Optical detection system for flow cytometry

• US 6,700,130 B2
• Filed: 06/29/2001
• Issued: 03/02/2004
• Est. Priority Date: 06/29/2001
• Status: Expired due to Term

• Current Assignee: Honeywell International Inc.
• Original Assignee: Honeywell International Inc.
• Inventors: Fritz, Bernard Steven
• Primary Examiner(s): Le, Que T.
• Assistant Examiner(s): SPEARS, ERIC J
• Application Number:
  US09/896,230
• Publication Number:
  US 20030002027A1
• Time in Patent Office: 977 Days
• Field of Search: 356/436, 356/39, 356/440, 356/335, 356/336, 356/441, 356/442, 422/82.09, 250/573, 250/574, 250/578.1, 250/436
• US Class Current: 250/573
• CPC Class Codes: G01N 15/1456 without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals
• CPC Class Codes: G01N 2015/1497 Particle shape

Abstract

An optical detection system for flow cytometry that uses two or more light sources positioned laterally at different distances from a central axis of a flow stream for providing light through different parts of the flow stream. One or more lenses are used to focus the light from the two or more light sources through the flow stream and onto a common focal point or region on the opposite side of the flow stream. One or more light detectors are then placed at, near or around the common focal point or region. A processor or the like receives at least one output signal from the one or more light detectors to analyze and determine selected characteristics of the flow stream.

Claims

1. An optical detection system for analyzing characteristics of a flow stream, the flow stream having a central axis along the direction of flow, the optical detection system comprising:

two or more spaced light sources positioned on a first side of the flow stream for providing light through the flow stream;

lens means positioned on the first side of the flow stream for focusing the light from each of the two or more light sources to a common focal point located on a second opposite side of the flow stream;

light receiving means for receiving the light from the two or more light sources, and for providing at least one signal in response thereto, at least a portion of the light receiving means located at the common focal point of the lens means; and

processing means for receiving the at least one signal from the light receiving means and for using the at least one signal for analyzing the characteristics of the flow stream.

2. An optical detection system according to claim 1, wherein each of the two or more light sources are positioned laterally at different distances from the central axis of the flow stream.

3. An optical detection system according to claim 1, wherein each of the two or more light sources are Vertical Cavity Surface Emitting Lasers (VCSELs).

4. An optical detection system according to claim 3, wherein the VCSELs operate in the red spectrum.

5. An optical detection system according to claim 1, wherein each of the two or more light sources are Light Emitting Diodes (LEDs).

6. An optical detection system according to claim 1, wherein the two or more light sources are an array of light sources.

7. An optical detection system according to claim 1, wherein the lens means includes two or more microlenses, one for each of the two or more light sources.

8. An optical detection system according to claim 7, wherein each microlens is laterally offset relative to the corresponding light source so that the light provided by each light source is focused onto the common focal point.

9. An optical detection system according to claim 1, wherein the light receiving means includes a centrally located light detector positioned at the common focal point.

10. An optical detection system according to claim 9, wherein the light receiving means includes a first annular shaped light detector positioned around the centrally located light detector.

11. An optical detection system according to claim 10, wherein the first annular shaped light detector is used for detecting the scattering produced by one or more particles in the flow stream.

12. An optical detection system according to claim 11, wherein the one or more particles include white blood cells.

13. An optical detection system according to claim 12, wherein the white blood cells include neutrophils and/or lymphocytes.

14. An optical detection system according to claim 10, wherein the light receiving means includes a second annular shaped light detector positioned around the first annular shaped light detector.

15. An optical detection system according to claim 14, wherein the second annular shaped light detector is used for detecting the scattering produced by one or more particles in the flow stream.

16. An optical detection system according to claim 15, wherein the one or more particles include white blood cells.

17. An optical detection system according to claim 16, wherein the white blood cells include neutrophils and/or lymphocytes.

18. An optical detection system according to claim 14, wherein the light receiving means includes at least one other annular shaped light detector positioned around the second annular shaped light detector.

19. An optical detection system according to claim 1, wherein the two or more spaced light sources are positioned along a light source axis that is angularly offset relative to the central axis of flow of the flow stream.

20. An optical detection system according to claim 19, wherein the light source axis is angularly offset by about 90 degrees relative to the central axis of flow of the flow stream.

21. An optical detection system according to claim 19, wherein the light source axis is angularly offset by less than 90 degrees relative to the central axis of flow of the flow stream.

22. An optical detection system according to claim 1, wherein the two or more spaced light sources collectively provide a substantially constant light intensity across the flow stream.

23. An optical detection system according to claim 1, wherein the light that is provided through the flow stream is used for determining the velocity of one or more particles in the flow stream.

24. An optical detection system according to claim 1, wherein the light that is provided through the flow stream is used for determining the size of one or more particles in the flow stream.

25. An optical detection system according to claim 1, wherein the two or more light sources include a first set of light sources positioned along a first light source axis and a second set of light sources positioned along a second light source axis, wherein the second light source axis is located downstream or upstream of the first light source axis.

26. An optical detection system according to claim 25, wherein light receiving means includes a first detector and a second detector.

27. An optical detection system according to claim 26, wherein the lens means includes a first set of microlenses associated with the first set of light sources and a second set of microlenses associated with the second set of light sources.

28. An optical detection system according to claim 27, wherein the first set of microlenses are adapted to focus the light from the first set of light sources to a first common focal point, and the second set of microlenses are adapted to focus the light from the second set of light sources to a second common focal point.

29. An optical detection system according to claim 28, wherein the first detector of the light receiving means has a centrally located light detector positioned at the first common focal point and the second detector of the light receiving means has a centrally located light detector positioned at the second common focal point.

30. An optical detection system according to claim 29, wherein the first detector includes at least one annular shaped light detector positioned around the centrally located light detector.

31. An optical detection system according to claim 29, wherein the second detector includes at least one annular shaped light detector positioned around the centrally located light detector.

32. An optical detection system according to claim 29, wherein the second detector does not include an annular shaped light detector around the centrally located light detector.

33. An optical detection system according to claim 29, wherein the first set of light sources and the first detector are used to detect the alignment of the flow of one or more particles relative to the central axis of the flow stream.

34. An optical detection system according to claim 29, wherein the first set of light sources and the first detector are used to detect the speed of one or more particles in the flow stream.

35. An optical detection system according to claim 29, wherein the first set of light sources and the first detector are used to detect the size of one or more particles in the flow stream.

36. An optical detection system according to claim 29, wherein the second set of light sources and the second detector are used in conjunction with the second set of light sources and the second detector to determine the speed of one or more particles in the flow stream.

37. A method for determining the position of one or more particles in a flow stream relative to a central axis of the flow stream, the method comprising:

activating two or more light sources positioned on a first side of the flow stream for providing light through the flow stream;

focusing the light from each of the two or more light sources to a common focal point located on a second opposite side of the flow stream;

monitoring an output response of a detector, wherein at least a portion of the detector is positioned at the common focal point, the output response providing an indication of the position of the one or more particles in the flow stream; and

determining the position of the one or more particles in the flow stream by examining the output response of the detector.

38. A method for determining the velocity of one or more particles in a flow stream, the method comprising:

activating two or more upstream light sources at an upstream position of the flow stream to provide light through the flow stream;

focusing the light from each of the at least two or more upstream light sources to a first common focal point behind the flow stream;

monitoring an output response of an upstream detector that receives the light from the two or more upstream light sources;

activating two or more downstream light sources at a downstream position of the flow stream to provide light through the flow stream;

focusing the light from each of the at least two or more downstream light sources to a second common focal point behind the flow stream;

monitoring an output response of a downstream detector that receives the light from the two or more downstream light sources;

detecting a change in the output response of the at least one upstream detector when a particle passes between the at least two upstream light sources and the upstream detector;

detecting a change in the output response of the downstream detector when the same particle passes between the at least two downstream light sources and the downstream detector; and

determining a time lag between the change in output response of the upstream detector and the change in output response of the downstream detector, the time lag being related to the speed of the particle.