Sample processing method, sample processing chip, and sample processing apparatus

Patent metadata

Field	Value
Publication number	US-10173217-B2
Application number	US-201715454397-A
Country	US
Kind code	B2
Filing date	Mar 9, 2017
Priority date	Mar 10, 2016
Publication date	Jan 8, 2019
Grant date	Jan 8, 2019

Abstract

Disclosed is a sample processing method for processing a target component in a sample by use of a sample processing chip having a storage portion and a droplet forming flow path, the sample processing method including: storing, in the storage portion, a mixture of the target component and a predetermined amount of a diluent for causing the target component to be encapsulated by one molecule or by one particle into a droplet; heating the mixture in the storage portion to cause thermal convection in the storage portion thereby to mix the target component and the diluent together; and in the droplet forming flow path, forming droplets in a dispersion medium, each droplet containing the diluted target component and a reagent that reacts with the target component.

First claim

What is claimed is:

1. A sample processing method for processing a target component in a sample by use of a sample processing chip having a storage portion and a droplet forming flow path, the sample processing method comprising:
storing, in the storage portion, a mixture of the target component and a predetermined amount of a diluent for causing the target component to be encapsulated by one molecule or by one particle into a droplet;
heating the mixture in the storage portion to cause thermal convection in the storage portion thereby to mix the target component and the diluent together; and
in the droplet forming flow path, forming droplets in a dispersion medium, each droplet containing the diluted target component and a reagent that reacts with the target component.

2. The sample processing method of claim 1 , wherein
in a state where either a longitudinal direction or a short direction in a main flat face of the sample processing chip having a flat plate shape is aligned with the gravity direction, the mixture in the storage portion is heated to cause thermal convection in the storage portion.

3. The sample processing method of claim 2 , wherein
the mixture in a lower portion in the gravity direction of the storage portion is heated to form temperature distribution for causing thermal convection in the storage portion.

4. The sample processing method of claim 2 , wherein
in a state where either the longitudinal direction or the short direction in the main flat face of the sample processing chip having the flat plate shape is aligned with the gravity direction, if a direction along the gravity direction is set as a vertical direction of the storage portion and a direction along either the other of the longitudinal direction or the short direction is set as a horizontal direction of the storage portion,
into the storage portion, the mixture is stored by a predetermined amount that realizes an aspect ratio of a length in the vertical direction by which the mixture occupies the storage portion to a length in the horizontal direction by which the mixture occupies the storage portion is not less than 0.1 and not greater than 10.

5. The sample processing method of claim 1 , wherein
the mixture is heated to a temperature of not less than 50° C. and not higher than 85° C. to cause thermal convection in the storage portion.

6. The sample processing method of claim 1 , wherein
the mixture is heated for a predetermined time of less than 10 minutes, thereby to complete mixing of the target component and the diluent together.

7. A sample processing chip to be set in a sample processing apparatus and configured to process a target component in a sample supplied by the sample processing apparatus, the sample processing chip comprising:
a dilution flow path including a storage portion in which to store a mixture of the target component and a predetermined amount of a diluent configured to cause the target component to be encapsulated by one molecule or by one particle into a droplet, the dilution flow path configured to mix the target component and the diluent together, by causing thermal convection in the storage portion by heat generated by a heating portion disposed in the sample processing apparatus; and
a droplet forming flow path configured to form droplets in a dispersion medium, each droplet containing the target component diluted in the dilution flow path and a reagent that reacts with the target component.

8. The sample processing chip of claim 7 , comprising:
a plurality of fluid modules in which the dilution flow path and the droplet forming flow path are formed, respectively;
a base plate on which the plurality of fluid modules are disposed; and
a connection flow path configured to connect the fluid modules disposed on the base plate, and configured to move the target component from the dilution flow path to the droplet forming flow path.

9. The sample processing chip of claim 8 , wherein
the base plate has a thickness of not less than 0.1 mm and not greater than 5 mm.

10. The sample processing chip of claim 7 , comprising
a plurality of the dilution flow paths connected to each other in series, wherein
of the mixture of the target component and the diluent diluted in dilution flow path in a former stage, a predetermined amount of the mixture is supplied to the dilution flow path in a latter stage.

11. The sample processing chip of claim 10 , wherein
in the plurality of the dilution flow paths, as a whole, the target component is diluted at a dilution rate obtained by multiplying dilution rates of the individual dilution flow paths.

12. The sample processing chip of claim 10 , wherein
in the plurality of the dilution flow paths, as a whole, the target component is diluted at a dilution rate of not less than 10 3 fold and not greater than 10 7 fold.

13. The sample processing chip of claim 7 , wherein
in the dilution flow path, the target component is diluted at a dilution rate of not less than 25 fold and not greater than 1500 fold.

14. The sample processing chip of claim 8 , wherein
the dilution flow path is formed so as to extend along a main surface of the base plate, and includes a first flow path configured to supply liquid to the storage portion, and
the storage portion has a shape in which, in a direction along the main surface, a flow path width of the storage portion is increased relative to a flow path width of the first flow path.

15. The sample processing chip of claim 14 , wherein
the storage portion has a shape in which an aspect ratio of a first length of the storage portion along a longitudinal direction of the main surface to a second length of the storage portion along a short direction of the main surface is not less than 0.1 and not greater than 10.

16. The sample processing chip of claim 7 , wherein
the dilution flow path further includes a second flow path configured to send out liquid in the storage portion to the droplet forming flow path, and
the second flow path has a flow path width smaller than a maximum flow path width of the storage portion.

17. The sample processing chip of claim 7 , wherein
the droplet forming flow path includes:
a first channel in which the mixture of the target component and the reagent flows;
a second channel in which the dispersion medium non-miscible with the mixture flows; and
a crossing part at which the first channel and the second channel cross each other.

18. The sample processing chip of claim 7 , wherein
the dilution flow path is formed from a cycloolefin polymer or a cycloolefin copolymer.

19. The sample processing chip of claim 8 , wherein
the dilution flow path and the droplet forming flow path are respectively provided in the fluid modules formed from materials different from each other.

20. A sample processing apparatus configured to process a target component in a sample by use of the sample processing chip of claim 7 , the sample processing apparatus comprising:
a setting portion in which to set the sample processing chip;
a liquid sending portion configured to supply to the sample processing chip a liquid containing the target component and a diluent for diluting the target component, and transfer the liquid and the diluent; and
a heating portion configured to heat a mixture of the diluent and the target component supplied to the storage portion in the sample processing chip, to cause thermal convection in the storage portion.

Assignees

• Sysmex Corp

Inventors

• Yamawaki Koya
• Tagawa Ayato
• Nakano Tsuyoshi

Classifications

• B01F5/0647

  Operations & Transport · mapped topic

• B01L3/502784 Primary

  specially adapted for droplet or plug flow, e.g. digital microfluidics · CPC title

• B01L2200/16

  Reagents, handling or storing thereof · CPC title

• B01L2300/0877

  Flow chambers · CPC title

• B01F13/0079

  Operations & Transport · mapped topic