WO1993014392A1 - Dispositif d'analyse avec une source de lumiere polychromatique - Google Patents

Dispositif d'analyse avec une source de lumiere polychromatique Download PDF

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Publication number
WO1993014392A1
WO1993014392A1 PCT/GB1993/000026 GB9300026W WO9314392A1 WO 1993014392 A1 WO1993014392 A1 WO 1993014392A1 GB 9300026 W GB9300026 W GB 9300026W WO 9314392 A1 WO9314392 A1 WO 9314392A1
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WO
WIPO (PCT)
Prior art keywords
light
wavelength
light source
source
polychromatic
Prior art date
Application number
PCT/GB1993/000026
Other languages
English (en)
Inventor
Nicholas John Goddard
Colin Hugh Maule
Douglas Alastair Stewart
Original Assignee
Fisons Plc
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 Fisons Plc filed Critical Fisons Plc
Publication of WO1993014392A1 publication Critical patent/WO1993014392A1/fr

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Classifications

    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/55—Specular reflectivity
    • G01N21/552—Attenuated total reflection
    • G01N21/553—Attenuated total reflection and using surface plasmons
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/41—Refractivity; Phase-affecting properties, e.g. optical path length
    • G01N21/43—Refractivity; Phase-affecting properties, e.g. optical path length by measuring critical angle
    • G01N2021/436—Sensing resonant reflection
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/41—Refractivity; Phase-affecting properties, e.g. optical path length
    • G01N21/43—Refractivity; Phase-affecting properties, e.g. optical path length by measuring critical angle
    • G01N2021/436—Sensing resonant reflection
    • G01N2021/438—Sensing resonant reflection with investigation of wavelength

Definitions

  • This invention relates to sensors, especially those termed biosensors, ie devices for the analysis of biologically active species such as antigens and antibodies in samples of biological origin.
  • the invention relates to biosensors based on resonant optical phenomena, eg surface plasmon resonance or resonant attenuated or frustrated total internal reflection.
  • biosensors include a sensitised coating layer which is located in the evanescent region of a resonant field.
  • Detection of the analyte typically utilizes optical techniques such as, for example, surface plasmon resonance (SPR) , and is based on changes in the thickness and/or refractive index of the coating layer resulting from interaction of that layer with the analyte. This causes a change, eg in the angular position of the resonance.
  • SPR surface plasmon resonance
  • optical biosensors include a waveguide in which a beam of light is propagated. The optical characteristics of the device are influenced by changes occurring at the surface of the waveguide.
  • One form of optical biosensor is based on frustrated total reflection.
  • the principles of frustrated total reflection (FTR) are well-known; the technique is described, for example, by Bosacchi and Oehrle [Applied Optics (1982), 21, 2167-2173].
  • An FTR device for use in immunoassay is disclosed in European Patent Application No 2205236A and comprises a cavity layer bounded on one side by the sample under investigation and on the other side by a spacer layer which in turn is mounted on a substrate.
  • the substrate-spacer layer interface is irradiated with monochromatic radiation such that total reflection occurs, the associated evanescent field penetrating through the spacer layer. If the thickness of the spacer layer is correct and the incident parallel wave vector matches one of the resonant mode propagation constants, the total reflection is frustrated and radiation is coupled into the cavity layer.
  • the cavity layer must be composed of material which has a higher refractive index than the spacer layer and which is transparent at the wavelength of the incident radiation.
  • the position of resonance may be monitored by scanning the angle at which monochromatic light is incident on the sensor, or by scanning the wavelength of light incident on the sensor at a constant angle.
  • the scanning of angle may be performed either sequentially or simultaneously ie by varying the angle of incidence of a parallel beam of light or by simultaneously irradiating over a range of angles using a fan-shaped beam of light as described (in connection with SPR) in European Patent Application No 0305109A.
  • prior proposals have involved a single-channel detector which is mechanically scanned over a range of angles; this necessitates synchronisation of the movement of the light source and the detector.
  • the second configuration in which a range of angles is irradiated simultaneously, it is generally necessary to use a multi-channel detector having angular resolution. This leads to relatively high manufacturing costs.
  • apparatus for the determination of a chemical or biochemical species comprising a resonant optical biosensor disposed in a light path between a source of polychromatic collimated light and a detector adapted to monitor some characteristic of the light, the detector including a wavelength-dispersive element.
  • the apparatus according to the invention is advantageous primarily in that it is of relatively simple and inexpensive construction, eg due to the absence of moving parts.
  • the source of polychromatic light is preferably a point light source, ie a source of sufficiently small physical size to provide, with simple colli ating optics, good collimation of the incident beam.
  • the light source may be a filament light source with a small aperture.
  • the light source is a semiconductor light source, eg a light emitting diode.
  • polychromatic light 7 is meant light which has a bandwidth sufficiently broad to encompass the wavelength at which resonance occurs. Where an LED is used, for example, the bandwidth is typically a few tens of nanometres.
  • 'light' may include not only visible light but also wavelengths above and below this range, eg in the ultra-violet and infra-red.
  • the wavelength-dispersive element may be a grating.
  • the pitch of the grating is preferably close to the wavelength of light at the high end of the polychromatic bandwidth. This maximises the separation of wavelengths across the bandwidth.
  • the wavelength- dispersive element may be a holographic lens. This simplifies the optics since no additional focussing lens is required.
  • the characteristic of the light which is monitored may be any characteristic which changes at resonance, eg the phase of reflected radiation or, in some cases, the intensity.
  • the sensor is preferably an FTR sensor.
  • Such a sensor will generally include an optical structure comprising a) a cavity layer of transparent dielectric material of refractive index n 3 , b) a dielectric substrate of refractive index n l and c) interposed between the cavity layer and the substrate, a dielectric spacer layer of refractive index n 2 .
  • the interface between the substrate and the spacer layer is irradiated with light such that internal reflection occurs. Resonant propagation of a guided mode in the cavity layer will occur, for a given angle of incidence, at a particular wavelength of the incident radiation.
  • the wavelength at which the resonant effect occurs depends on various parameters of the sensor device, such as the refractive indices and thicknesses of the various layers. In general, it is a pre-requisite that the refractive index n 3 of the cavity layer and the refractive index n r of the substrate should both exceed the refractive index n 2 of the spacer layer. Also, since at least one mode must exist in the cavity to achieve resonance, the cavity layer must exceed a certain minimum thickness.
  • the cavity layer is preferably a thin-film of dielectric material. Suitable materials for the cavity layer include zirconium dioxide, titanium dioxide, aluminium oxide and tantalum oxide.
  • the cavity layer may be prepared by known techniques, eg vacuum evaporation, sputtering, chemical vapour deposition or in-diffusion.
  • the dielectric spacer layer must have a lower refractive index than both the cavity layer and the substrate.
  • the layer may. for example, comprise an evaporated or sputtered layer of magnesium fluoride.
  • suitable materials include lithium fluoride and silicon dioxide.
  • the spacer layer may be deposited on the substrate by a sol-gel process, or be formed by chemical reaction with the substrate.
  • the sol-gel process is particularly preferred where the spacer layer is of silicon dioxide.
  • the refractive index of the substrate (n must be greater than that (n 2 ) of the spacer layer but the thickness of the substrate is generally not critical.
  • the spacer layer will typically have a thickness of the order of several hundred nanometres, say from about 200nm to 2000nm, more preferably 500 to 1500nm, eg lOOOnm.
  • the cavity layer typically has a thickness of a few tens of nanometres, say 10 to 200nm, more preferably 30 to 150nm, eg lOOnm.
  • the cavity layer has a thickness of 30 to 150nm and comprises a material selected from zirconium dioxide, titanium dioxide, tantalum oxide and aluminium oxide
  • the spacer layer has a thickness of 500 to 1500nm and comprises a material selected from magnesium fluoride, lithium fluoride and silicon dioxide, the choice of materials being such that the refractive index of the spacer layer is less than that of the cavity layer.
  • Preferred materials for the cavity layer and the spacer layer are tantalum oxide and silicon dioxide respectively.
  • the incident light is coupled into the cavity layer by FTR, propagates a certain distance along the cavity layer, and couples back out (also by FTR) .
  • the propagation distance depends on the various device parameters but is typically of the order of 1 or 2mm.
  • the cavity layer and/or spacer layer may absorb at resonance, resulting in a reduction in the intensity of the reflected light.
  • the surface of the sensor ie the surface of the cavity layer in the case of an FTR sensor
  • the immobilised biochemicals may be covalently bound to the sensor surface by methods which are well known to those skilled in the art.
  • Figure 1 is a schematic view (not to scale) of an apparatus according to the invention.
  • Figure 2 depicts the dependence of the intensity of the detected light on the wavelength
  • Figure 3 is a schematic view of part of a second embodiment of an apparatus according to the invention.
  • a biosensor comprises a glass prism 1 coated over an area of its base with a first coating 2 of magnesium fluoride and a second coating 3 of titanium dioxide.
  • the prism 1 and first and second coatings 2,3 together constitute a resonant optical structure, the first coating 2 acting as a spacer layer and the second coating 3 as a cavity layer.
  • the first coating 2 has a thickness of approximately lOOOnm and the second coating 3 a thickness of approximately lOOnm.
  • Immobilised on the surface of the second coating 3 is a layer 4 of immobilised biochemicals, which act as specific binding partner for the analyte under test.
  • the interface between the base of the prism 1 and the first coating 2 is irradiated by a beam of polychromatic light from a light emitting diode (LED) 5.
  • LED light emitting diode
  • Light from the LED 5 has a bandwidth of about 50nm, centred at about 640nm.
  • Light from the LED 5 is collimated by a lens 6 and passes through a polariser 7.
  • the polariser 7 is arranged to produce linearly polarised light with two components : transverse electric (TE) and transverse magnetic (TM) .
  • the polariser is set at 45° to the TE and TM transmission axes and thus provides equal components of TE and TM light.
  • the reflected light is passed through a compensator 8 to a polarisation analyser 9.
  • the compensator 8 is manually adjusted to remove any phase difference which is introduced into the TE and TM components on reflection and by birefringence in the optical path.
  • the analyser 9 is arranged at 90° to the polariser 7.
  • the TE and TM components are interfered at the analyser to allow the phase change to be detected.
  • both components undergo a similar phase shift on reflection and the relative phase between the components is adjusted by the compensator 8 to give zero transmission through the analyser 9. This will apply for all wavelengths except near resonance. Near resonance of either component, the phase shift between the TE and TM components will vary rapidly with wavelength, resulting in maximum throughput of light through the analyser 9 at resonance.
  • polychromatic light is incident on the interface between the base of the prism 1 and the first coating layer 2 at a fixed angle of incidence. At that angle, resonance occurs for one particular wavelength. At off-resonance wavelengths, no light intensity is detected at the detector 12; progressively closer to resonance, the detected light intensity increases and then falls.
  • FIG. 1 shows a plot of the measured signal intensity against wavelength before and (dotted line) after complexation of the immobilised biochemicals with the analyte.
  • the grating 10 and lens 11 are replaced by a holographic lens 13 which simultaneously disperses and focusses the reflected light onto the detector 12.

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  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • General Physics & Mathematics (AREA)
  • Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Analytical Chemistry (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

L'appareil utilisé pour l'analyse d'un composé chimique ou biochimique comprend un biodétecteur optique résonant (1-4) disposé sur le trajet optique entre une source de lumière polychromatique collimatée (5) et un détecteur (10, 12) conçu pour surveiller une caractéristique particulière de la lumière. Le détecteur (10, 12) comprend un élément (10) dispersant la lumière selon sa longueur d'onde. La source de lumière polychromatique (5) est de préférence une source de lumière ponctuelle, par exemple une source de lumière d'un semi-conducteur tel qu'une diode émettrice de lumière, et l'élément (10) dispersant la lumière selon sa longueur d'onde peut être un réseau de diffraction ou une lentille holographique.
PCT/GB1993/000026 1992-01-11 1993-01-08 Dispositif d'analyse avec une source de lumiere polychromatique WO1993014392A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9200562.8 1992-01-11
GB929200562A GB9200562D0 (en) 1992-01-11 1992-01-11 Analytical device with polychromatic light source

Publications (1)

Publication Number Publication Date
WO1993014392A1 true WO1993014392A1 (fr) 1993-07-22

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Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0651252A2 (fr) * 1993-10-28 1995-05-03 Hewlett-Packard Company Bioanalyse holographique
WO1997032212A1 (fr) * 1996-03-01 1997-09-04 Beckman Instruments, Inc. Systeme d'essais multiples simultanes de fixation de ligands
WO1998034098A1 (fr) * 1997-02-04 1998-08-06 Biacore Ab Procede et dispositif permettant l'analyse
WO2001088506A1 (fr) * 2000-05-19 2001-11-22 Schmidt & Haensch Gmbh & Co. Refractometre
DE19811150C2 (de) * 1998-03-14 2002-05-02 Bernd Spangenberg Dünnschichtchromatographiegerät
WO2003014715A1 (fr) * 2001-08-06 2003-02-20 Cambridge Consultants Limited Interferometre de detection par resonance plasmonique de surface
DE19615366B4 (de) * 1996-04-19 2006-02-09 Carl Zeiss Jena Gmbh Verfahren und Einrichtung zum Nachweis physikalischer, chemischer, biologischer oder biochemischer Reaktionen und Wechselwirkungen
US7094595B2 (en) 2000-10-30 2006-08-22 Sru Biosystems, Inc. Label-free high-throughput optical technique for detecting biomolecular interactions
US7309614B1 (en) 2002-12-04 2007-12-18 Sru Biosystems, Inc. Self-referencing biodetection method and patterned bioassays
US7497992B2 (en) 2003-05-08 2009-03-03 Sru Biosystems, Inc. Detection of biochemical interactions on a biosensor using tunable filters and tunable lasers
WO2011147383A1 (fr) * 2010-05-25 2011-12-01 City University Of Hong Kong Dispositifs de capture optique et procédés de détection d'échantillons utilisant ces dispositifs
US8111401B2 (en) 1999-11-05 2012-02-07 Robert Magnusson Guided-mode resonance sensors employing angular, spectral, modal, and polarization diversity for high-precision sensing in compact formats
CN103454254A (zh) * 2013-09-09 2013-12-18 中国科学院苏州生物医学工程技术研究所 一种spr仪探测单元
US9134307B2 (en) 2007-07-11 2015-09-15 X-Body, Inc. Method for determining ion channel modulating properties of a test reagent
US9778267B2 (en) 2007-07-11 2017-10-03 X-Body, Inc. Methods for identifying modulators of ion channels
US10359573B2 (en) 1999-11-05 2019-07-23 Board Of Regents, The University Of Texas System Resonant waveguide-granting devices and methods for using same
JP2019128157A (ja) * 2018-01-19 2019-08-01 国立大学法人電気通信大学 分光用デバイス、分光器、及び分光測定方法
TWI803997B (zh) * 2021-05-28 2023-06-01 采鈺科技股份有限公司 生物感測器

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0257955A2 (fr) * 1986-08-19 1988-03-02 AMERSHAM INTERNATIONAL plc Capteur chimique
GB2197068A (en) * 1986-11-03 1988-05-11 Stc Plc Optical sensor device
EP0305109A1 (fr) * 1987-08-22 1989-03-01 AMERSHAM INTERNATIONAL plc Senseurs biologiques
WO1991010122A1 (fr) * 1989-12-29 1991-07-11 Battelle Development Corporation Detecteur spectroscopique a couche mince
EP0452095A1 (fr) * 1990-04-13 1991-10-16 Hughes Aircraft Company Spectromètre dispersif utilisant un réseau de diffraction holographique
WO1992003720A1 (fr) * 1990-08-17 1992-03-05 Fisons Plc Dispositif analyseur

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0257955A2 (fr) * 1986-08-19 1988-03-02 AMERSHAM INTERNATIONAL plc Capteur chimique
GB2197068A (en) * 1986-11-03 1988-05-11 Stc Plc Optical sensor device
EP0305109A1 (fr) * 1987-08-22 1989-03-01 AMERSHAM INTERNATIONAL plc Senseurs biologiques
WO1991010122A1 (fr) * 1989-12-29 1991-07-11 Battelle Development Corporation Detecteur spectroscopique a couche mince
EP0452095A1 (fr) * 1990-04-13 1991-10-16 Hughes Aircraft Company Spectromètre dispersif utilisant un réseau de diffraction holographique
WO1992003720A1 (fr) * 1990-08-17 1992-03-05 Fisons Plc Dispositif analyseur

Cited By (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0651252A2 (fr) * 1993-10-28 1995-05-03 Hewlett-Packard Company Bioanalyse holographique
EP0651252A3 (fr) * 1993-10-28 1996-03-20 Hewlett Packard Co Bioanalyse holographique.
WO1997032212A1 (fr) * 1996-03-01 1997-09-04 Beckman Instruments, Inc. Systeme d'essais multiples simultanes de fixation de ligands
DE19615366B4 (de) * 1996-04-19 2006-02-09 Carl Zeiss Jena Gmbh Verfahren und Einrichtung zum Nachweis physikalischer, chemischer, biologischer oder biochemischer Reaktionen und Wechselwirkungen
US6714303B2 (en) 1997-02-04 2004-03-30 Biacore Ab Analytical method and apparatus
US6493097B1 (en) 1997-02-04 2002-12-10 Biacore Ab Analytical method and apparatus
US7460236B2 (en) 1997-02-04 2008-12-02 Ge Healthcare Bio-Sciences Ab Analytical method and apparatus
US7081958B2 (en) 1997-02-04 2006-07-25 Biacore Ab Analytical method and apparatus
US7262866B2 (en) 1997-02-04 2007-08-28 Biacore Ab Analytical method and apparatus
WO1998034098A1 (fr) * 1997-02-04 1998-08-06 Biacore Ab Procede et dispositif permettant l'analyse
US6999175B2 (en) 1997-02-04 2006-02-14 Biacore Ab Analytical method and apparatus
DE19811150C2 (de) * 1998-03-14 2002-05-02 Bernd Spangenberg Dünnschichtchromatographiegerät
US6485687B1 (en) 1998-03-14 2002-11-26 Bernd Spangenberg Thin-layer chromatography apparatus
US8111401B2 (en) 1999-11-05 2012-02-07 Robert Magnusson Guided-mode resonance sensors employing angular, spectral, modal, and polarization diversity for high-precision sensing in compact formats
US10359573B2 (en) 1999-11-05 2019-07-23 Board Of Regents, The University Of Texas System Resonant waveguide-granting devices and methods for using same
US6876444B2 (en) * 2000-05-19 2005-04-05 Franz Schmidt & Haensch Gmbh & Co. Refractometer
WO2001088506A1 (fr) * 2000-05-19 2001-11-22 Schmidt & Haensch Gmbh & Co. Refractometre
US7094595B2 (en) 2000-10-30 2006-08-22 Sru Biosystems, Inc. Label-free high-throughput optical technique for detecting biomolecular interactions
US7084980B2 (en) 2001-08-06 2006-08-01 Cambridge Consultants Limited SPR interferometer
WO2003014715A1 (fr) * 2001-08-06 2003-02-20 Cambridge Consultants Limited Interferometre de detection par resonance plasmonique de surface
US7309614B1 (en) 2002-12-04 2007-12-18 Sru Biosystems, Inc. Self-referencing biodetection method and patterned bioassays
US7497992B2 (en) 2003-05-08 2009-03-03 Sru Biosystems, Inc. Detection of biochemical interactions on a biosensor using tunable filters and tunable lasers
US9134307B2 (en) 2007-07-11 2015-09-15 X-Body, Inc. Method for determining ion channel modulating properties of a test reagent
US9778267B2 (en) 2007-07-11 2017-10-03 X-Body, Inc. Methods for identifying modulators of ion channels
WO2011147383A1 (fr) * 2010-05-25 2011-12-01 City University Of Hong Kong Dispositifs de capture optique et procédés de détection d'échantillons utilisant ces dispositifs
CN103454254A (zh) * 2013-09-09 2013-12-18 中国科学院苏州生物医学工程技术研究所 一种spr仪探测单元
JP2019128157A (ja) * 2018-01-19 2019-08-01 国立大学法人電気通信大学 分光用デバイス、分光器、及び分光測定方法
TWI803997B (zh) * 2021-05-28 2023-06-01 采鈺科技股份有限公司 生物感測器

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