Microchip optical transport technology for use in a personal flow cytometer

• US 6,097,485 A
• Filed: 03/08/1999
• Issued: 08/01/2000
• Est. Priority Date: 03/08/1999
• Status: Expired due to Fees

• Current Assignee: Integrated Waveguides, Inc.
• Original Assignee: Integrated Waveguides, Inc.
• Inventors: Lievan, Bonnie A.
• Primary Examiner(s): Font, Frank G.
• Assistant Examiner(s): Punnoose, Roy M.
• Application Number:
  US09/264,178
• Time in Patent Office: 512 Days
• Field of Search: 356/337, 356/338, 356/317, 356/244, 356/246, 356/72, 356/73, 356/39, 422/70, 422/68.1, 422/108, 422/81
• US Class Current: 356/338
• CPC Class Codes: G01N 15/14 Optical investigation techniques, e.g. flow cytometry
• CPC Class Codes: G01N 2021/6421 Measuring at two or more wavelengths
• CPC Class Codes: G01N 21/645 Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 2201/0221 Portable; cableless; compact; hand-held

Abstract

An ultra-miniature personal flow cytometer (pFCM) for the measurement of laser-induced fluorescence. The pFCM is approximately the size of a fluorescent microscope and includes a miniature optical module onto which the flow cytometry components are coupled. The miniature optical module is closely integrated with a flow cell through which a sample cell stream flows. The advantage of the pFCM is its compact size and efficiency that is made possible due to the unique microchip demultiplexing waveguide utilized in the separation of fluorescent wavelengths. The microchip demultiplexing waveguide is wholly contained in a tiny microchip consisting of a wave channel layer, a buffer layer, a substrate layer, and a plurality of micrograting filters. Photodetectors may either be coupled to the microchip demultiplexing waveguide by individual fiber optic members or incorporated into the wave channel layer in a photodiode array. The pFCM has wide ranging applications, but in particular is very useful in the analysis of sperm chromatin structure assay (SCSA) because of its small size and simplicity in operating.

Claims

1. A cell analysis apparatus comprising:

a unitary optical module;

a microchip demultiplexing waveguide integral to said optical module,

a flowing sample stream closely integrated with said optical module;

a light source for generating a light beam disposed so that the light beam interacts with the fluidic sample stream adjacent to an opening;

a plurality of photodetectors integral to said optical module;

means for collecting light scattered and emitted from the fluidic sample stream in response to the light beam;

means for transmitting collected light to the microchip waveguide; and

means for transmitting light from the microchip waveguide to the photodetectors.

2. The cell analysis apparatus of claim 1, wherein the flowing sample stream passes through an aperture in said optical module.

3. The cell analysis apparatus of claim 1, further comprising a lens device disposed between said opening and said light source.

4. The cell analysis apparatus of claim 1, wherein said microchip demultiplexing waveguide further comprises:

a substrate layer;

a buffer layer disposed on top of said substrate layer;

a wave channel layer disposed on top of said buffer layer; and

a plurality of micrograting filters disposed within said wave channel layer.

5. The cell analysis apparatus of claim 4, further comprising:

a photodiode array disposed in contact with said wave channel layer of said microchip demultiplexing waveguide; and

a plurality of operational amplifiers coupled to said photodiode array.

6. The cell analysis apparatus of claim 1, wherein the means for transmitting collect light to the microchip waveguide comprises at least one fiber optic member and wherein the means for transmitting light from the microchip waveguide comprises at least one fiber optic member.

7. The cell analysis apparatus of claim 1, wherein at least one of said photodetectors is a photodiode.

8. The cell analysis apparatus of claim 6, wherein at least one photodiode is coupled to the microchip waveguide.

9. The cell analysis apparatus of claim 1, further comprising a plurality of operational amplifiers coupled to said photodetectors.

10. The cell analysis apparatus of claim 9, further comprising a multiplexer coupled to said operational amplifiers.

11. The cell analysis apparatus of claim 6, further comprising a multiplexer.

12. The cell analysis apparatus of claim 10, wherein said multiplexer is coupled to an analog/digital converter.

13. The cell analysis apparatus of claim 11, wherein said multiplexer is coupled to an analog/digital converter.

14. The cell analysis apparatus of claim 4, wherein said wave channel layer is made of a sol-gel material.

15. The cell analysis apparatus of claim 4, wherein said wave channel layer further comprises a plurality of subchannels.

16. The cell analysis apparatus of claim 4, wherein said micrograting filters are etched into said wave channel layer through a computer-controlled electron beam writing process.

17. The cell analysis apparatus of claim 4, wherein each one of said micrograting filters has the same slant angle but different periods.

18. The cell analysis apparatus of claim 4, wherein said micrograting filters are in a transmission grating configuration.

19. The cell analysis apparatus of claim 4, wherein said micrograting filters are in a reflection grating configuration.

20. The cell analysis apparatus of claim 1, wherein said unitary optical module comprises a card which is between 10 cm and 14 cm wide, and 18 cm and 22 cm long.

21. The cell analysis apparatus of claim 1, further comprising a housing which is between 52 cm and 62 cm wide, between 46 cm and 56 cm deep, and between 72 cm and 92 cm tall.

22. The cell analysis apparatus of claim 1, further comprising a host computer coupled to said photodetectors by means of an analog/digital converter.

23. An analysis system for detecting cell characteristics comprising:

a fluidic cell stream for providing cells to be analyzed;

light means for emitting light to illuminate said cells in said fluidic cell stream;

an optical module comprising a microchip demultiplexing waveguide for separating different wavelengths of said light from said illuminated cells, said optical module closely integrated with said fluidic cell stream;

detection means for detecting said different wavelengths separated by said waveguide; and

amplifying means coupled to said detection means and said separation means for amplifying signals.

24. The cell analysis system of claim 23, wherein said light means is an argon ion laser.

25. The cell analysis system of claim 23, wherein said detection means is a plurality of photodiodes.

26. The cell analysis system of claim 23, wherein said microchip demultiplexing waveguide comprises:

a substrate layer;

a buffer layer disposed on top of said substrate layer;

a wave channel layer disposed on top of said buffer layer; and

a plurality of micrograting filters disposed within said wave channel layer.

27. The cell analysis system of claim 26, wherein the detection means are coupled to said microchip demultiplexing waveguide by optical fiber members.

28. The cell analysis system of claim 26, wherein said wave channel layer is made of a sol-gel material.

29. The cell analysis apparatus of claim 26, wherein said wave channel layer further comprises a plurality of subchannels.

30. The cell analysis system of claim 26, wherein said micrograting filters are etched into said wave channel layer through a computer-controlled electron beam writing process.

31. The cell analysis system of claim 26, wherein each one of said micrograting filters has the same slant angle but different periods.

32. The cell analysis system of claim 26, wherein said micrograting filters are in a transmission grating configuration.

33. The cell analysis system of claim 26, wherein said micrograting filters are in a reflection grating configuration.

34. The cell analysis system of claim 23, further comprising a housing for covering and fastening components of said system.

35. The cell analysis system of claim 34, wherein said housing is between 30 cm and 62 cm wide, between 24 cm and 56 cm deep, and between 60 cm and 92 cm tall.

36. The cell analysis system of claim 23, further comprising computational means for assembling and displaying information gathered from said scattered light signals.

37. An ultra-miniature optical module closely integrated with a flowing sample stream, the ultra-miniature optical module comprising:

a collection lens disposed to collect light from a flowing sample stream when the flowing sample stream is illuminated;

a fiber optic member operationally coupled to said collection lens;

a microchip demultiplexing waveguide optically coupled to said collection lens; and

a photodetector operationally coupled to said waveguide.

38. The ultra-miniature optical module of claim 37, wherein said microchip demultiplexing waveguide further comprises:

a substrate layer;

a buffer layer disposed on top of said substrate layer;

a wave channel layer disposed on top of said buffer layer; and

a plurality of micrograting filters disposed within said wave channel layer.

39. The ultra-miniature optical module of claim 38, further comprising a photodiode array disposed in contact with said wave channel layer.

40. The ultra-miniature optical module of claim 38, wherein said wave channel layer is made of a sol-gel material.

41. The ultra-miniature optical module of claim 38, wherein said wave channel layer further comprises a plurality of subchannels.

42. The ultra-miniature optical module of claim 38, wherein said micrograting filters are etched into said wave channel layer through a computer-controlled electron beam writing process.

43. The ultra-miniature optical module of claim 38, wherein each one of said micrograting filters has the same slant angle but different periods.

44. The ultra-miniature optical module of claim 38, wherein said micrograting filters are in a transmission grating configuration.

45. The ultra-miniature optical module of claim 38, wherein said micrograting filters are in a reflection grating configuration.

46. The ultra-miniature optical module of claim 38, wherein said micrograting filters are in a transmission grating configuration.

47. The ultra-miniature optical module of claim 37, further comprising a plurality of operational amplifiers coupled to said detectors.

48. The ultra-miniature optical module of claim 37, further comprising:

a plurality of fiber optic members coupled to said microchip demultiplexing waveguide; and

a plurality of detectors coupled to said fiber optic members.