Chemistry: analytical and immunological testing – Optical result – With fluorescence or luminescence
Patent
1986-02-13
1989-03-07
Richman, Barry S.
Chemistry: analytical and immunological testing
Optical result
With fluorescence or luminescence
250227, 356244, 356440, 422 68, 422 73, G01N 2164
Patent
active
048106585
DESCRIPTION:
BRIEF SUMMARY
This invention relates to improvements in photometric instruments, and their use in methods of optical analysis, and in ancillary devices for use therewith.
The prior art contains numerous disclosures of analytical devices for handling and metering small volumes of test samples.
G.B. No. 2 090 659 (Instrumentation Laboratory, Inc.) describes test strips constructed with a self-filling metering channel and a lip or inlet on which a sample of more than about 10 microliters of for example whole blood can be placed, so that (for example) 10 microliters is taken up by capillary action to react with a reagent carried on a fibrous pad above a filter layer beneath a transparent window. The result can be viewed by the unaided eye, e.g. as a colour reaction.
G.B. Nos. 2 036 075 (H. E. Mennier), 1 104 774 (J. P. Gallagher), EP Nos. 0 057 110, 0 034 049, 0 010 456 (Kodak), all describe some other aspect of the uses of capillary channel or chamber dimensions for handling biological or test fluids.
G.B. No. 1 530 997 (Monsanto) describes the use of coated optical fibres which can be used in tests that change the light transmitting capabilities of the waveguides via reactions. WO No. 81/00912 (Buckles) also describes fibre-optical devices in which the fibre surface or surrounding modify the light transmission through the core.
U.S. Pat. No. 3,939,350 describes optical measurement of fluorescent material bound to the surface of a solid transparent prism by a method involving a single total internal reflection and interaction of the evanescent wave at the surface of the prism with the bound material.
EP No. 0 075 353 (Battelle) makes specific reference to the exponentially-decaying (evanescent) external radiation due to light which is propagated longitudinally in a fibre, and its interaction with coatings, and this principle is also taken up in immunoassay test devices of EP No. 0 103 426 (Block) in which light of fluorescence excitation as well as emission wavelengths is propagated within a antigen--or antibody--coated optical fibre or plate contacting a capillary-dimensional sample liquid volume bounded by a tube or another plate and containing a fluorescent-tagged binding partner of the material coated on the fibre or plate.
It is an aim of the present invention to provide instrumental arrangements by which very small liquid samples can be optically analysed in a convenient and flexible manner to discriminate sample material which is bound to a solid surface from sample material that remains free in solution.
According to the present invention we provide methods and instrumental arrangements for carrying out immunoassays or other chemical or biological tests, in the course of which a material with light-absorbing or fluorescence or luminescence properties becomes bound to the surface of a transparent solid body (especially from a solution or dispersion contacting the solid body), for example a prism, sheet or fibre, to a variable extent depending on the presence or amount of an analyte under test. In these arrangements the transparent solid body is optically coupled to a photodetector in such a way that the light path from the material to the detector passes through the solid body and may be therein totally internally reflected once or a plurality of times, i.e. the solid body acts as an optical waveguide. Usually the detector yields an electrical output signal which is processed and used in per se known manner not in itself constituting this invention, to yield a signal or indication representative of a parameter of interest in connection with the test. The arrangement includes a diaphragm or other limitation of the angle of view of the detector in order to ensure that substantially only that light is detected which comes from material which is bound to the surface of the transparent solid body. The transparent solid body acts as a waveguide for the light which comes from the surface-bound material, and which can pass by for example transmission, scattering, reflection, luminescence, fluorescence, or phosphorescence, (
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Harrick, Analytical Chemistry 45(4), pp. 687-691.
Chabay, Analytical Chemistry 54(9), pp. 1071(A)-1080(A).
Lee, et al., Applied Optics 18(6), pp. 862-868.
Shanks Ian A.
Smith Alan M.
Ares-Serono Research & Development
Johnston Jill
Richman Barry S.
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