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

Patent metadata

Field	Value
Publication number	US-10473652-B2
Application number	US-201615081070-A
Country	US
Kind code	B2
Filing date	Mar 25, 2016
Priority date	Apr 30, 2015
Publication date	Nov 12, 2019
Grant date	Nov 12, 2019

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 method of detecting a test substance contained in a sample, comprising:
applying a sample to a cartridge comprising:
at least first and second chambers filled with liquid-based first and second reagents, respectively; and
a passage adjacent to an upper surface of the cartridge and connecting the first and second chambers with a gas-phase space, wherein openings are formed in upper parts of the first and second chambers, the first and second chambers are connected through the respective openings by the passage, the passage is provided above the first and second chambers and covered with a cover part, and the first and second chambers are filled with the first and second reagents up to the cover part so that a first liquid phase formed by the first reagent and a second liquid phase formed by the second reagent are separated with the gas-phase space in the passage;

transferring at least a part of the sample to the first chamber so that magnetic particles contained in the first reagent react with a test substance in the sample, the magnetic particles carrying the test substance in response to the magnetic particles reacting with the test substance;
attracting, in the first liquid phase of the first reagent, the magnetic particles close to the cover part with a magnetic source;
transferring, by moving the magnetic source along the cover part, a complex of the test substance and the magnetic particles from the first liquid phase to the second liquid phase through the gas-phase space so that the complex reacts with a labeled substance contained in the second reagent; and
detecting the test substance in the complex based on the labeled substance.

2. The method of detecting a test substance, according to claim 1 , wherein
the magnetic particles are moved in a vertical direction within the first chamber by moving the magnetic source.

3. The method of detecting a test substance, according to claim 1 , wherein
the cartridge further includes a liquid reaction part in which a reaction of the magnetic particles with the test substance takes place, and
the magnetic particles are transported from the first chamber to the liquid reaction part through the gas-phase space of the passage.

4. The method of detecting a test substance, according to claim 3 , wherein
the cartridge further comprises a sample flow path connected to the liquid reaction part, and
a mixture of the first reagent and the sample containing the test substance is agitated by an air pressure inside the sample flow path, and the mixture is discharged to the liquid reaction part.

5. The method of detecting a test substance, according to claim 1 , wherein
the cartridge further comprises a third chamber that is located between the first and second chambers and contains a cleaning liquid, and
unwanted substances attached to the magnetic particles are dispersed into the cleaning liquid by transporting the magnetic particles coupled to the test substance to the third chamber through the gas-phase space of the passage.

6. The method of detecting a test substance, according to claim 1 , wherein
the cartridge further comprises a third chamber containing a cleaning liquid, and
the complex of the test substance and the labeled substance is carried by the magnetic particles by transporting the magnetic particles coupled to the test substance from the third chamber to the second chamber adjacent thereto through the gas-phase space of the passage.

7. The method of detecting a test substance, according to claim 6 , wherein
the magnetic particles are sequentially transported to the third chamber on an upstream side, the second chamber, and the third chamber on a downstream side in the recited order through the gas-phase space of the passage.

8. The method of detecting a test substance, according to claim 1 , wherein
the cartridge further comprises a fourth chamber that contains a buffer liquid, and
the magnetic particles carrying the complex of the test substance and the labeled substance are dispersed into the buffer liquid by transporting the magnetic particles carrying the complex to the fourth chamber through the gas-phase space of the passage.

9. The method of detecting a test substance, according to claim 8 , wherein
the cartridge further includes a detection tank in which a reaction of the labeled substance with a substrate takes place, and
a mixed liquid of the complex and the buffer liquid in the fourth chamber is transported to the detection tank through a mixed liquid flow path.

10. The method of detecting a test substance, according to claim 1 , wherein
an area of a bottom inner surface of each of the first and second chambers is larger than an opening area of the openings that connect each of the first and second chambers to the passage.

11. A method of detecting a test substance contained in a sample by use of a cartridge, comprising:
receiving a sample with the cartridge;
transferring at least a part of the sample to a first chamber, of the cartridge, which accommodates a liquid-based first reagent filled up to a cover part, so that magnetic particles contained in the first reagent react with a test substance in the sample, the magnetic particles carrying the test substance in response to the magnetic particles reacting with the test substance;
attracting, in a first liquid phase formed by the first reagent, the magnetic particles close to the cover part with a magnetic source;
transferring, by moving the magnetic source along the cover part, a complex of the test substance and the magnetic particles from the first liquid phase to a second liquid phase formed by a second liquid-based reagent through a gas phase defined by a passage connecting the first chamber and a second chamber, of the cartridge, which accommodates the second reagent filled up to the cover part, so that the complex reacts with a labeled substance contained in the second reagent, wherein the passage is provided adjacent to an upper surface of the cartridge and wherein openings are formed in upper parts of the first and second chambers, and the first and second chambers are connected through the respective openings by the passage, and wherein the passage is provided above the first and second chambers and covered with the cover part so that the first reagent and the second reagent filled up to the cover part are separated with the gas-phase in the passage; and
detecting the test substance in the complex based on the labeled substance.

Assignees

• Sysmex Corp

Inventors

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

Classifications

• G01N33/48

  Biological material, e.g. blood, urine (G01N33/02, G01N33/26, G01N33/44, G01N33/46 take precedence); Haemocytometers (counting blood corpuscules distributed over a surface by scanning the surface G06M11/02) · CPC title

• G01N33/50 Primary

  Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing (measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q) · CPC title

• B01L2200/0673

  Handling of plugs of fluid surrounded by immiscible fluid · CPC title

• B01L2300/0627

  Sensor or part of a sensor is integrated · CPC title

• B01L2300/0883

  Serpentine channels · CPC title