. 183E, the example precision shim 18300 is associated with a total length L5 of 16 millimeters. The distance L4 between the flow channel inlet opening and the flow channel outlet opening is 15 mm. The distance T6 between the channel cover portions of the exemplary precision shim 18300 is 0.75 millimeters. The total width T7 of the exemplary precision shim 18300 is 2.6 millimeters. The corner radius R1 of the exemplary precision shim 18300 is 0.5 millimeters. The flow channel input opening/flow channel output opening radius R2 of the example precision shim 18300 is 0.4 millimeters.
Continuing with the example shown in fig. 183E, an exemplary precision spacer 18300 is secured to the parallel flow microfluidic cover. In some embodiments, the parallel flow microfluidic cover is associated with a total length L3 of 25.6 millimeters and a total width T4 of 5.3 millimeters.
Fig. 183F illustrates an exemplary enlarged view of an exemplary portion 18331 of the exemplary precision shim 18300 illustrated in fig. 183E, according to some embodiments of the present disclosure.
Fig. 183G illustrates an example cross-sectional view of at least a portion of an example precision shim 18300, according to some embodiments of the disclosure. In the example shown in fig. 183G, the example precision shim 18300 includes alignment ribs that are each associated with a width W6 of 0.35 millimeters and a corner radius R6 of 0.1 millimeters. In some embodiments, the example precision shim 18300 includes channel cover portions that are each associated with a width W7 of 0.4 millimeters.
Various embodiments of the present disclosure provide an integrated precision gasket that includes a substrate with fluid channels and ports, and a chevron channel top to enhance contact between a sample stream and a sensor. In some embodiments, the integrated precision shim further includes a backside alignment feature that is bonded to the rigid cover for precision alignment. Referring now to fig. 184A and 184B, exemplary views associated with an exemplary fluid cap and an exemplary multi-channel waveguide sensor 18400 are shown.
Fig. 184A illustrates an exemplary perspective view of an exemplary parallel flow microfluidic cover 18402 and an exemplary thermal control sensor base 18404. Fig. 184B illustrates an exemplary exploded view of an exemplary parallel flow microfluidic cover 18402 and an exemplary thermal control sensor base 18404, according to some embodiments of the disclosure.
In some embodiments, an exemplary precision shim 18406 is affixed to the bottom surface of the exemplary parallel flow microfluidic cover 18402. For example, the example precision shim 18406 includes a plurality of alignment ribs positioned based on a plurality of alignment grooves on the parallel flow microfluidic cover such that when the plurality of alignment ribs are engaged with the plurality of alignment grooves, the example precision shim 18406 is secured to the example parallel flow microfluidic cover 18402.
Similar to the various examples described above, the example thermal control sensor base 18404 includes a waveguide 18408 that is secured to a top surface of the example thermal control sensor base 18404. In some embodiments, the example precision shim 18406 is precisely aligned with the waveguide 18408 when the example parallel flow microfluidic cover 18402 is secured to the example thermal control sensor base 18404.
As mentioned above, there are many technical challenges and difficulties associated with sample testing. For example, many microfluidic systems and methods (such as but not limited to biochemical sensing applications) may utilize peristaltic pumps to push solutions through a test channel. However, peristaltic pumps may create periodic ripple in the flow of the solution, which may create pulsating noise in fluid sensing applications and reduce the accuracy of solution flow rate detection.
Various embodiments of the present disclosure overcome the technical challenges and difficulties described above and provide various technical improvements and advantages. For example, various embodiments of the present disclosure provide a flow rate compensator that improves the accuracy of flow rate determination with minimal ripple noise, thereby achieving high sensitivity of biochemical sensing.
In some embodiments, the exemplary flow rate compensator may be in the form of an electromechanically variable volume reservoir (also referred to as an "active flow rate compensator"). In some embodiments, an exemplary flow rate compensator may comprise an electromechanical membrane. In some embodiments, the electromechanical film may be actuated by a voice coil and/or due to a piezoelectric effect. In some embodiments, the example flow rate compensator includes a fluid housing (e.g., comprising a material such as, but not limited to, plastic) defining a reservoir input opening (also referred to as an "inlet port") and a reservoir output opening (also referred to as an "outlet port"). In some embodiments, the reservoir input opening and the reservoir output opening allow the example flow rate compensator to be integrated into the fluid path through a series configuration. In some embodiments, the example flow rate compensator may be integrated into a lab-on-a-chip solution.
In some embodiments, an exemplary flow rate compensator may be added to the flow path of the solution to compensate for flow rate ripple created by a limited number of peristaltic pump rollers of the peristaltic pump. In some embodiments, one or more closed loop controllers are integrated into the flow path of the solution and pick up the actual flow ripple waveform of the solution in the flow path. In some embodiments, the one or more closed loop controllers provide feedback to the example flow compensator in the form of a flow rate adjustment signal such that the example flow compensator adjusts the volume of solution in the solution reservoir to compensate for flow ripple in real time. In some embodiments, the one or more closed loop controllers may also adjust the pump speed of the peristaltic pump based on the desired flow rate setting to achieve a precise flow rate with minimal delay.
Thus, an exemplary flow rate compensator according to some embodiments of the present disclosure provides closed loop flow control with active ripple compensation that can effectively improve flow accuracy through low to no flow ripple. In contrast to compression ripple filters, exemplary flow rate compensators according to some embodiments of the present disclosure provide accurate active compensation without compression-related delays in flow rate control, thereby meeting the needs of many real-time instant applications.
Referring now to fig. 185A-185D, exemplary views associated with an exemplary flow rate compensator 18500 according to some embodiments of the present disclosure are provided. Specifically, fig. 185A shows an exemplary perspective view of an exemplary flow rate compensator 18500. Fig. 185B illustrates an exemplary cross-sectional view of an exemplary flow rate compensator 18500. Fig. 185C shows another perspective view of the example flow rate compensator 18500. Fig. 185D illustrates an example bottom view of an example flow rate compensator 18500, according to some embodiments of the disclosure.
In some embodiments, the flow rate compensator 18500 comprises a fluid housing 18501. In various embodiments, fluid enclosure 18501 defines a solution reservoir 18503. For example, in the example shown in fig. 185A and 185B, the fluid housing 18501 may be shaped like a flat cylinder. In some embodiments, the fluid enclosure 18501 may define a solution reservoir 18503 in the form of an interior cavity, as shown in fig. 185B. In some embodiments, fluid enclosure 18501 comprises one or more rigid materials, such as, but not limited to, plastic. Additionally or alternatively, the fluid enclosure 18501 may comprise other materials.
In some embodiments, the solution reservoir 18503 of the fluid enclosure 18501 is connected to a flow path of a solution (such as, but not limited to, a sample solution, a reference solution, etc., as described above). For example, in some embodiments, the solution reservoir 18503 defines a reservoir input opening 18509 and a reservoir output opening 18515.
In the example shown in fig. 185A-185D, the input fluid conduit 18511 is connected to the reservoir input opening 18509. In some embodiments, the flow rate compensator 18500 comprises an input fluid fitting 18513 secured to the fluid housing 18501. In some embodiments, the input fluid conduit 18511 is positioned within the input fluid fitting 18513. In some embodiments, input fluid fitting 18513 comprises a rigid material (such as, but not limited to, metal, plastic, etc.) that provides protection for input fluid conduit 18511.
In some embodiments, the input fluid fitting 18513 includes threads disposed on an outer surface of the input fluid fitting 18513. In such an example, the fluid housing 18501 can define threads disposed proximate to the reservoir input opening 18509 of the fluid housing 18501. In some embodiments, when the threads of input fluid fitting 18513 are engaged with the threads of fluid housing 18501, input fluid fitting 18513 is secured to fluid housing 18501 while the opening of input fluid conduit 18511 is aligned with reservoir input opening 18509 such that input fluid conduit 18511 can inject one or more solutions into solution reservoir 18503 through reservoir input opening 18509.
In some embodiments, input fluid conduit 18511 receives one or more solutions (such as, but not limited to, a sample solution, a reference solution, etc., as described above) from, for example, but not limited to, a peristaltic pump. In some embodiments, the input fluid conduit 18511 provides one or more solutions to the solution reservoir 18503 of the fluid enclosure 18501 through the reservoir input opening 18509.
In some embodiments, the output fluid conduit 18517 is connected to the reservoir output opening 18515. In some embodiments, the flow rate compensator 18500 comprises an output fluid fitting 18519 secured to the fluid housing 18501. In some embodiments, the output fluid conduit 18517 is positioned within the output fluid fitting 18519. In some embodiments, the output fluid fitting 18519 comprises a rigid material (such as, but not limited to, metal, plastic, etc.) that provides protection for the output fluid conduit 18517.
In some embodiments, the output fluid fitting 18519 includes threads disposed on an outer surface of the output fluid fitting 18519. In such an example, the fluid housing 18501 can define threads disposed proximate to the reservoir output opening 18515 of the fluid housing 18501. In some embodiments, when the threads of the output fluid fitting 18519 are engaged with the threads of the fluid housing 18501, the output fluid fitting 18519 is secured to the fluid housing 18501 while the opening of the output fluid conduit 18517 is aligned with the reservoir output opening 18515 such that the output fluid conduit 18517 can drain one or more solutions from the solution reservoir 18503 through the reservoir output opening 18515.
In some embodiments, the flow rate compensator 18500 comprises a membrane 18505. In some embodiments, the membrane 18505 comprises a flexible material, such as, but not limited to, a polymeric material. Additionally or alternatively, the membrane 18505 may include other materials.
In some embodiments, the membrane 18505 covers the solution reservoir 18503. In the example shown in fig. 185B, the membrane 18505 provides a wall for the solution reservoir 18503. For example, the membrane 18505 includes an inner surface that faces the solution reservoir 18503 defined by the fluid enclosure 18501.
In some embodiments, the flow rate compensator 18500 comprises at least one actuator 18507. In some embodiments, at least one actuator 18507 is disposed on an outer surface of membrane 18505. In some embodiments, the outer surface of film 18505 is opposite the inner surface of film 18505. For example, the at least one actuator 18507 is not in contact with any solution in the solution reservoir 18503.
In some embodiments, the at least one actuator 18507 may comprise at least one piezoelectric actuator. In this example, the film 18505 is referred to as a piezoelectric film.
In the present disclosure, the term "piezoelectric actuator" refers to a transducer that converts electrical energy into mechanical displacement or stress based on the piezoelectric effect. For example, the at least one actuator 18507 may include a material such as, but not limited to, quartz crystal, tourmaline, or the like. In some embodiments, at least one actuator 18507 is electrically coupled to the flow controller and receives at least one flow rate adjustment signal from the flow controller. In some embodiments, the at least one flow rate adjustment signal may be in the form of an electrical current. In such an example, upon receipt of the current, the at least one actuator 18507 may expand or compress due to the piezoelectric effect, and the amount of expansion or compression may be proportional to the amount of the current. As described above, at least one actuator 18507 is disposed on the outer surface of the membrane 18505. Accordingly, the at least one actuator 18507 may cause at least one deformation of the membrane 18505 based at least in part on the at least one flow rate adjustment signal.
Although the above description provides an example of at least one actuator 18507 in the form of a piezoelectric actuator, it is noted that the scope of the present disclosure is not limited to the above description. In some examples, the example actuator may include one or more additional and/or alternative elements. For example, an example actuator according to some embodiments of the present disclosure may include at least one voice coil actuator. In such an example, the at least one voice coil actuator may include voice coils that are at least partially wrapped around the permanent magnet and connected to the flow controller. When the flow controller transmits a flow rate adjustment signal (e.g., in the form of an electrical current) to the voice coil, the magnetic field generated by the voice coil reacts to the magnetic field generated by the permanent magnet, thereby causing the voice coil to move along the permanent magnet. In some embodiments, a voice coil is disposed on an outer surface of the membrane 18505. Thus, movement of the voice coil may cause at least one deformation of the membrane 18505.
Referring now to fig. 186A-186C, exemplary cross-sectional views of an exemplary flow rate compensator 18600 according to some embodiments of the present disclosure are provided.
Similar to the example flow rate compensator 18500 described above in connection with fig. 185A-185D, the example flow rate compensator 18600 may include a fluid housing 18602 defining a solution reservoir 18604. For example, the solution reservoir 18604 may be in the form of an interior cavity of the fluid enclosure 18602 that includes a reservoir input opening and a reservoir output opening. Similar to the examples described above in connection with fig. 185A-185D, one or more solutions may flow from the reservoir input opening to the solution reservoir 18604 and may be discharged from the solution reservoir 18604 through the reservoir output opening.
In some embodiments, the example flow rate compensator 18600 includes a membrane 18606. Similar to the exemplary membrane 18505 shown and described above in connection with fig. 185A-185D, the membrane 18606 includes a flexible material, such as, but not limited to, a polymeric material.
In some embodiments, the membrane 18606 covers the solution reservoir 18604. For example, as shown in fig. 186A-186C, the membrane 18606 provides a bottom wall for the solution reservoir 18604. As described above, one or more solutions may flow into the solution reservoir 18604 from the reservoir input opening and drain from the reservoir output opening. In such an example, an inner surface of the membrane 18606 may be in contact with and provide support for one or more solutions in the solution reservoir 18604.
In some embodiments, at least one actuator 18608 is disposed on an outer surface of the membrane 18606. For example, the at least one actuator 18608 may include at least one piezoelectric actuator, at least one voice coil actuator, and the like. In such an example, the at least one actuator 18608 may receive one or more flow rate adjustment signals and exert a mechanical force on the membrane 18606 to cause at least one deformation of the membrane 18606. In some embodiments, the amount of mechanical force applied by the at least one actuator 18608 and/or the degree of deformation of the membrane 18606 caused by the at least one actuator 18608 is proportional to the flow rate adjustment signal received by the at least one actuator 18608. Thus, by adjusting the flow rate adjustment signal, various embodiments of the present disclosure provide for controlled adjustment of the deformation of the membrane 18606.
For example, fig. 186A illustrates an exemplary cross-sectional view of an exemplary flow rate compensator 18600 when no flow rate adjustment signal is applied to at least one actuator 18608. Fig. 186B and 186C illustrate exemplary cross-sectional views of an exemplary flow rate compensator 18600 when different flow rate adjustment signals are applied to at least one actuator 18608.
Specifically, the example shown in fig. 186B illustrates at least one actuator 18608 exerting an inward force on the membrane 18606. In such an example, the flow rate adjustment signal may be in the form of a current signal that causes the at least one actuator 18608 to generate a mechanical force toward the solution reservoir 18604. Due to this mechanical force, the one or more solutions are pushed through the reservoir output opening of the solution reservoir 18604, thereby increasing the flow rate of the one or more solutions from the solution reservoir 18604.
In contrast, the example shown in fig. 186C illustrates at least one actuator 18608 exerting an outward force on the membrane 18606. In such an example, the flow rate adjustment signal may be in the form of a current signal that causes the at least one actuator 18608 to generate a mechanical force away from the solution reservoir 18604. Due to the mechanical force, the one or more solutions are pulled into the solution reservoir 18604, thereby reducing the flow rate of the one or more solutions from the solution reservoir 18604.
As shown in the above examples, an example flow rate compensator according to some embodiments of the present disclosure may adjust the flow rate of one or more solutions from solution reservoir 18604 based on one or more flow rate adjustment signals received by at least one actuator 18608. In some embodiments, the one or more flow rate adjustment signals are provided to a flow controller in an exemplary flow rate compensation system. Referring now to fig. 187, an exemplary block diagram illustrating an exemplary flow rate compensation system 18700 is provided in accordance with some embodiments of the present disclosure.
In the example shown in fig. 187, the example flow rate compensation system 18700 includes a flow rate compensator 18701 that is similar to the various example flow rate compensators described above in connection with at least fig. 185A-186C.
In some embodiments, the exemplary flow rate compensation system 18700 includes a peristaltic pump 18703. Similar to the various exemplary peristaltic pumps described above, peristaltic pump 18703 may push one or more solutions to flow compensator 18701. For example, the flow compensator 18701 may comprise an input fluid conduit, and one end of the input fluid conduit is connected to the reservoir input opening of the flow compensator 18701. In some embodiments, the other end of the input fluid tubing of the flow rate compensator 18701 is connected to the output of the peristaltic pump 18703. Thus, peristaltic pump 18703 may push one or more solutions to flow compensator 18701.
In some embodiments, the example flow rate compensation system 18700 includes a flow meter 18705. In some embodiments, the speed compensator 18701 may comprise an output fluid conduit, and one end of the output fluid conduit is connected to the reservoir output opening of the flow rate compensator 18701. In some embodiments, the other end of the output fluid conduit is connected to a flow meter 18705.
In some embodiments, flow meter 18705 is configured to generate a flow rate signal indicative of the flow rate of one or more solutions from flow rate compensator 18701. For example, the flow meter 18705 may include a velocity flow meter such as, but not limited to, a coriolis flow meter, a differential pressure flow meter, an electromagnetic flow meter, and the like. Additionally or alternatively, the flow meter 18705 may include one or more other types of flow meters.
In some embodiments, the example flow rate compensation system 18700 includes a flow controller 18707. In some embodiments, the flow meter 18705 is electrically coupled to the flow controller 18707 and transmits a flow rate signal to the flow controller 18707. In some embodiments, the flow controller may include one or more processing circuits and/or processors, such as, but not limited to, microcontrollers, programmable Logic Devices (PLDs), and the like.
In some embodiments, the flow controller 18707 is configured to determine at least one flow rate adjustment signal based on the flow rate signal. For example, the flow controller 18707 may determine whether one or more flow rates indicated by the flow rate signal are within a predetermined flow rate threshold. If the one or more flow rates are above the predetermined flow rate threshold, the flow controller 18707 may generate one or more flow rate adjustment signals that indicate an adjustment to reduce the flow rate, and may determine the amount of reduction based on a difference between the one or more flow rates and the predetermined flow rate threshold as indicated by the flow rate signals. If the one or more flow rates are below a predetermined flow rate threshold, the flow controller 18707 may generate one or more flow rate adjustment signals that indicate an adjustment to increase the flow rate, and may determine the amount of increase based on a difference between the one or more flow rates and the predetermined flow rate threshold as indicated by the flow rate signals.
Similar to the various exemplary flow rate compensators described above, the flow rate compensator 18701 includes a membrane covering the solution reservoir and at least one actuator disposed on an outer surface of the membrane. In some embodiments, at least one actuator is electrically coupled to the flow controller 18707. In some embodiments, the flow controller 18707 transmits one or more flow rate adjustment signals to at least one actuator of the flow rate compensator 18701.
As described above, the at least one flow rate adjustment signal may be indicative of an increase in flow rate or a decrease in flow rate. In some embodiments, at least one actuator disposed on an outer surface of the membrane may cause at least one deformation of the membrane based on the at least one flow rate adjustment signal.
For example, the at least one flow rate adjustment signal may indicate an increase in flow rate for adjustment. In such an example, the at least one actuator may exert an inward mechanical force on the membrane to cause an increase in the flow rate of the one or more solutions from the flow rate compensator, similar to the example described in connection with at least fig. 186B. In some embodiments, the amount of mechanical force applied by the at least one actuator is based on the at least one flow rate adjustment signal. Thus, by adjusting the at least one flow rate adjustment signal, the flow controller 18707 may increase the flow rate of the one or more solutions discharged from the flow rate compensator by actuating at least one actuator on the membrane of the flow rate compensator.
Additionally or alternatively, the at least one flow rate adjustment signal may indicate a decrease in flow rate for adjustment. In such an example, the at least one actuator may exert an outward mechanical force on the membrane to cause a reduction in the flow rate of the one or more solutions from the flow rate compensator, similar to the example described in connection with at least fig. 186C. In some embodiments, the amount of mechanical force applied by the at least one actuator is based on the at least one flow rate adjustment signal. Thus, by adjusting the at least one flow rate adjustment signal, the flow controller 18707 may reduce the flow rate of the one or more solutions discharged from the flow rate compensator by actuating at least one actuator on the membrane of the flow rate compensator.
Accordingly, various embodiments of the present disclosure provide a closed loop feedback control system that enables the flow rate of solution exiting a flow rate compensator to be adjusted, thereby overcoming the various technical challenges and difficulties described above. Referring now to fig. 188A-190B, exemplary diagrams are provided highlighting various technical benefits and advantages provided by exemplary flow rate compensators according to some embodiments of the present disclosure.
Specifically, fig. 188A and 188B illustrate exemplary flow rates associated with exemplary sample solution injection (e.g., by peristaltic pumps) without a flow rate compensator. Specifically, fig. 188A shows an exemplary flow rate when injection of the sample solution is started, and fig. 188B shows an exemplary flow rate when injection of the sample solution becomes stable.
As shown in fig. 188A, the flow rate increases rapidly initially when the solution is injected by the peristaltic pump. But even in the case of stable injection, the flow rate fluctuates as shown in fig. 188B. As described above, fluctuations in flow rate may be caused by ripple noise of the peristaltic pump.
Referring now to fig. 189A and 189B, exemplary diagrams are provided that illustrate exemplary flow rates associated with exemplary sample solution injections by an exemplary peristaltic pump having a compressed ripple filter. Specifically, fig. 189A shows an exemplary flow rate at the beginning of injection of the sample solution. Fig. 189B shows an exemplary flow rate when injection of the sample solution becomes stable.
As shown in fig. 189A, when the solution is injected by a peristaltic pump, the flow rate increases slowly initially, which may be caused by a compression ripple filter. In addition, even in the case of stable injection, the flow rate may still fluctuate as shown in fig. 189B.
Referring now to fig. 190A and 190B, exemplary diagrams are provided illustrating exemplary flow rates associated with exemplary sample solution injections by an exemplary peristaltic pump having an exemplary flow rate compensator, according to some embodiments of the present disclosure. Specifically, fig. 190A shows an exemplary flow rate at the beginning of injection of the sample solution. Fig. 190B shows an exemplary flow rate when injection of the sample solution becomes stable.
As shown in fig. 190A, the flow rate initially increases faster when the solution is injected by the peristaltic pump than the flow rate shown in fig. 189A. As shown in fig. 190B, the flow rate becomes stable once the injection stabilizes, as compared to the flow rates shown in fig. 188B and 189B. Accordingly, various embodiments of the present disclosure provide technical improvements and advantages.
As shown in the various examples above, waveguide interferometric sensors require light input from the edges of the sensor. In many examples, the visible wavelength waveguide has a cross-section with a width less than 4 microns and a height less than 0.0002 microns. The small cross section can cause a number of technical challenges and difficulties. For example, the waveguide input area is much smaller than the size of the input laser beam, which may introduce efficiency losses. As another example, small waveguide input areas require sub-micron precise alignment with respect to the input laser beam, but sub-micron alignment suffers from problems such as high manufacturing costs and long operating times.
Various embodiments of the present disclosure overcome these technical challenges and difficulties and provide various technical improvements and advantages.
For example, various embodiments of the present disclosure provide an exemplary edge-optically coupled waveguide device that expands the size of the light input area to be larger than the size of the laser beam to increase the optical coupling efficiency. In some embodiments, an excessive light input area may reduce the alignment requirements from sub-micron to micron. In some embodiments, reduced alignment requirements may enable non-tuned plug-in alignment in applications with waveguide chips and mounting tolerance control. In some embodiments, the manufacturing cost and operating time of the exemplary edge-optically coupled waveguide device may be substantially reduced.
Referring now to fig. 191A, 191B, 191C, 191D, and 191E, exemplary views associated with exemplary edge optical coupling waveguide devices 19100 according to some embodiments of the present disclosure are provided. The example edge optical coupling waveguide device 19100 shown in fig. 191A-191E illustrates an example in which a multi-channel waveguide input can be implemented using an edge optical coupler array (e.g., one or more top light pipes and/or one or more bottom light pipes) added to the multi-channel waveguide.
In the example shown in fig. 191A, an exemplary exploded view of an exemplary edge optical coupling waveguide device 19100 according to some embodiments of the present disclosure is provided. In some embodiments, the edge optical coupling waveguide device 19100 includes a top light pipe 19101, a bottom light pipe 19103, a silicon nitride waveguide layer 19105, a silicon dioxide layer 19107, and a silicon substrate 19109.
In some embodiments, the top light pipe 19101 includes two curved side surfaces. In some embodiments, these curved side surfaces may provide technical benefits and advantages, such as, but not limited to, improving the optical coupling efficiency of the top light pipe 19101.
In some embodiments, the bottom light pipe 19103 is positioned below the top light pipe 19101. In some embodiments, the bottom light pipe 19103 includes two curved side surfaces. In some embodiments, these curved side surfaces may provide technical benefits and advantages, such as, but not limited to, improving the light coupling efficiency of the bottom light pipe 19103.
In some embodiments, the top light pipe length associated with the top light pipe 19101 is shorter than the bottom light pipe length associated with the bottom light pipe 19103. In such an example, the top light pipe 19101 being shorter than the bottom light pipe 19103 may provide technical benefits and advantages such as, but not limited to, improved light coupling efficiency and reduced alignment requirements.
In some embodiments, a bottom light pipe 19103 is disposed on top of the silicon nitride waveguide layer 19105. In some embodiments, the silicon nitride waveguide layer 19105 includes a silicon nitride waveguide 19111. For example, a silicon nitride waveguide 19111 is positioned at a middle portion of the silicon nitride waveguide layer 19105. In some embodiments, the bottom surface of the bottom light pipe 19103 mates with the top surface of the silicon nitride waveguide 19111, providing technical benefits and advantages such as, but not limited to, improving optical coupling efficiency and reducing alignment requirements.
In some embodiments, a silicon nitride waveguide layer 19105 is disposed on top of the silicon dioxide layer 19107. In some embodiments, the silicon dioxide layer 19107 is disposed on top of the silicon substrate 19109.
Fig. 191B and 191C illustrate exemplary perspective views of an exemplary edge optical coupling waveguide device 19100 according to some embodiments of the present disclosure. Fig. 191D and 191E illustrate exemplary perspective views of exemplary portions of an exemplary edge optical coupling waveguide device 19100 according to some embodiments of the present disclosure.
As shown in fig. 191B-191E, an exemplary edge optical coupling waveguide device 19100 provides stacked light pipes (including a top light pipe 19101 and a bottom light pipe 19103) on a silicon nitride waveguide layer 19105 for reducing the equivalent cross-section of an input laser beam in the width and height directions. For example, arrow 19121 in FIG. 191B shows the input direction of the laser light to the top light pipe 19101 and the bottom light pipe 19103. As shown, the laser light may be coupled into a silicon nitride waveguide 19111 of a silicon nitride waveguide layer 19105 by a stacked light pipe. In some embodiments, the silicon nitride waveguide 19111 is ribbed to provide a sensing area for evanescent wave detection. In such an example, light in a single mode of the ribbed silicon nitride waveguide may further travel through the waveguide sensing region for evanescent wave detection.
Referring now to fig. 192A-192C, exemplary views associated with an exemplary top light pipe 19200 of an exemplary edge light coupling waveguide device according to some embodiments of the present disclosure are shown. In particular, FIG. 192A illustrates an example top view associated with an example top light pipe 19200.
FIG. 192B illustrates an example side view associated with an example top light pipe 19200. FIG. 192C illustrates an exemplary perspective view associated with an exemplary top light pipe 19200.
In some embodiments, the exemplary top light pipe 19200 includes a material such as, but not limited to, SU-8 polymer.
In the example shown in FIG. 192A, the example top light pipe 19200 is associated with a front end width W1 of 0.01 millimeters, a total length L1 of 0.3 millimeters, and a rear end width W2 of 0.001 millimeters. In some embodiments, both side edges of the example top light pipe 19200 are curved (e.g., R10 as shown in FIG. 192A) to obtain maximum light coupling efficiency.
In the example shown in fig. 192B, the example top light pipe 19200 has a thickness T1 of 0.003 millimeters and a front angle R1 of 10 degrees to prevent back reflection of the input light.
Referring now to fig. 193A-193D, exemplary views associated with an exemplary bottom light pipe 19300 of an exemplary edge light coupling waveguide device according to some embodiments of the present disclosure are shown. In particular, FIG. 193A shows an exemplary top view associated with an exemplary bottom light pipe 19300.
FIG. 193B shows an exemplary side view associated with an exemplary bottom light pipe 19300. FIG. 193C shows an exemplary bottom view associated with an exemplary bottom light pipe 19300. FIG. 193D shows an exemplary perspective view associated with an exemplary bottom light pipe 19300.
In the example shown in FIG. 193A, the example bottom light pipe 19300 is associated with a front end width W1 of 0.01 millimeters and a rear end width W2 of 0.005 millimeters. In some embodiments, the exemplary bottom light pipe 19300 is associated with a length L1 of 1 millimeter. In some embodiments, both side edges of the exemplary bottom light pipe 19300 are curved (e.g., R194 as shown in fig. 193A) to obtain maximum light coupling efficiency.
In the example shown in FIG. 193B, the example bottom light pipe 19300 is associated with a thickness T1 of 0.003 millimeters. In some embodiments, the front end has a front angle R1 of 10 degrees to prevent back reflection of the input light.
In the example shown in FIG. 193C, the bottom surface of the example bottom light pipe 19300 houses a silicon nitride waveguide input end. For example, the bottom surface of the exemplary bottom light pipe 19300 includes a waveguide portion associated with a front end width W3 of 0.001 millimeters and a rear end width W4 of 0.0035 millimeters. In some embodiments, the height associated with the waveguide portion is 0.0002 millimeters. In some embodiments, the distance D1 from the front end of the waveguide portion to the front end of the exemplary bottom light pipe 19300 is 0.1 millimeters.
Referring now to fig. 194A-194C, exemplary views associated with an exemplary silicon nitride waveguide layer 19400 of an exemplary edge optical coupling waveguide device according to some embodiments of the present disclosure are provided. Specifically, fig. 194A shows an exemplary side view of an exemplary silicon nitride waveguide layer 19400.
Fig. 194B illustrates an exemplary portion of an exemplary silicon nitride waveguide layer 19400. Fig. 194C illustrates an exemplary perspective view of an exemplary silicon nitride waveguide layer 19400.
In the example shown in fig. 194A, an example length L1 of the example silicon nitride waveguide layer 19400 is 1.2 millimeters. An exemplary waveguide region width W1 is 0.05 millimeters. An exemplary distance D1 between the front of the waveguide and the front end of the exemplary silicon nitride waveguide layer 19400 is 0.1 millimeters. An exemplary width W2 of the front end of the exemplary silicon nitride waveguide is 0.001 millimeters. An exemplary width W3 of the rear end of the exemplary silicon nitride waveguide is 0.0035 millimeters. In some embodiments, the side surfaces of the exemplary silicon nitride waveguide are curved (as shown by R324 in fig. 194A).
Fig. 194B illustrates an exemplary portion 19406 of the exemplary silicon nitride waveguide layer 19400 shown in fig. 194A. Specifically, fig. 194B highlights waveguide ribs 19404 of an exemplary silicon nitride waveguide layer 19400. In the example shown in fig. 194B, the thickness T5 associated with the waveguide rib 19404 is 0.0035 millimeters.
Referring now to fig. 195A-195F, exemplary views associated with exemplary edge optical coupling waveguide device 19500 according to some embodiments of the present disclosure are shown. In particular, fig. 195A and 195B illustrate exemplary side views of an exemplary edge optical coupling waveguide device 19500. Fig. 195C shows an exemplary top view of an exemplary edge optical coupling waveguide device 19500. Fig. 195D illustrates an exemplary cross-sectional view of an exemplary edge optical coupling waveguide device 19500. Fig. 195E and 195F illustrate exemplary details of an exemplary edge-optically coupled waveguide device 19500.
In the example shown in fig. 195A, the exemplary edge light coupling waveguide device 19500 includes a top light pipe having a width D1 of 0.01 millimeters.
In the example shown in fig. 195B, the example edge optical coupling waveguide device 19500 includes a bottom light pipe having a width D2 of 0.005 millimeters.
In the example shown in fig. 195C, the example edge optical coupling waveguide device 19500 includes a waveguide area associated with a width W1 of 0.05 millimeters. In some embodiments, the waveguide region includes a waveguide associated with a width W3 of 0.0035 millimeters.
In the example shown in fig. 195D, the total length L1 of the bottom light pipe of the example edge light coupling waveguide device 19500 is 1 millimeter, and the total length L2 of the top light pipe of the example edge light coupling waveguide device 19500 is 0.3 millimeter. In some embodiments, the overall length L3 of the exemplary edge optical coupling waveguide device 19500 is 1.2 millimeters. In some embodiments, the front end thickness T1 associated with the top light pipe and the front end thickness T2 associated with the bottom light pipe are 0.003 millimeters. In some embodiments, the front end angle R1 of the top light pipe is 10 degrees. In some embodiments, the rear end thickness T3 of the bottom light pipe is 0.0002 millimeters.
Fig. 195E illustrates an exemplary cross-section of the exemplary portion 19511 shown in fig. 195D. Specifically, exemplary portion 19511 is a front end portion of exemplary edge optical coupling waveguide device 19500.
In the example shown in fig. 195E, the exemplary silicon nitride waveguide layer 19400 includes a top light pipe 19521 disposed on top of a bottom light pipe 19523. In some embodiments, both the top light pipe 19521 and the bottom light pipe 19523 comprise SU-8 material. In some embodiments, bottom light pipe 19523 is disposed on top of silicon oxide layer 19525. In some embodiments, the silicon oxide layer 19525 comprises silicon oxide. In some embodiments, a silicon oxide layer 19525 is disposed on top of the exemplary silicon substrate 19527. In some implementations, the silicon substrate 19527 comprises silicon.
Fig. 195F illustrates an exemplary cross-section of the exemplary portion 19513 illustrated in fig. 195D. Specifically, exemplary portion 19513 is a rear end portion of exemplary edge optical coupling waveguide device 19500. In the example shown in fig. 195F, an exemplary silicon nitride waveguide layer 19400 includes a bottom light pipe 19523 disposed on top of a waveguide 19529. In some embodiments, waveguide 19529 is ribbed and includes a Si3N4 material. In some embodiments, waveguide 19529 is disposed on top of silicon oxide layer 19525.
It is to be understood that the disclosure is not to be limited to the specific examples disclosed and that modifications and other examples are intended to be included within the scope of the appended claims. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation, unless otherwise specified.
Claims (10)
1. A method for manufacturing a waveguide device, comprising:
Forming a thermal silicon dioxide layer on a silicon wafer;
Forming a stress reduction pattern on the thermal silicon dioxide layer, wherein the stress reduction pattern comprises a plurality of polygonal pattern units; and
And forming a silicon nitride film on the stress reduction pattern.
2. The method of claim 1, wherein when forming the thermal silicon dioxide layer, the method further comprises thermally oxidizing the silicon wafer.
3. The method of claim 1, wherein when forming the stress reduction pattern on the thermal silicon dioxide layer, the method further comprises:
The thermal silicon dioxide layer is etched according to the stress reduction pattern.
4. The method of claim 3, wherein an etch depth associated with the stress reduction pattern is based at least in part on a film depth associated with the silicon nitride film.
5. The method of claim 1, wherein after forming the silicon nitride film on the stress-reducing pattern, the method further comprises:
Forming a single mode region on the silicon nitride film; and
At least one waveguide rib is formed in an analysis window portion of the silicon nitride film.
6. The method of claim 5, wherein a distance between a pattern edge of the stress reduction pattern and an analysis window edge of the analysis window portion is at least 250 microns.
7. The method of claim 1, wherein when forming the silicon nitride film, the method further comprises:
the silicon nitride film is fabricated based at least in part on a Low Pressure Chemical Vapor Deposition (LPCVD) process.
8. A parallel flow multichannel pathogen sensing system, comprising:
a multichannel peristaltic pump including a plurality of pump flow channel tubes through which a buffer solution flows;
A sample valve array comprising a plurality of sample valves, wherein each of the plurality of sample valves comprises a buffer solution injection port for receiving the buffer solution and a sensing channel connection port connected to a sensing channel input port on a waveguide fluidic component; and
A waveguide fluidic assembly including a parallel flow microfluidic cover defining a plurality of sensing channel input ports.
9. The parallel flow multichannel pathogen sensing system of claim 8, wherein the multichannel peristaltic pump includes:
A pump frame; and
A plurality of pump wheels fixed to the pump frame, wherein a plurality of pump tubes are disposed on the plurality of pump wheels.
10. The parallel flow multichannel pathogen detection system of claim 9, further comprising:
a multi-channel flow sensor array comprising a plurality of flow sensor input ports and a plurality of flow sensor output ports, wherein the plurality of pump tubes are connected to the plurality of flow sensor input ports.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63/476,350 | 2022-12-20 | ||
| US18/508,021 US20240085408A1 (en) | 2020-05-07 | 2023-11-13 | Apparatuses, systems, and methods for sample testing |
| US18/508,021 | 2023-11-13 |
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| Publication Number | Publication Date |
|---|---|
| CN118225732A true CN118225732A (en) | 2024-06-21 |
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| CN202311664309.6A Pending CN118225732A (en) | 2022-12-20 | 2023-12-06 | Apparatus, system and method for sample testing |
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| Country | Link |
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| CN (1) | CN118225732A (en) |
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