Lens and associatable flow cell

• US 6,611,634 B2
• Filed: 03/11/2002
• Issued: 08/26/2003
• Est. Priority Date: 03/19/1996
• Status: Expired due to Term

• Current Assignee: University of Utah Research Foundation (State of Utah)
• Original Assignee: University of Utah Research Foundation (State of Utah)
• Inventors: McEachern, Richard D., Pollak, Victor A., Simon, Eric M., Christensen, Douglas A., Herron, James N.
• Primary Examiner(s): Healy, Brian
• Application Number:
  US10/095,540
• Publication Number:
  US 20020094147A1
• Time in Patent Office: 533 Days
• Field of Search: 385/14, 385/12, 385/129, 385/130, 385/131, 385/132, 385/33, 422/82.05, 422/82.08, 422/82.09, 422/82.11, 422/55, 422/57, 422/58, 356/317, 356/318, 356/244, 356/246, 436/518
• US Class Current: 385/12
• CPC Class Codes: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 2021/058 Flat flow cell
• CPC Class Codes: G01N 21/0303 Optical path conditioning in cuvettes, e.g. windows; adapted optical elements or systems; path modifying or adjustment G01N21/031 - G01N21/15 take precedence
• CPC Class Codes: G01N 21/05 Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10

Abstract

Improvements in a biosensor are disclosed. A biosensor includes a waveguide, at least a portion of which is substantially planar. One or more reservoirs may be formed adjacent to a chemistry-bearing surface of the waveguide. The biosensor may include a gasket to form a seal between the waveguide and side walls of the reservoir. A sample solution may be introduced into the reservoir or otherwise onto the surface of a waveguide through an input port. Waveguides of varying composition (e.g., plastic, quartz, glass, or other suitable waveguide materials) may be used in the biosensor. Also disclosed is a sled-shaped waveguide, which includes a planar portion and a lens at an end thereof and angled relative thereto for coupling light into the waveguide.

Claims

1. An apparatus for analyzing a biological fluid, comprising:

a waveguide, comprising;

a planar portion with opposite first and second planar surfaces and opposite front and rear ends, said planar portion capable of transmitting light from said front end to said rear end;

at least one ramp comprising a lens for receiving light, said at least one ramp in optical communication with and extending from said front end of said planar portion, a surface of said at least one ramp being oriented at an angle other than 0°

from a plane of said planar portion;

at least one type of capture molecule immobilized relative to said first planar surface of said planar portion of said waveguide;

a light source oriented so as to direct at least one wavelength of light into said lens; and

a light detector oriented to receive light emitted through said second planar surface.

2. The apparatus of claim 1, wherein said first planar surface is configured to receive a sample or solution comprising a sample.

3. The apparatus of claim 1, wherein the biological fluid comprises ay least one of blood cells and portions of blood cell.

4. The apparatus of claim 1, wherein said first planar surface of said planar portion of said waveguide is orientated to face in an at least partially downward direction.

5. The apparatus of claim 4, wherein said planar portion is orientated substantially horizontal.

6. The apparatus of claim 4, wherein said planar portion is oriented nonhorizontally.

7. The apparatus of claim 4, wherein said first planar surface is configured to receive a sample or a sample solution comprising at least one of blood cells and portions of blood cells.

8. The apparatus of claim 1, wherein said planar portion is oriented substantially vertically.

9. The apparatus of claim 1, wherein said first planar surface of said planar portion of said waveguide is oriented to face in an at least partially upward direction.

10. The apparatus of claim 9, wherein said planar portion is oriented substantially horizontal.

11. The apparatus of claim 9, wherein said planar portion is oriented nonhorizontally.

12. The apparatus of claim 1, wherein said waveguide comprises an optical plastic.

13. The apparatus of claim 1, wherein said angle comprises an angle of from about 15°

to about 32°

.

14. The apparatus of claim 1, wherein at least one type of capture molecule is arranged over said first planar surface of said planar portion of said waveguide in an array of reaction sites.

15. The apparatus of claim 1, comprising capture molecules that react selectively with different, corresponding selected analytes.

16. The apparatus of claim 15, wherein said capture molecules are arranged over said first planar surface of said planar portion of said waveguide in discrete reaction sites.

17. The apparatus of claim 16, wherein said discrete reaction sites are arranged over said first planar surface in an array.

18. The apparatus of claim 1, further comprising:

a flow cell cover configured to be positioned adjacent to said first planar surface of said planar portion of said waveguide, said flow cell cover forming at least one wall of at least one reservoir adjacent to said first planar surface.

19. The apparatus of claim 18, further comprising:

an inlet in fluid communication with said at least one reservoir to facilitate introduction of a sample over at least a portion of said first planar surface.

20. The apparatus of claim 1, wherein said waveguide comprises a single material layer.

21. The apparatus of claim 20, wherein said single material layer comprises an optical plastic.

22. The apparatus of claim 1, further comprising an optical substrate that supports said waveguide.

23. The apparatus of claim 22, wherein said optical substrate comprises at least one of polystyrene, polymethylmethacrylate, polyvinyl chloride, polyimide, polyester, polyurethane, an organically modified ceramic, a polymer of diethylene glycol bisallyl carbonate, allyldiglycolcarbonate, and polycarbonate.

24. The apparatus of claim 22, wherein said waveguide comprises at least one of an optical plastic, TiO₂, SiO₂, ZnO₂, Nb₂O₂, a silicon nitride, a silicon oxynitride, Ta₂O₅, HfO₂, and ZrO₂.

25. A biosensor, comprising:

a waveguide, comprising;

a planar portion with opposite first and second planar surfaces, said planar portion capable of transmitting light from a front end to a rear end thereof; and

at least one type of capture molecule immobilized relative to said first planar surface of said planar portion of said waveguide, said at least one type of capture molecule arranged over said first planar surface in a plurality of discrete reaction sites.

26. The biosensor of claim 25, wherein said plurality of discrete reaction sites comprises an array of reaction sites.

27. The biosensor of claim 25, comprising capture molecules that react selectively with different, corresponding selected analytes.

28. The biosensor of claim 27, wherein said capture molecules that react selectively with different, corresponding selected analytes are arranged in different reaction sites of said plurality of discrete reaction sites from one another.

29. The biosensor of claim 25, further comprising:

a flow cell cover positioned adjacent to at least a portion of said first planar surface of said planar portion, said flow cell cover forming at least one wall of at least one reservoir adjacent to said first planar surface.

30. The biosensor of claim 29, further comprising:

an inlet in fluid communication with said at least one reservoir to facilitate introduction of a sample over at least a portion of said first planar surface.

31. The biosensor of claim 25, further comprising:

at least one ramp comprising a lens for receiving light, said at least one ramp in optical communication with and including a surface that extends from said front end of said planar portion at an angle other than 0°

from a plane of said planar portion.

32. The biosensor of claim 25, wherein said waveguide comprises a single material layer.

33. The biosensor of claim 32, wherein said single material layer comprises an optical plastic.

34. The biosensor of claim 25, further comprising an optical substrate that supports said waveguide.

35. The biosensor of claim 34, wherein said optical substrate comprises at least one of polystyrene, polymethylmethacrylate, polyvinyl chloride, polyimide, polyester, polyurethane, an organically modified ceramic, a polymer of diethylene glycol bisallyl carbonate, allyldiglycolcarbonate, and polycarbonate.

36. The biosensor of claim 34, wherein said waveguide comprises at least one of an optical plastic, TiO₂, SiO₂, ZnO₂, Nb₂O₂, a silicon nitride, a silicon oxynitride, Ta₂O₅, HfO₂, and ZrO₂.

37. A biosensor for use in an apparatus which uses light to analyze a sample solution comprising a biological liquid, the biosensor comprising:

a waveguide including at least one planar surface;

a taper extending from said at least one planar surface and optically associated therewith, said taper configured to receive and convey light into said waveguide;

capture molecules associated with said at least one planar surface;

a flow cell cover positioned adjacent to and spaced apart from said at least one planar surface and, with said at least one planar surface, defining at least one reservoir for containing the biological liquid; and

at least an inlet in fluid communication with said at least one reservoir to facilitate introduction of the sample solution therein so as to permit the biological liquid to contact said capture molecules for interaction therewith.

38. The biosensor of claim 37, wherein said flow cell cover comprises a flow cell top.

39. The biosensor of claim 37, further comprising:

at least one outlet in fluid communication with said at least one reservoir.

40. The biosensor of claim 39, wherein said at least one outlet is configured to be contacted by sample solution within said at least one reservoir.

41. The biosensor of claim 39, wherein said at least said inlet, said at least one reservoir, and said at least one outlet are in fluid-tight communication.

42. A method for analyzing a sample solution comprising a biological liquid, the method comprising:

providing a biosensor comprising a waveguide and a plurality of capture molecules on a surface of said waveguide;

exposing said capture molecules to the sample solution, the biological liquid of which may comprise molecules of at least one selected analyte;

adding tracer molecules to the sample solution, each tracer molecule including a site capable of binding with at least a portion of a complementary capture molecule or at least a portion of said at least one selected analyte, each tracer molecule including a component that emits fluorescent radiation of an emission wavelength when exposed to radiation of an excitation wavelength;

introducing light of said excitation wavelength into said waveguide; and

detecting light of said emission wavelength passing through another surface of said waveguide.

43. The method according to claim 42, further comprising:

determining an amount of said at least one selected analyte based on said detecting.

44. The method according to claim 43, wherein said determining comprises determining amounts of a plurality of selected analytes based on said detecting.

45. The method according to claim 42, wherein said detecting comprises positioning a light detector within a cone of collection angles having an axis oriented substantially orthogonal to a plane of said waveguide.

46. The method according to claim 42, wherein said providing said waveguide comprises providing said waveguide with said capture molecules arranged in discrete reaction sites.

47. The method according to claim 46, wherein said providing said waveguide comprises providing said waveguide with said discrete reaction sites organized in an array.

48. The method according to claim 47, wherein said providing said waveguide comprises providing said waveguide with capture molecules of at least one discrete reaction site of said array having specificity for a different selected analyte than another selected analyte for which capture molecules of at least another discrete reaction site have specificity.

49. A method for fabricating a biosensor comprising:

forming a waveguide to have at least one substantially planar surface; and

immobilizing capture molecules over said at least one substantially planar surface, said capture molecules being arranged over said at least one substantially planar surface at a plurality of discrete reaction sites.

50. The method according to claim 49, wherein said immobilizing comprises immobilizing said capture molecules over said at least one substantially planar surface in an array of reaction sites.

51. The method according to claim 49, wherein said immobilizing comprises:

immobilizing capture molecules having specificity for a first selected analyte at a first reaction site of said plurality of discrete reaction sites; and

immobilizing capture molecules having specificity for a different, second selected analyte at a second reaction site of said plurality of discrete reaction sites.

52. The method according to claim 49, wherein said immobilizing comprises patterning said capture molecules over said at least one substantially planar surface.

53. The method according to claim 49, wherein said forming comprises forming said waveguide to comprise a single material layer.

54. The method according to claim 53, wherein said forming said waveguide comprises forming said waveguide from an optical plastic.

55. The method according to claim 49, wherein said forming comprises forming said waveguide on an optical substrate.

56. The method according to claim 55, comprising forming said optical substrate from at least one of polystyrene, polymethylmethacrylate, polyvinyl chloride, polyimide, polyester, polyurethane, an organically modified ceramic, a polymer of diethylene glycol bisallyl carbonate, allyldiglycolcarbonate, and polycarbonate.

57. The method according to claim 55, comprising forming said waveguide from at least one of an optical plastic, TiO₂, SiO₂, ZnO₂, Nb₂O₂, a silicon nitride, a silicon oxynitride, Ta₂O₅, HfO₂, and ZrO₂.