WO2009021964A2 - Plate-forme de biopuce optique dotée d'une structure plasmonique - Google Patents

Plate-forme de biopuce optique dotée d'une structure plasmonique Download PDF

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Publication number
WO2009021964A2
WO2009021964A2 PCT/EP2008/060621 EP2008060621W WO2009021964A2 WO 2009021964 A2 WO2009021964 A2 WO 2009021964A2 EP 2008060621 W EP2008060621 W EP 2008060621W WO 2009021964 A2 WO2009021964 A2 WO 2009021964A2
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Prior art keywords
optical
chip
excitation
optical element
operably
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PCT/EP2008/060621
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English (en)
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WO2009021964A3 (fr
Inventor
Brian Maccraith
Michal Trnavsky
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Dublin City University
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Publication of WO2009021964A3 publication Critical patent/WO2009021964A3/fr

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    • 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
    • G01N21/648—Specially adapted constructive features of fluorimeters using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
    • 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
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • 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
    • G01N21/6452—Individual samples arranged in a regular 2D-array, e.g. multiwell plates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G01N33/54373—Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Definitions

  • This present disclosure relates to luminescent sensors and particularly to luminescent sensors which are configured such that operably plasmonic effects contribute to the output of the sensors.
  • an optical sensor which operably provides an output signal resultant from an excitation of a detection moiety to generate a first signal and an enhancement of that first signal by surface plasmon coupled excitation effects.
  • the invention also provides an optical biochip platform with plasmonic structure for detecting fluorescence or other luminescent signals and optical sensor configurations or systems that utilize an optical chip.
  • Luminescent sensors which are based on detection of an optical signal emitted upon excitation of a detection moiety are known. Based on the specifics of the detection moiety chosen and the nature of the excitation source used, these sensors may be used to detect the presence of one or more analytes.
  • Such a sensor includes an optical element having a recognition area coated with a semi-transparent metallic film and a detection or capture moiety responsive to the presence or otherwise of predetermined analytes. By exposing the optical element to an environment, one or more of the predetermined analytes will bind to the detection moiety to form a complex that is optically linked or coupled to the optical element.
  • the complex provided by the combination of the capture moiety with the desired analyte may include a luminophore.
  • a further treatment of the capture moiety/analyte complex may be required so as to effect a binding of a luminophore thereto.
  • An example of a typical complex will include a sandwich assay wherein the analyte being detected is provided between two antibodies in a complex structure.
  • the excitation of the luminophore through for example surface plasmon resonance and the efficient collection of generated luminescence through surface plasmon coupled emission.
  • the metallic film is provided on an upper surface of the optical element and the excitation is from below; this serves to effect generation of a luminescence output through surface plasmon resonance, the luminescence signal generated being coupled back into the optical element through surface plasmon coupled emission.
  • the excitation is from above the detection moiety and the plasmon effects provide for enhanced capture of the generated luminescence; a generated signal being coupled into the optical element by surface plasmon coupled emission.
  • excitation may be effected through exposure of the optical element to an optical excitation source which may be provided either above or below the optical element.
  • excitation may be provided by forming a complex having an electro-chemi-luminescent tag and effecting a subsequent electro-chemi-luminescent excitation of that optical element.
  • the optical element is desirably substantially paraboloid in form, having side walls extending upwardly from a planar substrate.
  • a structure may be considered as being the resultant surface obtained by revolving a parabola around its axis.
  • the paraboloid, or other three dimensional form has a truncated upper surface such that the side walls are separated at the top of the optical element by a substantially planar surface.
  • the recognition area is provided on this upper planar surface of the optical element, separated from the substrate by the side walls of the optical element.
  • the plurality of optical elements share a common substrate.
  • the optical element is desirably a solid structure configured to operate by total internal reflection in order to convert the strong intensity maximum emitted by the excited analyte/detection moiety from large surface angles into collimated and conveniently detectablejays along the optical axis.
  • the optical element will desirably preferentially direct light that enters into the optical element from the recognition area at an angle greater than or equal to the critical angle of the macroscopic elements forming the sensing environment, downwardly through the optical element for detection below the optical element.
  • the macroscopic elements defining the sensing environment are typically the materials used for fabrication of the optical element- such as glass or a polymer- and the aqueous environment where the sensor is used. For a glass water interface this is about 61 degrees.
  • An optical element that may usefully be employed is desirably formed of a polymer having a refractive index greater than that of water. In this way the optical element may typically be fabricated using injection moulding techniques.
  • Useful polymers have a refractive index of about 1.45-1.65, an example of which being ZEONEXTM which has a refractive index of about 1.52.
  • the optical element By configuring the optical element to totally internally reflect light it is possible, when illuminating the optical element from below, to effect generation of evanescent waves along the boundary surface between optical element and the medium where it is located. These evanescent waves contribute to the generation of surface plasmon resonance which can be used to effect excitation of the detection moiety.
  • Suitable detection moieties are any molecules that specifically bind to an analyte of interest and include, for example, antibodies and oligonucleotides. Where a plurality of optical elements are provided, individual ones of the plurality may comprise the same or different detection moieties depending upon the application.
  • the detection moiety is desirably optically coupled to the optical element.
  • optically coupled when referring to the relationship between a moiety and an optical element, includes but is not limited to luminescent molecules directly bound to or adsorbed onto the optical element; luminescent molecules indirectly attached to the optical element through one or more linker molecules; luminescent molecules entrapped within a film (e.g., a polymer or sol-gel matrix) that is coated onto the optical element; a non-luminescent molecule that is capable of binding to a luminescent molecule of interest.
  • a particular preferred type of optical coupling that may be employed within the context of the present teaching is a covalent attachment to the substrate.
  • the detection moiety itself exhibits a preference for binding to specific target analytes within the detection medium- typically an aqueous medium.
  • the resultant structure or complex may in itself be capable of exhibiting luminescence on excitation.
  • a secondary label may be required, typically a secondary antibody, to create the necessary structure capable of luminescence on excitation.
  • the complexes that are optically coupled to the optical element may be configured to have distinguishable spectral emission properties such that the output of a first optical element may be spectrally distinguished from the output of a second optical element.
  • Figure IA shows an example of the angular distribution of radiation data of a plasmon-coupled fluorescence, with the specifics of the data illustrated being representative of an air/glass interface and SiO 2 lOOnm spacer layer.
  • Figure IB is a schematic showing the propagation of light into an optical element that does not have such a plasmonic enhancement, as is provided by the prior art.
  • Figure 1C shows is a schematic showing how plasmonic enhancement preferentially directs light within a prescribed angular distribution into the optical element, in accordance with the teaching of the present invention.
  • Figure 2 is a schematic of an optical element provided in accordance with the present teaching.
  • Figure 3 shows a sensor array including a plurality of optical elements.
  • Figure 4 is a schematic showing light paths within a structure such as provided in Figure 3.
  • Figure 5 is schematic showing selective excitation of the optical elements from above in a manner that allows for individual optical elements to be illuminated differently to other optical elements.
  • Figure 6 is a schematic showing how a broad illumination may be used to concurrently illuminate a plurality of optical elements in the same array.
  • Figure 7 is a schematic showing how the excitation source may be angularly offset from the optical array.
  • Figure 8 is an example of an experimental chip having individual optical elements arranged to preferentially target specific analytes.
  • Figure 9 shows results from the use of the chip of Figure 8.
  • an array of optical elements are provided each of which is configured to provide for enhancement of the optical output through a combination of plasmonic effects including surface plasmon resonance and surface plasmon coupled emission.
  • plasmonic enhancement may be effected by incorporating onto individual ones of the optical elements, a semistransparent metallic film and a spacer layer so as to provide means for enhanced excitation via surface plasmon resonance (SPR) and/or collection of the resultant signal using surface -plasmon coupled emission (SPCE).
  • SPR surface plasmon resonance
  • SPCE surface -plasmon coupled emission
  • Such an optical element may also be geometrically configured to preferentially discriminate the angular distribution of light propagating into the optical element, such as is provided by configurations that are optimized to take advantage of supercritical angle fluorescence phenomena.
  • the incorporation of a plasmonic enhancement phenomenon into a highly efficient collector of a surface-generated fluorescence from a biochip can provide highly efficient optical elements which have application in detection of small amounts of analytes.
  • Each of the techniques involved act independently, without causing any limitation to each other, and an optical element as provided in accordance with the teaching of the present invention may provide a highly sensitive device useful in particular in biomedical diagnostic application.
  • an optical biochip platform By having a plurality of optical elements on a shared substrate, an optical biochip platform is provided that may be used in a wide variety of commercial applications that require a compact, highly sensitive device.
  • the optical biochip platform is suitable for fast, accurate readout from micro-arrays with high sensitivity. No bioassay device based on conjunction of plasmon-enhanced fluorescence and efficient fluorescence collection is currently available.
  • An optical element that may be usefully employed within the context of the present disclosure is one which preferentially allows for propagation of light derived from plasmonic effects into the optical element for subsequent detection.
  • plasmonic effects it is possible to deliver a highly collimated light cone into the optical element.
  • fluorescence emission 100 fluorescence being a specific type of luminescence
  • a substrate as derived from excitation of a luminescent source 105 is highly directional with respect to the polar angle of the substrate surface and the angular distribution of radiation is relatively narrow .
  • the specific figures or values shown are related to the nature of the substrate and the medium within which it is placed.
  • the generated fluorescence which is derived from excitation of a source on the surface of the substrate 120 propagates at a highly contained angle of about 62 degrees.
  • Figure IB shows in schematic form a prior art arrangement which is not configured to include enhanced plasmonic effects.
  • excitation of a source 105 effects generation of a fluorescent signal 125 that will propagate into the substrate at angles about the critical angle ⁇ c of the system.
  • Figure 1C is similar to Figure IA but shows the comparable arrangement of Figure IB modified to provide for plasmonic effects. It will be appreciated that the resultant propagation- which may be traced back to a surface plasmon coupled emission effect (SPCE), is at an angle, Bm 1n , greater than the critical angle, ⁇ c ⁇ ticai.
  • SPCE surface plasmon coupled emission effect
  • the optical geometry of the optical element within which the fluorescence is introduced is selected to preferentially allow for propagation of light introduced at angles greater than the critical angle, i.e is of the type that is optimized for detection of light resultant from the super critical angle fluorescence (SAF) phenomena that such a geometry will also be suitable for detection of SPCE effects.
  • SAF super critical angle fluorescence
  • the range of angles of SPCE is a sub-manifold of the SAF effects.
  • the present disclosure is directed to a design to optimize the performance of a luminescent, typically fluorescence-based, biosensor that integrates a plasmonic structure into a low-cost, mass-producible optical biochip.
  • a luminescent system is provided which couples an optical biochip contains an array of paraboloid or other suitably dimensioned optical elements with an excitation source.
  • an optical element is provided in an environment or medium where potential analytes are to be found. This is typically an aqueous environment and operably could be provided as part of a flow through system.
  • Target analytes within the medium will preferentially bind with or couple to the detection moiety so as to form a sandwich arrangement.
  • This sample may be capable of luminescence in its own right or may require a secondary label such as an antibody which will then adhere to the detection moiety/analyte combination.
  • a secondary label such as an antibody which will then adhere to the detection moiety/analyte combination.
  • Collectively these structure can be categorized as complexes having as a component element lumiphores or a luminophore or in more specific examples fiuorophores; the category indicating the ability to exhibit luminescence or fluorescence on excitation. In either scenario once the optical element has been exposed for a sufficient time period to allow the formation of such structures, subsequent excitation will provide for generation of a luminescence output which be detected to provide evidence of the presence of the analyte within the test medium.
  • the excitation source is an optical excitation source and is arranged below the optical element it is possible, in accordance with the present teaching to provide for generation of evanescent waves at the boundary between the optical element and the acqueous environment to provide for surface plasmon resonance which can be used to induce excitation of the sample.
  • a plasmonic structure comprising a semi-transparent metallic film and a spacer layer formed on an optical element substrate provides a means for enhanced excitation via surface plasmon resonance (SPR) and enhanced collection of that luminescence through surface-plasmon coupled emission (SPCE).
  • SPR surface plasmon resonance
  • SPCE surface-plasmon coupled emission
  • optical element geometry that may be usefully employed within the teaching of the present invention is described in US Application No. 11/431,349, MacCraith et al., which is incorporated herein by reference.
  • a plurality of solid parabolic optical elements are provided on a shared substrate so as to provide a chip.
  • the geometry of the individual parabolic or indeed paraboloid elements on the chip are designed to facilitate both efficient excitation of surface-bound analyte molecules and collection of surface-generated fluorescence emitted above the critical angle of respective dielectric interface (supercritical angle fluorescence).
  • an optical element 200 in the form of a solid paraboloid structure having side walls 205 extending upwardly from a planar substrate 210 is provided.
  • a planar top surface 215 which separates the two side walls is provided. This planar surface is desirably parallel with the surface of the substrate.
  • This optical element is shown as being bottom illuminated in that excitation light 220 enters the optical element through the substrate.
  • a recognition area 216 is provided on the top or upper surface of the optical element.
  • the optical element 200 is desirably a solid structure configured to operate by total internal reflection in order to efficiently collect the strong intensity maximum emitted by the excited complex of the analyte/detection moeity and received into the optical element.
  • the generated fluorescence signal is desirably detected by a detector provided below the substrate. 210.
  • an annular aperture 240 may be provided below a bottom surface 211 of the substrate 210 to ensure that light entering the detecting surface at an angle less than the critical angle impinges on the aperture. It will be understood that as surface plasmon coupled emission preferentially directs light having an angle greater than or equal to the critical angle, that the use of such an aperture is not essential.
  • the recognition area 216 is modified to provide for enhanced plasmonic effects.
  • the recognition area of the parabolic elements is coated with a thin semi transparent metal film 250 ( ⁇ 50nm, e.g. silver, gold, aluminum) and a thin dielectric spacer layer 251 (oxide, polymer film, polyelectrolyte multilayer etc.) with required thickness and dielectric constants.
  • a detection moiety 253 is optically coupled to the optical element and is capable of binding with or tagging to a suitable analyte.
  • Suitable detection moieties are any molecules that specifically bind to an analyte of interest and include, for example, antibodies and oligonucleotides.
  • individual ones of the plurality may comprise the same or different detection moieties depending upon the application.
  • subsequent excitation will generate a luminescent response from those detection moieties that have formed complexes including luminophores.
  • the metal film 250 enhances the excitation intensity via the surface plasmon resonance (SPR) wave generated at the interface by a light source such as a focused laser beam with appropriate polarization.
  • SPR surface plasmon resonance
  • the generated SPR can then induce an excitation response from the luminophore component of the complex provided.
  • the system polymer-metal film- spacer-ambient medium selects the range of excitation angles according to its reflection curve.
  • the excitation light intensity above the film is strongly enhanced.
  • the level of enhancement will depend on the specific s of the structure including for example the thicknesses and nature of the materials used.. This local enhancement can be used to excite a surface bound fluorescence analyte with high efficiency. The proximity of the sample to the metal has also strong influence on the fluorescence emission properties.
  • the fluorescence emission is highly directional with respect to the polar angle of the substrate surface and the angular distribution of radiation shows a very narrow maximum around the plasmon resonance angle
  • the dielectric space layer 251 between metal 250 and the sample surface is required in order to avoid quenching of the fluorescence which occurs at metal-fluorophore distances below IOnm.
  • This, so called surface-plasmon coupled emission (SPCE) is very surface-specific; thus effectively suppressing fluorescence generated within a bulk of a sample.
  • the generated luminescence is coupled into the optical element within a narrow optical angular range.
  • One of the key issues is the choice of the spacer layer thickness in order to maximize the detectable fluorescence intensity, i.e., attain a trade-off between SPR excitation and plasmon- coupled intensity.
  • the appropriate choice of the spacer thickness is also required to tune the emission maximum to range of angles collectable by the parabolic element.
  • FIGs 3 and 4 show an alternative configuration for optical elements that may be provided in accordance with the teaching of the present disclosure.
  • a biochip 300 is provided comprising an array of a plurality of individual optical elements 305, each being formed from a truncated cone structure.
  • the optical elements are upstanding from a common substrate 310 and are typically formed from a plastic material so as to enable fabrication using moulding techniques.
  • a recognition surface or area 315 may be provided on an upper 316 surface of each of the optical elements, the upper surface 316 being separated from the substrate 310 via side walls 317 of the optical element.
  • a luminescent system incorporating such an array will typically provide a detector 400 below the substrate 310.
  • the detector may be provided in the form of a
  • CMOS complementary metal-oxide-semiconductor
  • the necessity for an aperture between the substrate and the detector is not essential.
  • an array 500 of individual light sources 505, such as may be provided by individual LED's or the like are targeted to as to selectively illuminate individual ones 305 of a plurality of optical elements provided in an array format 300 below.
  • the light 510 emitted from each of the light sources can be targeted or focused onto specific ones of the optical elements below- as shown- or could be targeted onto two or more of the optical elements. By providing such targeted illumination it is possible to discriminate in the excitation provided to each of the detection moieties provided on the individual optical elements.
  • the whole top surface of the chip 300 can be illuminated by an expanded beam 600 (i.e. flood-lit) directed downwards.
  • the arrangement of Figure 7 is similar apart from the fact that the light source 700 is offset from the chip, such that the length of the light path travelled from the light source to individual ones of the optical elements varies depending on their relative orientation. This may be usefully employed where a more intense excitation is required at one portion of the chip as opposed to another. Another preferred way to achieve such selective illumination would be through use of filters or the like.
  • excitation of the detection moiety has been described with reference to optical excitation. However in a modification to that described, optical elements may be provided which are capable of forming complexes that are responsive to electro-chemi-luminesence excitation.
  • Electrochemiluminescence is the effect whereby a molecule is caused to be in an excited state by an external electric field-induced chemical reaction. Its depopulation is accompanied by an emission of light in a form of fluorescence or phosphorescence.
  • the major advantage of the ECL-based approach for optical sensing is the low level of the background signal because an optical excitation source is not required. Since the sample is not excited optically, there is no need to suppress the scattered excitation light (e.g. from a laser or LED) or the sample auto- fluorescence. ECL can be usefully combined with SPCE if the plasmon-coupling structure (i.e.
  • metal film also functions as an electrode for generating the ECL.
  • Such an arrangement may be provided by integrating an ECL dye onto the SPCE layered structure (metal, spacers) of the optical elements. This could then be provided as a single optical element or an array platform featuring high collection efficiency and an inherently low noise level (i.e. a very high signal to noise ratio (SNR) is achievable).
  • SNR signal to noise ratio
  • the use of SPCE here obviates the need for a transparent conducting electrode (such as Indium Tin Oxide) which would typically be required in convention ECL sensor arrangements- the metallic layer that generates the plasmonic effects serving a dual purpose in providing the necessary electrode for the ECL effect.
  • SPCE exhibits a spectral effect whereby the angle of emission depends on the wavelength of the light used for excitation.
  • an array structure as provided in accordance with the present teaching may be configured to have the response characteristics of a first optical element distinguishable from the response characteristics of a second optical element.
  • the layered structure also needs to be designed to provide an optimum trade-off between the fluorescence intensities and angular positions and bandwidths for the whole set of labels used
  • optical elements that utilize plasmonic effects to generate highly efficient detection arrangements.
  • a chip providing for the parallel and highly efficient detection of fluorescence or other types of luminescence signals is provided.
  • the chip takes advantage of the angular selective propagation of plasmonic effects and large angle optics of for example solid parabolic optical elements and may be used for biodiagnostics including, for example, "lab-on-a-chip” applications.
  • Such an optical chip is designed for the parallel real-time readout of surface-bound fluorescence obtained from biochemical reactions. Fluorescence is obtained from an array of optical elements, each having a receptive molecule optically coupled to its surface.
  • the receptive molecule is capable of detecting the analyte of interest, wherein detection results in luminescence radiated into the optical element.
  • Each optical element in the array may be coated with the same or different detection moiety and is varied by the user based on the analyte of interest.
  • Figures 8 and 9 show exemplary results that may be achieved using a system incorporating such SPCE configurations.
  • an array of nine optical elements 800 (numbered elements 1, 2, 3, 4, 5, 6, 7, 8, & 9) were provided on a shared substrate 810.
  • PEL polyelectrolyte multilayer
  • PAC- polyacrylic acid final layer were coated onto all elements to provide the desired metallic and dielectric layers on an upper surface of each of the topical elements.
  • the assembled chip was then incubated for an hour such that a first three of the optical elements (elements 1, 2, 3) were provided with a capture moiety of hlgG (50ug/ml) in PBS (phosphate buffered saline) and the remainder of the optical elements were treated with a blocking agent including BSA (bovine serum albumen) (1% in wt).
  • a blocking agent including BSA (bovine serum albumen) (1% in wt).
  • This signal may be easily detected using a suitable positioned detector and shows response characteristics indicative of the presence of the hIgG-Cv5 after 10 minutes.
  • the optical elements that were not capable of forming the complexes having luminophores show no optical response as a result of exposure to an excitation source.
  • one or more surfaces of the optical element could be adapted or configured to provide refractive or diffractive optical elements thereon. In this way, light, which would normally impinge on the bottom surface of the substrate at angles greater than the substrate-air critical angle and would thereby undergo total internal reflection, would be transmitted out of the substrate towards the detector.

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Abstract

La présente invention a trait à des capteurs luminescents qui sont configurés de manière à ce que des effets plasmoniques contribuent de façon opérationnelle à la sortie des capteurs. Selon un agencement préféré, la présente invention fournit un capteur doté d'un élément optique qui procède de façon opérationnelle à la génération d'un signal de luminescence pour une détection ultérieure, l'élément optique étant configuré de manière à ce que les effets plasmoniques contribuent de façon opérationnelle à la génération et/ou à la capture du signal de luminescence. L'invention a également trait à une plate-forme de biopuce optique dotée ayant une structure plasmonique destinée à détecter une fluorescence au tout autre signal luminescent et à des configurations ou à des systèmes de capteur optique qui utilisent une puce optique.
PCT/EP2008/060621 2007-08-13 2008-08-13 Plate-forme de biopuce optique dotée d'une structure plasmonique WO2009021964A2 (fr)

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US95550407P 2007-08-13 2007-08-13
US60/955,504 2007-08-13
US2255908P 2008-01-22 2008-01-22
US61/022,559 2008-01-22

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Cited By (7)

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WO2011141530A3 (fr) * 2010-05-12 2012-02-16 Dublin City University Capteur utilisant la luminescence
WO2013060989A1 (fr) 2011-10-26 2013-05-02 Thibaut Mercey Puce microstructurée comprenant des surfaces convexes pour analyse par résonance des plasmons de surface, dispositif d'analyse contenant ladite puce microstructurée et utilisation dudit dispositif
WO2013060988A1 (fr) 2011-10-26 2013-05-02 Thibaut Mercey Puce microstructurée pour analyse par résonance des plasmons de surface, dispositif d'analyse comprenant ladite puce microstructurée et utilisation dudit dispositif
WO2016015701A1 (fr) 2014-07-31 2016-02-04 Schebo Biotech Ag Dispositif d'analyse biologique, sa fabrication et procédé de détection d'analytes biologiques au moyen du dispositif
EP3112870A4 (fr) * 2014-02-26 2017-09-06 Konica Minolta, Inc. Puce de détection pour spectroscopie de fluorescence activée par champ de plasmons de surface
WO2018046689A1 (fr) * 2016-09-08 2018-03-15 Danmarks Tekniske Universitet Système de puce polymère et ses utilisations
WO2024080956A1 (fr) * 2022-10-11 2024-04-18 Bilkent Universitesi Ulusal Nanoteknoloji Arastirma Merkezi Procédé d'obtention d'un dispositif utilisé dans la détection de biomarqueurs

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WO2011141530A3 (fr) * 2010-05-12 2012-02-16 Dublin City University Capteur utilisant la luminescence
US9291558B2 (en) 2010-05-12 2016-03-22 Dublin City University Luminescence based sensor
CN104105956A (zh) * 2011-10-26 2014-10-15 蒂博·梅塞 用于表面等离子体共振分析的微结构化芯片，包含所述微结构化芯片的分析装置和所述装置的使用
FR2982028A1 (fr) * 2011-10-26 2013-05-03 Thibaut Mercey Puce microstructuree comprenant des surfaces convexes pour analyse par resonance des plasmons de surface, dispositif d'analyse contenant ladite puce microstructuree et utilisation dudit dispositif
FR2982027A1 (fr) * 2011-10-26 2013-05-03 Aryballe Technologies Puce microstructuree pour analyse par resonance des plasmons de surface, dispositif d'analyse comprenant ladite puce microstructuree et utilisation dudit dispositif
CN104081187A (zh) * 2011-10-26 2014-10-01 蒂博·梅塞 用于表面等离子体共振分析的包括凸表面的微结构化芯片，包含所述微结构化芯片的分析装置和所述装置的使用
WO2013060988A1 (fr) 2011-10-26 2013-05-02 Thibaut Mercey Puce microstructurée pour analyse par résonance des plasmons de surface, dispositif d'analyse comprenant ladite puce microstructurée et utilisation dudit dispositif
WO2013060989A1 (fr) 2011-10-26 2013-05-02 Thibaut Mercey Puce microstructurée comprenant des surfaces convexes pour analyse par résonance des plasmons de surface, dispositif d'analyse contenant ladite puce microstructurée et utilisation dudit dispositif
US9739713B2 (en) 2011-10-26 2017-08-22 Prestodiag Microstructured chip comprising convex surfaces for surface plasmon resonance analysis, analysis device containing said microstructured chip and use of said device
US9746467B2 (en) 2011-10-26 2017-08-29 Prestodiag Microstructured chip for surface plasmon resonance analysis, analysis device containing said microstructured chip and use of said device
EP3112870A4 (fr) * 2014-02-26 2017-09-06 Konica Minolta, Inc. Puce de détection pour spectroscopie de fluorescence activée par champ de plasmons de surface
WO2016015701A1 (fr) 2014-07-31 2016-02-04 Schebo Biotech Ag Dispositif d'analyse biologique, sa fabrication et procédé de détection d'analytes biologiques au moyen du dispositif
WO2018046689A1 (fr) * 2016-09-08 2018-03-15 Danmarks Tekniske Universitet Système de puce polymère et ses utilisations
WO2024080956A1 (fr) * 2022-10-11 2024-04-18 Bilkent Universitesi Ulusal Nanoteknoloji Arastirma Merkezi Procédé d'obtention d'un dispositif utilisé dans la détection de biomarqueurs

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