Method of reaction in flow channel of microchip and analysis device

• US 20100261290A1
• Filed: 06/18/2010
• Published: 10/14/2010
• Est. Priority Date: 03/29/2006
• Status: Active Grant

• Current Assignee: Konica Minolta Medical & Graphic Incorporated (Konica Minolta Inc.)
• Original Assignee: Konica Minolta Medical & Graphic Incorporated (Konica Minolta Inc.)
• Inventors: Tanimoto, Kohsuke, Higashino, Kusunoki, Aoki, Youichi, Sando, Yasuhiro, Nakajima, Akihisa
• Granted Patent: US 8,257,974 B2
• Time in Patent Office: Days
• US Class Current: 436/174
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 3/502723 characterised by venting arrangements
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502784 specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: G01N 2035/00158 Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 27/44756 Apparatus specially adapted therefor
• CPC Class Codes: G01N 35/1095 for supplying the samples to flow-through analysers for a specific analyser see relevant groups, e.g. under G01N15/00, G01N21/00, G01N27/00, G01N30/00, H01J49/00
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/255 including use of a solid sorbent, semipermeable membrane, or liquid extraction
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

In the case of passing a reagent in a reaction channel in a microchip, which carries a reactant capable of reacting with the reagent on the wall thereof, and bringing the reactant into contact with the reagent so as to carry out a reaction, the reagent is efficiently passed to the reactant to thereby promote the progress of the reaction. In carrying out the reaction as described above, the reagent (30a) is passed in such a manner that the periphery of the gas/liquid interface at the front end of the reagent moves forward and backward along the wall face of the reaction channel (10). After the completion of the reaction between the reagent (30a) and the reactant, another reagent (30b), which is to be reacted with the reactant capable of reacting with the reagent that is carried on the reaction channel, is passed into the reaction channel (10) while providing a gas in the front edge side thereof. In carrying out the reaction, the reagent (30b) is passed in such manner that the periphery of the gas/liquid interface at the front end of the reagent moves forward and backward along the wall face of the reaction channel (10).

Claims

1. A method of reaction in a flow channel of a microchip, which performs a reaction by bringing reagent in contact with reacting material by flowing the reagent into a reaction flow channel in which the reacting material which reacts with the reagent is carried on a wall surface of the reaction flow channel of the microchip, when the reaction is performed, the method comprising performing, after a peripheral portion of the gas-liquid boundary surface at a front end of the reagent passes in a forward direction on the wall surface of the reaction flow channel and reaches to a flow channel ahead of the reaction flow channel, at least once an operation which flows back the reagent such that the peripheral portion passes in a reverse direction on the wall surface of the reaction flow channel to an upstream side of the reaction flow channel and then flows the reagent in the forward direction such that the peripheral portion once again passes in the forward direction on the wall surface of the reaction flow channel.

2. The method of reaction in the flow channel of the microchip according to claim 1, wherein, after the reaction between the reagent and the reacting material has been performed,

then, the method further comprises:

flowing other reagent to react with the reacting material on the reaction flow channel into the reaction flow channel with intervening gas at a front end side of the other reagent; and

when the reaction between the other reagent and the reacting material is performed, flowing the other reagent such that the peripheral portion of the gas-liquid interface at the front end of the other reagent moves back and forth on the wall surface of the reaction flow channel.

3. The method of reaction in the flow channel of the microchip according to claim 2, wherein, the microchip comprises:

a reagent holding flow channel which stores the other reagent;

a gas storage flow channel which is disposed at a downstream of the reagent holding flow channel, communicates directly or indirectly at further downstream side thereof with the reaction flow channel, and stores gas; and

a water repellent valve which intervenes between a downstream end of the reagent holding flow channel and an upstream end of the gas storage flow channel and includes a flow control path that has a smaller cross-sectional area than these flow channels and passes the other reagent forward from the reagent holding flow channel by applying a flow fluid pressure larger than a predetermined pressure from an upstream side, and,

wherein, after the reaction between the reagent and the reacting material is performed, the reaction between the other reagent and the reacting material is performed,

by pushing the other reagent stored in the reagent holding flow channel forward from the reagent holding flow channel through the water repellent valve to an ahead of the reagent holding flow channel;

flowing the other reagent into the reaction flow channel with intervening the gas stored in the gas storage flow channel at the front end of the other reagent; and

flowing the other reagent such that the peripheral portion of the gas-liquid interface at the front end of the other reagent moves back and forth on the wall surface of the reaction flow channel and the other reagent reacts with the reacting material.

4. The method of reaction in the flow channel of the microchip according to any one of claim 1, wherein a flow channel ahead of the reaction flow channel forms a closed air tight space and the peripheral portion of the gas-liquid interface at the front end of the reagent moves back and forth on the wall surface of the reaction flow channel by reducing a pressure from out side after flowing the reagent into the reaction flow channel by the pressure.

5. The method of reaction in the flow channel of the microchip according to claim 4, wherein a volume of the closed flow channel ahead of the reaction flow channel is larger than a volume of the reaction flow channel.

6. The method of reaction in the flow channel of the microchip according to claim 4, wherein a gas vent channel which has an end opened to an outer atmosphere is provided at a position before the reaction flow channel.

7. The method of reaction in the flow channel of the microchip according to claim 4, wherein the at least once is a plurality of times.

8. A method of reaction in a flow channel of a microchip, which performs a reaction by bringing reagent in contact with reacting material by flowing the reagent into a reaction flow channel in which the reacting material which reacts with the reagent is carried on a wall surface of the reaction flow channel of the microchip, when the reaction is performed, the method comprising performing, after the peripheral portion of the gas-liquid boundary surface at the front end of the reagent passes in a forward direction on the wall surface of the reaction flow channel and reaches to a flow channel ahead of the reaction flow channel, at least once an operation which flows back the reagent such that the peripheral portion reaches to a position located at the wall surface of the reaction flow channel, and then flows the reagent in the forward direction such that the peripheral portion once again passes in the forward direction on the wall surface of the reaction flow channel.

9. The method of reaction in the flow channel of the microchip according to claim 8, wherein, after the reaction between the reagent and the reacting material has been performed,

then, the method further comprises:

flowing other reagent to react with the reacting material on the reaction flow channel into the reaction flow channel with intervening gas at a front end side of the other reagent; and

when the reaction between the other reagent and the reacting material is performed, flowing the other reagent such that the peripheral portion of the gas-liquid interface at the front end of the other reagent moves back and forth on the wall surface of the reaction flow channel.

10. The method of reaction in the flow channel of the microchip according to claim 9, wherein, the microchip comprises:

a reagent holding flow channel which stores the other reagent;

a gas storage flow channel which is disposed at a downstream of the reagent holding flow channel, communicates directly or indirectly at further downstream side thereof with the reaction flow channel, and stores gas; and

a water repellent valve which intervenes between a downstream end of the reagent holding flow channel and an upstream end of the gas storage flow channel and includes a flow control path that has a smaller cross-sectional area than these flow channels and passes the other reagent forward from the reagent holding flow channel by applying a flow fluid pressure larger than a predetermined pressure from an upstream side, and,

wherein, after the reaction between the reagent and the reacting material is performed, the reaction between the other reagent and the reacting material is performed,

by pushing the other reagent stored in the reagent holding flow channel forward from the reagent holding flow channel through the water repellent valve to an ahead of the reagent holding flow channel;

flowing the other reagent into the reaction flow channel with intervening the gas stored in the gas storage flow channel at the front end of the other reagent; and

flowing the other reagent such that the peripheral portion of the gas-liquid interface at the front end of the other reagent moves back and forth on the wall surface of the reaction flow channel and the other reagent reacts with the reacting material.

11. The method of reaction in the flow channel of the microchip according to any one of claims 8, wherein a flow channel ahead of the reaction flow channel forms a closed air tight space and the peripheral portion of the gas-liquid interface at the front end of the reagent moves back and forth on the wall surface of the reaction flow channel by reducing a pressure from out side after flowing the reagent into the reaction flow channel by the pressure.

12. The method of reaction in the flow channel of the microchip according to claim 11, wherein a volume of the closed flow channel ahead of the reaction flow channel is larger than a volume of the reaction flow channel.

13. The method of reaction in the flow channel of the microchip according to claim 11, wherein a gas vent channel which has an end opened to an outer atmosphere is provided at a position before the reaction flow channel.

14. The method of reaction in the flow channel of the microchip according to claim 8, wherein the at least once is a plurality of times.