Optical detection system for flow cytometry

• US 20050122522A1
• Filed: 01/06/2005
• Published: 06/09/2005
• 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 7,671,987 B2
• Time in Patent Office: Days
• US Class Current: 356/436
• 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

An optical detection system for flow cytometry that uses light sources positioned laterally at different distances from the central axis of the flow stream for providing light through different parts of the flow stream. By using two or more light sources, the particle position can be detected, and the alignment and width of the core stream can be monitored and controlled.

Claims

1. An optical detection system for analyzing predetermined characteristics of a flow stream, the flow stream having a width dimension perpendicular to the direction of flow, the optical detection system comprising:

two or more light sources, each for providing light primarily through a different part of the flow stream in the width dimension;

light receiving means for receiving the light from a single selected light source, and for providing at least one signal in response thereto; 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 predetermined characteristics of the flow stream.

2. The optical detection system of claim 1 wherein at least some of the different part of the flow stream overlap.

3. The optical detection system of claim 1 wherein the at least one signal includes a scattering signature.

4. The optical detection system of claim 3 wherein the single selected light source is the light source that produces a scattering signature with the greatest amplitude.

5. The optical detection system of claim 3 wherein the single selected light source is the light source that produces a smallest amplitude signal detected at the light receiving means.

6. The optical detection system of claim 1 wherein at least one of the predetermined characteristics of the flow stream includes a count of cells in the flow stream, and wherein the single selected light source is the light source that produces a largest cell count.

7. The optical detection system of claim 1 wherein the two or more light sources are Vertical Cavity Surface Emitting Lasers (VCSELs).

8. The optical detection system of claim 1 wherein the light receiving means includes at least one photodetector.

9. The optical detection system of claim 1, wherein each of the two or more light sources have a corresponding lens.

10. An optical detection system for analyzing predetermined characteristics of a flow stream, the optical detection system comprising:

a light source for providing a light beam through the flow stream;

aligning means for aligning the light beam produced by the light source relative to the flow stream;

light receiving means for receiving the light from the light source, and for providing at least one signal in response thereto; 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 predetermined characteristics of the flow stream.

11. The optical detection system of claim 10 wherein the flow stream travels down a flow channel, and the aligning means includes means for moving the flow channel relative to the light source.

12. The optical detection system of claim 10 further comprising a lens and wherein the aligning means including means for moving the lens to steer the light beam produced by the light source.

13. A method for analyzing predetermined characteristics of a flow stream, the flow stream having a width dimension perpendicular to the direction of flow, the method comprising the steps of:

providing two or more light sources, each for providing light primarily through a different part of the flow stream in the width dimension;

selecting one of the two or more light sources;

activating the selected light source, while deactivating the other light sources;

receiving the light from the selected light source, and providing at least one signal in response thereto; and

analyzing the predetermined characteristics of the flow stream using the at least one signal.

14. The method of claim 13 wherein at least some of the different part of the flow stream overlap.

15. The method of claim 13 wherein the at least one signal includes a scattering signature.

16. The method of claim 15 wherein the selected light source is the light source that produces a scattering signature with the greatest amplitude.

17. The method of claim 13 wherein the two or more light sources are Vertical Cavity Surface Emitting Lasers (VCSELs).

18. A method for determining the alignment of one or more particles in a flow stream relative to a width dimension of the flow stream, the method comprising:

activating in sequence two or more light sources, each providing light primarily through a different part of the flow stream in the width dimension;

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

detecting a change in the response of the at least one detector when a particle passes between the detector and a corresponding light source;

determining which of the light sources, when activated, produces the largest change in the response of the at least one detector;

selecting the light source that produces the largest change in the response of the at least one detector; and

activating the selected light source.

19. The method of claim 18 wherein at least some of the different part of the flow stream overlap.

20. The method of claim 18 wherein the response of the at least one detector includes a scattering signature.

21. The method of claim 20 wherein the selected light source is the light source that produces a scattering signature with the greatest amplitude.

22. The method of claim 18 wherein the selected light source is the light source that produces the smallest amplitude signal when a particle passes between the detector and a corresponding light source.

23. The method of claim 18 wherein the selected light source is the light source that produces a largest particle count.

24. The method of claim 18 wherein the two or more light sources are Vertical Cavity Surface Emitting Lasers (VCSELs).

25. A method for aligning a light beam with a flow stream, wherein flow stream has a width dimension perpendicular to the direction of flow, the method comprising the steps of:

providing a light beam; and

steering the light beam such that the light beam passes through a designated spot along the width dimension of the flow stream.

26. The method of claim 25 further comprising the step of:

detecting a light signal after the light beam passes through the flow stream; and

steering the light beam until the detected light signal has a predetermined characteristic.

27. A method for aligning a light beam with a flow stream, wherein flow stream has a width dimension perpendicular to the direction of flow, the method comprising the steps of:

providing a light beam; and

moving the light beam and/or flow stream until the light beam passes through a designated spot along the width dimension of the flow stream.

28. The method of claim 27 wherein the flow stream is included in a substrate, and wherein the moving step includes moving the substrate relative to the light beam until the light beam passes through a designated spot along the width dimension of the flow stream.

29. The method of claim 27 wherein the light beam is produced by a light source and the flow stream is included in a substrate, and wherein the moving step includes moving the light source relative to the substrate until the light beam passes through a designated spot along the width dimension of the flow stream.