Method of detecting test substance, sample analysis cartridge, and sample analyzer

Patent metadata

Field	Value
Publication number	US-11073514-B2
Application number	US-201916575449-A
Country	US
Kind code	B2
Filing date	Sep 19, 2019
Priority date	Apr 30, 2015
Publication date	Jul 27, 2021
Grant date	Jul 27, 2021

Abstract

In a method of detecting a test substance, a test substance is detected using a sample analysis cartridge supplied with a sample. The sample analysis cartridge includes: a passage part having a gas-phase space; and liquid containers communicating with the passage part through openings. The liquid containers include: a first liquid container containing a first liquid containing magnetic particles; and a second liquid container containing a second liquid containing a labeled substance. The magnetic particles are sequentially transported to the liquid containers through the gas-phase space in the passage part. Thus, the magnetic particles carry a complex of the test substance and the labeled substance. The test substance is detected based on the labeled substance in the complex.

First claim

The invention claimed is:

1. A cartridge-based sample analysis method, comprising:
accommodating a sample in a cartridge comprising at least: a first chamber; a second chamber; a third chamber; and a passage connecting the chambers;
transferring at least a part of the sample to the first chamber to contact a target substance in the sample with a magnetic particle in a first liquid phase in the first chamber, the magnetic particle being bound to the target substance to form a complex;
attracting the complex in the first liquid phase with a magnetic source;
transferring the complex, by moving the magnetic source relatively to the cartridge while attracting the magnetic particle with the moving magnetic source, from the first liquid phase in the first chamber to the passage where at least one gas phase is defined to isolate the first liquid phase and a second liquid phase in the second chamber; and
transferring the complex, by moving the magnetic source relatively to the cartridge while attracting the magnetic particle with the moving magnetic source, from the passage to the second liquid phase in the second chamber where the complex contacts with a labeled substance in the second liquid phase;
transferring the complex, by moving the magnetic source relatively to the cartridge while attracting the magnetic particle with the moving magnetic source, from the second liquid phase in the second chamber to a third liquid phase in the third chamber where the labeled substance in the complex is reacted with a substrate in the third liquid phase to generate a detectable signal; and
detecting the sample based on the detectable signal in the third chamber.

2. The method of claim 1 , wherein the at least part of sample is transferred to the first chamber by applying an air pressure to the passage.

3. The method of claim 1 , wherein the complex is attracted in a vertical direction within the first chamber and then moved horizontally out of the first chamber by the magnetic source.

4. The method of claim 1 , wherein
the method further comprises
transferring the complex, by moving the magnetic source relatively to the cartridge, from the passage to the third chamber where the complex contacts with a cleaning liquid, before transferring to the second chamber.

5. The method of claim 1 , wherein
the cartridge further comprises a fourth chamber, and
the method further comprises
transferring the complex, by moving the magnetic source relatively to the cartridge, from the second chamber to the fourth chamber where the complex is dispersed into a buffer liquid.

6. The method of claim 1 , wherein the sample comprises a body fluid or a blood collected from a subject.

7. The method of claim 1 , further comprising controlling a temperature of the sample and a reagent in the cartridge by heating the cartridge with an electric heating device.

8. The method of claim 1 , wherein the at least part of sample is transferred back and forth in the first passage by applying a positive or a negative air pressure to the passage.

9. An analyte separation method, comprising:
receiving a sample with a cartridge comprising at least a first chamber;
forming a complex of an analyte in the sample and a magnetic particle in a first reagent accommodated in a liquid phase in the first chamber;
applying a magnetic force to the first chamber by a magnetic source; and
moving the magnetic source away from the first chamber and transferring the complex while attracting the magnetic particle with the moving magnetic source, from the liquid phase to a gas phase which is defined outside of the first chamber, thereby separating the analyte in the complex from the sample.

10. The method of claim 9 , further comprising moving the magnetic source close to a second chamber, of the cartridge, where a cleaning liquid is accommodated.

11. The method of claim 9 , further comprising moving the magnetic source close to a third chamber of the cartridge, thereby to contact the complex with a labeled substance in the third chamber.

12. The method of claim 11 , wherein the cartridge further comprises a detection tank, and
the method further comprises
moving the magnetic source close to the detection tank where the labeled substance in the complex is reacted with a substrate to generate a detectable signal.

13. The method of claim 9 , wherein the magnetic particle is attracted in a vertical direction within the first chamber and then moved horizontally out of the first chamber by the magnetic source.

14. The method of claim 9 , wherein the sample is a body fluid or a blood collected from a subject.

15. A cartridge-based sample analysis method, comprising:
accommodating a sample in a cartridge comprising at least: a first chamber; a second chamber; and a passage connecting the chambers;
transferring at least a part of the sample to the first chamber to form a complex including a target substance in the sample, a magnetic particle and a labeled substance, the magnetic particle and the labeled substance being bound to the target substance;
attracting the complex in a first liquid phase in the first chamber with a magnetic source;
transferring the complex, by moving the magnetic source relatively to the cartridge while attracting the magnetic particle with the moving magnetic source, from the first liquid phase in the first chamber to the passage where at least one gas phase is defined to isolate the first liquid phase and a second liquid phase in the second chamber; and
transferring the complex, by moving the magnetic source relatively to the cartridge while attracting the magnetic particle with the moving magnetic source, from the passage to the second liquid phase in the second chamber where the labeled substance in the complex is reacted with a substrate to generate a detectable signal; and
detecting the sample based on the detectable signal in the second chamber.

16. The method of claim 15 , further comprising moving the magnetic source close to a third chamber, of the cartridge, where a cleaning liquid is accommodated.

17. The method of claim 15 , wherein the magnetic particle is attracted in a vertical direction within the first chamber and then moved horizontally out of the first chamber by the magnetic source.

18. The method of claim 15 , wherein the sample is a body fluid or a blood collected from a subject.

Assignees

• Sysmex Corp

Inventors

• Horii Kazuyoshi
• Nose Tomoyuki
• Fujiwara Takao
• Kosako Tatsuya

Classifications

• B01F33/452

  using independent floating stirring elements · CPC title

• B01F31/65

  the materials to be mixed being directly submitted to a pulsating movement, e.g. by means of an oscillating piston or air column · CPC title

• B01F31/441

  performing a rectilinear reciprocating movement · CPC title

• B01F25/4338

  Mixers with a succession of converging-diverging cross-sections, i.e. undulating cross-section · CPC title

• B01F25/4331

  Mixers with bended, curved, coiled, wounded mixing tubes or comprising elements for bending the flow · CPC title