WO2022053971A1 - Dispositif de mesure ou biopuce comprenant une microcavité optique - Google Patents

Dispositif de mesure ou biopuce comprenant une microcavité optique Download PDF

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Publication number
WO2022053971A1
WO2022053971A1 PCT/IB2021/058207 IB2021058207W WO2022053971A1 WO 2022053971 A1 WO2022053971 A1 WO 2022053971A1 IB 2021058207 W IB2021058207 W IB 2021058207W WO 2022053971 A1 WO2022053971 A1 WO 2022053971A1
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WIPO (PCT)
Prior art keywords
measurement device
previous
optical
fluidic channel
layer
Prior art date
Application number
PCT/IB2021/058207
Other languages
English (en)
Inventor
Nicolas Descharmes
Raphaël BARBEY
Original Assignee
Ecole Polytechnique Federale De Lausanne (Epfl)
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Publication of WO2022053971A1 publication Critical patent/WO2022053971A1/fr

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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
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • 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
    • 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
    • B01L2300/02—Identification, exchange or storage of information
    • B01L2300/025—Displaying results or values with integrated means
    • B01L2300/028—Graduation
    • 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
    • B01L2300/16—Surface properties and coatings
    • B01L2300/168—Specific optical properties, e.g. reflective coatings
    • 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
    • G01N21/03—Cuvette constructions
    • G01N2021/0346—Capillary cells; Microcells
    • 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
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N2021/6463—Optics
    • 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
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N2021/6482—Sample cells, cuvettes

Definitions

  • the present invention relates to a measurement device/chip or biochip, and more particular relates to a measurement device/chip or biochip comprising an optical structure including or defining an optical microcavity.
  • Standard measurement supports such as glass slides, petri dishes, multiwell plates and flow chambers are known. However, measurements carried out using known measurement supports are limited in quality and/or quantity.
  • Fluidic devices used in association with optical measurements are also known.
  • Optical measurement scanning can be carried out over a large area or sample.
  • multiple measurements from different zones may be performed with stitching of the measured results performed to provide an overall measurement result.
  • such optical measurements can be inefficient and/or time consuming.
  • the often low intensity of the measured signal makes focusing of the optical measurement system difficult, which may result in a poor measurement results, and possibly repeated measurements.
  • the present disclosure addresses the above-mentioned limitations by providing a device according to claim 1 .
  • Another aspect of the present disclosure concerns a measurement method according to claim 28.
  • the present disclosure concerns a measurement device/chip or biochip having an optical coating that includes an optical microcavity.
  • the biochip can be or is loaded with one or several biological specimens to be processed and optically interrogated.
  • the microcavity-based optical coating allows for the passive electromagnetic control of light emitting or scattering species present in the biological specimens at the time of observation. This passive electromagnetic control allows, for example, enhanced luminescence/light, improved imaging, improved contrast, improved or more sensitive detection or improved signal to noise ratio.
  • the device and method of the present disclosure thus provides a solution to the above- mentioned problems.
  • the device and method of the present disclosure assures a reduced exposure time and consequently a reduced scanning speed and an increased measurement efficiency.
  • the device and method of the present disclosure also assures better optical focusing or setup of the optical measurement system in view of the higher quantity of light transferred by the device of the present disclosure to the optical measurement system. This assures a more reliable measurement and avoids poor measurement results, and the necessity for repeated measurements.
  • Figure 1 shows an exemplary embodiment of a system including an exemplary device according to the present disclosure, the device being shown in a cross-sectional view.
  • Figure 2 is an enlarged view of the exemplary device of Figure 1 .
  • Figure 3 is a cross-sectional and side-view of the exemplary device of Figure 1 .
  • Figure 4 is a cross-sectional of a portion of the exemplary device of Figure 1 .
  • Figure 5A is a top view showing an exemplary device that include a single fluidic channel or chamber.
  • Figure 5B is a top view showing an exemplary device that include a plurality of fluidic channels or chambers.
  • Figure 6 shows exemplary markings or structures included in an exemplary device of the present disclosure to delimit and identify optical measurement regions.
  • Figure 7 is an image of an exemplary device of the present disclosure.
  • Figure 8 shows a comparison between fluorescence readouts achieved using a device of the present disclosure (left) versus a standard glass substrate (right).
  • Figure 9 shows a reflectance spectrum of a luminescence measurement substrate comprising spectral features and in particular spectral characteristics that are a reflectivity resonance dips introduced by the presence of an optical cavity enclosed or formed by the two mirrors.
  • Figure 10 to 12 show possible exemplary embodiments of optical structures comprising an optical microcavity.
  • Figures 1 to 4 and 5A to 5B show exemplary measurement devices 1 , or measurement devices/chips or biochips according to the present disclosure.
  • the device 1 comprises or consists of, for example, a biochip or bio-fluidic chip.
  • the measurement device 1 includes at least one or a plurality of optical measurement regions R and at least one fluidic channel or a plurality of fluidic channels (or chambers) 10 for providing a liquid or at least one specimen 119 in a liquid to the optical measurement region R of the device 1 .
  • the device 1 and the fluidic channel or channels 10 are configured to provide at least one liquid to at least one specimen 119 located inside the fluidic channel or channels 10.
  • the measurement device 1 includes at least one optical structure or optical device OD contacting the at least one or the plurality of fluidic channels 10.
  • the optical structure OD may directly or indirectly contact the fluidic channel or channels 10.
  • the optical structure OD may define or delimit the fluidic channel or channels 10, or a portion thereof.
  • the optical measurement region R of the measurement device 1 is defined by the optical structure OD.
  • the optical structure or optical device OD comprises or consists of, for example, a layered optical coating.
  • the optical structure or optical device OD is or defines a passive optical device OD.
  • the optical structure OD includes a first mirror (or bottom mirror) 9, at least a second mirror (or top mirror) 11 and an intermediate layer IL located between the first and second mirrors 9, 11 and acting as or defining an optical cavity OM, or a portion thereof (see, for example, Figure 4).
  • the optical structure OD includes or defines an optical microcavity OM.
  • the optical microcavity OM is, for example, configured to allow electromagnetic control or passive electromagnetic control of light emitting species or light scattering species present in the at least one specimen 119.
  • the optical microcavity OM is further detailed below.
  • the optical structure OD or optical microcavity may, for example, be configured to set or determine a surface electric field located in the fluidic channel or channels 10 at or in proximity of the location of the specimens 119, to enhance emission of or light interaction with light emitting or scattering species present in the biological specimens 119.
  • the specimen or specimens 1 19 may include, for example, one or more light emitting or light scattering species or markers.
  • the light emitting species may for example comprise luminescent species or markers such as atoms, ions, molecules or quantum dots.
  • a luminescent specie or marker Upon illumination, a luminescent specie or marker absorbs part of the incoming, primary radiation and emits a secondary radiation.
  • the secondary radiation often possesses different properties compared to the primary radiation such as frequency and/or polarization. This difference allows for a selective filtering of the secondary radiation and, for example, a high contrast imaging of specimen or objects having regions of varying concentration in luminescent markers. This is typically the case of fluorescence imaging.
  • the luminescent function or property of the markers or labels may be inherent or intrinsic to the object to be detected or imaged, or luminescent markers or labels may be combined or conjugated with the object 119.
  • Scattering species or markers include for example, micron sized particles, nanoparticles or sub-micron particles of, for example, Au, or silica, or a polymer, or iron.
  • the scattering can additionally or alternatively be produced by the specimen 1 19 itself without such added scattering species or markers.
  • the device 1 may also include a support piece or base 6 configured to support the optical structure OD and the fluidic channel or channels 10.
  • the fluidic channel or channels 10 are, for example, superposed on the optical structure OD.
  • the fluidic channel or channels 10 and the optical structure OD are, for example, superposed on the support 6.
  • the optical structure OD defines or delimits a first side or wall or floor 21 of the fluidic channel or channels 10.
  • a floor 21 is defined or delimited in the exemplary embodiments of the Figures.
  • the optical structure OD defines or delimits, for example, a floor or base 21 of the fluidic channel 10 in the optical measurement region R or in a portion of the optical measurement region R.
  • the optical structure OD may define or delimit a portion of the floor or base 21 , or define or delimit all of the floor or base 21 of the fluidic channel or channels 10.
  • the first or second mirror 9, 11 defines or delimits, for example, the floor 21 of the fluidic channel 10.
  • the measurement device 1 further includes a cover layer 11 1 , for example, a translucid or transparent cover layer 11 1.
  • the cover layer 11 1 is positioned or superposed on the fluidic channel or channels 10.
  • the cover layer 11 1 for example, defines or delimits at least partially or fully the fluidic channel or channels 10.
  • the cover layer 11 1 may define or delimit a second side or wall, or ceiling 23 of the fluidic channel or channels 10 as shown in the exemplary device 1 of the Figures.
  • the measurement device 1 further includes a spacing (or spacer) layer 12.
  • the spacing layer also defines the fluidic channel or channels 10.
  • the spacing layer 12 includes a material layer 27 that comprises at least one or a plurality of hollow regions or depressions (or cavities) 25.
  • the hollow region or regions 25 extend in a planar direction (X-Y) inside the spacing layer 12 and in a direction (substantially) perpendicular (Z) to the planar direction (X-Y), that is, in a superposition direction of the superposed layers or elements of the device 1 or in the direction 5 in which electromagnetic radiation is propagated into the device 1 .
  • the hollow region or regions 25 may extend partially or fully in the planar direction (X-Y).
  • the hollow region or regions 25 may extend partially or fully in the direction (substantially) perpendicular (Z) to the planar direction (X-Y).
  • the spacing layer 12 includes at least one or a plurality of structures or pillars 29 defining the one or more depressions 25.
  • the structure 29 includes or defines at least one or a plurality of walls 31 defining the depressions 25.
  • the walls 31 for example, lateral walls, extend between the optical structure OD (the floor 21) and the cover layer 1 11 (ceiling 23) to define or delimit the fluidic channel or channels 10.
  • the walls 31 may directly or indirectly contact the ceiling 23 and floor 21 .
  • the structure 29 may define one depression 25, the wall 31 extends between the cover layer 11 1 and optical structure OD to define a height H of the channel 10.
  • the wall 31 extends in the planar direction (X-Y) to define a form or profile of the channel 10.
  • the structure 29 defines a plurality of depressions 25A, 25B, 25C
  • the walls 31 extend between the cover layer 1 11 and optical structure OD to define the height H of the channels 10.
  • the walls 31 extends in the planar direction (X-Y) to define a form or profile of the channels 10, an exemplary elongated profile in Figure 5B.
  • the optical structure OD and/or the cover layer 111 define or delimit the height H of the at least one fluidic channel 10.
  • An adhesion Iayer 8 may, for example, be provided on the optical structure OD.
  • the adhesion layer 8 may fully or partially cover the optical structure OD, or fully or partially cover a portion of the optical structure OD that defines the fluidic channel or channels 10, or fully or partially cover a portion of the optical structure OD located (directly) below that the depression or depressions 25.
  • the adhesion layer 8 may, for example, comprise or consist of multiple superposed layers forming an assembly 8 for temporarily holding one or more specimens 119.
  • the adhesion layer 8 is, for example, configured to receive or at least temporarily hold one or more specimens 1 19, permitting investigation of the specimens 119.
  • the optical structure OD and/or the adhesion layer 8 may define or delimit the floor 21 of the fluidic channel or channels 10.
  • the optical structure OD and/or the adhesion layer 8 may define or delimit the thickness or height H of the fluidic channel or channels 10.
  • the measurement device 1 may further include at least one inlet 13 in fluid communication with the fluidic channel 10 and at least one outlet 33 in fluid communication with the at least one fluidic channel 10 and the inlet 13.
  • Each fluidic channel 10 may be in fluid communication with one inlet 13 and one outlet 33 (see for example Figures 5A and 5B, or one inlet 13 and/or one outlet 33 may be in fluid communication with a plurality of fluidic channels 10.
  • the inlet 13 and/or the outlet 33 may be defined by an outer surface OS or outer material of the device 1.
  • the outer surface OS can be, for example, a surface defined by the support layer 6 or the cover layer 111 .
  • the outer surface OS can be a lower surface of the device 1 opposite the surface for receiving the incident measurement electromagnetic radiation, or a lateral or side surface of the device 1 that extends in the direction of propagation of the incident measurement electromagnetic radiation.
  • the channel or channels 10 may extend directly to the inlet 13 and/or outlet 33, or may be fluidly connected to the to the inlet 13 and/or outlet 33 via a further fluidic channel 35 having or defining a different cross-section al profile, for example, a tapered profile.
  • each channel 10 may be associated with solely one inlet 13 and outlet 33, or solely one inlet 13 and outlet 33 may in fluid communication with the plurality of channels 10.
  • the device 1 may, for example, include multiple groupings of a plurality of channels 10, each grouping in fluid communication with solely one inlet 13 and outlet 33 for that grouping.
  • the fluidic channel or each channel 10 is a micro-fluidic channel.
  • the channel 10 may, for example, have a height H between 1 pm and 1000pm for example 250pm or 400pm, a length L between 5mm and 500mm for example 70mm, and a width W between 1 pm and 45mm for example 1 mm or 20mm.
  • the width W and/or height H may vary as the channel 10 extends along the length L of the channel 10.
  • the translucid or transparent cover layer 11 1 comprises or consists of a material that is translucid or transparent to the incident electromagnetic radiation provided for analysis of the specimens 119, and translucid or transparent to the electromagnetic radiation generated by the specimens 119 and that is collected/measured for analysis.
  • the cover layer 111 may, for example, be a removable cover layer or include at least one portion or lid that is removable or displaceable (partially removable cover layer) permitting access to the fluidic channel or channels 10.
  • the portion or lid may, for example, be removable or displaceable and re-positioned to allow temporary access to the channel 10.
  • the cover layer 11 1 includes an opening permitting access to the at least one fluidic channel (10), and the portion or lid is configured to seal and/or close the opening.
  • the measurement device 1 may further include at least one or a plurality of markings or structures 37 visible to the naked eye and/or for imaging by an optical system or device 4 that is configured to image the optical structure OD or upper portions thereof.
  • the markings or structures 37 comprise or consist of boundary markings or landmarks configured to delimit the optical measurement region R of the measurement device 1 into sub-regions SR.
  • the optical structure OD includes the markings or structures 37, for example, on the first mirror 9 or the second mirror 11 .
  • Figure 1 shows a measurement system 39 comprising the measurement device 1 .
  • the system 39 may further comprise a liquid providing apparatus 2, for example, a reservoir or container connected to the inlet or inlets 13 by tubing.
  • the system 39 may further comprise a liquid receiving/removal apparatus 3, for example, a reservoir or container connected to the outlet or outlets 33 by tubing.
  • a liquid receiving/removal apparatus 3 for example, a reservoir or container connected to the outlet or outlets 33 by tubing.
  • the liquid providing apparatus 2 may include, for example, a pump to inject a liquid into the fluidic channel or channels 10 via the inlets 13.
  • the liquid receiving/removal apparatus 3, may, for example, an aspiration pump for transferring the liquid from the liquid providing apparatus 2, through the fluidic channel or channels 10 and into the container of the liquid receiving/removal apparatus 3.
  • the liquid providing apparatus 2 and the liquid receiving/removal apparatus 3 may, for example, be absent.
  • the fluidic channel or channels 10 may be configured to transport liquid into and/or inside the device 1 via capillary forces or capillary action, or centrifugal forces or centrifugal action.
  • the system 39 may further comprise an optical system or device 4 configured to provide electromagnetic radiation to the measurement device 1 for exciting light emitting species of the specimen or specimens 119, or for scattering from light emitting species of the specimen or specimens 119.
  • the optical system or device 4 may, for example, include one or more light sources such a laser sources, or LEDs or lamps optionally associated with one or more filters for wavelength selection of the incident electromagnetic radiation.
  • the optical system or device 4 may additionally be configured to collect electromagnetic radiation 5 emanating, emitted or scattering from the measurement device 1 , for example, from the species of the specimen or specimens 119, and/or from the optical structure OD.
  • the optical system or device 4 may, for example, include one or more lens and/or mirrors to collect the received light and direct the light to a spectrometer and/or an image sensor included therein, for example, a CMOS device or camera comprising a plurality of pixels each configured to individually capture incoming light or an active pixel sensor (APS) containing an array of pixel sensors each comprising for example a photodetector and amplifier.
  • CMOS device or camera comprising a plurality of pixels each configured to individually capture incoming light or an active pixel sensor (APS) containing an array of pixel sensors each comprising for example a photodetector and amplifier.
  • APS active pixel sensor
  • the optical system or device 4 may include one or more lens and/or mirrors arranged to capture images of the measurement device 1 or a portion thereof, in particular, the optical structure OD to image the sub region SR under investigation and the boundary markings or landmarks.
  • the system 39 may further include processing/analysis means 41 , 43 for processing/analysing the collected signal/data collected by the optical device or system 4 from the measurement device 1 .
  • the system 39 may include calculation means or a processor 41 connected to and configured to receive the captured or measured data/signals from the optical system or device 4, for example, the image sensor.
  • the calculation means or processor 41 may also be configured to control and command the image sensor or elements of the optical system or device 4.
  • the calculation means or a processor 41 may also be connected to the other elements of the system 39 and configured to control and command these elements to permit operation of the system 39.
  • the system 39 may include a memory 43 (for example, semiconductor memory, HDD, or flash memory) configured to store or storing at least one program or processor executable instructions.
  • the at least program or processor executable instructions may comprise instructions permitting, for example, to control and command optical system or device 4 or the image sensor and the other system elements.
  • the processor executable instructions may comprise instructions permitting to receive and process the captured signals/data or image data from the optical system or device 4, or the image sensor.
  • the calculation means or a processor 41 and the memory 43 can be, for example, included in a computer, portable laptop or a portable device such as a smart phone or device.
  • the program or processor executable instructions can be provided, for example, as custom Matlab functions.
  • the device 1 that is described herein concerns for example a biochip, that is, a fluidic chip intended to treat/process and study biological material or specimens 119 such as, but not limited to, tissue microsections, organoids, surface-bound antibodies or clusters of the latter, DNA, RNA, cells or cellular extracts, proteins, aptamers, oligonucleotics, aminoacid branches or clusters of the latter, or any other biological samples.
  • biological material or specimens 119 such as, but not limited to, tissue microsections, organoids, surface-bound antibodies or clusters of the latter, DNA, RNA, cells or cellular extracts, proteins, aptamers, oligonucleotics, aminoacid branches or clusters of the latter, or any other biological samples.
  • the biochip 1 Prior to or throughout the analysis the biochip 1 , see Figure 1 , can be or is operated using, for example, the liquid providing apparatus 2 and the liquid receiving apparatus 3. Optical interrogation of the analysis is performed with the help of the at least one optical system 4 that provides/emits and/or collects electromagnetic radiations5.
  • the measurement device or biochip 1 comprises or consists of several parts some of which are depicted on Figure 2.
  • the support piece 6 may constitute the base of the biochip 1 .
  • the support piece 6 can be made of a variety of materials such as one or more of a thermo- injectable polymer, glass or metal.
  • a layered optical coating (that is the optical structure/passive optical device) OD that may be in direct or indirect contact with the support piece 6.
  • the optical coating OD can either be deposited directly on the support piece 6 or on a substrate (e.g. a glass piece) that is itself deposited onto the support piece 6.
  • the optical coating OD includes an optical microcavity OM.
  • the optical coating OD can be covered (fully or partially) with the adhesion layer 8 that is dependent on the biological specimen 119 under investigation or to be investigated. It can, for example, comprise or consist of a positively-charged coating, an epoxy-coating, an amine- coating, a hydrophobic coating, a nitrocellulose coating, a hydrophilic coating, an aldehyde coating, an avidin coating, a biotin coating, an active-ester coating, or any other coating that would help the adhesion of the biological sample 119 of interest.
  • the biological specimen 1 19 is located on top of this assembly 8, in the fluidic channel or chamber 10. In the case where the device 1 includes a plurality of fluidic channels or chambers 10, each channel or chamber may include a different adhesion layer 8.
  • the fluidic chamber or channel 10 allows for the immersion of the specimen 1 19 in one or a sequence of liquids such as biochemical or staining agents.
  • the specimen 119 includes, for example, either natural or externally added light emitting or scattering elements that can be detected using the interrogation radiation 5.
  • the optical coating OD may define or delimit (at least partially or fully) the fluidic channel or chamber 10.
  • the optical coating OD may define or delimit a first side/wall or floor 21 of the fluidic channel or chamber 10.
  • the biochip 1 is covered, for example, with a translucid, optically thin, cover layer 111.
  • the cover layer 1 11 may define or delimit (at least partially or fully) the fluidic channel or chamber 10.
  • the cover layer 1 11 defines or delimits a second side/wall or ceiling 23 of the fluidic channel or chamber 10, the first and second sides or walls 21 , 23 being opposite to one another.
  • the cover layer 11 1 comprises or consists of one or more materials chosen so as to minimize or fully avoid autofluorescence, to minimize or fully avoid absorption, to minimize or fully avoid scattering of the measurement light provided to the device 1 and/or the light reflected back from the optical structure OD or scattered or emitted back from the specimens 119.
  • the cover layer 11 1 may, for example, comprise or consist of glass, fused silica, quartz or a polymer.
  • the cover layer 111 may, for example, have a thickness between 0.05mm and 1 mm.
  • the height/thickness H of the channel 10 and the thickness of the cover layer 111 may, for example, be chosen so as to ensure high resolution optical imaging.
  • the thicknesses may, for example, be defined so that advantages of the microcavity-based optical coating OD permitting the passive electromagnetic control of light emitting or scattering species present in the biological specimens are preserved.
  • the thickness (Z-direction) and/or material of the cover layer 11 and/or the thickness (Z-direction) and/or of the channel 10 can, for example, be varied to tune a surface electric field located in the fluidic channel or channels 10 at or in proximity of the location of the specimens 119.
  • the fluidic channels or chamber 10 are, for example, formed (see Figure 3) with the help of the spacing layer 12 that comprises hollow regions 25. Liquids are fed to the fluidic chamber or channels 10 with the help of the inlets 13, for example, either in the support piece 6, which is the most convenient, or the cover layer 11 1. This can alternatively be done laterally.
  • the spacing layer 12 may, for example, comprises or consists of one or more materials chosen so as to minimize scattering of the measurement light and/or minimize light emission from the material of spacing layer 12 that may deteriorate detection of the light signal under measurement.
  • the spacing layer 12 may, for example, comprise or consist of glass, fused silica, polymer, or metal.
  • the spacing layer 12 may, for example, have a thickness between 1 pm and 1000pm.
  • the cover layer 111 may be removable or a part of the cover layer 111 may be removable to provide an upper access to the fluidic channel or chamber 10. Where part of the cover layer 11 1 is removable, the device 1 or cover layer 111 may, for example, include a lid (not shown) that is fully reversibly removable, or alternatively a lid configured to move between (i) an open position permitting access to the fluidic channel or chamber 10, and (ii) a closed position closing or sealing the fluidic channel or chamber 10.
  • the device 1 or cover layer 11 1 also includes the opening extending fully through the cover layer 11 1 into the fluidic channel or chamber 10. The opening has, for example, a surface area smaller than the surface area delimited by the cover layer 1 11.
  • the lid has, for example, a complementary form to that of the opening to assure a closure or sealing of the opening.
  • the lid allows an entity or specimen to be introduced through the opening into the fluidic channel or chamber 10 from the top of the device 1.
  • the opening is, for example, in addition to the fluidic communication inlets 13 and outlets 33 of the device 1 .
  • the optical structure or coating OD (see, for example, Figure 4) comprises or consists of three main parts: a first mirror 9, that is for example in contact with the support piece 6 or the deposition substrate, an intermediate layer IL that acts as or defines the optical cavity, and a second mirror 11 that is located on top of the intermediate layer IL.
  • the optical cavity defines or consist of an optical microcavity configured to allow passive electromagnetic control of light emitting or light scattering species present in a specimen 1 19. Exemplary optical structures OD are described in detail below.
  • Figures 5A and 5B depicts two possible exemplary configurations for the biochip or device 1 .
  • the top configuration illustrates a single fluidic chamber 10 configuration.
  • the black areas correspond to the spacing layer 12 and delimitate the contours of the fluidic chamber 10.
  • the white areas indicate the inlets 13 / outlets 23 and periphery of the flow chamber 10, while the grey area corresponds to the central part of the fluidic chamber located above the optical coating OD.
  • the biological specimen 119 for example a tissue microsection, is located at the centre of the chamber 10, precisely above the optical coating region OD and, for example, in an optical measurement region R of the biochip 1 .
  • the bottom configuration ( Figure 5B) shows a multiple fluidic channel configuration.
  • the black regions correspond to the edges of the channels 10.
  • the white and grey areas correspond to the hollow regions 25 (inlets, outlets, channels, incubation regions) where the liquids and reagents can flow.
  • the grey areas specifically indicate the regions located above the optical coating OD, and, for example, in an optical measurement region R of the biochip or device 1.
  • the optical coating layer OD can be etched or engraved, for example with a laser or a photolithographic process.
  • the engraved features 37 can be used as means to ensure quality control through the production lot tracking, indicate the optical coated surface in the view of the chip assembly 1 , and most importantly as distinctive landmarks that can be used to reconstruct a whole slide or sample image from individually acquired, smaller frames (see Figure 6).
  • the optical coating layer OD for example includes the markings or structures 37, for example, boundary markings.
  • the markings or structures 37 may be visible to the naked eye and/or can be imaged/recorded by the optical system 4.
  • FIG. 7 An image of an exemplary implementation of the herein described biochip or device 1 can be seen in Figure 7.
  • the configuration shown in this case is that of a four-channel biochip 1 .
  • the optical coating OD regions are clearly distinguishable within the fluidic channels 10 owing to their shiny appearance.
  • the spacing layer 12 appears as a diffuse aspect.
  • Figure 8 shows a comparison between fluorescence readouts achieved using a microcavitybased optical coating OD (left) versus a standard glass substrate (right).
  • a solution of fluorescently-labelled proteins 1 19 is spotted on each of the support pieces. Fluorescence imaging of both samples is performed using the same apparatus and identical imaging conditions. The enhancement provided by the microcavity-based optical coating OD is confirmed by the increased signal strength.
  • the present disclosure also concerns a measurement method.
  • the measurement device 1 is provided for carrying out measurements.
  • the device 1 may be provided with or without the adhesion Iayer 8.
  • an adhesion layer 8 may be provided on a surface of the fluidic channel or channels 10. This can be done for example by introduction of elements to form the adhesion layer 8 in a liquid flowed into the fluidic channels 10 via the inlet 13, or introduced via the removable cover layer 111 (or the lid thereof).
  • the measurement device 1 can, for example, be adhesion layer-less or adhesion layer free.
  • One or more specimens 119 can then be introduced into the fluid channel or channels 10 in the same manner.
  • the adhesion layer 8 and/or the at least one specimen 119 is, for example, provided to the fluidic channel or channels 10 using the liquid providing apparatus 2 and/or the liquid removal apparatus 3.
  • Electromagnetic radiation 5 is provided by the optical device 4 to the measurement device 1 through the cover layer 111. Electromagnetic radiation 5 is collected from the measurement device 1 , the received electromagnetic radiation emanating, being emitted or scattered from the measurement device 1 , from the specimen or specimens 119, and/or from the optical structure OD.
  • the measured signals or data is processed and analysed by the processing/analysis means 41 , 43.
  • the adhesion layer 8 and/or the specimen or specimens 119 may be removed from the fluidic channel or channels 10 using the liquid receiving apparatus 2 and/or the liquid removal apparatus 3.
  • the optical structure or coating OD may comprise or consist of three main parts: the first mirror 9, that is for example in contact with the support piece 6 or the deposition substrate, an intermediate layer IL that acts as or defines the optical cavity, and a second mirror 11 that is located on top of the intermediate layer IL.
  • the optical coating or structure OD can, for example, comprise or consist of any one of (or any combination thereof) the optical structures described in patent application WO 2020/183341 entitled SURFACE-BASED LUMINESCENCE MEASUREMENT SUBSTRATE, PCT APPLICATION n° PCT/IB2020/052019 filed on March 9, 2020 fully incorporated herein by reference.
  • the optical cavity defines or consist of an optical microcavity configured to allow passive electromagnetic control of light emitting or light scattering species present in the specimen 119 or any other technical effect.
  • the optical structure OD (see, for example, Figure 4) includes at least one or a plurality of optical cavity layers 7, the first optical mirror 9 and the second optical mirror 11.
  • the optical structure OD comprises or consists of, for example, a multilayer coating.
  • the first and second optical mirrors 9, 11 contact (directly or indirectly) and enclose the optical cavity layer 7 and defining an optical cavity or optical microcavity.
  • the first optical mirror 9 and the second optical mirror 11 are attached or fixed to the optical cavity layer 7 to sandwich the optical cavity layer 7 between the first and second mirrors 9, 1 1.
  • the optical cavity layer 7 may directly contact either or both of the first and second mirrors 9, 11 .
  • the adhesion layer or coating 8 may be provided on for example on the second or top mirror 11 .
  • the first mirror 9 defines a bottom mirror located below the second or top mirror 11 .
  • the adhesion layer or coating 8 is external to the optical cavity.
  • the adhesion layer or coating 8 can be in direct or indirect contact with the top mirror 11 .
  • the optical cavity layer 7 or the optical cavity may, for example, be devoid of electromagnetic radiation emitting markers or labels, and/or devoid scattering particles or light scattering species.
  • the optical cavity layer 7 or the optical cavity is, for example, an electromagnetic radiation emitting marker-free layer or marker-free cavity, or a scattering species-free cavity.
  • the optical cavity layer 7 comprises or consists of, for example, a solid substance.
  • the optical cavity layer 7 is, for example, a solid-state cavity layer.
  • the optical cavity layer 7 or the optical cavity may, for example, be impermeable to electromagnetic radiation emitting markers.
  • the optical cavity layer 7 or the optical cavity may define a closed substance and markers or labels cannot be inserted into the optical cavity layer 7 or the optical cavity.
  • the optical structure OD is, for example, configured to receive markers or labels on an outer surface of the optical structure OD.
  • the optical cavity layer 7 thickness and constituent material define an optical microcavity and the measurement device 1 includes an optical microcavity OM.
  • the thickness of the cavity layer 7 is, for example, in the micrometre or nanometre range.
  • the first and second mirrors 9, 1 1 may also, for example, be devoid of electromagnetic radiation emitting markers or labels inside the constituent material of the mirrors.
  • the first and second mirrors 9, 11 and the cavity layer 7 may for example define a multilayer coating located on the support piece 6.
  • the measurement device 1 defines a vertical cavity device or structure in which the optical cavity or resonator is defined in a vertical direction or between the top and bottom of the optical structure OD, where the vertical direction is defined by the direction of layer superposition of the layers of the measurement device 1 .
  • the first optical mirror 9, the second optical mirror 1 1 and the optical cavity layer 7 define a vertical optical cavity structure.
  • the optical cavity layer 7 may for example delimit a layer thickness de (in the vertical direction) defining at least one or a plurality of spectral features or spectral dips 121 in reflectance from the measurement device 1 (see, for example, the exemplary profile of Figure 9). For example, one, two, or three spectral features 121 may be present.
  • the reflectance is measured in the vertical direction.
  • the layer thickness value de of the optical cavity layer 7 to locate the spectral feature(s) at (a) targeted wavelength(s) or within a wavelength range will of course be determined by the material of the cavity layer 7 and the refractive index of that material.
  • the spectral feature(s) or spectral dip(s) 121 is/are generated or defined by the optical cavity and the optical cavity layer 7.
  • the spectral feature(s) or spectral dip(s) 121 is/are present in a wavelength range of the reflectance from the measurement device 1 .
  • the spectral feature or spectral dip 21 defines a U-shaped feature or a feature whose reflectance value firstly decreases to a minimum or lowest value before then increasing in value as a function of wavelength.
  • the spectral feature 121 is associated with or corresponds to a resonance of the optical cavity.
  • the spectral feature is, for example, a cavity resonance spectral feature or dip.
  • the optical cavity layer 7 may, for example, delimit a layer thickness de defining at least two such spectral features 121 simultaneously generated in the reflectance wavelength profile with at least one or only one reflectance band 123 defined between the at least two such spectral features 121.
  • the reflectance band 123 defines, for example, an inverted U-shaped reflectance profile or one that, between the at least two such spectral features 121 , increases as a function of wavelength, increases at a smaller rate, decreases and then decreases at a faster rate.
  • the mirrors 9, 1 1 and the optical cavity layer 7 may be configured, for example, to define a reflectance band 123 whose full-width half maximum FWHM reflectance wavelength range includes at least one scattering wavelength or emission wavelength of the electromagnetic radiation emitting markers or species, or a plurality (at least two) of scattering wavelengths or emission wavelengths of different electromagnetic radiation emitting markers or species.
  • the at least one spectral feature 121 is for example offset in wavelength from a scattering wavelength or an (peak) emission wavelength of the electromagnetic radiation emitting marker or markers destined to be used or being used.
  • the at least one spectral feature 121 is for example offset in wavelength from the excitation wavelength of the marker or markers, or scattering species.
  • the at least one spectral feature 121 is for example offset in wavelength by at least 10 nm, or at least 20 nm, or at least 30 nm or at least 40 nm or at least 50 nm from a scattering wavelength or an (peak) emission wavelength of the electromagnetic radiation emitting marker or markers. This advantageously assures that emitted light from the markers is strongly reflected.
  • the optical cavity layer 7 may delimit, for example, a layer thickness de defining at least one or a plurality of spectral features or spectral dips 121 in reflectance from the measurement device 1 at a wavelength or wavelengths for example within the range ⁇ 1500nm and >190nm, or ⁇ 900nm and > 190nm.
  • the optical cavity layer 7 may for example delimit a layer thickness de defining at least one spectral feature or spectral dip 21 in reflectance from the measurement device 1 at wavelength ⁇ 1500nm and > 190nm, or ⁇ 900nm and > 190nm, or ⁇ 850nm and > 250nm, or ⁇ 850nm and
  • the optical cavity layer 7 may delimit for example a layer thickness de defining a first spectral feature or spectral dip 121 in reflectance from the measurement substrate 1 at wavelength ⁇ 850nm and > 250nm, or ⁇ 850nm and > 400nm, or ⁇ 700nm and > 350nm, or ⁇ 600nm and > 400nm, or ⁇ 650nm and > 500nm, or ⁇ 700nm and > 550nm; and a second spectral feature or spectral dip 121 separated from the first spectral feature or spectral dip 121 by between 50nm and 400nm, or between 300nm and 400nm, or between 200nm and 300nm, or between 100nm and 200nm, or between 50nm and 100nm.
  • the second spectral feature is for example at a longer wavelength.
  • the reflectance being measured at 0° incident angle of the measuring light or a 5° incident angle or a 10° incident angle or a 15° incident angle.
  • the spectral feature or spectral dip 121 is, for example, a cavity resonance or generated by a cavity resonance.
  • the presence of the at least one spectral feature 121 assures, for example, a faster and simpler quality control of the fabricated measurement devices 1 .
  • the optical cavity layer 7 may, for example, comprise or consist solely of a material or materials having an emission profile that is non-emitting or only weakly emitting at the emission wavelength peak or line of the electromagnetic radiation emitting marker or markers, or at the scattering wavelengths.
  • the optical cavity layer 7 may, for example, comprise or consist solely of a material or materials having an emission profile that is non-emitting or only weakly emitting at the cavity resonance wavelength.
  • the optical cavity layer 7 or the optical cavity can be, for example, a luminescent material-free layer or cavity; or a quantum well-free layer or cavity; or a quantum dot-free layer or cavity.
  • the first optical mirror 9 and/or the second optical mirror 11 may, for example, comprise or consist solely of a single layer S, a stack of two layers T or a periodic stack of multiple layers P (see, for example, Figures 10 to 12).
  • the layers may, for example, comprise or consist of a dielectric, insulating or metallic material.
  • the first optical mirror 9 and/or the second optical mirror 11 may, for example, comprise or consist solely of any combination of the following: a single layer S, a stack of two layers T or a periodic stack of multiple layers P.
  • the first optical mirror 9 and/or the second optical mirror 11 may, for example, comprise or consist solely of:
  • the first and the second optical mirrors 9, 11 may, for example, have the same or a different central design wavelength.
  • the optical cavity layer 7 has a thickness and refractive index value defining a resonance at a cavity resonance wavelength Ac and the resonance can, for example, be detuned or nondetuned relative to a central design wavelength of the first and/or the second optical mirrors 9, 11.
  • a thickness of the optical cavity layer 7 may be, for example, greater than or less than a thickness of any one of the constituent layer or layers of the first and/or second mirrors 9, 11.
  • the measurement device 1 may, for example, comprise or consist solely of an arrangement of alternating layers having a central design wavelength outside of a reflection band or reflection stop-band wavelength range of the first and/or second mirrors 9,11 .
  • the multilayer coating 219 may comprise or consist of, for example, a sequence of layers made of materials having alternatively a high and a low refractive index.
  • the materials used may, for example, be fully transparent or do not display strong absorption lines in the spectral region where the measurement device 1 is destined to operate.
  • the materials used for the multilayer coating 19 may be chosen amongst the large choice of materials compatible, for example, with thin film deposition or growth techniques. This includes, but not limited to, for example: (i) oxide compounds such as silicon oxide, titanium oxide, aluminium oxide, tantalum pentoxide, zinc oxide, hafnium oxide, or (ii) nitride compounds such as silicon nitride, aluminium nitride, gallium nitride, or (iii) fluoride compounds such as magnesium fluoride, calcium fluoride, or (iv) chalcogenide compounds such as zinc selenide and zinc sulphide, or (v) intrinsic semiconductors such as silicon and germanium, or (iv) metals such as gold, silver or aluminium. This list is non-exhaustive and is not restricted to the exact stoichiometry of the compounds listed. Mixtures of the above families of compounds, for example oxynitrides materials, can also be utilized.
  • the materials can be deposited or grown using a variety of methods such as: (i) chemical vapor deposition techniques (CVD) for example plasma-enhanced chemical vapor deposition (PECVD), or (ii) evaporation techniques such as thermal evaporation, electron-beam evaporation, ion assisted evaporation, or (iii) sputtering techniques such as magnetron sputtering, ion-beam assisted sputtering, or (iv) molecular beam epitaxy.
  • CVD chemical vapor deposition techniques
  • PECVD plasma-enhanced chemical vapor deposition
  • evaporation techniques such as thermal evaporation, electron-beam evaporation, ion assisted evaporation
  • sputtering techniques such as magnetron sputtering, ion-beam assisted sputtering, or (iv) molecular beam epitaxy.
  • the bottom and top mirrors 9, 11 may for example comprise or consist of an arrangement of one or several layers of the materials listed or described previously.
  • a variety of configurations are possible for the realisation of the mirror 9, 11 such as the use of: (i) a single layer of a material displaying a large refractive index contrast with the neighbouring materials (e.g. silicon) or a thin metallic layer; (ii) a set of two layers (two-layer stack) of two distinct materials having two distinct refractive indices and whose thicknesses are chosen so as to satisfy an appropriate or predetermined phase relationship; (iii) a periodic repetition of a two-layer stack; (iv) a combination of the above (i), (ii) or (iii).
  • the mirror 9, 11 is constituted of or comprises at least one of or a combination of one or more of the following: a single layer s, a stack of two layers T and a periodic stack P.
  • a single layer s a stack of two layers T
  • a periodic stack P a large variety of mirror architectures for the top and/or bottom mirrors 9, 11 are thus possible, for example, S, P, T, SP, PS, STP, PST, etc.
  • a PTS mirror corresponds to a mirror consisting of, first a periodic stack (at the bottom), then a pair of layers and finally a single layer.
  • Each configuration (S, T, P) is characterized by a set of parameters: the choice of material(s) used, the thickness of each layer: s 0 for the S configuration, ti and t 2 for the T configuration, pi and p 2 for the P configuration.
  • the P-configuration is also characterized by the number of repetitions of the periodic stack N.
  • N the number of repetitions of the periodic stack N.
  • Figure 10 shows an exemplary mirror with a PTS architecture illustrating the design parameters.
  • DBR Distributed Bragg Reflector
  • the periodic arrangement is constituted of a repetition of a pattern of two layers.
  • the thickness of each layer (material 1) and d 2 (material 2) verifies the following phase relationship: is the central design wavelength of the mirror.
  • the most common approach to this design constraint is to choose d T and d 2 such that:
  • phase relationship can be written as: where K is a weighting parameter analogous to a duty cycle in electronics that verifies: 0 ⁇ K ⁇ 1.
  • K is a weighting parameter analogous to a duty cycle in electronics that verifies: 0 ⁇ K ⁇ 1.
  • This approach leads to different set of values for and d 2 .
  • the peak reflectivity of the mirrors is controlled by selecting the materials used and the number of lattice periods N constituting the mirror where N is a positive integer (/V > 1).
  • the bottom (M1) and top (M2) mirrors 9, 11 may not necessarily be designed using the same central design wavelength (A M1 A M2 ).
  • the cavity layer 7 may comprise or consist of one or several layers chosen, for example, among the afore-mentioned materials and whose thickness d c can be chosen to satisfy a constructive phase relationship and hence provide a resonance or spectral feature 21 .
  • n c is the refractive index of the cavity layer material
  • d c is the cavity layer thickness
  • a c is the central design wavelength of the cavity
  • C is a positive integer (C > 1).
  • a c can be chosen such that:
  • a c can be detuned compared to A M1 and/or A M2 (by, for example, detuned between 1 and 3 nm, or between 1 and 5nm, or between 1 and 10nm or between 10 and 50nm, or detuned by >50nm or >100nm) in order to tailor the reflectivity spectrum and/or response surface electric field of the measurement device 1 .
  • a cavity by introducing an arrangement of alternating layers similar to that of a Distributed Bragg reflector, having a central design wavelength chosen outside of the reflection band of the top and bottom mirrors 9,11 .
  • the optical cavity layer thickness d c can be chosen to provide the spectral feature or features 121 in reflectance from the measurement device 1 (see, for example, Figure 9) as well as the reflectance band 123.
  • the spectral feature or features 121 is associated with or correspond to a resonance of the optical cavity.
  • the optical layer 7 or the optical cavity is, for example, an active laser medium-free layer or an active laser medium-free cavity, or a light emitting diode active medium-free layer or an active light emitting diode medium-free cavity, or a quantum structure active medium-free layer or a quantum structure active medium-free cavity, or an electrical or optical pumping-free layer or an electrical or optical pumping-free cavity.
  • the cavity can include or consist of a material that is absorbing (an absorption coefficient a, where 1000000cm 1 > a > 0cm 1 , or 700000 cm 1 > a > 0cm 1 , or 500000 cm 1 > a > 0cm 1 , or 100000 cm 1 > a > 0cm 1 ) or alternatively a material, non-absorbing at or near (within at least 3nm or 5nm or 10nm or 15nm or 25nm or 30nm or 40nm or 50nm or 60nm or 75 nm or 100nm thereof) the scattering wavelength or the wavelength of emission of the luminescent object or marker or markers, and/or the cavity resonance wavelength.
  • the material for example does not display any absorption line such as an electronic transition in the vicinity of the wavelength of interest.
  • the light emitters e.g. a luminescent material, a quantum well, quantum dots
  • the measurement substrate 1 of the present disclosure is a non-cavity light emission device.
  • the optical cavity layer 7 may comprise or consist solely of a material or materials having an emission profile that is non-emitting at the emission wavelength peak or line of the electromagnetic radiation emitting marker or markers and/or at the cavity resonance wavelength as defined in the reflectance of the measurement device 1 .
  • the optical cavity layer 7 may comprise or consist solely of a material or materials having an emission profile that is non-emitting within a FWHM wavelength range of the emission wavelength profile of the electromagnetic radiation emitting marker or markers and/or nonemitting within a FWHM wavelength range of the cavity resonance 121 .
  • the optical cavity layer 7 may comprise or consist solely of a material or materials having an emission wavelength range that is non-overlapping with a scattering wavelength or an emission wavelength range of the electromagnetic radiation emitting marker or markers and/or is non-overlapping with a wavelength range or a FWHM wavelength range of the cavity resonance wavelength.
  • the cavity layer 7 can be significantly thickerthan layers used for the realisation of the mirrors 9, 11 .
  • the cavity layer 7 is necessarily embedded in between the two mirrors 9, 1 1.
  • a non-limiting further exemplary of the optical structure OD is shown in Figure 12.
  • the device consists of a glass support 17, on top of which a multilayer coating 219 is deposited by means of plasma-enhanced chemical vapor deposition (PECVD).
  • the multilayer coating 219 is composed of alternating amorphous silicon (aSi) and silicon oxide (SiO2) layers.
  • the bottom mirror 9 (M1) follows a S-type configuration and consists in a single amorphous silicon layer.
  • the cavity layer 7 consists in a single thick silicon oxide layer.
  • the top mirror 11 (M2) follows a T-type configuration and consists in a single pair of layers verifying a quarter-wave stack relationship.
  • the main design criteria are the low number of layers which advantageously ensures a minimization of the manufacturing cost and the use of amorphous silicon as an inexpensive, abundant, well-established and high refractive index material.

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Abstract

La présente invention concerne un dispositif de mesure comprenant au moins un canal fluidique pour fournir au moins un échantillon dans au moins un liquide à au moins une région de mesure optique du dispositif de mesure; et au moins une structure optique en contact avec le ou les canaux fluidiques, la structure optique définissant une microcavité optique.
PCT/IB2021/058207 2020-09-09 2021-09-09 Dispositif de mesure ou biopuce comprenant une microcavité optique WO2022053971A1 (fr)

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EP2522981A1 (fr) * 2011-05-09 2012-11-14 Universiteit Twente Système de détection par lumière 2D compact pour une analyse sur puce
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WO2020183341A1 (fr) 2019-03-08 2020-09-17 Ecole Polytechnique Federale De Lausanne (Epfl) Substrat de mesure de luminescence basée sur la surface

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US9103787B2 (en) * 2010-05-25 2015-08-11 Stmicroelectronics S.R.L. Optically accessible microfluidic diagnostic device
EP2522981A1 (fr) * 2011-05-09 2012-11-14 Universiteit Twente Système de détection par lumière 2D compact pour une analyse sur puce
WO2020052019A1 (fr) 2018-09-13 2020-03-19 惠科股份有限公司 Substrat de réseau et panneau d'affichage
WO2020183341A1 (fr) 2019-03-08 2020-09-17 Ecole Polytechnique Federale De Lausanne (Epfl) Substrat de mesure de luminescence basée sur la surface

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