Method of reaction in flow channel of microchip and analysis device

• US 8,257,974 B2
• Filed: 06/18/2010
• Issued: 09/04/2012
• 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: Higashino, Kusunoki, Sando, Yasuhiro, Nakajima, Akihisa, Aoki, Youichi, Tanimoto, Kohsuke
• Primary Examiner(s): Sines, Brian J
• Application Number:
  US12/803,060
• Publication Number:
  US 20100261290A1
• Time in Patent Office: 809 Days
• Field of Search: 422/50, 422/68.1, 422/502, 422/503, 422/504, 422/505, 422/506, 422/507, 422/129, 436/43, 436/63, 436/174, 436/177, 436/178, 436/179, 436/180
• US Class Current: 436/43
• 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 reaction method for performing a reaction in a reaction flow channel of a microchip, the microchip including (i) the reaction flow channel, wherein a reacting material is fixed on an inner wall surface of the reaction flow channel, (ii) a first flow channel connected upstream of the reaction flow channel, wherein a gas is stored in the first flow channel, and (iii) a second flow channel connected downstream of the reaction flow channel, and the reaction method comprising:

flowing a first reagent liquid into the second flow channel through the first flow channel and the reaction flow channel in a forward direction, whereby a peripheral portion of a gas-liquid interface at a front end of the first reagent liquid passes along the inner wall surface of the reaction flow channel in the forward direction;

flowing back the first reagent liquid into the first flow channel through the reaction flow channel in a reverse direction, whereby the peripheral portion passes along the inner wall surface of the reaction flow channel in the reverse direction; and

flowing the first reagent liquid into the second flow channel through the reaction channel again in the forward direction, whereby the peripheral portion once again passes along the inner wall surface of the reaction flow channel in the forward direction,

wherein the reaction is performed by contacting the first reagent liquid with the reaction material fixed on the inner wall surface of the reaction flow channel.

2. The reaction method according to claim 1, further comprising performing, after the reaction between the first reagent liquid and the reacting material has been performed:

flowing a second reagent liquid to react with the reacting material fixed on the inner wall surface of the reaction flow channel into the reaction flow channel with intervening gas at a front end of the second reagent liquid; and

flowing the second reagent liquid such that a peripheral portion of a gas-liquid interface at the front end of the second reagent liquid moves back and forth on the inner wall surface of the reaction flow channel,

whereby a reaction between the second reagent liquid and the reacting material is performed.

3. The reaction method according to claim 2, wherein the microchip further comprises:

a reagent holding flow channel which stores the second reagent liquid, wherein the reagent folding flow channel is connected upstream of the reaction flow channel;

a gas storage flow channel which stores gas, wherein the gas storage flow channel is disposed at a downstream side of the reagent holding flow channel and communicates with the reaction flow channel directly or indirectly at downstream side of the gas storage flow channel; 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 the reagent holding flow channel and gas storage flow channel, wherein the water repellent valve passes the second reagent liquid forward from the reagent holding flow channel when a flow fluid pressure larger than a predetermined pressure is applied from an upstream side, and

wherein, after the reaction between the first reagent liquid and the reacting material is performed, the reaction between the second reagent liquid and the reacting material is performed by;

pushing the second reagent liquid stored in the reagent holding flow channel forward from the reagent holding flow channel through the water repellent valve to downstream of the reagent holding flow channel;

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

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

4. The reaction method according to claim 1, wherein the second flow channel downstream 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 first reagent liquid moves back and forth on the inner wall surface of the reaction flow channel by reducing a pressure from outside after flowing the first reagent liquid into the reaction flow channel by the pressure.

5. The reaction method according to claim 4, wherein a volume of the second flow channel downstream of the reaction flow channel is larger than a volume of the reaction flow channel.

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

7. The reaction method according to claim 1, wherein flowing back the first reagent liquid into the first flow channel through the reaction flow channel in the reverse direction and flowing the first reagent liquid into the second flow channel through the reaction channel again in the forward direction are performed a plurality of times.