Particle analyzer and particle analysis method

• US 9,429,509 B2
• Filed: 01/27/2003
• Issued: 08/30/2016
• Est. Priority Date: 01/28/2002
• Status: Active Grant

• Current Assignee: Sysmex Corporation
• Original Assignee: Sysmex Corporation
• Inventors: Nagai, Takaaki, Yamada, Kazuhiro, Tobimatsu, Hiroaki
• Primary Examiner(s): Fritchman, Rebecca M
• Application Number:
  US10/352,485
• Publication Number:
  US 20030143117A1
• Time in Patent Office: 4,964 Days
• Field of Search: 422/73, 436/63
• US Class Current: 1/1
• CPC Class Codes: G01N 15/1459 the analysis being performed on a sample stream
• CPC Class Codes: G01N 2015/1006 for cytology
• CPC Class Codes: G01N 2015/1402 Data analysis by thresholding or gating operations performed on the acquired signals or stored data
• CPC Class Codes: G01N 2015/1477 Multiparameters
• CPC Class Codes: G01N 2015/1486 Counting the particles
• CPC Class Codes: G01N 2015/1488 Methods for deciding
• CPC Class Codes: G01N 33/49 Blood chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80

Abstract

Particle analyzers are described that include a cell for receiving a particles-containing liquid; a light source for irradiating light onto the particles-containing liquid; a photo-detector for detecting optical information from particles in the particles-containing liquid and converting the optical information into an electric signal; a temperature sensor for detecting a temperature of the particles-containing liquid; and a signal processing section for calculating an analysis result of the particles on the basis of an output of the photo-detector and an output of the temperature sensor. Particle analysis methods are also described.

Claims

1. A flow cytometer comprising:

a flow cell comprising an outlet, wherein the flow cell is configured to;

receive a cells-containing liquid and form a flow of the cells-containing liquid;

surround the cells-containing liquid with a sheath liquid to form a sample liquid; and

discharge the sample liquid at the outlet;

a light source that irradiates light onto the flow of the cells-containing liquid formed by the flow cell;

a photo-detector that detects optical information from cells in the flow of the cells-containing liquid and converts the optical information into an electric signal;

a temperature sensor configured to detect a temperature of the sample liquid, wherein the temperature sensor is arranged at the outlet of the flow cell such that the temperature sensor is configured to detect the temperature of the sample liquid after the flow of the cells-containing liquid is irradiated by the light source; and

a signal processing section that comprises a processor that executes instructions encoded on a computer readable medium that classifies cells and measures the classified cells on the basis of an output of the photo-detector and an output of the temperature sensor.

2. The flow cytometer of claim 1, wherein the signal processing section interfaces:

a temperature dependent variable amplifier that amplifies the electric signal, thereby producing an amplified electric signal;

a controlling section for receiving the output of the temperature sensor and thereby controls the amplifier; and

further comprises an analyzing section that executes instructions encoded on the computer readable medium for processing and analyzing the amplified electric signal.

3. The flow cytometer of claim 2, wherein:

the temperature dependent variable amplifier comprises an A/D converter that converts an inputted analog signal into an outputted digital signal of predetermined bits; and

the controlling section comprises the processor that executes instructions encoded on a computer readable medium that controls a ratio between the inputted analog signal and the outputted digital signal of the A/D converter.

4. The flow cytometer of claim 2, wherein the controlling section comprises a memory storing a relation formula for indicating an amplification factor corresponding to a temperature, and thereby controlling the amplifying section based on the relation formula.

5. The flow cytometer of claim 4, wherein the memory stores a plurality of relation formulae, each of which corresponds to classified cells to be measured.

6. The flow cytometer of claim 1, wherein the temperature sensor comprises a thermistor.

7. The flow cytometer of claim 1, wherein the flow cell comprises:

a cell having an inlet, the outlet, and a through-hole communicating therebetween; and

a nozzle inserted from the inlet into the through-hole coaxially, and wherein the sheath liquid is supplied from the inlet to the outlet of the cell, while the cells-containing liquid is supplied through the nozzle into the cell.

8. The flow cytometer of claim 1, wherein the light source comprises a laser light source, and irradiates light from the outside of the flow cell in a direction perpendicular to a flow of the sample liquid.

9. The flow cytometer of claim 1, wherein the optical information from the cells in the cells-containing liquid comprises information on luminescent light emitted from the cells excited by irradiated light from the light source.

10. The flow cytometer of claim 2, wherein the analyzing section processes the amplified electric signal, and thereby classifies the cells and counts the classified cells.

20. The flow cytometer of claim 1, wherein the signal processing section classifies the cells into nucleated erythrocytes and other cells, and measures the classified nucleated erythrocytes.

21. The flow cytometer of claim 1, wherein the signal processing section classifies the cells into basophiles and other leucocytes and measures the classified basophiles.

22. The flow cytometer of claim 1, wherein the signal processing section classifies cells into lymphocytes, monocytes, neutrophiles, basophiles, and eosinophils and measures the classified lymphocytes, monocytes, neutrophiles, basophiles, and eosinophils.

23. The flow cytometer of claim 1, wherein the signal processing section classifies the cells into reticulocytes and other cells and measures the classified reticulocytes.

24. The flow cytometer of claim 1, wherein the optical information comprises scattered light and/or fluorescent light.

11. A flow cytometer comprising:

a flow cell for receiving a cells-containing liquid that forms a flow channel for the cells-containing liquid;

a light source for irradiating the flow of the cells-containing liquid within the flow channel;

a photo-detector optically linked to the flow channel that detects optical information from cells in the flow of the cells-containing liquid in the flow-channel and converts the optical information into an electric signal;

a temperature sensor arranged to receive the cells-containing liquid after the cells-containing liquid has been irradiated by the light source for detecting a temperature of the cells-containing liquid after irradiation; and

a processor that executes instructions retained on a computer readable medium that;

analyzes the electric signal and thereby classifies the cells, and measures the classified cells as an analysis result; and

corrects the electric signal obtained by the photo-detector or the analysis result obtained by the analysis of on an output of the temperature sensor.

12. The flow cytometer of claim 11, further comprising an amplifier for amplifying the electric signal obtained by the photo-detector, thereby producing an amplified electric signal, wherein a controlling section comprising the processor that executes instructions retained on a computer readable medium receives the output of the temperature sensor, controls the amplifier, and thereby corrects the electric signal obtained by the photo-detector.

13. The flow cytometer of claim 12, wherein:

the amplifier comprises an A/D converter that converts an analog signal into a digital signal; and

the controlling section controls a ratio between the analog signal and the digital signal.

14. The flow cytometer of claim 12, wherein the controlling section comprises a memory storing a relation formula for indicating an amplification factor corresponding to a temperature, and thereby controlling the amplifying section based on the relation formula.

15. The flow cytometer of claim 14, wherein the memory stores a plurality of relation formulae, each of which corresponds to the classified cells to be measured.

16. The flow cytometer of claim 11, wherein the flow cell receives the cells-containing liquid, surrounds the cells-containing liquid with a sheath liquid, and thereby forms and discharges a sample liquid.

17. The flow cytometer of claim 16, wherein the temperature sensor comprises a thermistor, and is arranged at an outlet of the flow cell so as to be exposed to the sample liquid.

18. The flow cytometer of claim 11, wherein the optical information from the cells in the cells-containing liquid comprises information on luminescent light emitted from the cells excited by irradiated light from the light source.

19. A flow cytometer comprising:

a flow cell for receiving a cells-containing liquid and for forming a flow of the cells-containing liquid;

a light source for irradiating the flow of the cells-containing liquid;

a photo-detector for detecting optical information from cells in the flow of the cells-containing liquid and for converting the optical information into an electric signal;

a temperature sensor positioned to detect a temperature of the cells-containing liquid after the cells-containing liquid is irradiated by the light source;

a variable gain amplifier that amplifies, based on the detected temperature, the electric signal, where the variable gain is based on the detected temperature; and

an analyzing section that comprises a processor that executes instructions encoded on a computer readable medium that processes and analyzes the amplified electric signal and thereby classifies cells, and measures the classified cells based on the amplified electric signal.

25. A flow cytometer comprising:

a flow cell configured to receive a cells-containing liquid and for forming a flow of the cells-containing liquid in a first direction;

a light source configured to irradiate light onto the flow of the cells-containing liquid formed by the flow cell;

a photo-detector configured to detect optical information from cells in the flow of the cells-containing liquid and for converting the optical information into an electric signal;

a temperature sensor configured to detect a temperature of the cells-containing liquid, wherein the temperature sensor is arranged at a position relative to the flow of the cells-containing liquid in the first direction that is after a position at which the cells-containing liquid is irradiated by the light source, wherein the position of the temperature sensor is such that the detected temperature of the cells-containing liquid is substantially the same as a temperature of the cells-containing liquid at a position where the cells-containing liquid is irradiated by the light source; and

a signal processor that executes instructions retained in a computer readable medium that classifies cells on the basis of an output of the photo-detector and an output of the temperature sensor.