Devices for use in chemical test procedures

• US 4,978,503 A
• Filed: 09/06/1988
• Issued: 12/18/1990
• Est. Priority Date: 06/13/1984
• Status: Expired due to Term

• Current Assignee: Applied Research Systems ARS Holding NV (Merck & Co., Inc.)
• Original Assignee: Ares-Serono Research & Development Limited Partnership
• Inventors: Smith, Alan M., Shanks, Ian A.
• Primary Examiner(s): Warden, Robert J.
• Assistant Examiner(s): Johnston, Jill
• Application Number:
  US07/240,478
• Time in Patent Office: 833 Days
• Field of Search: 422/101, 422/102, 422/68, 422/58, 422/82.11, 435/288, 435/301, 435/311, 435/817, 435/7, 204/403, 427/2, 356/244, 356/440, 250/227, 350/96.3, 156/61
• US Class Current: 422/412
• CPC Class Codes: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/03 Cuvette constructions
• CPC Class Codes: G01N 21/64 Fluorescence; Phosphorescence
• CPC Class Codes: G01N 21/645 Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 21/7703 using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

A specifically-reactive sample-collecting and testing device possessing a cavity or cavities each having a dimension small enough to enable sample liquid to be drawn into the cavity by capillary action, wherein a surface of the cavity carries an immobilized reagent appropriate to the test to be carried out in the device, and wherein said surface is a surface of a transparent solid plate to act as a light-transmissive waveguide and forming a wall of the cavity, said plate having an edge which is substantially optically smooth and transverse to the plane of the plate.

Claims

1. A sample collecting and testing device for use in the fluoroimmunoassay of an analyte present in sample liquid, said device comprising a planar capillary cell for the collection and retention of a volume of sample liquid to be tested therein, said capillary cell comprising a pair of flat, parallel plates fixed together with an air space therebetween and sealed along two opposite sides so as to provide fixed opposed inner surfaces defining a capillary cavity with a first aperture at one end thereof to allow uptake of sample liquid in the capillary cavity and a second aperture at the other end thereof to allow exit of air from the capillary cavity as it fills with sample liquid, wherein at least one of said plates is a light transmissive waveguide having an optically smooth edge which is transverse to the plane of the waveguide and perpendicular to the sealed sides thereof, said waveguide having bound to at least a portion of its inner surface, so as to be contacted by the sample liquid collected within the capillary cavity, an immobilised reagent capable of binding, either directly or indirectly, a fluorescent-labelled ligand, wherein said immobilised reagent and said fluorescent-labelled ligand is releasably retained within said device so as to be contacted by and released into the sample liquid collected therewithin.

2. A device according to claim 1 wherein the edges of the waveguide, except for said optically smooth edge, are coated with light-absorbing material.

3. A device according to claim 1 wherein interposed between the inner surface of the waveguide and the immobilised reagent bound thereto is a thin layer of dielectric material to enhance transfer of light across the surface of the waveguide by any fluorescent-labelled ligand which becomes bound to the immobilised reagent.

4. A device according to claim 3 wherein said dielectric material comprises magnesium fluoride or silica.

5. A device according to claim 1 wherein interposed between the inner surface of the waveguide and the immobilised reagent is a thin coating of conductive material capable of showing a surface plasmon resonance effect.

6. A device according to claim 5 wherein the thin coating of conductive material is a coating of silver up to about 50 nm thick.

7. A device according to claim 1 wherein the immobilised reagent is selected from the group consisting of an antigen, an antibody, a derivative of an antigen or an antibody, and a non-immunological binding agent.

8. A device according to claim 7 wherein the immobilised reagent is covalently bound to the inner surface of the waveguide.

9. A device according to claim 1 wherein at least one ancillary reagent is dry releasable form is coated on at least one of said inner surfaces.

10. A device according to claim 1 wherein the waveguide comprises a material selected from the group consisting of glass, silica and plastics material.

11. A device according to claim 1 further comprising a handling-piece or holder extending therefrom.

12. A device according to claim 1 further comprising conductive connections extending from the interior of the capillary cavity to the exterior of the device.

13. A device according to claim 1 wherein the optically smooth edge of said waveguide is perpendicular to the plane thereof.

14. A device according to claim 1 adapted to collect and retain a predetermined volume of sample liquid.

15. A device according to claim 1 wherein said immobilised reagent is positioned on the inner surface of said waveguide such that all of the sample liquid entering the capillary cavity must pass over it.

16. A device according to claim 1 wherein said fluorescent-labelled ligand is releasably coated onto at least one of said inner surfaces.

17. A device according to claim 16 wherein said fluorescent-labelled ligand is releasably coated onto the inner surface of the plate opposite said waveguide.

18. A device according o claim 1 further comprising a selective barrier-type filter located one of within and in the inlet path to, the first aperture of the capillary cavity such that sample fluid entering the capillary must pass through said selective barrier.

19. A device according to claim 18 wherein said fluorescent-labelled ligand is releasably retained within said selective barrier.

20. A device according to claim 1 wherein one of said plates extends longitudinally beyond the other of said plates so as to form a lip in communication with the first aperture of said capillary cavity so that sample liquid applied to said lip will enter the capillary cavity.

21. A device according to claim 1 wherein the immobilised reagent comprises a specific binding agent for the analyte to be assayed and wherein the fluorescent-labelled ligand has a specific affinity for one of the binding agent and the analyte and is releasably bound to at least one of said inner surfaces.

22. A device according to claim 21 wherein the plate opposite said waveguide has a light-absorbing surface.

23. A device according to claim 1 wherein the plate opposite said waveguide has a light-absorbing surface.

24. A device according to claim 23 wherein the edges of the waveguide, except for said optically smooth edge, are coated with light-absorbing material.

25. A process for manufacturing sample collecting and testing devices for use in the fluorescent or luminescent immunoassay of an analyte comprising the steps of (a) immobilizing a reagent appropriate to the test to be carried out in the device onto portions of the surface of a transparent flat sheet material which is capable of acting as a light-transmissive waveguide and which is to provide a part of a multiplicity of the devices, (b) attaching to said sheet material an additional flat sheet material in parallel, spaced relation thereto so as to provide for each device of the multiplicity of devices a capillary cavity sealed along two opposite sides thereof and containing said immobilised reagent on at least a portion of the inner surface thereof, said capillary cavity adapted for collecting and retaining by capillarity a volume of sample liquid in contact with said immobilised reagent and (c) separating the assembled sheets into portions, each portion providing one or a plurality of the sample collecting and test devices, such that the transparent sheet material of each device has at least one optically smooth edge transverse to the plane of the sheet and perpendicular to the sealed sides thereof.

26. A process according to claim 25 wherein the immobilised reagent is provided as a pattern of discrete patches.

27. A process according to claim 26 wherein the patches forming the pattern are made by first forming a continuous coating and then removing portions of it to leave the desired pattern of discrete patches.

28. A process according to claim 26 wherein said discrete patches of immobilised reagent are applied by printing.

29. A process according to claim 25 wherein the immobilised reagent is selected from the group consisting of an antigen, an antibody, a derivative of an antigen or an antibody, and a non-immunological binding agent.

30. A process according to claim 29 wherein prior to application of the immobilised reagent, a thin coating of conductive material capable of showing a surface plasmon resonance effect is applied to the surface of the transparent sheet material which is to carry said immobilised reagent.

31. A process according to claim 30 wherein the thin coating of conductive material is a coating of silver up to about 50 nm thick.

32. A process according to claim 29 wherein prior to application of the immobilised reagent a thin dielectric layer is deposited on the surface of the transparent sheet material which is to carry said immobilised reagent.

33. A process according to claim 32 wherein the thin dielectric layer comprises magnesium fluoride or silica.

34. A process according to claim 25 wherein prior to step (b) one or more ancillary reagents are applied in dry releasable form to portions of the surface of one of said flat sheet materials so as to become part of the inner surface of each device to be contacted in use by sample liquid.

35. A process according o claim 34 wherein at least one of the ancillary reagents is a fluorescent-labelled ligand appropriate to the test for analyte to be carried out in each device.

36. A process according to claim 35 wherein said immobilised reagent comprises a specific binding reagent for the analyte to be assayed in each device.

37. A process according to claim 36 additionally comprising coating a light-absorbing material onto a surface of said additional flat sheet material.

38. A process according to claim 25 wherein said additional flat sheet material is bonded to said transparent flat sheet material by means of intermittent strips of a suitable bonding adhesive, wherein said strips seal the sides of each device.

39. A sample collecting and testing device for use in the luminescent immunoassay of an analyte present in sample liquid, said device comprising a planar capillary cell for the collection and retention of a volume of sample liquid to be tested therein, said capillary cell comprising a pair of flat, parallel plates fixed together with an air space therebetween and sealed along two opposite sides so as to provide fixed opposed inner surfaces defining a capillary cavity with a first aperture at one end thereof to allow uptake of sample liquid in the capillary cavity and a second aperture at the other end thereof to allow exit of air from the capillary cavity as it fills with sample liquid, wherein at least one of said plates is a light transmissive waveguide having an optically smooth edge which is transverse to the plane of the waveguide and perpendicular to the sealed sides thereof, said waveguide having bound to at least a portion of its inner surface, so as to be contacted by the sample liquid collected within the capillary cavity, an immobilised reagent capable of binding, either directly or indirectly, a luminescent-labelled ligand, wherein said immobilised reagent and said luminescent-labelled ligand are appropriate to the test for analyte to be carried out in the device, and wherein said luminescent-labelled ligand is releasably retained within said device so as to be contacted by and released into the sample liquid collected therewithin.