Chip device for manipulating object component, and method using the same

Patent metadata

Field	Value
Publication number	US-9714445-B2
Application number	US-201214365104-A
Country	US
Kind code	B2
Filing date	Nov 5, 2012
Priority date	Dec 22, 2011
Publication date	Jul 25, 2017
Grant date	Jul 25, 2017

Abstract

A chip device for manipulating an object component is described, in which multiple liquid substances such as reagents required for a series of manipulations on a sample are stably secured in separated states throughout the manipulations within the device. The chip device includes a manipulation chip, magnetic particles, and a magnetic field application means. The manipulation chip includes a substrate, a groove formed in the surface of the substrate, and a manipulation medium accommodated in the groove such that gel phases and aqueous liquid phases are alternately disposed in the longitudinal direction of the groove and are in contact with each other. The magnetic particles are for capturing and carrying the object component. The magnetic field application means is capable of moving the magnetic particles in the longitudinal direction of the groove in the substrate by the application of a magnetic field to the substrate.

First claim

What is claimed is:

1. A chip device adapted for manipulating an object component, comprising:
a manipulation chip comprising a substrate, a groove formed in a surface of the substrate, a plurality of opening sections communicating with the groove, and a manipulation medium accommodated in the groove connected between the opening sections such that gel phases and aqueous liquid phases are alternately arranged in a longitudinal direction of the groove and are in contact with each other, wherein the gel phases and the aqueous liquid phases are in contact also on two sidewalls of the groove, and the aqueous liquid phases are secured by the gel phases;
magnetic particles for capturing and transporting the object component; and
a magnetic field application device capable of moving the magnetic particles in the longitudinal direction of the groove in the substrate by applying a magnetic field to the substrate.

2. The chip device of claim 1 , wherein among the aqueous liquid phases, the aqueous liquid phase accommodated at a position closest to one end or the other end of the groove is to be initially supplied with a sample containing the object component.

3. The chip device of claim 1 , wherein the groove is composed of a main groove and a branching groove that branches from the main groove.

4. The chip device of claim 3 , wherein the aqueous liquid phase accommodated at a position closest to the end of the groove on the main groove side is to be initially supplied with the object component.

5. The chip device of claim 3 , wherein the aqueous liquid phase accommodated at a position closest to the end of the groove on the branching groove side is to be initially supplied with the object component.

6. The chip device of claim 3 , wherein
the magnetic field application device comprises a plurality of magnets that are substantially parallel to the surface of the substrate, and are disposed in a one-dimensional array or a two-dimensional array,
in a state that the plurality of magnets are attracted to each other, the plurality of magnets are movable substantially parallel to the surface of the substrate and in the longitudinal direction of the main groove, and
a separation auxiliary tool is disposed on a path of the magnets and at a branch point between the main groove and the branching groove for separating the plurality of magnets.

7. The chip device of claim 1 , wherein the groove is composed of a plurality of grooves that intersect each other in a grid pattern.

8. The chip device of claim 1 , wherein a portion of a surface of the groove, which is in contact with the gel phases, has been subjected to a hydrophobic treatment.

9. The chip device of claim 1 , wherein a portion of the surface of the groove, which is in contact with the aqueous liquid phases, has been subjected to a hydrophilic treatment.

10. The chip device of claim 1 , wherein the groove has a width of 0.005 mm to 10 mm and a depth of 0.005 mm to 5 mm.

11. The chip device of claim 1 , wherein a cover is provided on the surface of the substrate on the side where the groove is formed.

12. The chip device of claim 11 , wherein the cover comprises a hole that penetrates the cover to communicate with the gel phase located at at least one end of the groove.

13. The chip device of claim 1 , wherein the aqueous liquid phases comprise a phase selected from the group consisting of a nucleic acid extraction solution phase, a nucleic acid cleaning solution phase, and a nucleic acid amplification reaction solution phase.

14. A method for manufacturing a manipulation chip included in the chip device of claim 1 , comprising the following processes:
(i) a process of preparing a gel phase section in which a plurality of gel blocks are disposed apart from each other in the longitudinal direction of the groove formed in the substrate; and
(ii) a process of preparing an aqueous liquid phase section by disposing an aqueous liquid in a groove space adjacent to the gel phase section.

15. The method of claim 14 , further comprising: (iii) a process of disposing the cover on the surface of the substrate on the side where the groove is formed.

16. A method for manipulating the object component with use of the chip device of claim 1 , comprising the following processes:
(i) a process of obtaining an aqueous liquid mixture comprising a sample that contains the object component, magnetic particles, and the aqueous liquid in the aqueous liquid phase located at one end of the manipulation chip;
(ii) a process of generating a magnetic field by the magnetic field application device and transporting the magnetic particles together with the object component from the phase of the aqueous liquid mixture at an endmost position to the adjacent aqueous liquid phase through the gel phase;
(iii) a process of performing a first desired treatment in the aqueous liquid phase;
(iv) a process of generating a magnetic field by the magnetic field application device and transporting the magnetic particles together with the object component from the aqueous liquid phase to another aqueous liquid phase;
(v) a process of performing a second desired treatment in the another aqueous liquid phase;
(vi) a process of reiterating the processes (iv) and (v) as required; and
(vii) a process of transporting the magnetic particles together with the object component to the aqueous liquid phase located at the other end of the manipulation chip.

17. The method of claim 16 , wherein a plurality of manipulation chips are provided, and the transportation is performed simultaneously by the magnetic particles in the plurality of manipulation chips.

18. The method of claim 16 , wherein the object component is a nucleic acid; and
in the process (i), the aqueous liquid contained in the aqueous liquid mixture in the phase located at the one end is a liquid that releases the nucleic acid and binds or adheres the nucleic acid to the magnetic particles, and nucleic acid extraction is performed in the aqueous liquid; and
in the processes (ii) to (vi), at least one of the aqueous liquid phases comprises a cleaning solution for the magnetic particles, and nucleic acid purification is performed by removing impurities that accompany the released nucleic acid in the cleaning solution.

19. The method of claim 18 , wherein in the process (vii), the aqueous liquid phase located at the other end comprises a nucleic acid amplification reaction solution, and amplification of a target nucleic acid in the purified nucleic acid is performed in the nucleic acid amplification reaction solution.

20. The method according to claim 19 , wherein a product of the nucleic acid amplification reaction is detected in real time.

Assignees

• Shimadzu Corp

Inventors

• Katasho Isao
• Ohashi Tetsuo

Classifications

• B01L3/502761 Primary

  specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules · CPC title

• G01N33/04

  Dairy products · CPC title

• G01N35/0098

  involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation (magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C) · CPC title

• G01N33/48707

  by electrical means (G01N33/49, G01N33/493 take precedence) · CPC title

• B01L2300/0816

  Cards, e.g. flat sample carriers usually with flow in two horizontal directions · CPC title