Resonant-cavity apparatus for cytometry or particle analysis

• US 5,793,485 A
• Filed: 01/13/1997
• Issued: 08/11/1998
• Est. Priority Date: 03/20/1995
• Status: Expired due to Term

• Current Assignee: Paul L. Gourley
• Original Assignee: Sandia Corporation (Martin Marietta Corporation)
• Inventors: Gourley, Paul L.
• Primary Examiner(s): Font, Frank G.
• Assistant Examiner(s): Ratliff, Reginald A.
• Application Number:
  US08/782,039
• Time in Patent Office: 575 Days
• Field of Search: 356/318, 356/417, 356/338, 356/339, 356/246, 356/471, 250/461.2, 250/458.1, 250/459.1
• US Class Current: 356/318
• CPC Class Codes: G01N 15/1429 Signal processing
• CPC Class Codes: G01N 15/1484 microstructural devices
• CPC Class Codes: G01N 15/149 specially adapted for sorting particles, e.g. by their size or optical properties
• CPC Class Codes: G01N 2015/1477 Multiparameters
• CPC Class Codes: G01N 2015/1486 Counting the particles
• CPC Class Codes: G01N 2015/1493 Particle size
• CPC Class Codes: G01N 2021/391 Intracavity sample
• CPC Class Codes: G02B 21/32 Micromanipulators structurally combined with microscopes

Abstract

A resonant-cavity apparatus for cytometry or particle analysis. The apparatus comprises a resonant optical cavity having an analysis region within the cavity for containing one or more biological cells or dielectric particles to be analyzed. In the presence of a cell or particle, a light beam in the form of spontaneous emission or lasing is generated within the resonant optical cavity and is encoded with information about the cell or particle. An analysis means including a spectrometer and/or a pulse-height analyzer is provided within the apparatus for recovery of the information from the light beam to determine a size, shape, identification or other characteristics about the cells or particles being analyzed. The recovered information can be grouped in a multi-dimensional coordinate space for identification of particular types of cells or particles. In some embodiments of the apparatus, the resonant optical cavity can be formed, at least in part, from a vertical-cavity surface-emitting laser. The apparatus and method are particularly suited to the analysis of biological cells, including blood cells, and can further include processing means for manipulating, sorting, or eradicating cells after analysis thereof.

Claims

1. Apparatus for analyzing cells or particles comprising:

(a) a resonant optical cavity comprising a pair of adjacent mirrors oriented parallel to each other, and further including a semiconductor optical gain medium located between the mirrors and an analysis region located between the mirrors for containing at least one cell or particle to be analyzed; and

(b) pump means for activating the gain medium to generate spontaneous emission within the resonant optical cavity, with the spontaneous emission having information about the cell or particle encoded thereupon.

2. The apparatus of claim 1 further including analysis means for receiving a portion of the spontaneous emission and recovering the information about the cell or particle.

3. The apparatus of claim 2 wherein the analysis means includes a spectrometer.

4. The apparatus of claim 1 wherein the information is in the form of an optical characteristic of the spontaneous emission selected from the group consisting of an emission spectrum, an optical intensity profile, or a combination thereof.

5. The apparatus of claim 1 wherein the analysis region is located within a flow cell.

6. The apparatus of claim 1 wherein the gain medium further includes a fluorescent stain.

7. The apparatus of claim 1 wherein the spontaneous emission has a wavelength of about 0.2 to 10 microns.

8. The apparatus of claim 1 wherein the resonant optical cavity is formed proximate to a semiconductor substrate.

9. The apparatus of claim 1 wherein the gain medium includes a semiconductor junction.

10. The apparatus of claim 9 wherein the pump means for activating the gain medium is an electrical current applied across the semiconductor junction.

11. The apparatus of claim 1 wherein the pump means for activating the gain medium is a pump laser providing a pump laser beam for activating at least a portion of the gain medium.

12. The apparatus of claim 11 further including steering means for steering the pump laser beam to define a plurality of different activated portions of the gain medium.

13. The apparatus of claim 1 wherein at least one mirror forming the resonant optical cavity is a distributed Bragg reflector mirror.

14. The apparatus of claim 13 wherein the distributed Bragg reflector mirror comprises a plurality of alternating layers of high-refractive-index and low-refractive-index materials.

15. The apparatus of claim 1 wherein the resonant optical cavity comprises, at least in part, a vertical-cavity surface-emitting laser, with the spontaneous emission being generated below a threshold for lasing of the vertical-cavity surface-emitting laser.

16. Apparatus for analyzing cells or particles comprising:

(a) a resonant optical cavity comprising a pair of optically coupled sub-cavities with the sub-cavities sharing a common mirror, and each sub-cavity having another adjacent mirror spaced at a distance from the common mirror and parallel thereto, one of the sub-cavities including an optical gain medium and the other of the sub-cavities including an analysis region for containing at least one cell or particle to be analyzed;

(b) pump means for activating the gain medium to generate a light beam within the resonant optical cavity, the light beam having information about the cell or particle encoded thereupon.

17. The apparatus of claim 16 further including analysis means for receiving a portion of the light beam and recovering the information about the cell or particle.

18. The apparatus of claim 17 wherein the analysis means includes at least one analysis element selected from the group consisting of a spectrometer and a pulse-height analyzer.

19. The apparatus of claim 16 wherein the information is in the form of an optical characteristic of the light beam selected from the group consisting of an emission spectrum, an optical intensity profile, or a combination thereof.

20. The apparatus of claim 16 wherein the gain medium includes a semiconductor junction.

21. The apparatus of claim 20 wherein the pump means for activating the gain medium is an electrical current applied across the semiconductor junction.

22. The apparatus of claim 16 wherein the pump means for activating the gain medium is a pump laser providing a pump laser beam for activating at least a portion of the gain medium.

23. The apparatus of claim 22 further including steering means for steering the pump laser beam to define a plurality of different activated portions of the gain medium.

24. The apparatus of claim 16 wherein the resonant optical cavity comprises, at least in part, a vertical-cavity surface-emitting laser.

25. Apparatus for analyzing cells or particles comprising:

(a) a first laser having a resonant optical cavity including a gain medium and an analysis region for containing at least one cell or particle to be analyzed;

(b) a second laser for providing a pump laser beam for activating the gain medium to generate a laser beam within the resonant optical cavity of the first laser, with the laser beam having information about the cell or particle encoded thereupon;

(c) steering means for steering the pump laser beam to activate different portions of the gain medium; and

(d) a pulse-height analyzer for analyzing the laser beam and recovering the information about each cell or particle therefrom.

26. The apparatus of claim 25 wherein the first laser is a vertical-cavity surface-emitting laser.

27. The apparatus of claim 25 further including a spectrometer for analyzing the laser beam and recovering additional information about each cell or particle therefrom.

28. A method for analyzing a plurality of cells or particles comprising the steps of:

(a) locating the cells or particles within an analysis region within a resonant optical cavity containing a gain medium;

(b) activating a portion of the gain medium by a pump means, scanning the activated portion across the gain medium, and generating a light beam within the resonant optical cavity at the location of at each cell or particle;

(c) encoding the light beam with information about each cell or particle;

(d) recovering the information about each cell or particle by analyzing the light beam; and

(e) plotting the recovered information about each cell or particle in a multi-dimensional coordinate space wherein the recovered information from a particular type of cell or particle is grouped to provide for identification thereof.