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
  • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
  • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
  • G01N21/7703—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator using reagent-clad optical fibres or optical waveguides
  • G01N21/774—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator using reagent-clad optical fibres or optical waveguides the reagent being on a grating or periodic structure
  • G01N21/7743—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator using reagent-clad optical fibres or optical waveguides the reagent being on a grating or periodic structure the reagent-coated grating coupling light in or out of the waveguide
• • 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
  • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
  • G01N2021/7769—Measurement method of reaction-produced change in sensor
  • G01N2021/7789—Cavity or resonator

Definitions

• the present invention concerns optical biosensors for detecting and or monitoring or qualifying the presence and or behaviour of specific assay molecular species in test fluid samples.
• the invention has application to for example immunoassay i.e. the detection of antibodies, antigens or hormones in blood samples; pollution monitoring; and to the monitoring of clinical diagnostic reactions which may involve for example enzymes and the like.
• the evanescent wave has a characteristic penetration depth of a fraction of a wavelength into the aqueous phase thus optically interacting with substances bound to or very close to the interface and only minimally with the bulk solution.
• the latter structure comprises an optically dense body having, on one of its surfaces a sensitised coating which acts as one mirror of the resonant cavity, and having at its other surface a partial mirror provided by a low index film or layered dielectric mirror sandwiched between the body and a coupling prism. It is a disadvantage that this latter structure is of somewhat bulky construction and assembly is demanding.
• an optical biosensor comprising; a test sample container; a dielectric resonant cavity, mounted adjacent to the test sample container, and formed of a body of optically dense dielectric material bounded at each of its opposite principal plane faces by media of lower refractive index, one of these media being a coating sensitised for a specific assay species, this coating being located immediately adjacent to the test sample container and exposed for contacting a test sample fluid to be contained therein; wherein an optical grating is provided at one of the principal plane faces of the dielectric body- for facilitating optical coupling between an optical source and an optical detector external thereto.
• the optical grating may be embossed upon or engraved in the dielectric body and may be provided either at the interface between the dielectric body and the sensitised coating or between the dielectric body and the other lower refractive index medium.
• the grating provides a means of coupling light from an external light source into the resonant cavity thus formed and of coupling light from the resonant cavity onto an external detector.
• the optical grating serves a dual purpose. Firstly it serves as a means of coupling light into the resonant cavity formed by the dielectric body, the sensitised layer and the other lower refractive index medium. Secondly it also will reflect and out-couple light and it is this light that would be monitored by an external detector. Changes in the phase and amplitude of this light are most marked around the coupling angle. Reactions between a test sample and the sensitised layer change the resonant mode wave vector K m and result in changes in the amplitude and phase of the reflected out-coupled beam.
• the incident beam may be directed at one or at a range of angles to the biosensor and the reflected out-coupled beam may be monitored at one or at a range of angles.
• the wavelength of light used can range from the ultra-violet through the visible to the infra-red the dimensions of the biosensor components being scaled accordingly.
• Various optical materials can be used to construct the biosensor depending on the design wavelengths.
• An example of a. system for use over a large wavelength range is silica for one of the lower refractive index media,- and nitrogen doped silica for the optically dense material of the dielectric body.
• the optical grating may be formed using a number of techniques, such as etching or embossing.
• embossing lends itself to high volume production of devices.
• Figure 1 is a cross-section of a biosensor constructed in accord with this invention and in which an optical grating is formed at the interface between the optically dense dielectric body and a single layer lower refractive index medium on the plane face of the body opposite to the sensitised coating;
• Figure 2 is a cross-section of an alternative construction of biosensor also in accord with the present invention and in which the optical grating is formed at the interface between the optically dense dielectric body and the sensitised coating;
• Figure 3 is a cross-section view of alternative construction of biosensor similar to that shown in the preceding Figure 2 but in which the single layer lower refractive index medium is replaced by a layered dielectric stack.
• a resonant grating biosensor 1 is shown in Figure 1. This is comprised of an optically dense body 3 bounded on each of its principal plane faces by lower refractive index media 5 and 7.
• One of these media, media 5 has the form of an organic coating which is sensitised to a specific assay species which it is intended to detect.
• the sensitised coating 5, for example, may consist in a layer of monoclonal antibodies (refractive index n ⁇ 1.4 to 1.5).
• the sensitised coating 5 is exposed to a test fluid sample 9 which is contained within a test sample container 1 1 the walls of which are shown in the figure.
• optical grating 13 which, as shown in this figure, is located at the interface between the optically dense body 3 and the lower refractive index medium 7.
• This optical grating 13 may be formed in either the optically dense body 3 or the lower refractive index medium 7 and may be formed for example by engraving. Alternatively and in preference to this however, the optical grating 13 may be formed upon the principal plane face of the optically dense body 3 or upon the lower refractive index medium 7 and may be produced for example by an embossing technique during the course of manufacture.
• Grating structures are described for example in the following article, A. Yariv, IEEE Journal Quantum Electronics, Vol. QE-9, No. 9, September 1973. page 919.
• ⁇ is the pitch of the grating.
• the grating profile is secondary to its periodicity, and although the profile may be controlled, for example to blaze the grating for a particular angle, this profile would usually be chosen . to be approximately sinusoidal.
• the structure is formed using silica and nitrogen doped silica respectively which are deposited by the process of magnetron sputtering.
• these materials In the visible spectrum, these materials have refractive indices of 1.46 and 1.5 to 1.55, respectively. The latter index value is dependant upon the content of nitrogen dopant.
• the target is of the pure base material, in this case silica, and is sputtered onto a sample substrate in an inert argon atmosphere. Typical sputtering powers are 200 watts.
• a second gas, nitrogen is mixed with the argon, in proportions of around 30% active to inert gas. Sputtering times are typically half an hour.
• An alternative arrangement is shown in Figure 2.
• the optical grating 13 is provided at the interface between the optically dense body 3 and the sensitised coating 5.
• the optical grating 13 may be embossed upon a principal plane surface of the optically dense body 3 or it may be a relief grating engraved in this body 3.
• FIG 3 a similar biosensor arrangement 17 is shown but in this construction the single layer lower refractive index medium 7 has been replaced by a multi-layer dielectric stack 19.
• the number of layers adopted is determined in accordance with the reflectivity required (See “Principles of Optics", M. Born & E. Wolf, Sixth Edition (1980) Pergamon Press, page 66 ff).

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

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• 1989
  • 1989-01-11 GB GB8900556A patent/GB2227089A/en not_active Withdrawn
  • 1989-12-06 WO PCT/GB1989/001461 patent/WO1990008318A1/en not_active Application Discontinuation
  • 1989-12-06 EP EP90900247A patent/EP0404900A1/de not_active Withdrawn

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