GB2197068A - Optical sensor device - Google Patents

Optical sensor device Download PDF

Info

Publication number
GB2197068A
GB2197068A GB8725502A GB8725502A GB2197068A GB 2197068 A GB2197068 A GB 2197068A GB 8725502 A GB8725502 A GB 8725502A GB 8725502 A GB8725502 A GB 8725502A GB 2197068 A GB2197068 A GB 2197068A
Authority
GB
Grant status
Application
Patent type
Prior art keywords
light
surface
film
device
sensor
Prior art date
Legal status (The legal status 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 status listed.)
Granted
Application number
GB8725502A
Other versions
GB2197068B (en )
GB8725502D0 (en )
Inventor
David Neville Batchelder
Jolyon Peter Willson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
STC PLC
Original Assignee
* STC PLC
STC 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

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366Apparatus specially adapted for solid-phase testing
    • G01N33/54373Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/55Specular reflectivity
    • G01N21/552Attenuated total reflection
    • G01N21/553Attenuated total reflection and using surface plasmons

Abstract

An optical sensor device uses surface plasmon resonance to detect the presence of a specific material e.g. antigen in blood. A transparent body 12 is coated with a thin gold film 14 which film may be coated e.g. with an antibody material. A divergent light beam is internally reflected at the face coated with the gold film to a photodiode array 16. The dielectric conditions adjacent the gold film 14 determine the reflection angle(s) at which surface plasmon resonance resonance in the gold film reduces the intensity of reflected light to produce a dark band(s) on the otherwise uniformly illuminated detector array 16. The intensity at each detector in the array is determined, a polynomial corresponding to the light intensity distribution is calculated, and the angle of reflection for which the reflected light is a minimum is determined from the polynomial. <IMAGE>

Description

SPECIFICATION Optical sensor device This invention relates to optical sensors, e.g. ffor chemical, biochemical or biological analysis.

Surface plasmon resonance is an optical surface phenomenon that has recently been employed in the construction of sensors. A surface plasmon is a surface charge density wave at a metal surface. A physical description of the phenomenon is given by H. Raether in Phys. Thin Films, 1977, 74 pp 237-244. The resonance can be observed when the evanescent field of a ppolarised light beam, totally internally reflected from a dielectric interface, interacts with a thin metal film applied to the interface. Typically the interface comprises a smooth surface of a transparent, e.g. glass, body. Light reflected internally from the surface exhibits a minimum intensity for a particular (resonant) angle of incidence, this angle being determined by the dielectric conditions adjacent the metal film and the properties of the metal film itself.

Plasmon resonance is observed when the component of the evanescent field wave vector parallel to the metal/dielectric interface (Kx) is equal to the surface plasmon wave vector (Ksp ) as given by the following equation: <img class="EMIRef" id="027097533-00010001" />

where W is the optical frequency, C the free space velocity of light and em is the real part of the dielectric constant of the metal. Ri is the dielectric constant of the prism and e2 is the dielectric constant of a dielectric applied to the metal. 0 is the angle of incidence of the optical beam at the metal/dielectric interface. Thus the value of the wave vector at resonance is a function of both dielectric constants, the optical wavelength and of the metal.

In a prior art sensor using this phenomenon, a metal film is applied to one surface of a glass prism. Such a device is described in Electronics Letters, 8th Nov. 1984, 20, No. 23, pp 968 to 970. In this device the resonant angle is determined by varying the angle of incidence of light directed through the prism to the surface and measuring the intensity of the reflected light. Such an arrangement requires a high degree of precision in the manufacture or its optical moving parts to provide accurate measurement.

The object of the present invention is to minimise or to overcome this disadvantage.

According to the invention there is provided an optical sensor device, the device including a transparent body having a major surface, a thin conductive film supported on said surface, means for directing a divergent light beam through the body towards said surface so as to excite surface plasmons in the conductive film, and means for detecting the pattern of light reflected internally from the major surface so as, in use, to determine the angle or angles of incidence at which plasmon resonance occurs.

As there are no moving parts the problem of high precision manufacture is alleviated. Typically the reflected light pattern is detected via a photodetector array e.g. of the type employed in a television camera tube. Typically the transparent body is formed of glass on a plastics material.

An embodiment of the invention will now be described with reference to the accompanying drawings in which: Fig. 1 is a sectional schematic view of the surface wave plasmon sensor device; Fig. 2 shows a data processing system for use with the sensor of Fig. 1, and Fig. 3 illustrates data format waveforms used in the system.

Referring to Fig. 1, the sensor device includes a transparent prism 11, e.g. of equilateral triangular cross-section, on one surface of which is mounted a glass microscope slide or cover slip 12. The airgap between the slide 12 and the prism 11 is filled with a quantity of index matching fluid 13. Where the prism 11 is of glass we prefer to employ glycerol (n = 1.47) as the index matching fluid. The upper surface of the slide 12 is coated witn a thin conductive layer 14 e.g. gold, typically 400 to 700 A (40 to 70 nm) in thickness. This layer 14 provides the conductive surface layer in which, in use, surface plasmons are excited.

Light is directed to the prism assembly from a light source 15 comprising e.g. a light emitting diode. Advantageously the light source 1 5 has an output wavelength in the range 500nm to 900nm. The light from the source 1 5 is incident on the prism in the form of a divergent beam.

This beam, after refraction at the glass/metal interface passes back through the prism 11 to a detector array 16. The image 'seen' by the array comprises a substantially uniformly illuminated area with a dark band corresponding to the angle or angles at which plasmon resonance reduces the intensity of reflected light. The position of the absorption band may be determined by a microprocessor (not shown) coupled to the detection array 16.

The angular position of the plasmon resonance is a function of the dielectric constant of a medium in contact with the gold film 14. As the electric field associated with the plasmon decays exponentially into the medium, the device is sensitive only to changes close to the gold surface, typically within 1000 Augstroms. In general the device is used in chemical or biological applications to detect species present in aqueous solutions, e.g. blood serum, whose refractive index is 1.33 to 1.35. For biosensing applications the gold film 14 may be coated with a layer, typically 50 to 100 A thick, of an antibody whose refractive index is 1.5 to 1.6.As the refractive index of the antibody layer differs from that of the adjacent solution, a change in the antibody layer thickness emitting from bonding sheets of a corresponding antigen causes a corresponding change in the plasmon resonance angle. Typically the sensitivity of the device is such that a change of 1A in the antibody layer thickness causes a change of 0.01 in the resonance angle for a source wavelength of 820nm.

The sensitivity of the device may be improved by the use of a light source of short wavelength so that the plasmon penetration depth is then smaller. For example, a source wavelength of 560nm gives a sensitivity of about 0.1O/A. However, it should be noted that, if lower sensitivity can be tolerated, working at longer wavelengths is to be preferred as, at such wavelength, the spectral line width (10-50nm) of LED sources does not unduly broaden the angular width of the resonance. At short wavelengths this effect can be mitigated by the use of a narrow band filter or by the use of a gas laser as the light source. For example, a helium/neon gas laser has suitable output wavelength at 543nm and 594nm.

In an alternative arrangement a pair of similar light sources may be employed. One light source is used to provide sensing whilst the other provides a reference channel to compensate e.g. for non-specific binding effects. The light sources and sample sites are arranged so that the reflected divergent beams are both received by the photodiode array. By selectively enabling the light sources the plasmon resonance angle can be accurately measured for two sample sites only one of which is coated with the antibody. The difference in plasmon resonance angle is then due solely to specific binding effects. For a more accurate cancellation of non-specific binding, the second site can be coated with a different antibody with similar dielectric characteristics, or a deposited dielectric film.

The accuracy of measurement of the sensor system of Fig. 1 may be enhanced by the use of a data aquisition arrangement. Such an arrangement is shown in Fig. 2 of the accompanying drawings. The operation of this data aquisition arrangement is described below with reference to a photodiode arrangement having 128 elements, but it will be clear that this description is given by way of example only, and that alternative arrangements may be employed.

The outputs of the photodiodes of the array are fed via a data aquisition module 21 to a computer 22. The computer determines the position of minimum light intensity, i.e. the plasma resonance angle, by a curve fitting process which identifies this minimum to a high degree of accuracy.

The data aquisition module 21 provides the computer 22 with the following signals which are illustrated in Fig. 3 of the accompanying drawing: (i) An analogue signal, which consists of a series of words where each word comprises 128 pulses and the height of each pulse corresponds to the intensity of the light falling on the corresponding photodiode.

(ii) A master oscillator signal which goes high at the beginning of each pulse in the analogue output signal.

(iii) A start of word signal which goes high at the beginning of each word of the analogue output signal. The master oscillator and therefore also the analogue output signal may have a frequency of about 10kHz.

Processing of the input data is effected by the computer in a two stage process. Firstly, each input word is evaluated to determine the position at which the minimum light intensity occurs.

Data corresponding to the outpots of the 40 photo detections measurement to this minimum position Is then stored for analysis in the second stage of the process.

The second stage involves fitting of a polynomial, e.g. a fourth order polynomial, to the 40 readings obtained from the previous stage. The method used is to minimise the sequences of the differences between the stored values and the values calculated for a general fourth order polynomial. Having obtained expressions for the spaces of the differences, there are one to form a system of linear homogeneous equations. This system of equations is solved by matrix invention to give the described polynomial. The characteristics of this polynomial are then evaluated to determine its turning points and thus to determine the precise position of the minimum value.

It is preferred that connection factors be applied to each element of the 128 element word to compensate for differences in the photo detector elements of the array.

it is known that each element of the array has a different dark-current and that each element becomes saturated at a different level of light intensity, i.e., the relationship between voltage output and light intensity is different for each element of the array, and they differ by at least two parameters. It is assumed that the relationship is linear and thus has exactly two parameters which can be calculated for each photodiode by taking two calibration readings. It is also assumed that for the Ith photodiode there exist numbers offset (I) and linmult (I) such that: V = (L x limult [I] + offset (I) where L = Light intensity on Ith photodiode and V, = Voltage od Ith pulse in analogue output signal word.

First, there is no light falling on the array, ten "words" are read from the photodiode array, and for each I an average height of the Ith pulse is calculated. These are the values of offset (I).

Then when each photodiode in the array has the same light intensity falling on it, ten more "words" again are read fron the photodiode array and an average output for each array element is again calculated. An average of ail the heights of all the pulses is also calculated (i.e., the average of 10 x 128 numbers) and this is assumed to be the true light intensity (i.e., L is the equation above). Thus for each I linmult (I) can be calculated using the formula.

linmult (I) = v - offset (I) L To illustrate the technique, a clear microscope slide was coated with a 45nm thick layer of gold. The gold surface was coated with a monolayer of thyroid stimulating hormone antibody.

Half the slide area was then coated with a monolayer of thyroid stimulating hormone. The slide was mounted on a glass prism and covered with a water film. The arrangement was illuminated using a Honeywell (registered Trade Mark) Sweetspot LED source. The difference in plasmon resonance angle determined by measurements of the two halves of the slide was found to be 0.07 . This illustrates the facility of detection of biochemical materials using the arrangement described herein.

Although the sensor has been described with particular reference to biological or biochemical applications it can of course also be employed as a sensor in purely chemical applications.

Claims (9)

1. An optical sensor device, including a transparent body having a major surface on which a thin conductive film is disposed, means for directing a divergent monochromatic light beam through the body towards said surface so as to excite surface plasmons in the conductive film, and means for detecting the pattern of light reflected internally from the major surface so as, in use, to determine the angle of incidence at which plasmon resonance occurs.
2. A sensor device as claimed in claim 1, wherein the conductive film comprises gold.
3. A sensor device as claimed in claim 1 or 2, wherein the conductive film is coated with a layer of an antibody.
4. A sensor device as claimed in any one of claims 1 to 3, wherein the transparent body is formed of glass or a plastics material.
5. A sensor device as claimed in claim 4, wherein said transparent body comprises a laminar body supported on and in optical contact with a further transparent body.
6. A sensor device as claimed in claim 1, 2 or 3, and incorporating a further reference light source.
7. A sensor device substantially as described herein with reference to and as shown in Fig. 1 of the accompanying drawings.
8. An optical sensor arrangement, including a transparent body having a major surface on which a thin conductive film is disposed, means for directing a divergent monochromatic light beam through the transparent body towards said surface so as to encite surface plasmorous in the conductive film, an array of photodetectors arranged so as to receive light reflected internally at a range of angles from the major surface, means for evaluating the intewnsity of light received from each photodetector, and means for detecting a polynomial corresponding to said light intensities whereby to determine the angle of reflection for which a minimum light intensity indicative of plasmon resonance is obtained.
9. An optical sensor arrangement substantially as described herein with reference to and as shown in the accompanying drawings.
GB8725502A 1986-11-03 1987-10-30 Optical sensor device Expired - Fee Related GB2197068B (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
GB8626221A GB8626221D0 (en) 1986-11-03 1986-11-03 Optical sensor device
GB8725502A GB2197068B (en) 1986-11-03 1987-10-30 Optical sensor device

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB8725502A GB2197068B (en) 1986-11-03 1987-10-30 Optical sensor device

Publications (3)

Publication Number Publication Date
GB8725502D0 GB8725502D0 (en) 1987-12-02
GB2197068A true true GB2197068A (en) 1988-05-11
GB2197068B GB2197068B (en) 1990-08-08

Family

ID=26291486

Family Applications (1)

Application Number Title Priority Date Filing Date
GB8725502A Expired - Fee Related GB2197068B (en) 1986-11-03 1987-10-30 Optical sensor device

Country Status (1)

Country Link
GB (1) GB2197068B (en)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990005295A1 (en) * 1988-11-10 1990-05-17 Pharmacia Ab Optical biosensor system
GB2225850A (en) * 1988-12-09 1990-06-13 Emi Plc Thorn Pressure sensing device
WO1990009576A1 (en) * 1989-02-08 1990-08-23 Plessey Overseas Limited A method for detecting optical phase changes during biosensor operation, biosensing apparatus and a biosensor adapted for use in the same
GB2248497A (en) * 1990-09-26 1992-04-08 Marconi Gec Ltd An optical sensor
GB2259765A (en) * 1991-09-19 1993-03-24 British Gas Plc Optical sensing
WO1993014392A1 (en) * 1992-01-11 1993-07-22 Fisons Plc Analytical device with polychromatic light source
WO1993014393A1 (en) * 1992-01-11 1993-07-22 Fisons Plc Analytical device with light scattering
US5413939A (en) * 1993-06-29 1995-05-09 First Medical, Inc. Solid-phase binding assay system for interferometrically measuring analytes bound to an active receptor
EP0863395A2 (en) * 1997-02-07 1998-09-09 Fuji Photo Film Co., Ltd. Surface plasmon sensor
WO1998057149A1 (en) * 1997-06-11 1998-12-17 Petr Ivanovich Nikitin A method of examining biological, biochemical, and chemical characteristics of a medium and apparatus for its embodiment
EP0957017A2 (en) * 1998-05-12 1999-11-17 Nippon Sheet Glass Co., Ltd. Liquid detector
WO2006023513A1 (en) * 2004-08-17 2006-03-02 Wei David T Using a polaron interaction zone as an interface to integrate a plasmon layer and a semiconductor detector
WO2006074350A2 (en) 2005-01-06 2006-07-13 Cellectricon Ab Systems and methods for rapidly changing the solution environment around sensors
US7488406B2 (en) * 2003-02-12 2009-02-10 The Secretary Of State For Defence Apparatus for collecting particles
EP2347824A2 (en) 2002-02-12 2011-07-27 Cellectricon Ab Systems and methods for rapidly changing the solution environment around sensors
CN103604775A (en) * 2013-07-04 2014-02-26 丹阳聚辰光电科技有限公司 Microbiological detection instrument based on micro-fluidic chip and SPR detection method thereof
US20140227136A1 (en) * 2011-09-28 2014-08-14 Ge Heathcare Bio-Sciences Ab Surface plasmon resonance biosensor system

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2173895A (en) * 1985-04-12 1986-10-22 Plessey Co Plc Optical assay

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2173895A (en) * 1985-04-12 1986-10-22 Plessey Co Plc Optical assay

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0534941B1 (en) * 1988-11-10 1999-06-16 Biacore Aktiebolag Optical interface means
US5313264A (en) * 1988-11-10 1994-05-17 Pharmacia Biosensor Ab Optical biosensor system
WO1990005295A1 (en) * 1988-11-10 1990-05-17 Pharmacia Ab Optical biosensor system
GB2225850A (en) * 1988-12-09 1990-06-13 Emi Plc Thorn Pressure sensing device
GB2225850B (en) * 1988-12-09 1992-12-23 Emi Plc Thorn Pressure sensing device
WO1990009576A1 (en) * 1989-02-08 1990-08-23 Plessey Overseas Limited A method for detecting optical phase changes during biosensor operation, biosensing apparatus and a biosensor adapted for use in the same
US5229833A (en) * 1990-09-26 1993-07-20 Gec-Marconi Limited Optical sensor
GB2248497A (en) * 1990-09-26 1992-04-08 Marconi Gec Ltd An optical sensor
GB2248497B (en) * 1990-09-26 1994-05-25 Marconi Gec Ltd An optical sensor
GB2259765B (en) * 1991-09-19 1995-12-20 British Gas Plc Optical sensing
US5508809A (en) * 1991-09-19 1996-04-16 British Gas Plc Optical sensor
GB2259765A (en) * 1991-09-19 1993-03-24 British Gas Plc Optical sensing
WO1993014393A1 (en) * 1992-01-11 1993-07-22 Fisons Plc Analytical device with light scattering
WO1993014392A1 (en) * 1992-01-11 1993-07-22 Fisons Plc Analytical device with polychromatic light source
US5413939A (en) * 1993-06-29 1995-05-09 First Medical, Inc. Solid-phase binding assay system for interferometrically measuring analytes bound to an active receptor
EP0863395A2 (en) * 1997-02-07 1998-09-09 Fuji Photo Film Co., Ltd. Surface plasmon sensor
US5923031A (en) * 1997-02-07 1999-07-13 Fuji Photo Film Co., Ltd. Surface plasmon sensor having a coupler with a refractive index matching liquid
EP0863395A3 (en) * 1997-02-07 1998-09-16 Fuji Photo Film Co., Ltd. Surface plasmon sensor
WO1998057149A1 (en) * 1997-06-11 1998-12-17 Petr Ivanovich Nikitin A method of examining biological, biochemical, and chemical characteristics of a medium and apparatus for its embodiment
US6628376B1 (en) 1997-06-11 2003-09-30 Petr Ivanovich Nikitin Method of examining biological, biochemical, and chemical characteristics of a medium and apparatus for its embodiment
EP0957017A2 (en) * 1998-05-12 1999-11-17 Nippon Sheet Glass Co., Ltd. Liquid detector
EP0957017A3 (en) * 1998-05-12 2000-07-12 Nippon Sheet Glass Co., Ltd. Liquid detector
EP2368635A2 (en) 2002-02-12 2011-09-28 Cellectricon Ab Systems and methods for rapidly changing the solution environment around sensors
EP2368636A2 (en) 2002-02-12 2011-09-28 Cellectricon Ab Systems and methods for rapidly changing the solution environment around sensors
EP2347824A2 (en) 2002-02-12 2011-07-27 Cellectricon Ab Systems and methods for rapidly changing the solution environment around sensors
US7488406B2 (en) * 2003-02-12 2009-02-10 The Secretary Of State For Defence Apparatus for collecting particles
WO2006023513A1 (en) * 2004-08-17 2006-03-02 Wei David T Using a polaron interaction zone as an interface to integrate a plasmon layer and a semiconductor detector
WO2006074350A2 (en) 2005-01-06 2006-07-13 Cellectricon Ab Systems and methods for rapidly changing the solution environment around sensors
US20140227136A1 (en) * 2011-09-28 2014-08-14 Ge Heathcare Bio-Sciences Ab Surface plasmon resonance biosensor system
CN103604775A (en) * 2013-07-04 2014-02-26 丹阳聚辰光电科技有限公司 Microbiological detection instrument based on micro-fluidic chip and SPR detection method thereof
CN103604775B (en) * 2013-07-04 2016-08-10 中国科学院苏州纳米技术与纳米仿生研究所 Based microbial detection instrument and its method of detecting spr microfluidic chip

Also Published As

Publication number Publication date Type
GB2197068B (en) 1990-08-08 grant
GB8725502D0 (en) 1987-12-02 grant

Similar Documents

Publication Publication Date Title
US3604927A (en) Total reflection fluorescence spectroscopy
US6320991B1 (en) Optical sensor having dielectric film stack
USRE37473E1 (en) Diffraction anomaly sensor having grating coated with protective dielectric layer
US6330062B1 (en) Fourier transform surface plasmon resonance adsorption sensor instrument
US5478755A (en) Long range surface plasma resonance immunoassay
US6124937A (en) Method and device for combined absorption and reflectance spectroscopy
US4857273A (en) Biosensors
US6287871B1 (en) System for determining analyte concentration
US3807870A (en) Apparatus for measuring the distance between surfaces of transparent material
Schmitt et al. An integrated system for optical biomolecular interaction analysis
US5804453A (en) Fiber optic direct-sensing bioprobe using a phase-tracking approach
US5577137A (en) Optical chemical sensor and method using same employing a multiplicity of fluorophores contained in the free volume of a polymeric optical waveguide or in pores of a ceramic waveguide
US6277330B1 (en) Optical sensor for detecting chemical substances dissolved or dispersed in water
US5641640A (en) Method of assaying for an analyte using surface plasmon resonance
US20050236554A1 (en) Optical interrogation system and method for 2-D sensor arrays
US6130439A (en) Instrument for measuring the refractive index of a fluid
US20050018949A1 (en) Multiple array surface plasmon resonance biosensor
US4745293A (en) Method and apparatus for optically measuring fluid levels
US5846843A (en) Sensor using long range surface plasmon resonance with diffraction double-grating
US6335793B1 (en) Planar waveguide chemical sensor
US6549687B1 (en) System and method for measuring physical, chemical and biological stimuli using vertical cavity surface emitting lasers with integrated tuner
US6534011B1 (en) Device for detecting biochemical or chemical substances by fluorescence excitation
US7652767B2 (en) Optical sensor with chemically reactive surface
US5583643A (en) Methods of and apparatus for measurement using acousto-optic devices
Melendez et al. Development of a surface plasmon resonance sensor for commercial applications

Legal Events

Date Code Title Description
PCNP Patent ceased through non-payment of renewal fee