Miniaturized cytometer for detecting multiple species in a sample

• US 20050105077A1
• Filed: 09/09/2004
• Published: 05/19/2005
• Est. Priority Date: 08/02/2000
• Status: Active Grant

• Current Assignee: Honeywell International Inc.
• Original Assignee: Honeywell International Inc.
• Inventors: Padmanabhan, Aravind, Fritz, Bernard S.
• Granted Patent: US 7,630,063 B2
• Time in Patent Office: Days
• US Class Current: 356/39
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150213 Venting means
• CPC Class Codes: A61B 5/150221 Valves
• CPC Class Codes: A61B 5/150274 Manufacture or production processes or steps for blood sampling devices
• CPC Class Codes: A61B 5/150343 Collection vessels for collecting blood samples from the skin surface, e.g. test tubes, cuvettes sampling from within body cavities A61B5/150015, A61B5/150045
• CPC Class Codes: A61B 5/150351 Caps, stoppers or lids for sealing or closing a blood collection vessel or container, e.g. a test-tube or syringe barrel caps for bottles or containers in general B65D41/00
• CPC Class Codes: A61B 5/157 Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: A61B 5/417 the bone marrow
• CPC Class Codes: A61B 5/7264 Classification of physiological signals or data, e.g. using neural networks, statistical classifiers, expert systems or fuzzy systems neural networks per se G06N3/00; expert systems per se G06N5/00
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: G01B 11/272 using photoelectric detection means
• CPC Class Codes: G01N 15/1404 Handling flow, e.g. hydrodynamic focusing
• CPC Class Codes: G01N 15/1434 Optical arrangements
• CPC Class Codes: G01N 15/1459 the analysis being performed on a sample stream
• CPC Class Codes: G01N 15/1484 microstructural devices
• CPC Class Codes: G01N 2015/011 with lysing, e.g. of erythrocytes
• CPC Class Codes: G01N 2015/012 Red blood cells
• CPC Class Codes: G01N 2015/016 White blood cells
• CPC Class Codes: G01N 2015/0238 Single particle scatter
• CPC Class Codes: G01N 2015/1027 Determining speed or velocity of a particle
• CPC Class Codes: G01N 2015/1486 : Counting the particles
• CPC Class Codes: G01N 33/5094 : for blood cell populations red blood cells G01N33/80
• CPC Class Codes: G01N 33/569 : for microorganisms, e.g. protozoa, bacteria, viruses
• CPC Class Codes: G01N 35/085 : Flow Injection Analysis
• CPC Class Codes: Y10T 436/24 : Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

A system for scattered light and simultaneous multi-color (e.g., greater than sixteen colors) fluorescence light detecting, and for analyzing, classifying and identifying biological particles and items of interest. A sample to be tested may be entered in a disposable microfluidic cartridge which in turn is insertable in a portable, hand-holdable, or wearable miniaturized cytometer instrument. The present system may be incorporated in the cytometer instrument. It may have significant application relative to biological warfare, environmental substances, the medical field and other fields.

Claims

1. A system comprising:

a channel;

a light source arrangement proximate to the channel;

a wavelength discriminator proximate to the channel; and

a light detector arrangement proximate to the wavelength discriminator.

2. The system of claim 1, wherein the system is a flow cytometer.

3. The system of claim 1, wherein the system is a hematology analyzer.

4. The system of claim 1, wherein the light detector arrangement may provide a plurality of electrical signals wherein each signal represents a wavelength range of detected light from the channel.

5. The system of claim 4, wherein the light detector arrangement comprises a fluorescent light detector arrangement.

6. The system of claim 4, wherein the light detector arrangement comprises a light scatter detector arrangement proximate to the channel.

7. The system of claim 6, wherein the light scatter detector arrangement comprises a FALS detector.

8. The system of claim 7, wherein the FALS detector is an annular detector.

9. The system of claim 7, wherein the light scatter detector arrangement further comprises a SALS detector.

10. The system of claim 4, wherein the light detector arrangement comprises a plurality of detectors.

11. The system of claim 10, wherein the plurality of detectors is an array of detectors situated in a miniaturized package.

12. The system of claim 11, wherein the detectors of the light detector arrangement may approximately simultaneously detect various wavelengths of light.

13. The system of claim 12, wherein the light detector arrangement may detect a plurality of colors greater than seven.

14. The system of claim 12, wherein the light detector arrangement may detect a plurality of colors greater than sixteen.

15. The system of claim 12, wherein the light detector arrangement may detect a plurality of colors greater than thirty-two.

16. The system of claim 10, wherein the detectors are avalanche photo detectors.

17. The system of claim 10, wherein the detectors are at least one charge coupled discharge (CCD) array.

18. The system of claim 10, wherein the detectors are silicon photo detectors.

19. The system of claim 10, wherein the detectors are photo multiplier tubes.

20. The system of claim 4, wherein the light source arrangement comprises at least one light source having a wavelength greater than 700 nanometers.

21. The system of claim 4, wherein the light source arrangement comprises at least one light source having a wavelength approximately between 450 nanometers and 700 nanometers.

22. The system of claim 4, wherein the light source arrangement comprises at least one light source having a wavelength less than 450 nanometers.

23. The system of claim 4, wherein the wavelength discriminator comprises a prism.

24. The system of claim 4, wherein the wavelength discriminator comprises one or more filters.

25. The system of claim 24, wherein the filters are band-pass filters.

26. The system of claim 4, wherein the wavelength discriminator comprises a dispersive element.

27. The system of claim 4, wherein the wavelength discriminator comprises a wavelength demultiplexer.

28. The system of claim 4, wherein the wavelength discriminator comprises an optical grating.

29. The system of claim 4, wherein the wavelength discriminator comprises an arrayed waveguide grating.

30. The system of claim 4, wherein the wavelength discriminator comprises one or more dichroic mirrors.

31. The system of claim 11, wherein the channel is situated in a miniature cartridge.

32. The system of claim 31, wherein the channel is for a core stream of blood cells.

33. The system of claim 31, wherein the channel is for a core stream of biological particles.

34. The system of claim 31, wherein the cartridge comprises a low autofluorescence non-glass material.

35. The system of claim 34, wherein the non-glass material is a cyclic olefin copolymer based plastic.

36. The system of claim 31, wherein the system comprises characteristics of good sensitivity, quantification of agent concentration, high specificity of detection of bacteria, viruses, spores, toxins and/or other like particles, automated sample preparation, very small handheld unit size and weight, and/or low power consumption.

37. A method comprising:

providing a flow path;

projecting light on the flow path;

detecting light according to wavelength from the flow path; and

obtaining information on particles in the flow path from light detected according to wavelength from the flow path.

38. The method of claim 37, further comprising identifying species of particles in the flow path approximately simultaneously according to wavelength of the light emitted from the flow path.

39. The method of claim 38, further comprising classifying the particles according to wavelength of the detected light.

40. The method of claim 37, further comprising detecting scattered light from the flow path.

41. The method of claim 40, further comprising counting particles in the flow path.

42. The method of claim 38, wherein the detecting light according to wavelength from the flow path is performed with a plurality of detectors in a miniaturized package.

43. The method of claim 42, wherein the flow path is situated in a miniature cartridge.

44. The method of claim 43, wherein the particles in the flow path are blood cells.

45. The method of claim 44, wherein the particles in the flow path are biological particles.

46. The method of claim 37, wherein the flow path is within a channel of a flow cytometer.

47. The method of claim 37, wherein the flow path is with in a channel of a hematology analyzer.

48. The method of claim 43, wherein the cartridge comprises a low autofluorescence non-glass material.

49. The method of claim 48, wherein the non-glass material is a cyclic olefin copolymer based plastic.

50. A system comprising:

a channel;

a light source arrangement proximate to the channel;

an interferometer proximate to the channel; and

a detector arrangement proximate to the interferometer.

51. The system of claim 50, wherein:

the detector arrangement has a plurality of detectors which are positioned relative to the interferometer to detect light of various intensity values; and

the various intensity values are processed to obtain spectral content of the light.

52. The system of claim 51, wherein the system is a flow cytometer.

53. The system of claim 51, wherein the system is a hematology analyzer.

54. The system of claim 51, wherein the plurality of detectors are situated in a miniaturized package.

55. The system of claim 51, wherein the detector arrangement further comprises a light scatter detector proximate to the channel.

56. The system of claim 54, wherein the channel is situated in a miniature cartridge.

57. The system of claim 56, wherein the channel is for a core stream of blood cells.

58. The system of claim 56, wherein the channel is for a core stream of biological particles.

59. The system of claim 56, wherein the cartridge comprises a low autofluorescence non-glass material.

60. The system of claim 59, wherein the non-glass material is a cyclic olefin copolymer based plastic.

61. The system of claim 56, wherein the system comprises characteristics of good sensitivity, quantification of agent concentration, high specificity of detection of bacteria, viruses, spores, toxins and/or other like particles, automated sample preparation, very small handheld unit size and weight, and/or low power consumption.

62. A means for cytometry comprising:

means for supporting a channel;

means for illuminating the channel; and

means for detecting light from the channel according to wavelength.

63. The means of claim 62, wherein:

the means for detecting comprises a wavelength discriminator and a plurality of detectors;

the plurality of detectors is situated in a miniaturized package; and

the detecting light from the channel according to wavelength is approximately simultaneous for all of the detected wavelengths.

64. The means of claim 63, wherein the means for detecting detects fluorescent light from markers associated with various types of particles in the channel.

65. The means of claim 64, wherein the markers associated with the various types of particles emit light different wavelengths so that each type of particle may be identified according to the wavelength emitted by the marker.

66. The means of claim 65, wherein the markers comprise phosphors.

67. The means of claim 65, wherein the markers are fluorescent dyes.

68. The means of claim 64, further comprising a means for detecting scattered light from the channel.

69. The means of claim 64, wherein the channel is situated in a miniature cartridge.

70. The means of claim 69, wherein the channel is for a core stream of blood cells.

71. The means of claim 69, wherein the channel is for a core stream of biological particles.

72. The means of claim 69, wherein the cartridge comprises a low autofluorescence non-glass material.

73. The means of claim 72, wherein the non-glass material is a cyclic olefin copolymer based plastic.

74. The means of claim 63, wherein the means for cytometry is a flow cytometer.

75. The means of claim 63, wherein the means for cytometry is a hematology analyzer.