WO1992005426A1 - Biological sensors - Google Patents
Biological sensors Download PDFInfo
- Publication number
- WO1992005426A1 WO1992005426A1 PCT/GB1991/001573 GB9101573W WO9205426A1 WO 1992005426 A1 WO1992005426 A1 WO 1992005426A1 GB 9101573 W GB9101573 W GB 9101573W WO 9205426 A1 WO9205426 A1 WO 9205426A1
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- WO
- WIPO (PCT)
- Prior art keywords
- layer
- incident
- block
- sensor
- transparent
- Prior art date
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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
- 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
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
Definitions
- This invention relates to sensors for use in biological, biochemical and chemical testing and in particular to immunosensors used to monitor the inter ⁇ action of antibodies with their corresponding antigens.
- SPR can be used to detect minute changes in the refractive index of the surface as the reaction between the antigen and the antibody proceeds.
- Surface plasmon resonance is the oscillation of the - - plasma of free electrons which exists at a metal boundary. These oscillations are affected by the refractive index of the material adjacent the metal surface and it is this that forms the basis of the sensor mechanism.
- Surface plasmon resonance may be 5 achieved by using the evanescent wave which is generated v. en a light beam is totally internally reflected at the boundary of a medium, e.g. glass, which has a high dielectric constant.
- the use of SPR in biological sensors has been known for some time, 0 se e for example our European patent application No. 0305109.
- the silver or other metallic layer necessary for SPR is applied not directly to the lens, but to a thin sheet of transparent material which latter is in turn optically coupled to the lens using a coupling fluid.
- a coupling fluid may take the form of a throw-away glass slide, such as a microscope slide or similar, or may take the form of a continuous or semi-continuous material which is moved to a fresh area in between each test. Whichever of these is used, there is a need to index match, with a coupling fluid of appropriate refractive index, the transparent slab to the remaining non-replaceable optical components of the sensor. It is clearly better to have a system where the manipulation of index matching fluids is avoided.
- a continuous transparent membrane is used as the throw-away component mentioned above.
- the membrane is supported not by a hemicylindrical lens as described above, but by a plane block of transparent material which, in the described embodiments, is rectangular in shape.
- the incident light beam is taken via a reflecting surface whose shape is suitably shaped so that the effects of refraction are eliminated, or at least reduced to an acceptable level .
- a sensor for use in biological, biochemical or chemical testing, said sensor comprising a block of material transparent to electromagnetic radiation, a layer of metallic material applied to at least part of a first surface of said block, a layer of sensitive material applied to the metallic layer, means for introducing onto the sensitive layer so as to react therewith a sample to be analysed, a source of electromagnetic radiation, said radiation being incident on a second surface of said block, said second surface being so formed as to cause at least a portion of the incident ray to be transmitted into the block in a direction such as to result in total internal reflection, and hence surface plasmon resonance, at said first surface, and detector means positioned to receive the internally reflected beam, the arrangement being such that the characteristics of the surface plasmon resonance, as detected by the detector means, is dependent upon the reaction between the sample and the sensitive layer.
- the invention is directed primarily towards those circumstances where the "block" of transparent material is relatively thin.
- Part of the object of the invention is to provide the apparatus with a non- expensive part which is thrown away or moved aside and replaced between each test.
- the other part of the object of the invention is to achieve this without the need to use an optical coupling fluid (see above) .
- the minimum requirements for a throw-away or replaceable part is to provide the metallic layer, and the sensitive layer. Since both of these layers are relatively thin, and are not readily self-supporting, clearly a third minimum requirement is a support layer. Physical requirements dictate that the support layer is positioned on the opposite side of the metallic layer from the sensitive layer and, since this is where the light is incident for SPR, the support layer must, in turn, be of transparent material.
- this transparent support layer has always been associated, from the optical point of view, with larger fixed optical components such as the aforementioned hemicylindrical lens and this immediately introduces the requirement of optical coupling fluids.
- What the present invention does, in essence, is to provide an apparatus in which the transparent support layer is used by itself to provide the internally reflected beam necessary for SPR.
- said first and second surfaces of the block will be generally parallel with one another and would then take the form of the a ⁇ r surfaces of a microscope slide or a film-like transparent membrane such as described in EP-A- 0343826.
- the second surface has to be so formed as to cause the beam transmitted into the block to be in such a direction that surface plasmon resonance occurs at the apposite (first) surface.
- the methods may be broadly divided into three groups:- 1) The formation, on the second surface, of an optical diffraction grating onto which the incident beam from the radiation source is applied.
- the zeroth order transmitted beam is substantially coaxial with the incident beam and is therefore of little value,- however the higher order transmitted beams are directed into the block at ever larger angles with respect to the incident beam. Even the first order diffracted beam is likely to be deflected through a sufficient angle to cause total internal reflection at the opposite (first) surface and this will therefore be the one to use. If not sufficient, however, still higher order beams could be used. There is some loss of beam power in this method, but this can be compensated for either by using a suitably blazed grating, adapted specifically for the desired order, or by increasing the source power, or both.
- the geometry of the second surface is such that, at the area of incidence, the angle of the first surface is such as to allow the incident wave to be transmitted.
- the area of incidence can be shaped to provide a converging effect, so that a parallel incident beam may be converted into a converging "fan" beam, which has a focus on the first surface - for more detail of the fan " beam concept, see our copending application EP-A-0305109.
- the light transmitted into the block will be scattered over a range of angles with respect to the incident beam, and some of these angles will be sufficiently great as to result in total internal reflection on the opposite (first) surface.
- a true " ⁇ 5 random roughness will cause this scattering to obey a cosine law of intensity with respect to the axis of the incident beam (Lambert's Law) and will guarantee that some at least of the transmitted light will be bent through a sufficient angle to be totally 0 internally reflected at the opposite surface.
- the layer applied to the metal film is described herein as an antibody layer for use in immunoassays, it will be seen that any sensitive layer whose refractive index changes upon an event occurring 25 can be used thus to provide a sensitive detector having a wide variety of applications in the fields of biology, biochemistry and chemistry.
- the material comprising the sensitive layer may be specific to a particular entity within the sample or may be non- 30 specific (i.e. may interact with several species of entity within the sample) .
- recognition molecules such as the aforementioned antibodies which will specifically bind an analyte of interest within the sample, DNA/RNA 35 probes which will bind with their complements in the sample liquid, or lectins, glycoproteins or enzyme substrates, all of which are capable of recognising and binding with the other partner in a bimolecular recognition pair.
- non-specific materials include hydrophobic materials, for example in the form of a monolayer of phospholipid-type molecules to capture amphipathic molecules, or hydrophilic materials which would capture polysaccharides.
- hydrophobic materials for example in the form of a monolayer of phospholipid-type molecules to capture amphipathic molecules, or hydrophilic materials which would capture polysaccharides.
- the surface of the metal layer itself can form an effective non-specific binding material. Silver or gold surfaces will bind proteins or polynucleotides such as DNA or RNA without the need for any further coating and, in this case, a separate sensitive layer is effectively dispensed with altogether, and the surface of the metal film used directly for the capture of entities within the sample to be tested.
- the metal layer material is commonly silver or gold, usually applied by evaporation.
- the layer needs to be as uniform as possible in order to cater for minute movement in the point of incidence of the incoming beam. It is assumed that a structural metal film will give the best resonance and there are various ways in which the transparent block can be pretreated to improve the performance of the metal layer and in particular to control the natural tendency of such films to form discontinuous islands • * -
- electroless plated films have a stronger tendency to an island structure and to bigger islands with greater spacing than evaporating films. This could be of advantage in tuning to light of a prescribed wavelength.
- Coating performance can also be improved by:-
- Figure 1 is a diagrammatic view of an SPR biosensor in which the incident light is deflected by means of a diffraction grating
- Figure 2 is a ray diagram showing the principle of operation of the embodiment of Figure 1
- Figure 3 is a view similar to that of Figure
- Figure 4 is a version of the Figure 3 embodiment utilising multiple test sites;
- Figure 5 is a perspective view of the Figure 3 embodiment, showing multiple test sites,-
- Figure 6 is a view similar to that of Figure
- Figure 7 is a view similar to Figure 1 , showing an alternative embodiment
- Figure 8 is an enlarged view of part of Figure 7, illustrating the manner of constructing the shape of the input surface of the transparent block; and
- Figure 9 is a diagrammatic side view of a
- membrane biosensor of the type suitable for use with the present invention.
- the apparatus comprises a housing 34 having a hollow interior 35 in which is positioned a printed circuit board 37 on which is mounted the electronic circuitry associated with the apparatus.
- An aperture is formed in the top part of the housing, which aperture is covered by a support plate 31 of transparent material.
- a radiation source 32 produces a collimated input beam 33 of electromagnetic radiation. The frequency of the radiation must be such as to result in the generation of surface plasmon waves and in practice will be within or near the visible region. Suitable sources include a helium neon laser or an infra red diode laser, but an ordinary light source, with suitable filters and collimators, could be used.
- the light beam 33 is applied to a mirror 36 which in turn directs the light onto a concave reflecting surface 38 and thence to the transparent support plate 31.
- the mirror 36 is driven by motor means (not shown) , to rotate in an oscillatory manner between the limit positions shown by the solid and dotted lines. The result of this is that the light beam applied to the reflecting surface 38 scans backwards and forwards between the positions represented by the beams 22 (solid line) and 23 (dotted line) .
- a membrane in the form of a continuous film 24 Positioned in the top surface of the support plate 31 is a membrane in the form of a continuous film 24 which is movable from left to right in
- the membrane takes the form of a layer of flexible transparent material to which is applied a metal film layer for example of silver and a final layer of sensitive material, such as an antibody layer.
- a metal film layer for example of silver
- a final layer of sensitive material such as an antibody layer.
- the arrangement is such that the layers are in the order - transparent support plate 31 - flexible transparent layer - metal film layer - sensitive layer.
- the sensitive layer is on the top when seen in Figure 9.
- the flexible transparent layer lies directly against the transparent plate, possibly with an optical coupling fluid in between.
- the refractive index of the plate 31 is the same as that of the flexible transparent layer so that the two effectively act as a single transparent block, as far as light is concerned.
- Light incident from reflecting surface 38 enters the block and is incident on the metal film layer.
- the metal film layer causes the light to be internally reflected at a point 27 lying on the interface between the flexible transparent layer and the metal film layer of the film 24.
- the internally reflected light passes out of the block, and is reflected off a further concave reflecting surface 28 to be incident on the sensitive surface of a light detector 29.
- the reflective surface 38 has a shape which is such as to bring light incident thereon from a range of angles to a single point 27, despite the refraction which inevitably occurs when the light enters the transparent plate 31.
- reflective surface 28 has a shape which is such as to bring light incident thereon from a range of angles to a single point at the sensitive area of detector 29.
- the sensitive layer is one whose refractive index changes as it reacts with a sample, in the manner described above. This changes the angle of incidence at which surface plasmon resonance occurs, and thus the reaction of a sample with the sensitive layer can be monitored by observing the dip as the test proceeds.
- the plate 31 is dispensed with, and that surface of the film 24 onto which the light from source 32 is incident is treated in such a way as to cause the incident beam at point 27 to be internally reflected to cause the necessary surface plasmon resonance. This is achieved by impressing a pattern onto the surface.
- FIG. 1 there is shown a block 1 of material transparent to the radiation.
- the block 1 takes the form of a thin block of glass having parallel major surfaces 2, 3.
- An example would be a microscope slide.
- An incoming parallel beam 4 from a radiation source, such as source 32, is passed through a convex lens 5 which causes the beam to converge to a focus 6 at the upper, input, surface 2 of the block 1.
- the beam 4 is illustrated for clarity as just two ray lines representing the outer limits of the beam. It will be appreciated that the beam 4 is in fact a "solid" beam between the drawn lines.
- That area of the surface 2 surrounding the focus point 6 is formed with an optical diffraction grating 7.
- the grating is simply a series of parallel triangular section ridges extending across the surface 2 in a direction orthogonal to the plane of Figure 1.
- Such a grating will provide 4 series of diffracted waves: two reflected, and two transmitted into the block 1. Only one of the transmitted beams, reference 8, is shown, for clarity. This beam represents the first order diffracted beam. A similar first-order beam (not shown) is diffracted in the other direction.
- the beam 8 passes through the block 1 , diverging as it does so, until it reaches the internal surface 3. At this surface, total internal reflection takes place, and the reflected beam 12 emerges from the block at the edge 9 for detection in a photo sensitive or similar detector (not shown) such as detector 29.
- a first layer 10 of silver overlayed by a second layer 11 of sensitive material Formed on the lower surface 3 of the block is a first layer 10 of silver overlayed by a second layer 11 of sensitive material. Provided the angle of incidence at surface 3 is correct, the arrangement shown will result in the generation of surface plasmons at the interface between the silver and the glass, in the manner described above.
- a sample (not shown) which is introduced into the area adjacent the sensitive layer 11 may or may not react with the sensitive layer, and any reaction which occurs between the two can be monitored by the surface plasmon resonance, using the information in the form of the internally reflected beam 12, as seen by the detector.
- the spread of angles in beam 8 incident on surface 3 ensures that the whole SPR dip can be monitored - for more detail, see EP-A-0305109.
- the shape of the ridges of the diffraction grating can be altered to tailor the grating output as required.
- the shape may be such as to give maximum output in the first order beams.
- a crossed or "eggbox" grating may alternatively be used, this giving a greater number of sets of beams emerging from the point 6.
- FIG. 2 there is shown a computer-generated ray diagram which illustrates the principle of operation of the device of Figure 1.
- the spread of the input beam 4 after being converged by lens 5 is shown as being great enough to provide a sufficient spread of the first-order diffracted beam 8 to give a situation in which, at surface 3, part 12 of the beam is totally internally reflected, as shown in Figure 1, and part 13 is transmitted into the medium below block 1, after undergoing refraction, as illustrated.
- Figure 3 illustrates an embodiment similar to that of Figure 1.
- This embodiment is intended for use with a block 1 which takes the form of a continuous strip of transparent material, for example polymer, such as described in our copending application EP-A-0343826.
- the formations illustrated in Figure 3 will be repeated along the strip to enable either simultaneous multiple testing (see below), or movement of the strip from one test station to the next, or both.
- the formations comprise firstly a convex protrusion 14 on surface 2, which protrusion carries the grating 7, and secondly a sawtooth-section groove 15 which defines a sloping surface 16 through which the internally reflected beam 12 may emerge.
- the lens 5 is omitted.
- the parallel incident beam 4 is applied directly to surface 2 in the area of the convex projection 14.
- the combined effect of the convex projection, and the diffraction grating 7 is to provide a first-order diffracted beam 8 which is converging.
- This beam is arranged to come to a focus 17 at the surface 3, and thus provides a fan beam, as referred to above, having a spread of angles to cover those necessary to cover the surface plasmon resonance dip. This arrangement thus avoids the problem of the somewhat larger area of interrogation found in the device of Figure 1 , and should therefore give improved sensitivity.
- the internally reflected beam 12 is able to emerge through the top surface 2 by virtue of the groove 15. Without this groove, the beam 12 would simply be internally reflected at the top surface 2 and would not therefore emerge from block 1.
- the surface 16 may be shaped to refract the beam m the manner required - perhaps to give a greater beam spread (which will give enhanced resolution at the detector) or to give no refraction at all.
- a bl ⁇ ck 1 in the form of a continuous strip illustrating the formation of a plurality of individual testing sites, of the type shown in Figures 1 and 3, along its length.
- each testing site comprises features from both Figures 1 and 3: an input lens 5, in association with a planar grating 7 gives a diverging incident beam 8 to the interrogation area on surface 3, while a sawtooth groove 15 is used to allow the internally reflected beam to emerge from the upper surface 2 to be incident on a suitable detector.
- the device is set up for multiple testing of 4 separate samples (not shown), each brought into contact with a respective sensitive layer 11 associated with one of the testing sites.
- Separate photo sensitive, or similar, detectors can be used to receive the internally reflected light from each site, or a single large photo-sensitive array detector 18 can be used, as shown. If using a single detector 18, care should be taken that adjacent beams 12 do not overlap at the sensitive surface of the detector since this will lead to ambiguity.
- the groove 15 is cut right across the width of the strip and so is used by all four testing sites across the width.
- the diffraction grating 7 may likewise extend right across the width, as a single grating, or may be formed as individual gratings, as shown. Separate light sources may be used, or a single light source whose output is split to provide the individual separate input beams 4.
- the input beam 4 may be in the form of a planar sheet extending widthwise of the strip, and lens 5 a single cylindrical lens extending right across the width of the strip.
- Figures 1 and 3 would show sections through the various parts, which extend above and below the plane of the drawing.
- the incoming fan beam 8 would in fact have a wedge shape in three dimensions, and the point of incidence on the surface 3 would be a line of incidence extending above and below the plane of the drawing.
- the metal layer ⁇ o may be provided as a continuous strip across the width with individual "patches" of sensitive material applied for each of the four sites; alternatively, individual patches of both metal and sensitive material may be provided for each site.
- a formation such as shown in Figure 5 may be repeated at equal intervals along the length of the continuous strip to enable a single such strip to be used for a plurality of tests by indexing between each test, or for multiple tests of an X-Y array, as mentioned above, or both.
- FIG. 6 there is shown a computer-generated ray diagram similar to Figure 2 which is intended to illustrate the "scattering" embodiment of the invention, referred to above.
- the input surface 2 of the block 1 is roughened, at least around the area where the input beam 4 impinges on the block.
- the beam 4 would in practice be a solid beam similar to that described above.
- the beam 4 is shown impinging on the block at 90 , but this is not essential.
- the effect of the roughened surface 2 is to cause the light to be scattered from the point 19 of impingement. Some light will be reflected, but this is not shown; the remainder is transmitted into the block and is scattered over a range of angles, as illustrated. Light will also be scattered to the left of the axis of incidence, but this is also not shown. At least some of the transmitted light will be bent through a sufficient angle at point 19 to be internally reflected when it reaches the surface 3; the remainder leaves the block 1 at the surface 3, as illustrated.
- the internally reflected light can be used in the manner described in more detail in Figure 1 to form the basis of an SPR sensor. It will further be appreciated that the teaching of Figure 6 could be applied to the embodiment of Figures 3, 4 or 5.
- the transmitted light is scattered to have a cosine distribution of intensity in relation to the incident beam.
- the intensity of the beam is highest along the axis of incidence (i.e. straight down in Figure 6), and reduces according to a cosine relationship as the viewer moves angularly away from the axis. That part of the beam which is incident at surface 3 at a suitable range of angles can be used to generate the surface plasmon which is used to monitor the progress of the reaction (if any) between a sample and an adjacent sensitive layer.
- FIG. 7 there is shown a further embodiment, comparable to Figure 4, showing multiple testing sites along the length of a block 1 in the form of a continuous strip of transparent material.
- the top surface 2 of block 1 is shaped to allow the passage of both incoming and outgoing beams for each test site. This is achieved by forming, across the width of the strip, a series of parallel spaced grooves 20 which allow, in a comparable manner to the groove 15 in Figure 3, the internally reflected beam 12 to leave the upper surface 2. At the same time, each groove also allows the incoming beam 4 for the next adjacent test site to enter the block 1 through the top surface 2 without being substantially deflected.
- the grooves 20 are defined by forming, on the surface 2, a series of parallel widthwise-extending spaced ridges 21. These ridges are convex in shape and, in the embodiment illustrated are in fact part- cylindrical. Thus the cross-sectional shape of each ridge 21, as seen in Figures 7 and 8, is an arc of a circle. Provided that the geometry is correct, this arrangement will bring to a focal point on lower surface 3 a parallel incident beam 4. By the same token, the internally reflected beam, diverging from the focal point on surface 3, will be converted into a parallel beam as it emerges from the upper surface of block 1 , and continues as a parallel beam to the common detector 18. Thus lens 5 is not needed, and the incident beam is brought to a point or narrow line at surface 3, thus providing maximum sensitivity. The calculation of the profile for the surface
- Figure 8 illustrates this for a continuous strip in the form of a polyester film of refractive index 1.65 where the angle of spread of the incoming fan beam is chosen to be about 6 to span the surface plasmon resonance modes for typical biosensor environments at a silver-coated surface 3.
- Other surface structures which focus in this way are possible, with the near-cylindrical or spherical surfaces displaced by greater or lesser amounts, and with the surfaces through which the internally reflected beams exit made with other profiles.
- the continuous film shown in Figure 7 could also be used for testing at a single station at a time, with indexing of the strip between tests.
- the strip could also be fabricated with a plurality of sites across the width, such as is illustrated in Figure 5.
- the various shapes and treatments of the surface 2 of the block 1 in the above-described embodiments can be formed in various ways. It is now possible, on a mass production basis, to impress patterns onto transparent surfaces to the standards necessary to meet optical requirements. Conventional moulding or hot forming techniques may be used, assisted or replaced by, for example, chemically assisted excimer laser ablation of the surface.
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Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB909019999A GB9019999D0 (en) | 1990-09-13 | 1990-09-13 | Biological sensors |
GB9019999.3 | 1990-09-13 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1992005426A1 true WO1992005426A1 (en) | 1992-04-02 |
Family
ID=10682129
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB1991/001573 WO1992005426A1 (en) | 1990-09-13 | 1991-09-13 | Biological sensors |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP0548215A1 (en) |
GB (1) | GB9019999D0 (en) |
WO (1) | WO1992005426A1 (en) |
Cited By (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1993014391A1 (en) * | 1992-01-11 | 1993-07-22 | Fisons Plc | Analytical device with variable angle of incidence |
US5474815A (en) * | 1993-10-01 | 1995-12-12 | Eastman Kodak Company | Production of carriers for surface plasmon resonance |
EP0805347A2 (en) * | 1996-04-30 | 1997-11-05 | Fuji Photo Film Co., Ltd. | Surface plasmon sensor |
EP0863395A2 (en) * | 1997-02-07 | 1998-09-09 | Fuji Photo Film Co., Ltd. | Surface plasmon sensor |
EP0866330A2 (en) * | 1997-03-21 | 1998-09-23 | Nippon Sheet Glass Co., Ltd. | A transparent substrate having a function of liquid detection |
EP0893317A2 (en) * | 1997-07-22 | 1999-01-27 | Nippon Sheet Glass Co. Ltd. | Transparent substrate having rain sensor |
WO2002073171A1 (en) * | 2001-03-14 | 2002-09-19 | Biacore Ab | Apparatus and method for total internal reflection spectroscopy |
EP1269158A2 (en) * | 2000-07-21 | 2003-01-02 | Vir A/S | Coupling elements for surface plasmon resonance sensors |
WO2004061434A1 (en) * | 2003-01-02 | 2004-07-22 | Hydrosense Ip Limited | Surface plasmon resonance sensor |
US6775003B2 (en) | 2001-03-14 | 2004-08-10 | Biacore Ab | Apparatus and method for total internal reflection spectroscopy |
DE10324973A1 (en) * | 2003-05-27 | 2004-12-30 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Arrangement and method for the optical detection of chemical, biochemical molecules and / or particles contained in samples |
EP1507139A2 (en) * | 2003-08-14 | 2005-02-16 | Agilent Technologies Inc | Arrays for multiplexed surface plasmon resonance detection of biological molecules |
WO2009078506A1 (en) * | 2007-12-17 | 2009-06-25 | Electronics And Telecommunications Research Institute | Sensor for biological detection |
DE202011001569U1 (en) * | 2011-01-14 | 2012-03-01 | Berthold Technologies Gmbh & Co. Kg | Device for measuring optical properties in microplates |
DE102010041426A1 (en) * | 2010-09-27 | 2012-05-03 | Siemens Aktiengesellschaft | Measuring unit for optical estimation of liquid for determining concentration of analytes, has two excitation light paths and device for adjusting wavelength or intensity or polarization direction |
DE102007033124B4 (en) * | 2007-07-16 | 2012-12-06 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Device for the optical detection of substances in a liquid or gaseous medium |
DE102017223851A1 (en) * | 2017-12-28 | 2019-07-04 | Biochip Systems GmbH | Sensor arrangement for detecting at least one material property of a sample and microtiter plate with a plurality of sensor arrangements |
DE102018202591A1 (en) * | 2018-02-21 | 2019-08-22 | Robert Bosch Gmbh | Optical system and method of making an optical system |
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-
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- 1990-09-13 GB GB909019999A patent/GB9019999D0/en active Pending
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1991
- 1991-09-13 WO PCT/GB1991/001573 patent/WO1992005426A1/en not_active Application Discontinuation
- 1991-09-13 EP EP19910916817 patent/EP0548215A1/en not_active Ceased
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GB2185308A (en) * | 1986-01-10 | 1987-07-15 | Stc Plc | Optical waveguide material sensor |
EP0305109A1 (en) * | 1987-08-22 | 1989-03-01 | AMERSHAM INTERNATIONAL plc | Biological sensors |
WO1989009394A1 (en) * | 1988-03-29 | 1989-10-05 | Ares-Serono Research & Development Limited Partner | Waveguide sensor |
EP0341928A1 (en) * | 1988-05-10 | 1989-11-15 | AMERSHAM INTERNATIONAL plc | Improvements relating to surface plasmon resonance sensors |
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Cited By (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1993014391A1 (en) * | 1992-01-11 | 1993-07-22 | Fisons Plc | Analytical device with variable angle of incidence |
US5491556A (en) * | 1992-01-11 | 1996-02-13 | Fisons, Plc | Analytical device with variable angle of incidence |
US5474815A (en) * | 1993-10-01 | 1995-12-12 | Eastman Kodak Company | Production of carriers for surface plasmon resonance |
EP0805347A2 (en) * | 1996-04-30 | 1997-11-05 | Fuji Photo Film Co., Ltd. | Surface plasmon sensor |
EP0805347A3 (en) * | 1996-04-30 | 1998-08-05 | Fuji Photo Film Co., Ltd. | Surface plasmon sensor |
US5907408A (en) * | 1996-04-30 | 1999-05-25 | Fuji Photo Film Co., Ltd. | Surface plasmon sensor |
EP0863395A3 (en) * | 1997-02-07 | 1998-09-16 | Fuji Photo Film Co., Ltd. | Surface plasmon sensor |
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GB9019999D0 (en) | 1990-10-24 |
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