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WO1993014393A1 - Dispositif d'analyse a diffraction de lumiere - Google Patents

Dispositif d'analyse a diffraction de lumiere Download PDF

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Publication number
WO1993014393A1
WO1993014393A1 PCT/GB1993/000027 GB9300027W WO9314393A1 WO 1993014393 A1 WO1993014393 A1 WO 1993014393A1 GB 9300027 W GB9300027 W GB 9300027W WO 9314393 A1 WO9314393 A1 WO 9314393A1
Authority
WO
WIPO (PCT)
Prior art keywords
light
sensor
source
refractive index
scattering element
Prior art date
Application number
PCT/GB1993/000027
Other languages
English (en)
Inventor
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
Priority to KR1019930701975A priority Critical patent/KR930703726A/ko
Application filed by Fisons Plc filed Critical Fisons Plc
Priority to JP5512241A priority patent/JPH07502815A/ja
Priority to EP93901849A priority patent/EP0620916A1/fr
Publication of WO1993014393A1 publication Critical patent/WO1993014393A1/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
    • G01N21/17—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
    • 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

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 Bosa ⁇ chi 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.
  • 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, requires relatively complex optics, which leads to relatively high manufacturing costs.
  • apparatus for the determination of a chemical or biochemical species comprising a resonant optical sensor disposed in a light path between a source of monochromatic light and a detector adapted to monitor some characteristic of the light, a light- scattering element being disposed in the light path between the source and the sensor.
  • the apparatus according to the invention is advantageous primarily in that it enables simultaneous irradiation at a range of angles, yet is of relatively simple and inexpensive construction, eg due to the absence of complex optics.
  • a laser Any convenient source of monochromatic light may be used but it is preferable to use a laser.
  • the choice of laser will depend inter alia on the particular form of sensor used.
  • 'light' may include not only visible light but also wavelengths above and below this range, eg in the ultra ⁇ violet and infra-red.
  • the light-scattering element is preferably a speckle plate or diffusion screen. To overcome the problem of speckle being transferred to the output, it may be necessary to translate or rotate the speckle plate rapidly, ie quicker than the integration time of the detector.
  • the speckle plate may be a separate component or it may be formed integrally with another component, eg as the output side of a half-wavelength plate comprising a mica sheet sandwiched between two glass sheets.
  • the light-scattering element is formed on the input side of the sensor, eg where the sensor is formed as a disposable unit.
  • the light source can be located very close to the sensor, enabling the use of a compact and inexpensive light source such as a laser diode.
  • 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 lf 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 wavelength, at a particular angle of incidence.
  • 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 x 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 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 angle of incidence
  • 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 monochromatic light from a laser 5.
  • Light from the laser 5 is collimated by optics 6 and passes through a speckle plate 7 and a polariser 8.
  • the polariser 8 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 laser 5 is arranged to maximise the intensity of the light transmitted through the polariser 8 ie with the polarisation axis aligned with that of the polariser 8.
  • the effect of the speckle plate 7 is to present light at a range of angles (including the angle at which resonance occurs) across the whole length of the interface between the base of the prism 1 and the first coating 2. This is a major advantage of this technique, avoiding errors due to imperfections such as dust or scratches on the surface as may occur when a narrow beam of light is used.
  • the reflected light is passed through a compensator 9 to a polarisation analyser 10.
  • the compensator 9 which may be of any conventional form, 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 compensator 9 is adjusted to allow for the difference in phase change occurring on reflection of the TE and TM components.
  • An approximately plane-polarised beam of light is therefore incident on the analyser 10 and this is adjusted to give zero transmission to a detector 12. This will apply for all angles except near resonance. Near resonance of either component, the phase shift produced by reflection will vary rapidly with angle, resulting in maximum throughput of light through the analyser 10 at resonance.
  • the lens 11 is telecentric, ie located at one focal length from the prism 1 and one focal length from the detector 12. This minimises the effects of positioning errors.
  • FIG. 1 shows a plot of the measured signal intensity against angle before and (dotted line) after complexation of the immobilised biochemicals with the analyte.
  • the resonant optical sensor (comprising the layers 2,3,4) is formed on a disposable glass block 31, the input window 32 of which is formed as a diffusion screen.
  • the light source is a laser diode 33 located, in use, very close to the screen 32 and aligned so as to give the major plane of polarisation at 45° to the TE and TM transmission axes.

Landscapes

  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (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 Or Analysing Materials By Optical Means (AREA)

Abstract

L'appareil pour la détermination d'un composé chimique ou biochimique comprend un détecteur optique résonant (1-4) disposé sur le trajet optique entre une source de lumière monochromatique (5) et un détecteur (12) conçu pour mesurer une caractéristique particulière de la lumière. Un élément diffractant la lumière (7) est disposé sur le trajet optique entre la source (5) et le détecteur (1-4). L'élément diffractant la lumière peut être une plaque à tavelures ou un écran de diffusion et il est de préférence formé sur le côté entrée du détecteur, qui peut être une unité que l'on jette après usage.
PCT/GB1993/000027 1991-01-07 1993-01-08 Dispositif d'analyse a diffraction de lumiere WO1993014393A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
KR1019930701975A KR930703726A (ko) 1991-01-07 1992-01-07 과전류 보호장치
JP5512241A JPH07502815A (ja) 1992-01-11 1993-01-08 光散乱を利用した分析装置
EP93901849A EP0620916A1 (fr) 1992-01-11 1993-01-08 Dispositif d'analyse a diffraction de lumiere

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB929200563A GB9200563D0 (en) 1992-01-11 1992-01-11 Analytical device with light scattering
GB9200563.6 1992-01-11

Publications (1)

Publication Number Publication Date
WO1993014393A1 true WO1993014393A1 (fr) 1993-07-22

Family

ID=10708450

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1993/000027 WO1993014393A1 (fr) 1991-01-07 1993-01-08 Dispositif d'analyse a diffraction de lumiere

Country Status (4)

Country Link
EP (1) EP0620916A1 (fr)
JP (1) JPH07502815A (fr)
GB (1) GB9200563D0 (fr)
WO (1) WO1993014393A1 (fr)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7384797B1 (en) 2000-10-12 2008-06-10 University Of Utah Research Foundation Resonant optical cavities for high-sensitivity high-throughput biological sensors and methods
EP2057498B1 (fr) * 2006-08-22 2015-08-12 Lumus Ltd Dispositif optique guidé par un substrat
US9518288B2 (en) 2008-04-11 2016-12-13 University Of Utah Research Foundation Methods and compositions related to quantitative, array based methylation analysis
US10437031B2 (en) 2016-11-08 2019-10-08 Lumus Ltd. Light-guide device with optical cutoff edge and corresponding production methods
US10564417B2 (en) 2016-10-09 2020-02-18 Lumus Ltd. Aperture multiplier using a rectangular waveguide
US10809528B2 (en) 2014-04-23 2020-10-20 Lumus Ltd. Compact head-mounted display system
US10962784B2 (en) 2005-02-10 2021-03-30 Lumus Ltd. Substrate-guide optical device
US11243434B2 (en) 2017-07-19 2022-02-08 Lumus Ltd. LCOS illumination via LOE
US11262587B2 (en) 2018-05-22 2022-03-01 Lumus Ltd. Optical system and method for improvement of light field uniformity
US11415812B2 (en) 2018-06-26 2022-08-16 Lumus Ltd. Compact collimating optical device and system
US11523092B2 (en) 2019-12-08 2022-12-06 Lumus Ltd. Optical systems with compact image projector
US11849262B2 (en) 2019-03-12 2023-12-19 Lumus Ltd. Image projector
US12210157B2 (en) 2019-04-04 2025-01-28 Lumus Ltd. Air-gap free perpendicular near-eye display

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3778248B2 (ja) * 1999-07-30 2006-05-24 独立行政法人科学技術振興機構 偏光を用いたｓｐｒ装置及びｓｐｒ測定方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2282117A1 (fr) * 1974-08-14 1976-03-12 Anvar Dispositif pour separer sans dephasage un faisceau lumineux et interferometre utilisant ledit dispositif
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

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2282117A1 (fr) * 1974-08-14 1976-03-12 Anvar Dispositif pour separer sans dephasage un faisceau lumineux et interferometre utilisant ledit dispositif
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

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PATENT ABSTRACTS OF JAPAN vol. 11, no. 32 (P-541)(2479) 30 January 1987 *

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7384797B1 (en) 2000-10-12 2008-06-10 University Of Utah Research Foundation Resonant optical cavities for high-sensitivity high-throughput biological sensors and methods
US10962784B2 (en) 2005-02-10 2021-03-30 Lumus Ltd. Substrate-guide optical device
EP2057498B1 (fr) * 2006-08-22 2015-08-12 Lumus Ltd Dispositif optique guidé par un substrat
US9488840B2 (en) 2006-08-22 2016-11-08 Lumus Ltd. Optical device having a light transmitting substrate with external light coupling means
US9518288B2 (en) 2008-04-11 2016-12-13 University Of Utah Research Foundation Methods and compositions related to quantitative, array based methylation analysis
US10809528B2 (en) 2014-04-23 2020-10-20 Lumus Ltd. Compact head-mounted display system
US10908426B2 (en) 2014-04-23 2021-02-02 Lumus Ltd. Compact head-mounted display system
US10564417B2 (en) 2016-10-09 2020-02-18 Lumus Ltd. Aperture multiplier using a rectangular waveguide
US10437031B2 (en) 2016-11-08 2019-10-08 Lumus Ltd. Light-guide device with optical cutoff edge and corresponding production methods
US11378791B2 (en) 2016-11-08 2022-07-05 Lumus Ltd. Light-guide device with optical cutoff edge and corresponding production methods
US11243434B2 (en) 2017-07-19 2022-02-08 Lumus Ltd. LCOS illumination via LOE
US11262587B2 (en) 2018-05-22 2022-03-01 Lumus Ltd. Optical system and method for improvement of light field uniformity
US11415812B2 (en) 2018-06-26 2022-08-16 Lumus Ltd. Compact collimating optical device and system
US11849262B2 (en) 2019-03-12 2023-12-19 Lumus Ltd. Image projector
US12210157B2 (en) 2019-04-04 2025-01-28 Lumus Ltd. Air-gap free perpendicular near-eye display
US11523092B2 (en) 2019-12-08 2022-12-06 Lumus Ltd. Optical systems with compact image projector

Also Published As

Publication number Publication date
GB9200563D0 (en) 1992-03-11
JPH07502815A (ja) 1995-03-23
EP0620916A1 (fr) 1994-10-26

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