Device for parallel and synchronous injection for sequential injection of different reagents

• US 20030082081A1
• Filed: 10/23/2002
• Published: 05/01/2003
• Est. Priority Date: 10/24/2001
• Status: Active Grant

• Current Assignee: Commissariat a L'Energie Atomique (AES Corporation)
• Original Assignee: Commissariat a L'Energie Atomique (AES Corporation)
• Inventors: Sarrut, Nicolas, Fouillet, Yves, Gruss, Antoine
• Granted Patent: US 7,094,379 B2
• Time in Patent Office: Days
• US Class Current: 422/105
• CPC Class Codes: B01F 33/3021 the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
• CPC Class Codes: B01F 33/3031 using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
• CPC Class Codes: B01F 33/3032 using magneto-hydrodynamic [MHD] phenomena to mix or move the fluids
• CPC Class Codes: B01F 35/20 Measuring; Control or regulation
• CPC Class Codes: B01F 35/2211 Amount of delivered fluid during a period
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00306 Reactor vessels in a multiple arrangement
• CPC Class Codes: B01J 2219/00353 Pumps
• CPC Class Codes: B01J 2219/00389 Feeding through valves
• CPC Class Codes: B01J 2219/00414 using suction
• CPC Class Codes: B01J 2219/00418 using pressure
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00657 One-dimensional arrays
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/0068 Means for controlling the apparatus of the process
• CPC Class Codes: B01J 2219/00783 Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00873 Heat exchange
• CPC Class Codes: B01J 2219/00891 : Feeding or evacuation
• CPC Class Codes: B01J 2219/0093 : Electric or magnetic energy
• CPC Class Codes: B01L 2200/027 : for microfluidic devices
• CPC Class Codes: B01L 2200/0605 : Metering of fluids
• CPC Class Codes: B01L 2300/1822 : using Peltier elements
• CPC Class Codes: B01L 2400/0403 : specific forces
• CPC Class Codes: B01L 2400/0475 : specific mechanical means and fluid pressure
• CPC Class Codes: B01L 2400/06 : Valves, specific forms thereof
• CPC Class Codes: B01L 2400/082 : Active control of flow resistance, e.g. flow controllers
• CPC Class Codes: B01L 3/563 : Joints or fittings in general F16L; Separable fluid transfer means to transfer fluids between at least two containers, e.g. connectors
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2035/00237 : Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 35/08 : using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
• CPC Class Codes: Y10T 137/0391 : Affecting flow by the addition of material or energy

Abstract

The invention relates to a microfluidic device for injecting series of mobile reaction chambers (102, 103) having non-miscible segmenters (101) in microchannels (21 to 26), comprising:

injection means (10) for injecting into microreaction channels alternatingly and in parallel liquid to form mobile reaction chambers and liquid for forming the segmenters;

means for controlling the progression of one of the two liquids, applied to act on one zone (31) of each microchannel delimiting an injection volume of said liquid; the control means being able to cause stopping or slowing of the progression of said liquid over the zone of each microchannel by exerting an action based on a physico-chemical property of the liquid and said action not affecting the other liquid.

Claims

1. A microfluidic device for parallel and synchronized injecting of series of mobile reaction chambers (102, 103) with non-miscible segmenters (101) in micro-channels (21 to 26), comprising:

injecting means (10) for injecting liquid alternately and in parallel into the micro-channels for forming mobile reaction chambers and liquid for forming the segmenters;

first controlling means for controlling the progression of one of the two liquids in the micro-channels, disposed so as to act on a zone (31) of each micro-channel delimiting an injection volume of said liquid in each micro-channel, the first controlling means being able to cause, when activated, the stopping or slowing of the progression of said liquid over said zone of each micro-channel by effecting an action based on a physico-chemical property of said liquid, said action not directly affecting the other liquid.

2. A microfluidic device according to claim 1, wherein said first controlling means is means enabling movement of said intervention zone of each microchannel in order to modify the volume to be injected of said one of the two liquids.

3. A microfluidic device according to one of claims 1 or 2, wherein the injecting means comprises a part (10) having an injection channel (12) communicating with the first ends of the micro-channels (21 to 16).

4. A microfluidic device according to claim 3, wherein the injection channel (12) has one of its ends communicating with a channel input (11) through which the liquids are injected, the other of its ends being equipped with evacuation means for the liquids present in the injection channel (12).

5. A microfluidic device according to claim 4, wherein the evacuation means comprises a valve (13).

6. A microfluidic device according to any one of claims 1 to 5, wherein the first controlling means is selected from means operating thermally, means operating by slowing on the basis of viscosity, means operating on the basis of magnetic effect, means operating by electrowetting and means operating by constriction of tubes.

7. A microfluidic device according to claim 6, wherein the first controlling means operating thermally, the controlling means is selected from devices using the Peltier effect and thermal-transfer devices.

8. A microfluidic device according to the claim 7, wherein the first controlling means operating thermally are means capable of inducing congealing of one of the two liquids.

9. A microfluidic device according to claim 3, wherein the injection channel (12) and said zone (31) of each micro-channel are arranged parallel, the micro-channels (21 to 26) being perpendicular to them.

10. A microfluidic device according to any one of claims 1 to 9, wherein it comprises in addition at least second controlling means for controlling the progression of said liquid of the two liquids, placed downstream of the first controlling means and being capable of causing, when activated, the stopping or slowing of the progression of said liquid over a zone (32) of each micro-channel by exerting an action based on a physico-chemical property of said liquid, said action not directly affecting the other liquid.

11. A microfluidic device according to claim 10, wherein the second controlling means are selected from among means operating thermally, means operating by slowing on the basis of viscosity, means operating on the basis of magnetic effect, means operating by electrowetting and means operating by constriction of tubes.

12. A microfluidic device according to claim 11, wherein the second controlling means operating thermally, the controlling means are selected from devices using the Peltier effect and thermal-transfer devices.

13. A microfluidic device according to claim 12, wherein the second controlling means operating thermally are means capable of inducing congealing of one of the two liquids.

14. A biological reactor comprising

first distributing means of the liquid for forming mobile reaction chambers;

second distributing means of liquid for forming non-miscible segmenters;

a microfluidic device (100) according to any one of claims 1 to 13, whose injection means (10) are connected alternatingly to the first distributing means and to the second distributing means so as to provide, in the micro-channels (21 to 26) of the microfluidic device, series of mobile reaction chambers with non-miscible segmenters;

a micro-system (80) enabling realization of a biological procedure on the samples circulating in the channels (81) of the micro-system, the micro-system comprising for each channel a first input opening (82) connected to a corresponding micro-channel (21 to 26) of the microfluidic device (100) and a second input opening (84) connected to corresponding sample injecting means in the reaction chambers.

15. , A method for implementing a biological, biochemical, or chemical procedure upon the samples, comprising:

the formation in a microfluidic device (100) according to any one of claims 1 to 13 of series of mobile reaction chambers with non-miscible segmenters in micro-channels (21 to 26), the series being formed in parallel and in a synchronized fashion

simultaneous injection of series of mobile reaction chambers with non-miscible segmenters, formed in the micro-channels (21 to 26) of the microfluidic device (100), into the channels (81) of a micro-system (80) in a number corresponding to that of the micro-channels (21 to 26) of the microfluidic device;

simultaneous and parallel injection of samples into the channels (81) of the micro-system (80) so as to mix them in synchronized fashion with the mobile reaction chambers circulating in the channels (81) of the micro-system (80);

realization of a biological, biochemical or chemical procedure on the samples having been mixed with the mobile reaction chambers.