WO2023064285A1 - Integrated surface acoustic wave biosensor system for point-of-care-diagnostic use - Google Patents
Integrated surface acoustic wave biosensor system for point-of-care-diagnostic use Download PDFInfo
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- WO2023064285A1 WO2023064285A1 PCT/US2022/046296 US2022046296W WO2023064285A1 WO 2023064285 A1 WO2023064285 A1 WO 2023064285A1 US 2022046296 W US2022046296 W US 2022046296W WO 2023064285 A1 WO2023064285 A1 WO 2023064285A1
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- Prior art keywords
- saw
- biosensor
- disposable cartridge
- saline
- sample
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N29/00—Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
- G01N29/22—Details, e.g. general constructional or apparatus details
- G01N29/222—Constructional or flow details for analysing fluids
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N29/00—Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
- G01N29/02—Analysing fluids
- G01N29/022—Fluid sensors based on microsensors, e.g. quartz crystal-microbalance [QCM], surface acoustic wave [SAW] devices, tuning forks, cantilevers, flexural plate wave [FPW] devices
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/16—Reagents, handling or storing thereof
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/069—Absorbents; Gels to retain a fluid
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0433—Moving fluids with specific forces or mechanical means specific forces vibrational forces
- B01L2400/0436—Moving fluids with specific forces or mechanical means specific forces vibrational forces acoustic forces, e.g. surface acoustic waves [SAW]
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2291/00—Indexing codes associated with group G01N29/00
- G01N2291/02—Indexing codes associated with the analysed material
- G01N2291/025—Change of phase or condition
- G01N2291/0255—(Bio)chemical reactions, e.g. on biosensors
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2291/00—Indexing codes associated with group G01N29/00
- G01N2291/02—Indexing codes associated with the analysed material
- G01N2291/025—Change of phase or condition
- G01N2291/0256—Adsorption, desorption, surface mass change, e.g. on biosensors
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2291/00—Indexing codes associated with group G01N29/00
- G01N2291/04—Wave modes and trajectories
- G01N2291/042—Wave modes
- G01N2291/0423—Surface waves, e.g. Rayleigh waves, Love waves
Definitions
- the present disclosure relates to methods and apparatus for identifying chemicals, toxins, gaseous materials and/or biomarkers related to disease or wellness or environmental issues including for instance, infectious disease (e.g., bacterial, fungal, parasitic infections, viral infections, etc.), chemotoxins, biotoxins that can cause illness or affect the well-being of humans and animals of interest. More particularly, the disclosure relates to integrated (both surface and bulk) acoustic wave sensor systems for detection of infectious agents such as bacteria or viruses. Furthermore, gaseous materials detection which could be used to determine alternative energy sources such as hydrogen is also included.
- infectious disease e.g., bacterial, fungal, parasitic infections, viral infections, etc.
- chemotoxins chemotoxins
- biotoxins that can cause illness or affect the well-being of humans and animals of interest.
- the disclosure relates to integrated (both surface and bulk) acoustic wave sensor systems for detection of infectious agents such as bacteria or viruses.
- gaseous materials detection which could be used to determine alternative energy sources such as hydrogen is also
- an acoustic wave knows as Surface acoustic wave (SAW) sensors which operate on the principal of passive wireless sensing mass/viscosity using piezoelectricity as a sensing agent is described followed by an electronic detection parameters when changes to the acoustic wave is conveyed as a change in electronic measures.
- SAW Surface acoustic wave
- Piezoelectricity is a phenomenon displayed in certain crystals, such as quartz and lithium tantalite, where voltage generation is induced by mechanical stress. Interestingly, the reverse is also true wherein application of voltage will induce a mechanical deformation or stress.
- SAW sensors are used in the detection of changes in mass, elasticity, conductivity, and dielectric properties derived from mechanical or electrical variations. SAW sensors also employ the piezoelectric effect to excite acoustic waves electrically at an input transducer and to receive the waves at the output transducer. In our case, in particular, we also employ a reflector as part of this pathway for the electronic acoustic wave.
- the present disclosure describes an integrated and mutually dependent system and method for diagnosing infectious disease, such as bacterial, fungal, parasitic infections, viral infections, and infectious disease caused by viruses, such as SARS-CoV-2, for example, and many non-infectious biomarkers such as hormones, proteins etc. amongst many others of biological interest, including determining real time biological binding activity detections such as real time binding of affinity agents such as antigen antibody binding dynamics under various biological conditions as described in the application.
- the disclosed system employs integrated surface acoustic wave sensor technology in an efficient, low-cost integrated surface acoustic wave (SAW) biosensor based system for point-of-care diagnostic use that is able to reliably identify biological samples having specific infectious agents along with an enhanced detection system and the integrated connectors and software to activate such a system and to provide the analytical tools and user interface for accurate biodetection.
- SAW surface acoustic wave
- aspects of the present disclosure include an integrated surface acoustic wave biosensor system for point-of-care diagnostic.
- the system includes a disposable cartridge component and a reusable reader which includes a novel contact region. It also includes the workings of a reuseable reader.
- the disposable cartridge component includes a sample well for addition of a biological sample, a saline-saturated absorbent pad or a buffer can containing a buffer of choice, an integrated surface acoustic wave (SAW) biosensor, a printed circuit board (PCB) coupled to the SAW biosensor, and a gasket.
- SAW surface acoustic wave
- PCB printed circuit board
- an off cartridge reagent disposable system will form an integral part of the system.
- the disposable cartridge also includes a cassette for housing the sample well, the saline-saturated or saline containing compression pad or can, the SAW biosensor, the printed circuit board and gaskets.
- Out of cartridge systems for sample processing may also be included, as are reagent tubes that contain a number of reagents such as gold nanoparticles and buffers.
- the reusable reader contact region includes a mating capacitive coupled PCB configured to couple to the capacitive coupled PCB to the SAW biosensor in the disposable cartridge component, and a connector configured for securing a cable for transmitting data from the mating capacitive coupled PCB to the reusable reader.
- An illustrative embodiment of the disclosed system may also include a dielectric material, such as Kapton TM tape coupled to the mating capacitive coupled PCB of the reusable reader contact region.
- the disposable cartridge component includes a sample well for addition of a biological sample, a saline-saturated absorbent pad, an integrated surface acoustic wave (SAW) biosensor, a printed circuit board (PCB) coupled to the SAW biosensor, a gasket; and a cassette for housing the sample well, the saline-saturated compression pad, the SAW biosensor, the printed circuit board, the gasket.
- the disposable cartridge may also include a sample cap with an air vent to secure the sample well, for example.
- the saline-saturated absorbent pad is compressed with a saline cap comprising a spring.
- the SAW biosensor includes a sample channel and one or more reference channels.
- the SAW biosensor includes a piezoelectric crystal base, such as a lithium tantalite crystal base.
- the SAW biosensor further comprises capacitive coupled contact pads.
- the disposable cartridge component includes a sample well for addition of a biological sample, a saline well comprising saline for coupling with the sample well, a cassette body structure comprising an integrated surface acoustic wave (SAW) biosensor, a printed circuit board (PCB) capacitively coupled to the SAW biosensor for, and a gasket, a docking station on the cassette body structure for coupling with the saline well and sample well, and an absorbent wicking pad.
- SAW surface acoustic wave
- PCB printed circuit board
- the sample well and the saline comprises foils to secure the biological sample and the saline.
- the cassette body structure comprises at least one saline pinch valve and at least one sample channel valve.
- the saline pinch valve is opened when the saline well is coupled to the docking station.
- the absorbent wicking pad pulls saline at a rate of 5pl/min.
- the gasket is made of poly dimethylsiloxane (PDMS).
- the SAW biosensor comprises a sample channel and a reference channel.
- the disposable cartridge component includes a sample well for addition of a biological sample, a reusable flexible hourglass with grains, a timer holder for holding the flexible hourglass with grains, a flexible sample cap for securing the sample well, a saline blister pack comprising saline, and a cassette body comprising an integrated surface acoustic wave (SAW) biosensor, a printed circuit board (PCB) coupled to the SAW biosensor for, and a gasket.
- SAW surface acoustic wave
- PCB printed circuit board
- the disposable cartridge component may also include a waste well with an air vent for the displaced biological sample and saline.
- the SAW biosensor is enclosed with an overmolded thermoplastic elastomer.
- the SAW biosensor includes a sample channel and a reference channel.
- Other iterations include a container containing buffer which can be released into the fluidics and a method for advancing the appropriate fluidics at the right time of testing by using a hand advanced crank or an automatic moving processes to move the fluid at the correct fluid volume / minute over the sensor as determined by external studies.
- Another aspect of the present disclosure provides a method for detecting a target analyte in a biological sample using an integrated surface acoustic wave biosensor system.
- the method includes steps of providing a disposable cartridge component of the integrated surface acoustic wave biosensor system, providing the biological sample into a sample well of the disposable cartridge component, applying surface acoustic waves to the sample in the sample well to generate a characteristic electrical signal of the biological sample, and detecting the target analyte based on the characteristic electrical signal.
- the disposable cartridge component includes a sample well for addition of the biological sample, a saline-saturated absorbent pad, an integrated surface acoustic wave (SAW) biosensor, a printed circuit board (PCB) coupled to the SAW biosensor, a gasket, and a cassette for housing the sample well, the saline-saturated compression pad, the SAW biosensor, the printed circuit board, the gasket.
- a sample well for addition of the biological sample
- a saline-saturated absorbent pad for addition of the biological sample
- an integrated surface acoustic wave (SAW) biosensor integrated surface acoustic wave (SAW) biosensor
- PCB printed circuit board
- FIG. 1 presents an exemplary design of a MHz SAW sensor.
- FIG. 2A shows an exemplary design of a MHz SAW sensor, which has been modified for capacitive coupling with metal contact pads.
- FIG. 2B shows an exemplary design of a MHz SAW sensor, which has been modified for capacitive coupling with metal contact pads and a third channel for temperature compensation.
- FIG. 2C shows an exemplary design of a SAW sensor, which has been redesigned for capacitive coupling with circular metal contact pads to improve the X Y positioning tolerance on the capacitive coupled PCB.
- FIG. 3 A presents an exemplary design of a top surface of a mating capacitive printed circuit board (PCB) onto which a SAW sensor is placed.
- PCB printed circuit board
- FIG. 3B presents an exemplary design of a bottom surface of a mating capacitive printed circuit board (PCB) introduced in FIG. 3 A, comprising a sub miniature push-on (SMP) connector connected to a reader unit via a subminiature version A (SMA) cable.
- FIG. 3C presents a bottom view of an alternate design of the PCB of FIG. 3A, showing a disposable capacitive coupled PCB for integration with the capacitive coupled holder and disposable cartridge.
- FIGS. 3D shows a bottom view of a mating capacitively coupled PCB involving an additional embodiment including the capacitive coupled holder and disposable cartridge system.
- FIG. 4 presents an exemplary schematic of an exemplary sensor including capacitive coupling integration.
- FIG. 5 A presents an image of an exemplary capacitive coupled holder including the bottom of a disposable cartridge system.
- FIG. 5B presents an image of an exemplary cartridge docked to a mating printed circuit board on the capacitive coupled holder.
- FIG. 5C presents an illustration of an alternate embodiment of the exemplary capacitive coupled holder of FIG. 5 A in an open position.
- FIG. 5D presents an illustration of an alternate embodiment of the exemplary capacitive coupled holder of FIG. 5 A in a closed position.
- FIG. 6 presents a schematic comparison between an exemplary miniaturized SAW sensor design according to the disclosure and an original SAW sensor design.
- FIG. 7 presents a schematic of an exemplary fabricated wall concept for a SAW sensor.
- FIG. 8 presents a diagram of an exemplary polydimethylsiloxane (PDMS) gasket.
- PDMS polydimethylsiloxane
- FIG. 9 present an exemplary SAW biosensor system with an enclosure comprising overmolded thermoplastic elastomers (TPE).
- TPE thermoplastic elastomers
- FIG. 10A presents a perspective view of an exemplary embodiment of a SAW biosensor cartridge system.
- FIG. 10B presents an exploded view of the exemplary embodiment of the SAW biosensor cartridge system in accordance to FIG. 10 A.
- FIG. 11 A presents a perspective view of another exemplary embodiment of a SAW biosensor cartridge system.
- FIG. 1 IB presents an exploded view of another exemplary embodiment of the SAW biosensor cartridge system in accordance with FIG. 11 A.
- FIG. 12A presents a perspective view of a further exemplary embodiment of a SAW biosensor cartridge system.
- FIG. 12B presents an exploded view of the further exemplary embodiment of the SAW biosensor cartridge system in accordance with FIG. 12 A.
- FIG. 13 presents a perspective view of an exemplary embodiment of a SAW biosensor cartridge system adapted for collection and detection of gaseous species from the atmosphere.
- FIG. 14 presents a perspective view of an exemplary embodiment of a SAW biosensor cartridge system adapted for collection and detection of bioaerosols from the atmosphere.
- FIG. 15 presents a schematic of capacitive coupling of a SAW biosensor cartridge system.
- FIG. 16 presents a schematic of a stackup view of a capacitive coupled device with PCB in cartridge.
- FIG. 17 presents a schematic of the multipanel system.
- FIG. 18 presents a schematic of the multipanel system.
- FIG. 19 presents a data table demonstrating the ability of the system to detect SARS- CoV-2 serology in clinical samples.
- FIG. 20A presents a perspective view of the disposable cartridge
- FIG. 20B presents an exploded view of the disposable cartridge.
- aspects of the present disclosure include apparatus, systems and platforms that are useful for the identification of chemicals, toxins, environmental agents and the like.
- the disclosed apparatus, systems and platforms may be used for diagnosis, treatment and/or prevention of any biological event of interest such as cardiac events, neurological events reproductive events and also include a variety of infectious diseases which may include those caused by bacteria, , immunological events fungi, viruses, and the like.
- the use of this biosensor is disclosed for human and animal use. The latter being used for both companion and food animals. Food safety and detection for biological research are also included in this application for the system described.
- the disclosed apparatus, systems and platforms may be used for detection of non- biological systems, such as chemotoxins and gaseous systems.
- an integrated acoustic detection device such as a Surface Acoustic Wave (SAW) device can provide extremely sensitive detection of infectious disease-related antigens (e.g., SARS-CoV-2, SARS-CoV, MERS-CoV, human coronavirus OC43, human coronavirus HKU1, human coronavirus 229E, human coronavirus NL63and the like) in a sample.
- infectious disease-related antigens e.g., SARS-CoV-2, SARS-CoV, MERS-CoV, human coronavirus OC43, human coronavirus HKU1, human coronavirus 229E, human coronavirus NL63and the like
- infectious disease-related antigens e.g., SARS-CoV-2, SARS-CoV, MERS-CoV, human coronavirus OC43, human coronavirus HKU1, human coronavirus 229E, human coronavirus NL63and the like
- Infections afflicting animals
- Crystals on the surface of acoustically transmissive materials such as quartz, lithium niobate and tantalate are typically only weakly responsive to the adhesion of biological materials.
- Chemical agents such as silane compounds following a series of proprietary application procedures along with reactive functional groups, such as amine residues, have been used to enhance adhesion of biological molecules on the surface crystals.
- a layer of silicone dioxide may enhance the binding ability of biological molecules without interfering with the transmission of the surface waver.
- the present disclosure fulfills all of these criteria and furthermore, takes advantage of many recent advances in semi-conductor industry (miniaturization, FPGA, software and hardware advances) and advances in cellular communications (on which these sensors are based) to provide a cost effective and easily used system that can replace 60 year old technologies such as lateral flow test.
- SAW surface acoustic wave
- an integrated surface biosensor system for the use as a rapid, cost-effective, and robust POC diagnostic for the detection of infectious events, agents, and systems is provided.
- the techniques herein provide acoustic wave-based POC devices suitable for biological events (e.g. infection agent-virus) systems testing.
- the acoustic devices and methods described herein utilize a responsive piezoelectric material that responds to an electrical signal by creating an acoustic wave (i.e., very high frequency sound) as the fundamental sensing property.
- aspects of the present disclosure include a disposable cartridge system utilizing a surface acoustic wave (SAW) biosensor that can be used for the detection of infectious agents.
- SAW surface acoustic wave
- FIG. 1 presents an exemplary design of a 300 MHz SAW biosensor 100.
- the frequency range can extend from 150-900 MHz.
- the SAW biosensor may be activated by high frequency radiofrequency (RF) waves from a RF source.
- the SAW biosensor comprises a piezoelectric crystal base 106 and one or more metal surfaces 108.
- the one or more metal surfaces 108 may be coated with a biofilm.
- the SAW biosensor may include a sample channel 102 and a reference channel 104. A biological sample may be contacted with the SAW biosensor via the sample channel 102 from which the biological sample may be analyzed.
- the output from the SAW biosensor may be processed by a printed circuit board (not shown in FIG. 1) coupled to the SAW biosensor for further analysis by the reader.
- sample channel 102 may be coated with one or more capture agents.
- the sensing area of the SAW device may be a metalized (e.g., Al layer) and the piezoelectric crystal base 106 chosen may be, e.g., Lithium tantalate (LiTaO3).
- the SAW generated on this crystal may be called a leaky wave, which may be principally composed of a shear horizontal wave so it can operate in a liquid while keeping a low propagation loss.
- a third channel (not shown in the figure) may be added to the SAW biosensor, which serves as a second reference channel to remove the effect of ambient temperature change on the SAW biosensor.
- FIG. 2 A shows an illustrative embodiment of a 300 MHz SAW sensor 200 according to an aspect of the present disclosure.
- the frequency range can extend from 150-900 MHz.
- the disclosed SAW sensor 200 includes a capacitive coupled contact pad 208 for establishing a capacitive coupling connection between the SAW sensor and a printed circuit board (PCB) supporting it.
- the disclosed SAW biosensor 200 includes a sample channel 204 for contacting the biological sample with the SAW biosensor and a reference channel 206.
- the sample channel 204 and reference channel 206 each have reflectors 202 and interdigitated transducers (IDTs) 203 for conversion of electrical energy to mechanical energy and vice versa.
- IDTs interdigitated transducers
- FIG. 2B shows an exemplary design of a 300 MHz SAW sensor 220, which has been modified for capacitive coupling with metal contact pads and a third channel for temperature compensation.
- the frequency range can extend from 150-900 MHz.
- the disclosed SAW sensor 220 includes a capacitive coupled contact pad 228 for establishing a capacitive coupling connection between the SAW sensor 220 and a printed circuit board (PCB) (not pictured) supporting it.
- the disclosed SAW biosensor 220 includes a sample channel 224 for contacting the biological sample with the SAW biosensor 240, a compensation channel 225, and a reference channel 226.
- the sample channel 224, compensation channel 225, and reference channel 226 each have reflectors 222 and interdigitated transducers (IDTs) 223 for conversion of electrical energy to mechanical energy and vice versa.
- IDTs interdigitated transducers
- FIG. 2C shows an exemplary design of a SAW sensor 240, which has been redesigned for capacitive coupling with circular metal contact pads to improve the X Y positioning tolerance on the capacitive coupled PCB.
- the disclosed SAW sensor 240 includes a capacitive coupled contact pad 248 for establishing a capacitive coupling connection between the SAW sensor 240 and a printed circuit board (PCB) (not pictured) supporting it.
- the disclosed SAW biosensor 240 includes a sample channel 244 for contacting the biological sample with the SAW biosensor 240, a compensation channel 245, and a reference channel 246.
- the sample channel 244, compensation channel 245, and reference channel 246 each have reflectors 242 and interdigitated transducers (IDTs) 243 for conversion of electrical energy to mechanical energy and vice versa.
- IDTs interdigitated transducers
- a reader (not shown in FIGs. 2A-2C) may be connected to the SAW biosensors via the capacitively coupled contact pads 208 for interrogating the SAW sensor.
- capacitive coupling eliminates the need for pin connectors or wire bonding, which are less efficient and less economical for the SAW biosensor system.
- the modified SAW biosensor may also include temporary contacts 210, 212 for probes used for quality control during fabrication.
- an input electrical signal from the reader is traversed through an IDT, a delay line, and then reflected back to the IDTs, where it is reconverted into an electrical signal. Changes in phase and amplitude of the electrical signal are measured by the reader. The phase change data and amplitude change data may then transformed by appropriate signal algorithms for detecting selected target components of a sample.
- multiple IDTs can be configured in a series or in an electrical parallel arrangement.
- FIG. 15 demonstrates capacitive coupling to the SAW sensor with the use of a differential signal, determined by the voltage difference between the two capacitors. In certain embodiments, FIG.
- the RF electrical signal in the range of 100 to 1000MHz, is transmitted to the SAW sensor and partially reflected by the SAW sensor. This partially reflected portion is subsequently modified by the sensing effect in phase and amplitude, and this change is detected by the reader.
- FIGS. 17 and 18 demonstrate a circuit of the electrical parallel arrangement, as the delay line connects the reader and a cartridge.
- multiple SAW sensors are housed together within a cartridge, along with a switch which selects a sensor to interrogate.
- the switch routes an RF electrical signal in the range of 100 to 1000MHz to the sensor currently being interrogated.
- capacitive coupling enables the transfer of phase change data and amplitude change data, along with the energy transfer, across the circuit.
- the system uses a 1 MHz carrier on/off control signal for the switch to enable the phase change data and amplitude change data, along with the energy transfer.
- a third signal is rectified and used as energy supply to the switch and to the microcontroller, decoding the on/off keying to control the switch.
- FIGS. 3A and 3B show a top view and a bottom view, respectively, of a mating capacitively coupled PCB 300.
- FIG. 3A shows PCB contacts 302A-C.
- a SAW sensor (not shown) is mated to a top surface 304 of a mating capacitive printed circuit board (PCB) 306 via the PCB contacts 302A - C.
- the PCB 306 also includes screw holes 305 along the perimeter through which screws will be used to secure the PCB 306 to a cartridge system (not shown in the figure).
- FIG. 3B shows the bottom surface 308 of PCB 306 of a mating capacitive coupled PCB 300 having a sub miniature push-on (SMP) connector 312 for connecting to a reader unit (not shown in the figure) via a subminiature version A (SMA) cable (not shown in the figure).
- the SMP connector 312 is connected to the PCB contacts through a via 318.
- the SMP connector 312 is also surrounded by a perimeter enclosure 314.
- the SAW sensor and a disposable capacitive coupled PCB supporting it will be integrated into a disposable cartridge system (shown in FIGs. 3C and 3D) to be used for the POC detection of biological events of interest such as the SARS- CoV-2 virus.
- the cartridge mounts onto a designated area on top of the reader (not shown in this figure) where capacitive coupling occurs.
- the cartridge is disposable, unidirectional in its docking, and queried by a mating PCB mounted on the top of the reader connected with the RF circuit board inside the reader.
- a dielectric material such as Kapton tape, may be used to protect the mating PCB. It is contemplated that the dielectric material can consist of several layers, including the piezoelectric substrate of the SAW element, an additional air layer, and additional layers from the cartridge housing or the reader housing, which can act as a dielectric layer.
- the capacitive coupling PCB relays information into the reader from the cartridge in a simple passive proximity coupling with no direct physical connection or mating pins required.
- aspects of the present disclosure further includes a disposable cartridge system utilizing a surface acoustic wave (SAW) biosensor, disposable capacitive coupled PCB assembly, fluid gasket, buffer can that contains saline, and a screw cap that can be used for the detection of infectious agents.
- SAW surface acoustic wave
- FIG. 20A shows a perspective view of the disposable cartridge 2010, and FIG. 20B presents an exploded view of the disposable cartridge 2010.
- disposable cartridge 2010 is akin to cartridge 566 as described and depicted in FIGs. 5C and 5D, and can be docked onto the capacitive coupled holder 550 and wait for calibration.
- cartridge system 2010 includes top foil 2012 disposed over buffer can 2014, which can be removed by a user once calibration is complete to pierce a foil (not shown) at the bottom of buffer can 2014.
- buffer can 2014 is configured to mated with cylinder 2016 during assembly.
- Cartridge system 2010 also includes screw cap 2018 and clamp 2022, which can be activated by a user to activate the flow of, for example, saline from the buffer can 2014 through the channel 2020 over the sensory aspect (not shown) of cartridge 2010.
- each of these components is located within perimeter 2024, and is disposed on base 2026.
- FIG. 3C presents a bottom view 320 of an alternate design of the PCB of FIG. 3A, showing a disposable capacitive coupled PCB 350, for integration with the capacitive coupled holder and disposable cartridge.
- the disposable capacitive coupled PCB 350 includes PCB contacts 352 A-B.
- a SAW sensor (not shown) is mated to a top surface (not shown) of the disposable capacitive PCB 350 via the PCB contacts 352A-B.
- the PCB 350 also includes screw holes 355 along the perimeter through which screws will be used to secure the PCB 350 to a cartridge system (not shown).
- the present embodiment incorporates a radio-frequency identification (RFID) tag (not shown), which is interrogated by the reader (not shown) via a mating capacitive coupled PCB 360 (introduced in FIG. 3D).
- RFID tag can contain data on the disposable cartridge, including but not limited to, test ID, lot number, expiration date, and calibration data.
- FIGS. 3D shows a bottom view 330 of a mating capacitively coupled PCB 360 involving an additional embodiment including the capacitive coupled holder and disposable cartridge system.
- FIG. 3D shows bottom surface 358 of PCB 360 of a mating capacitive coupled PCB having a sub miniature push-on (SMP) connector 352 for connecting to a reader unit (not shown) via a subminiature version A (SMA) cable (not shown).
- SMP connector 352 is connected to the PCB contacts through a via 368.
- the PCB 360 also includes screw holes 365 along the perimeter through which screws will be used to secure the PCB 360 to a holder (not shown).
- the SAW sensor and a disposable capacitive coupled PCB supporting it will be integrated into disposable cartridge systems to be used for the POC detection of biological events of interest such as the SARS-CoV-2 virus.
- the cartridge mounts onto a designated area on top of the reader (not shown in this figure) where capacitive coupling occurs.
- the cartridge is disposable, unidirectional in its docking, and queried by a mating PCB mounted on the top of the reader connected with the RF circuit board inside the reader.
- a dielectric material, such as Kapton tape, may be used to protect the mating PCB.
- the dielectric material can consist of several layers, including the piezoelectric substrate of the SAW element, an additional air layer, and additional layers from the cartridge housing or the reader housing, which can act as a dielectric layer.
- the capacitive coupling PCB relays information into the reader from the cartridge in a simple passive proximity coupling with no direct physical connection or mating pins required.
- the disposable cartridge region 418 may include a top surface 402 for holding the biological sample, a SAW biosensor 406 for contacting the biological sample and at least one gasket 404 to prevent the fluid from directly overwhelming and damaging the SAW biosensor 406.
- the SAW biosensor 406 and the at least one gasket 404 are held in place with a top securing portion 426 and a bottom securing portion 424.
- the top securing portion 426 directly rests on the bottom securing portion 424 and the at least one gasket 404 to hold at least one gasket 404 and the SAW biosensor 406 in place.
- a top layer securing unit 428 comprising a flange 430 mates with the top securing portion 426 such that the flange 430 secures the region of the SAW biosensor 406 not covered by the at least one gasket 404.
- the top layer securing unit 428 is flanked by microfluidic channels 422 for fluid flow.
- the SAW biosensor 406 may be directly coupled to a disposable PCB with no connector 408 for interfacing with a reusable contact region 420 of a reader.
- the disposable PCB with no connector 408 may be contacted with a dielectric material 410 such as polytetrafluoroethylene (PTFE) or Kapton TM tape for protecting the mating PCB 412 from environmental factors and providing an immunity barrier.
- a dielectric material 410 such as polytetrafluoroethylene (PTFE) or Kapton TM tape for protecting the mating PCB 412 from environmental factors and providing an immunity barrier.
- the data from the mating PCB 412 may be transmitted through a connector 414 and a cable 416 directed to the reader.
- FIGS. 5A and 5B exemplary images of the cartridge-reader complex in an open position 500 and a closed position 510, respectively.
- FIG. 5A presents an exemplary image of the cartridge-reader complex in an open position 500, and shows that the reader 502 includes a base 508 and a mating PCB region 504 for connecting with a PCB 506 of the cartridge (not shown in this figure) where the PCB 506 of the cartridge is not connected to the mating PCB region 504 of the reader 502.
- FIG. 5B presents an exemplary image of the cartridge-reader complex in the closed position 510, and shows PCB 506 of the cartridge when reader 502 is in a closed position 510.
- FIGS. 5C and 5D exemplary images of the capacitive coupled holder and disposable cartridge system in an open position 520 and a closed position 530, respectively.
- FIG. 5C presents an exemplary image of the capacitive coupled holder and disposable cartridge system 550 in an open position 520, and shows that the system 550 includes a top 562, latch 564, base 558 and a capacitive coupled pad 554 for connecting with a mating PCB 556 which interfaces cartridge 566 to the holder 550.
- FIG. 5D presents an illustration of the alternate embodiment of the capacitive coupled holder and disposable cartridge system 550 in a closed position 530. Further, screw cap 560 disposed on cartridge 566 can be actuated by the user in some embodiments.
- the cartridge 566 is placed onto the capacitive coupled pad 554 and secured in place by closing the holder assembly via latch 564.
- a user can dock a cartridge 566 onto the capacitive coupled holder 550 and wait for calibration.
- a user may remove the top foil 572 from the buffer can 568.
- the user can then turn the buffer can 568, which pierces a foil (not pictured) at the bottom of it.
- the user can turn the screw cap 560, which activates the flow of saline from the buffer can through the channel over the sensory aspect of cartridge 566.
- the miniaturized SAW sensor 604 may be designed for capacitive coupling with a pair of contact pads opposing each other.
- FIG. 7 an exemplary schematic of a fabricated wall 700 for a SAW sensor is presented.
- a fabricated wall concept may be adopted where the SAW biosensor 716 has been identified to have open sensing areas 704 and liquid-proof protecting areas 702. In the regions of liquid-proof protection 702, regions of contacts pads 706 and regions of IDTs 708 are isolated from the fluid flow via lid silicon glass 710 adhered on to the SAW biosensor 716 visa seal-proof silicon rubber wall 712.
- the system may include a PDMS gasket 800 to prevent the SAW biosensor from directly interacting with the fluid flow.
- the PDMS gasket 800 comprises a fluidic channel 804 created by the gasket to allow the biological sample to flow through.
- the gasket may be made of PDMS.
- the SAW biosensor system 900 may include an overmolded TPE gasket 904 on a top surface 902 of a cassette component 906.
- the system may be completely enclosed using walls of silicone or overmolded thermoplastic elastomers (TPE) which are precisely tooled to the dimensions of the sensor, allowing for a flow well with the characteristics needed for a dynamic flow cell.
- TPE thermoplastic elastomers
- Such an enclosure would work for acoustic sensors using other types of acoustic waves, such as Rayleigh, with or without a Love layer, transmission and reflective delay lines, and with bulk acoustic waves. Any type of acoustic wave traversing a piezoelectric crystal could be used in such an enclosure. All electronic components are protected, and the flow cell ties perfectly to the larger fluidic channel.
- FIGS.10A and 10B present perspective and exploded views of an exemplary embodiment of disposable cartridge system 1000 comprising a SAW biosensor for the detection of infectious diseases.
- the exemplary embodiment of the disposable cartridge system 1000 may include a cassette 1003 including a cassette body 1010 and a cassette bottom 1012 secured together for holding the sample. The cassette body 1010 and the cassette bottom 1012 may be secured to each other via vertical posts 1020, for example.
- the disposable cartridge system 1000 also includes a SAW biosensor 1016 attached to a printed circuit board 1018. The printed circuit board 1018 is then attached to the cassette bottom 1012. The printed circuit board 1018 may be secured to the cassette bottom 1012 via screws (not shown in the figure) through the screw holes 1026 along the perimeter of the printed circuit board 1018, for example.
- the disposable cartridge system also includes a gasket 1014 to separate the biological sample from coming in contact with the SAW biosensor 1016 and the printed circuit board 1018.
- the printed circuit board 1018 includes a region 1024 comprising printed circuit board contacts (not shown).
- the cassette 1003 includes outlines of internal fluidic pathways 1005, 1007.
- a biological sample may be placed in a sample well 1004 and secured with a sample cap 1002 on the cassette body 1010.
- the sample cap 1002 includes an air vent 1003.
- the disposable cartridge system 1000 may be secured onto a reader (not shown) for calibration.
- a saline cap 1006 comprising a spring 1007 is pushed down on a saline-saturated compression pad 1008 on the cassette body 1010.
- the rebounding spring force of the spring 1007 in the saline cap 1006 may be designed to allow the saline-saturated compression pad 1008 to decompress and pull the saline back into the saline-saturated compression pad 1008 at a controlled rate.
- the saline cap 1006 is then pushed down against the spring 1007 causing the saline in the saline-saturated compression pad 1008 to flow through a channel over the SAW biosensor 1016 to the sample well 1004.
- the SAW biosensor 1016 is in direct communication with the printed circuit board 1018 which processes the output response of the SAW biosensor 1016 to the biological sample.
- the disposable cartridge system 1000 may be operatively placed in a reader so that an output of the disposable cartridge system may be received by the reader.
- the output of the disposable cartridge system 1000 may include a measurement or indication of SARS-CoV-2 virus being present in the biological sample, for example.
- FIGS. 11A and 11B present a perspective and exploded view of another illustrative embodiment of disposable cartridge system 1100 comprising a SAW biosensor for the detection of infectious diseases according to aspects of the present disclosure.
- the disposable cartridge system 1100 comprises a cassette body structure 1112 and a cassette top cover 1113 secured together and comprising a SAW biosensor, a printed circuit board, and a gasket to prevent the biological sample from directly being contacted with the SAW biosensor.
- a biological sample may be placed in a sample well 1104 and secured with a sample cap 1102.
- the cassette body structure 1112 may be placed on a reader (not shown) for calibration. Saline pinch valves (not shown) in the cassette body structure 1112 may be activated when the cassette body structure 1112 is placed on a reader for calibration.
- the sample well 1104 containing the biological sample secured with a sample cap 1102 is attached to a saline well 1106 to form a sample-saline complex 1103 and loaded onto the cassette top cover 1113 via a docking location 1108.
- the docking location 1108 comprises at least two loading wells 1109.
- the sample well 1104 and the saline well 1106 comprise foils securing the respective liquids in their respective well.
- the saline pinch valves are designed to be opened first to allow saline to flow over the SAW biosensor and contact the absorbent wi eking pad 1110 on the cassette body structure 1112.
- the absorbent wi eking pad 1110 pulls the saline at a rate of 5pl/min. Proceeding the opening the saline pinch valve for 5 minutes, the saline pinch valve is closed and the sample is allowed to be exposed to the SAW biosensor and then contact the absorbent wi eking pad 1112.
- the SAW biosensor may be in direct communication with the printed circuit board which in turn processes the output of the SAW biosensor due to the biological sample and an output of measurement (e.g., presence of an infectious virus in the biological sample) may be noted by the reader when the disposable cartridge system 1100 is placed in the reader.
- an output of measurement e.g., presence of an infectious virus in the biological sample
- FIGS.12A and 12B present a perspective and exploded view of a further exemplary embodiment of disposable cartridge system 1200 comprising a SAW biosensor for the detection of infectious diseases.
- the exemplary embodiment of the disposable cartridge system 1200 comprises a cassette body 1212 further comprising a saline blister pack 1208, SAW biosensor 1214 attached to a printed circuit board 1218, and a gasket 1216 to separate the biological sample from coming in contact with the SAW biosensor 1214 and the printed circuit board 1218.
- the printed circuit board 1218 is secured onto the cassette body 1212 via posts 1219 which fit on the post voids 1217 on the perimeter of the printed circuit board 1218.
- the biological sample may be placed in a sample well 1211 and secured with a flexible sample cap 1206 on the cassette body 1212.
- the disposable cartridge system 1200 may be secured onto a reader (not shown) for calibration. Following calibration, a reusable flexible hourglass with grains 1202 held by a holding platform 1203 of a timer holder 1204 may be placed on the cassette body 1212, leading to opening the saline blister pack 1208. As grains in the hourglass 1202 slowly transfer to the bottom of the hour-glass 1207 and compress the indented region 1209 of a flexible sample cap 1206, the biological sample may be forced into the channel (not shown in the figures) in the cassette body 1212, and allowed to interact with the SAW biosensor 1214 Eventually the saline from the saline blister pack 1208 and the biological sample are displaced to the waste well with an air vent 1210.
- the SAW biosensor 1214 may be in direct communication with the printed circuit board 1218 which in turn processes the output of the SAW biosensor 1214 due to the biological sample and an output of measurement (e.g., presence of a virus in the biological sample) may be noted in the reader when the disposable cartridge system 1200 is placed in the reader.
- an output of measurement e.g., presence of a virus in the biological sample
- the SAW biosensor cartridge system 1300 includes a cassette 1302 with a sensor 1306 which may include a liquid-proof sealing 1318, only revealing a sensing area 1309 coated with an active nanomaterial layer 1308.
- the cassette 1302 includes a porous inlet 1316 with a filter 1314 for gaseous species input from the atmosphere.
- the gaseous species input may travel through a channel 1304 connected to a micropump (not shown in the figure) allowing the gaseous species input to flow through the channel 1304 for interaction with the sensing area 1309 coated with an active nanomaterial layer 1308.
- the data from the sensor 1306 may then be transmitted to a tablet 1312 connected to a reader (not shown in the figure) via a wireless radio frequency interrogator 1310.
- the SAW biosensor cartridge system 1400 includes a cassette 1406 with a sensor 1410 which may include a liquid-proof sealing 1408, only revealing a sensing area 1416 coated with a capture agent 1414.
- the cassette 1402 includes a bioaerosol sampler system 1422 with a bioaerosol collection reservoir 1420 for holding the bioaerosol input from the atmosphere.
- the bioaerosol collection reservoir 1420 is fluidly connected to a channel 1412 via a valve 1418.
- the sample bioaerosol may travel through the channel 1412 connected to a micropump (not shown in the figure) allowing the bioaerosol input to flow through the channel 1412 for interaction with the sensing area 1416 coated with the capture agent 1414.
- the data from the sensor 1410 may then be transmitted to a tablet 1402 connected to a reader (not shown in the figure) via a wireless radio frequency interrogator 1404.
- FIG. 19 presents a data table 1900 demonstrating the ability of the systems of the present disclosure to detect SARS-CoV-2 serology in clinical samples.
- a sensor surface was immobilized with a recombinant SARS-CoV-2 spike receptorbinding domain (RBD) protein for capturing SARS-CoV-2 IgG antibodies.
- RBD SARS-CoV-2 spike receptorbinding domain
- the results from this preliminary study indicate ability of the system to detect SARS-CoV-2 IgG antibodies in clinical samples with 100% sensitivity and 100% specificity.
- data table 1900 shows that the platform and the systems and devices of the present disclosure have the potential to be a POC method for improved detection of host generated antibodies against SARS-CoV-2 and other infectious diseases.
- the disposable cartridge handling potential infectious or other material needs to be biologically isolated from the reader being reused and may need to be discarded since it now may contain biological fluids. Having only a flat surface and no electrical or mechanical contacts is therefore preferable and eases the disinfection of the reader after usage.
- This implementation may implement a noncontact drive for pumping the analytes if this pump is needed.
- a pump in the cartridge can be energized by means of a magnet in the reader moving a piston in the cartridge through magnetic coupling through a protection diaphragm.
- the diaphragm can be displaced by pressurizing a cavity underneath a diaphragm on the reader side and pushing in a corresponding diaphragm on the cartridge side.
- a rapid, portable, and accurate testing platform can add critical data to diagnose, leading to diagnosis of rapidly evolving biological events including proper treatment and decrease spread of infectious agents.
- Such a system which can trace, analyze and handle large amounts of data related to such a diagnosis is critical for prevention, treatment, and managing future outbreaks.
- Other examples of such utility can include non- infectious conditions such as chemo or bio toxin threats, where remote and constant monitoring can identify and isolate a person or non-persons carrying or distributing such materials using this technology.
- diagnosis of veterinary and human situations that can identify and treat rapidly can make a difference such as biomarkers which can rapidly identify traumatic brain injury, stroke, or myocardial infarction.
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Abstract
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LANGE K ET AL: "Packaging of surface acoustic wave (SAW) based biosensors: an important issue for future biomedical applications", FREQUENCY CONTROL SYMPOSIUM AND EXPOSITION, 2004. PROCEEDINGS OF THE 2 004 IEEE INTERNATIONAL MONTREAL, CANADA 23-27 AUG. 2004, PISCATAWAY, NJ, USA,IEEE, 23 August 2004 (2004-08-23), pages 321 - 325, XP010784633, ISBN: 978-0-7803-8414-9, DOI: 10.1109/FREQ.2004.1418473 * |
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