WO2014165879A1 - Micro-dispositif de détection de fluorescence ainsi que procédé associé - Google Patents

Micro-dispositif de détection de fluorescence ainsi que procédé associé Download PDF

Info

Publication number
WO2014165879A1
WO2014165879A1 PCT/AT2014/000066 AT2014000066W WO2014165879A1 WO 2014165879 A1 WO2014165879 A1 WO 2014165879A1 AT 2014000066 W AT2014000066 W AT 2014000066W WO 2014165879 A1 WO2014165879 A1 WO 2014165879A1
Authority
WO
WIPO (PCT)
Prior art keywords
prism
excited
analyzed
micro
detection device
Prior art date
Application number
PCT/AT2014/000066
Other languages
German (de)
English (en)
Inventor
Eduard Gilli
Frank Reil
Stefan Köstler
Volker Schmidt
Original Assignee
Joanneum Research Forschungsgesellschaft Mbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Joanneum Research Forschungsgesellschaft Mbh filed Critical Joanneum Research Forschungsgesellschaft Mbh
Publication of WO2014165879A1 publication Critical patent/WO2014165879A1/fr

Links

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
    • G01N21/648—Specially adapted constructive features of fluorimeters using evanescent coupling or surface plasmon coupling for the excitation of fluorescence

Definitions

  • the present invention relates to a micro-fluorescence detection device comprising a light source for generating linearly polarized excitation light, at least one prism with the base surface of which a carrier for a material to be excited or analyzed is connected, and one parallel to the carrier for the excitation or to be analyzed And a method for detecting fluorescent light in a micro fluorescence detection device, a material disposed, to be excited or analyzed on a support connected to a base surface of a prism, wherein linearly polarized light from an excitation light source is directed to a side surface of the prism wherein at the base surface of the prism, the material to be excited or to be analyzed for the emission of fluorescent light with simultaneous reflection of the excitation light is excited and that of the to be excited or to ana luminescent material detected fluorescent light is evaluated in a detection unit.
  • US 2010/0225915 describes a prism for inducing a Brewster angular transmission and a fluorescence detection device for increasing a signal-to-noise ratio thereof in which structure evanescent waves are generated when light is applied to fluorescent material, wel When applied to a sample surface, it is incident at an angle greater than a critical angle.
  • the evanescent waves are used here as fluorescence excitation light to induce total internal reflection of light such that light passes through the prism at a Brewster angle.
  • a disadvantage of such a device is that the light entry is not at a Brewster angle but normal to the prism surface resulting unwanted reflections of the excitation light on the light entry side result, and that at least between the prism and a support for the sample to be analyzed, an interface exists at which unwanted light scattering can take place. Furthermore, in order to connect the support for the sample to be analyzed with the integrated prism used an immersion medium to achieve the necessary total reflection at the surface of the support.
  • the light source in this system comprises a laser diode and the system further comprises beam splitters, apertures and a stepper motor driven control mirror in which after filtering the fluorescent light, the punctiform field has been detected by an uncooled CCD camera.
  • miniaturized devices employing direct detection of, in particular, biomolecules or pathogens in applications such as diagnostics, food testing or environmental monitoring
  • the so-called "lab-on-a-chip” or “micro total analysis systems ( ⁇ TAS ) have been developed to perform the entire process from sample preparation, measurement, reaction, incubation, etc., to detection on the same chip
  • ⁇ TAS micro total analysis systems
  • the present invention now aims to provide a miniaturized fluorescence detection device and a method for detecting fluorescent light, in which as much excitation light is coupled into a fluorescent dye of a material to be excited or analyzed and at the same time as little excitation light reaches the detector, to achieve an effective, geometric separation of fluorescent light and excitation light and thus an increased measurement accuracy. Furthermore, the invention aims to minimize the unwanted reflection of the excitation light when entering and exiting the prism and a subsequent possible scattering of excitation light and thus after an effective excitation of the fluorescent material in a material to be analyzed or to be detected Material to measure the fluorescent light sufficiently sensitive and accurate with a spatially resolving detector.
  • the device according to the invention is characterized in that the at least one prism and the carrier for the material to be excited or analyzed are formed as a monolithic microchip, wherein a base surface of the prism forming side of the microchip the carrier for the material to be excited or analyzed on which the material to be excited or analyzed in the total reflection of the excitation light is arranged and that both side surfaces of the prism are arranged in the Brewster angle to the excitation light.
  • Attenuated total reflection (ATR) excitation is achieved.
  • the material to be excited or analyzed on the side of the prism is illuminated at an angle which is greater than the critical angle of total reflection, for which reason no excitation light intensity emanates from the prism in the region of the material to be excited or analyzed. penetrates, but is completely reflected inside the prism.
  • the substance to be stimulated or to be analyzed which is simultaneously an absorbing substance for the excitation light and is applied to the same base surface of the prism, is thus excited by an evanescent wave emerging in the near field and causes the emission of fluorescent light, which fluorescence light, subsequently in the Detection unit is evaluated. Furthermore, by locating both side faces of the prism at Brewster's angle to the excitation light, the excitation light is coupled into or out of the prism, substantially without producing any reflections.
  • linearly polarized light which may for example come from a laser diode as a light source whose polarization plane is set parallel to the plane of incidence, ie p-polarized light in the Brewster angle on the side surfaces of the prism.
  • a further increase in the efficiency of the coupling-in and coupling-out of the excitation light without undesired reflection of the excitation light when light enters and exits is hereby achieved according to the invention in that the microchip of the fluorescence detection device is formed from a non-absorbing material which is suitable for p polarized light is not reflective at the Brewster angle.
  • Such a configuration thus maximizes the coupling and decoupling of the excitation light and at the same time minimizes or completely eliminates the scattered light, which is why, in particular, fluorescent light of the material to be excited or analyzed can be exactly detected without any scattered light.
  • the fluorescence detection device is designed such that the base of the microchip representing the carrier for the material to be excited or analyzed is structured and that the structuring comprises one or more components or structures Includes microfluidic structures and channels, micro-optical structures, electrodes, valves or membranes, it is possible to provide a so-called lab-on-a-chip system in a simple manner, in which the number of interfaces between the material to be excited or to be analyzed on a minimum is reduced, whereby as much excitation light is coupled into the luminescent dye contained in the material to be excited or analyzed. Moreover, with such a device when used for fluid materials, the use of immersion liquids can be avoided.
  • the material to be excited or analyzed as a grid of fluorescent dots on the carrier forming side or the base surface of the microchip is applied, it is possible with simultaneous effective excitation with a conventional spatially resolving detector, such as a CCD camera, sufficiently sensitive to measure the fluorescence of the material to be excited or analyzed.
  • a conventional spatially resolving detector such as a CCD camera
  • a diameter of each point of the grid of fluorescent dots is 0.05 to 1 mm, in particular 0, 1 and 0.4 mm, with simultaneous homogeneous irradiation and a quantification of the average intensity of individual sensor points can be achieved.
  • the device is designed such that a plurality of prisms is arranged on a common microchip and that the prisms are integrated into a surface of the microchip.
  • the plurality of prisms arranged on a common microchip makes it possible to provide a plurality of carriers for material to be analyzed or stimulated, and in particular, for example, a plurality of microfluidic channels which are cut into the prism base area.
  • the fluorescence detection device can be designed in this case such that the plurality of
  • Prisms is arranged parallel to each other with directed to the excitation light side surfaces. Another variant is achieved in that the plurality of prisms is arranged one behind the other and a light incidence of the excitation light on the prisms takes place one after the other. By arranging a plurality of prisms parallel to one another with side faces directed towards the excitation light, it is possible to obtain a plurality of mutually different samples or a plurality of mutually identical samples be displayed simultaneously with excitation light to emissions of fluorescent light.
  • Such a device is preferred, for example, for an application for the examination of biological fluids or the like, since only very small amounts of substance are contained in the sample and with such a configuration a simultaneous, yet very sensitive measurement of several parameters can be achieved a plurality of prisms is arranged one behind the other.
  • the micro-fluorescence detection device can be developed such that the detection unit is arranged opposite to the prism of the prism.
  • the detection unit is arranged opposite the vertex of the prism.
  • a micro-fluorescence detection device in which the detection unit is arranged opposite the apex of the prism, it is possible to provide a device in which an extremely simple replacement of the biochip is made possible due to the ready accessibility thereof and thus the times and the outlay to the change, which are generally determined for single use, analysis chips compared to conventional designs are significantly reduced.
  • the entire microchip of the micro-fluorescence detection device is made of one and the same material, in particular made of plastic, it is possible on the one hand to provide a non-absorbing medium for the p-polarized light and on the other hand can Such device simple, for example, in a single manufacturing step, such as injection molding,
  • Hot embossing and the like are manufactured, whereby a total of manufacturing costs for the production of disposable, analysis chips is significantly reduced. Furthermore, by making the entire microchip of one and the same material, it is possible to provide an inert carrier for the material to be analyzed while at the same time providing a prism which is suitable for the
  • Beam geometry which is required for the apparatus of the present invention to provide required refractive indices.
  • the microchip in particular the biochip, is made of a polymer material based on cycloolefin polymer (COP), cycloolefin copolymer (COC), polycarbonate (PC), polymethyl methacrylate (PMMA), poly (poly (meth) acrylate).
  • COP cycloolefin polymer
  • COC cycloolefin copolymer
  • PC polycarbonate
  • PMMA polymethyl methacrylate
  • PS polyethylene terephthalate
  • PAT polyacrylate
  • PPA polyurethane acrylate
  • PUMA polyuretane methacrylate
  • PP polypropylene
  • COP / COC cycloolefin polymer or copolymer
  • PC polycarbonate
  • PMMA polymethyl methacrylate
  • PS polystyrene
  • the device is designed according to a development that it is arranged in a housing, in particular an aluminum housing or plastic housing and that inside the housing, a partition for a separation in a compartment containing the light source and a compartment containing the detection device is arranged.
  • a partition for a separation in a compartment containing the light source and a compartment containing the detection device is arranged.
  • the invention is developed such that the side surfaces of the prism are formed as curved free-form surfaces.
  • the present invention further relates to a method for detecting fluorescent light in a micro-fluorescence detection device, in which the amount of interfering stray light impinging on a detection unit is minimized, while at the same time reliably and reproducibly reproducible results are achieved.
  • the method according to the invention is essentially characterized in that the excitation light is irradiated at the Brewster angle on the side surface of the prism that the material to be excited or to be analyzed is arranged directly on the base surface of the prism at an angle which is greater as a critical angle of total reflection is excited to emit fluorescent light.
  • the material to be excited or analyzed directly on the base surface of the prism and illuminated at an angle greater than the critical angle of total reflection, it is further ensured that no excitation intensity of the excitation light from the prism at the surface of the prism Prism, on which the to be detected or to be excited sample or the material to be excited is applied, penetrates, which in turn the signal-to-noise ratio of a measurement can be significantly improved and in particular exact and sharp measurement points or lines of the generated Fluorescent light can be obtained in a detection unit.
  • the speed of the measuring method is increased on the one hand and on the other hand it is ensured that a plurality of different substances to be analyzed are analyzed quickly or simply a plurality of mutually identical substances can be analyzed, whereby, after a corresponding communication, the measurement errors can be significantly reduced compared to conventional measurement methods.
  • the method is carried out such that the plurality of materials to be excited or analyzed simultaneously are applied to a plurality of prism faces arranged parallel to one another or to be simultaneously detected If a plurality of materials to be stimulated or analyzed are applied to a plurality of prisms arranged in a row, the plurality of prisms are applied and excited in succession with one and the same excitation light, whereby one and the same sample can be excited several times and thus faulty Measurements or read-out errors after detection in the detection device tion can be withheld by direct comparison of the measurement results with certainty.
  • the material to be excited or analyzed as a grid of fluorescent dots on the base surface of the prism, as is the case with a further development of the invention, it is possible with sufficient sensitivity to simultaneously excite with a conventional spatially resolving detector, such as a CCD camera Fluorescence of the material to be excited or analyzed.
  • a conventional spatially resolving detector such as a CCD camera Fluorescence of the material to be excited or analyzed.
  • the fluorescent dots are formed by binding fluorescently labeled molecules from a solution to capture or probe molecules fixed to the prism base surface, the apparatus permits the detection and quantification of samples present in the sample solution analytes.
  • the fluorescent points are determined by the attachment / binding of fluorescence-dye-labeled molecules or particles, such as oligonucleotides, proteins, peptides, biomarkers, antibodies, antigens, etc., from the binding partner applied to the analyzing solution at the base surface of the prism, ie In turn corresponding complementary oligonucleotides, proteins, antigens, etc. are formed, the detection and quantification of existing in the sample solution analytes is possible.
  • fluorescence-dye-labeled molecules or particles such as oligonucleotides, proteins, peptides, biomarkers, antibodies, antigens, etc.
  • 1 is a schematic representation of a micro-fluorescence detection device according to the present invention.
  • 2 shows a schematic representation of light incident at the Brewster angle on the side surfaces of a prism integrated in a carrier substrate.
  • Fig. 3 is a partial perspective view of a prism applied to a carrier substrate and the schematic representation of the passage of light through this prism.
  • FIG. 4 shows a representation similar to FIG. 3 with a plurality of prisms integrated on a support
  • FIG. 5 shows a plurality of successively arranged prisms, which are gradually penetrated by excitation light, according to another embodiment of the invention.
  • FIG. 6 shows a diagram relating to the fluorescence imaging and the temporal evaluation of the fluorescence intensity for a streptavidin concentration of 7 nM.
  • FIG. 1 shows a schematic representation of a micro-fluorescence detection device 1, in which a bundle of linearly polarized light is applied from a light source 2, for example a laser diode, to a beam sharpener 3 and from this the schematically illustrated beam 4, which is a Polarization in a plane parallel to the plane of incidence 5 of the prism 6, is incident.
  • the beam 4, which includes the Brewster angle with the plane of incidence 5 not shown in FIG. 1, is refracted inside the prism 6, is completely reflected at a base surface 7 of the prism 6 and enters at a second side surface 8 of the prism 6 again from the inside of the prism 6 at the Brewster angle.
  • a plurality of fluorescent dots 9, in particular a grid of fluorescent dots 9 are applied in a microfluidic system, in particular in the area where the total reflection of the beam 4 takes place.
  • the microfluidic system is shown schematically in FIG. 1 through the depression 10, which is formed on the base surface 7 of the prism 6, and is intended, for example, to symbolize a microchannel.
  • the fluorescent dots 9 can have a diameter of 0.05 to 1 in particular 0, 1 to 0.4 mm in such a configuration.
  • an absorbing substance in particular at points 9, is located on surface 7 of prism 6, it can be excited by an evanescent wave emerging in the near field and the fluorescent light 1 1 emitted after excitation is subsequently focused by a camera lens 12, which is a converging lens, again and evaluated by a detector 13, which is for example a CCD camera and an evaluation, not shown in Fig. 1.
  • a camera lens 12 which is a converging lens
  • detector 13 which is for example a CCD camera and an evaluation, not shown in Fig. 1.
  • the prism 6 is formed of a non-absorbing medium, since non-absorbing media for p-polarized light, ie light, the plane of polarization is set parallel to plane of incidence 5 of the prism 6, ie for light, which in the Brewster- Angle incident on the plane of incidence 5 of the prism 6, are not reflective. Finally, the light is irradiated at the Brewster angle on the surface of the prism.
  • the Brewster angle (q ⁇ ) is given here by the formula tan (qe) ni and n2 are the refractive indices of the participating media, ie in the present case air and the material of the prism 6.
  • the detection unit 13 is arranged on the side of the vertex 14, in the present case a vertex surface, of the prism 6.
  • the detection unit 13 is disposed on the side of the sample 9 to be analyzed, because of its reduced space requirement, by arranging both the light source 2 and of the
  • FIG. 2 shows a schematic representation of a carrier with integrated prism, ie a microchip 15 according to the invention.
  • the prism 6 is formed as part of the base surface of the microchip 15, and an interface between the chip 15 and the prism 6 does not exist, so that the number of optical interfaces is minimized.
  • the bundle of incident light beams 4 is further shown, which incident on the surface 5 of the prism 6 at the Brewster angle qe.
  • the incident light beam 4 is refracted to the base surface 7 and reflected therefrom and exits at the on the side surface 8 again at the Brewster angle qß from the prism 6.
  • the prism 6 shown in FIG. 2 is a conventional prism 6 having a vertex and a base surface 7.
  • Fig. 3 is a similar view as shown in Fig. 2 in perspective, wherein the prism 6 is formed in Fig. 3 as a blunt prism 6 with two horizontal sides. Also in Fig. 3, the path of the light is indicated schematically by the line 16.
  • the base surface 7 as well as in Fig. 1 of the prism 6 is shown extended and thus represents the base of the microchip 15. In this case, the prism 6 is formed directly on the microchip 15, as this is shown schematically by the dotted line 17 in order to minimize the number of interfaces.
  • a plurality of prisms 6, which are formed analogously to those of FIG. 3, are arranged parallel to each other on a microchip 15, wherein each of the prisms 6 is acted upon by light, wherein the light path is again schematically designated 16.
  • the light source 2, which acts on the plurality of prisms 6, may be a common light source 2 or a plurality of light sources 2 arranged parallel to one another may be used.
  • a plurality of prisms 6 are shown, which are arranged one behind the other and which are penetrated successively by a light bundle 4. Due to the fact that the incident light 6 again impinges on the surface 5 of the prism 6 at the Brewster angle qB and emerges from the first prism 6 exactly at the Brewster angle q ⁇ , it is possible to apply all the prisms 6 with exactly the same light geometry. so that errors due to stray light, which may be caused by non-observance of the light geometry, are avoided.
  • recesses 10 are again shown in the base surface 7 of the prism 6, which are intended to symbolize microchannels in which fluid material can be guided. Needless to say that the Prismengeometrie can be chosen arbitrarily and that, for example, free-form prisms can be used, which are used to compensate for possible radiation divergences.
  • a biochip according to FIG. 3 with external dimensions of 25 ⁇ 75 mm is produced by hot pressing or injection molding of COP material, namely a thermoplastic polyolefin resin marketed under the trade name Zeonor® 1060R (a trademark of Zeon Corporation), the chip incorporating a includes integrated prism whose angle of the side surfaces to the base surface amount to 33.2 °.
  • COP material namely a thermoplastic polyolefin resin marketed under the trade name Zeonor® 1060R (a trademark of Zeon Corporation)
  • Zeonor® 1060R a trademark of Zeon Corporation
  • Biotin-functionalized bovine serum albumin (BSA) is imprinted on the base surface of this prism in the form of a dot-shaped raster. Subsequently, this chip is incorporated with another chip, in which a microfluidic channel system consisting of at least one channel, which allows a sample solution to be passed over the grid applied on the base surface of the prism and in which a liquid inlet and outlet is further incorporated, connected.
  • a microchip in particular a biochip, was prepared for the detection of biotin or biotin-binding proteins, such as streptavidin or neutravidin.
  • a sample or solution containing a certain amount of biotin and streptavidin labeled with the fluorescent dye Cy3 is then introduced into the microfluidic channel and the fluorescence intensity of the grid printed on the base surface of the prism is subsequently monitored with a CCD camera.
  • Fluorescence intensity with incubation time indicates binding of the Cy3-labeled streptavidin to the printed halftone dots of biotinylated BSA.
  • the rate of this increase or the achievable fluorescence intensities depend on the concentration of biotin and streptavidin in the sample solution.
  • the corresponding fluorescence imaging and the temporal evaluation of the fluorescence intensity are shown for a Cy3 streptavidin concentration of 7 nM in FIG.

Landscapes

  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

L'invention concerne un micro-dispositif de détection de fluorescence (1) comprenant une source lumineuse (2) pour générer de la lumière d'excitation (4) linéairement polarisée, au moins un prisme (6) à la surface de base (7) duquel un support pour un matériau à exciter ou à analyser est relié ainsi qu'une unité de détection (13) disposée parallèlement au support pour le matériau à exciter ou à analyser, caractérisé en ce que ledit prisme (6) et le support pour le matériau à exciter ou à analyser sont conçus comme une micropuce d'une seule pièce, un côté de la micropuce (15) formant la surface de base (7) du prisme (6) servant de support pour le matériau à exciter ou à analyser sur lequel le matériau à exciter ou à analyser est disposé dans la région de la réflexion totale de la lumière d'excitation (4), et en ce que les deux surfaces latérales (5, 8) du prisme (6) sont disposées au moins à un angle de Brewster par rapport à la lumière d'excitation (4).
PCT/AT2014/000066 2013-04-12 2014-03-31 Micro-dispositif de détection de fluorescence ainsi que procédé associé WO2014165879A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AT2992013A AT513859B1 (de) 2013-04-12 2013-04-12 Mikro-Fluoreszenzdetektionsvorrichtung sowie Verfahren zur Detektion
ATA299/2013 2013-04-12

Publications (1)

Publication Number Publication Date
WO2014165879A1 true WO2014165879A1 (fr) 2014-10-16

Family

ID=50721502

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/AT2014/000066 WO2014165879A1 (fr) 2013-04-12 2014-03-31 Micro-dispositif de détection de fluorescence ainsi que procédé associé

Country Status (2)

Country Link
AT (1) AT513859B1 (fr)
WO (1) WO2014165879A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113109314A (zh) * 2021-05-28 2021-07-13 上海睿钰生物科技有限公司 多荧光信号检测系统和方法
DE102020201112A1 (de) 2020-01-30 2021-08-05 Robert Bosch Gesellschaft mit beschränkter Haftung Optische Auslesung von Prozessen innerhalb einer mikrofluidischen Vorrichtung
CN115097617A (zh) * 2022-07-15 2022-09-23 中国科学技术大学 一种基于平面芯片的全内反射荧光显微镜系统

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106680258A (zh) * 2017-02-09 2017-05-17 重庆科技学院 一种全内反射检测工作平台
DE102017115661A1 (de) 2017-07-12 2019-01-17 Endress+Hauser Conducta Gmbh+Co. Kg Optischer Sensor
CN108414480B (zh) * 2018-01-26 2023-03-24 中国海洋石油集团有限公司 一种原油荧光测量装置和方法
CN109520939B (zh) * 2019-01-03 2024-05-24 华域视觉科技(上海)有限公司 一种材料检测装置

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19615380A1 (de) * 1995-08-29 1997-03-06 Hewlett Packard Co Abklingende Abtastung eines biochemischen Arrays
EP1079226A1 (fr) * 1999-08-24 2001-02-28 Leuze electronic GmbH + Co. Dispositif de dosage immunologique
WO2008072156A2 (fr) * 2006-12-12 2008-06-19 Koninklijke Philips Electronics N. V. Capteur microélectronique pour détecter des particules de marquage
US20100225915A1 (en) 2009-03-04 2010-09-09 Korea Advanced Institute Of Science And Technology Prism for inducing Brewster's angle transmission and fluorescence detection apparatus for improving signal-to-noise ratio using thereof

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5538850A (en) * 1994-04-15 1996-07-23 Hewlett-Packard Company Apparatus and method for intracavity sensing of microscopic properties of chemicals
JP3562912B2 (ja) * 1996-09-04 2004-09-08 富士写真フイルム株式会社 表面プラズモンセンサー
JP5469900B2 (ja) * 2009-04-03 2014-04-16 株式会社日立ハイテクノロジーズ ナノ構造体デバイスを利用した計測装置及び計測方法
EP2524260A4 (fr) * 2009-08-11 2013-07-24 Chromx Llc Microscope à fond ultrasombre

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19615380A1 (de) * 1995-08-29 1997-03-06 Hewlett Packard Co Abklingende Abtastung eines biochemischen Arrays
EP1079226A1 (fr) * 1999-08-24 2001-02-28 Leuze electronic GmbH + Co. Dispositif de dosage immunologique
WO2008072156A2 (fr) * 2006-12-12 2008-06-19 Koninklijke Philips Electronics N. V. Capteur microélectronique pour détecter des particules de marquage
US20100225915A1 (en) 2009-03-04 2010-09-09 Korea Advanced Institute Of Science And Technology Prism for inducing Brewster's angle transmission and fluorescence detection apparatus for improving signal-to-noise ratio using thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
A. BRANDENBURG ET AL., SENSOR. ACTUAT. B-CHEM., vol. 139, 2009, pages 245 - 249
BRANDENBURG A ET AL: "Biochip readout system for point-of-care applications", SENSORS AND ACTUATORS B: CHEMICAL: INTERNATIONAL JOURNAL DEVOTED TO RESEARCH AND DEVELOPMENT OF PHYSICAL AND CHEMICAL TRANSDUCERS, ELSEVIER S.A, CH, vol. 139, no. 1, 9 March 2009 (2009-03-09), pages 245 - 251, XP026095315, ISSN: 0925-4005, [retrieved on 20090309], DOI: 10.1016/J.SNB.2009.02.052 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102020201112A1 (de) 2020-01-30 2021-08-05 Robert Bosch Gesellschaft mit beschränkter Haftung Optische Auslesung von Prozessen innerhalb einer mikrofluidischen Vorrichtung
CN113109314A (zh) * 2021-05-28 2021-07-13 上海睿钰生物科技有限公司 多荧光信号检测系统和方法
CN115097617A (zh) * 2022-07-15 2022-09-23 中国科学技术大学 一种基于平面芯片的全内反射荧光显微镜系统
CN115097617B (zh) * 2022-07-15 2022-12-30 中国科学技术大学 一种基于平面芯片的全内反射荧光显微镜系统

Also Published As

Publication number Publication date
AT513859A4 (de) 2014-08-15
AT513859B1 (de) 2014-08-15

Similar Documents

Publication Publication Date Title
DE102007033124B4 (de) Vorrichtung zur optischen Detektion von Substanzen in einem flüssigen oder gasförmigen Medium
AT513859B1 (de) Mikro-Fluoreszenzdetektionsvorrichtung sowie Verfahren zur Detektion
DE19725050C2 (de) Anordnung zur Detektion biochemischer oder chemischer Substanzen mittels Fluoreszenzlichtanregung und Verfahren zu deren Herstellung
EP1327135B1 (fr) Systeme et procedes pour determiner plusieurs analytes
DE69926230T2 (de) Optische sensorvorrichtung mit evaneszenter felddetektion
EP1307728B1 (fr) Structure reticulaire de guide d'ondes et dispositif de mesure optique
DE10008006C2 (de) SPR-Sensor und SPR-Sensoranordnung
EP2522988A1 (fr) Dispositif d'analyse optique, procédé d'analyse optique et programme informatique d'analyse optique
EP0910792A1 (fr) Procede et dispositif pour mettre en oeuvre des tests quantitatifs d'affinite a fluorescence
WO1998022803A1 (fr) Cellule micromecanique de mesure de transmission
WO2001092870A2 (fr) Kit et procede pour la detection d'une pluralite d'analytes
DE202010018623U1 (de) Strukturen zur Steuerung der Lichtwechselwirkung mit mikrofluidischen Vorrichtungen
WO1999040415A1 (fr) Procede et dispositif de mesure de la luminescence
EP1347284B1 (fr) Porte-échantillon avec optique intégrée
WO2003096018A2 (fr) Trousse de mise au point de dosage et d'analyses en serie
WO2002046756A1 (fr) Kit et procede de detection d'analytes multiples comprenant des mesures de referenciation a resolution locale d'une intensite de lumiere d'excitation
WO2008135566A2 (fr) Unité de mesure et procédé d'examen optique d'un liquide pour déterminer une concentration d'un analyte
DE60301821T2 (de) Küvette für ein Lesegerät zur Bestimmung von Substanzen mittels der Evaneszenzfeldmethode
EP1497651B1 (fr) Guide d'ondes dans des substrats poreux
DE10324973B4 (de) Anordnung und Verfahren zur optischen Detektion von in Proben enthaltenen chemischen, biochemischen Molekülen und/oder Partikeln
DE102004034486B4 (de) Verfahren zum Nachweis von Lumineszenzlicht aus einer porösen Trägerstruktur
DE10221115B4 (de) Vorrichtung und Verfahren zur Bestimmung von in Proben enthaltenen chemischen oder biochemischen Partnern allgemeiner Rezeptor-Ligand-Systeme
DE102018133037B4 (de) Anordnung und Verfahren zur Erfassung von optischen Eigenschaften einer Probe, insbesondere zum selektiven Nachweis von biologischen Molekülen und zum Auslesen einer Molekülbelegung
DE102021201147A1 (de) Vorrichtung und Verfahren zum Analysieren biologischer Partikel
WO2022263036A1 (fr) Puce microfluidique

Legal Events

Date Code Title Description
DPE2 Request for preliminary examination filed before expiration of 19th month from priority date (pct application filed from 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14723665

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 14723665

Country of ref document: EP

Kind code of ref document: A1