Microfluidic methods

• US 8,672,532 B2
• Filed: 12/18/2009
• Issued: 03/18/2014
• Est. Priority Date: 12/31/2008
• Status: Active Grant

• Current Assignee: IntegenX Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: IntegenX Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Jovanovich, Stevan B., Nielsen, William D., Nguyen, Michael Van
• Primary Examiner(s): SORKIN, DAVID L
• Application Number:
  US12/642,665
• Publication Number:
  US 20100165784A1
• Time in Patent Office: 1,551 Days
• Field of Search: 366/181.5, 366/181.8, 366/341, 366/DIG.2
• US Class Current: 366/181.5
• CPC Class Codes: B01F 25/40 Static mixers colloid-mills B02C; mixing valves F16K11/00
• CPC Class Codes: B01F 31/31 using receptacles with deformable parts, e.g. membranes, to which a motion is imparted
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01L 2400/0622 distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: F16K 99/0001 Microvalves microdevices B81B1/00; manufacture or treatment of devices or systems in or on a substrate B81C1/00; microfluidic structures B01L3/5027; micropumps F04B19/006
• CPC Class Codes: F16K 99/0015 Diaphragm or membrane valves
• CPC Class Codes: F16K 99/0036 operated by temperature variations
• CPC Class Codes: F16K 99/0046 using magnets
• CPC Class Codes: F16K 99/0059 actuated by a pilot fluid
• CPC Class Codes: Y10T 137/0318 Processes
• CPC Class Codes: Y10T 137/87153 Plural noncommunicating flow paths
• CPC Class Codes: Y10T 137/877 With flow control means for branched passages

Abstract

This invention provides microfluidic devices that comprise a fluidics layer having microfluidic channels and one or more regulating layers that regulate the movement of fluid in the channels. The microfluidic devices can be used to mix one or more fluids. At least a portion of the fluidics layer can be isolated from the regulating layer, for example in the form of a shelf. Such isolated portions can be used as areas in which the temperature of liquids is controlled. Also provided are instruments including thermal control devices into which the microfluidic device is engaged so that the thermal control device controls temperature in the isolated portion, and a movable magnetic assembly including magnets with shields so that a focused magnetic field can be applied to or withdrawn from the isolated portion or any other portion of the microfluidic device. Also provided are methods of mixing fluids. The methods include stacking a plurality of alternating boluses of different liquids in a microfluidic channel, and moving the stacked boluses through the channel. In another method, the boluses are moved into a diaphragm valve having a volume able to accommodate several boluses, and then pumping the liquids out of the valve.

Claims

1. A method for combining a first liquid and a second liquid in a microfluidic mixing channel comprising:

a) providing a device with a first liquid channel and a second liquid channel each fluidically connected to the microfluidic mixing channel, wherein a first diaphragm valve is positioned within the first liquid channel, a second diaphragm valve is positioned within the second liquid channel, and a third diaphragm valve and a fourth diaphragm valve are positioned within the microfluidic mixing channel; and

b) using the first, second, third and fourth diaphragm valves to sequentially pump the first liquid and the second liquid into the microfluidic mixing channel to form a plurality of boluses of the first liquid and the second liquid,

wherein the first, third, and fourth diaphragm valves are used to pump the first liquid into the microfluidic mixing channel and the second, third, and fourth diaphragm valves are used to pump the second liquid into the microfluidic mixing channel, and

wherein the first liquid and the second liquid are different.

4. The method of claim 1, wherein one or more of the first, second, third and fourth diaphragm valves are pneumatically actuated.

5. The method of claim 1, further comprising moving the plurality of boluses down the microfluidic mixing channel, whereby an amount of interfacial area between adjacent boluses increases as the plurality of boluses move down the microfluidic mixing channel.

6. The method of claim 1, wherein the microfluidic mixing channel has a cross-sectional area and a length, and the cross-sectional area of the microfluidic mixing channel increases or decreases along the length of the microfluidic mixing channel.

7. The method of claim 1, wherein the second diaphragm valve is a flow-through valve.

8. The method of claim 1, wherein the first liquid and the second liquid move in the microfluidic mixing channel under laminar flow conditions.

9. The method of claim 1, wherein the plurality of boluses are mixed due to moving of the plurality of boluses down the microfluidic mixing channel.

10. The method of claim 1, wherein the first liquid channel and the second liquid channel are microfluidic channels.

2. A method for providing a first liquid and a second liquid to a mixing channel comprising the steps of:

a. providing a device with a first liquid channel and a second liquid channel each fluidically connected to the mixing channel,

wherein a first valve is positioned within the first liquid channel, a second valve is positioned within the second liquid channel, a pumping valve is positioned within the mixing channel, and an exit valve is positioned downstream of the pumping valve within the mixing channel, and

wherein the first liquid and the second liquid are different;

b. providing the first liquid to the first liquid channel and the second liquid to the second liquid channel;

c. configuring the valves such that the first valve is open and the second valve, the pumping valve, and the exit valve are closed;

d. opening the pumping valve;

e. configuring the valves such that the pumping valve and the exit valve are open and the first valve and the second valve are closed;

f. closing the pumping valve;

g. configuring the valves such that the second valve is open and the first valve, the pumping valve and the exit valve are closed;

h. opening the pumping valve;

i. configuring the valves such that the pumping valve and the exit valve are open and the first valve and the second valve are closed; and

j. closing the pumping valve.

11. The method of claim 2, wherein one or more of the first valve, the second valve, the pumping valve, and the exit valve are pneumatically actuated.

12. The method of claim 2, wherein step d) moves the first liquid and step h) moves the second liquid.

13. The method of claim 2, wherein steps c) through j) are repeated.

14. The method of claim 2, wherein the second valve is a flow-through valve that joins the second liquid channel to the mixing channel.

15. The method of claim 2, further comprising moving the first liquid and the second liquid within the mixing channel.

16. The method of claim 15, wherein the moving of the first liquid and the second liquid occurs under laminar flow conditions.

17. The method of claim 2, wherein the mixing channel has a cross-sectional area and a length, and the cross-sectional area of the mixing channel increases or decreases along the length of the mixing channel.

3. A method of mixing fluids in a microfluidic device comprising:

a) stacking alternating boluses of a first liquid and a second liquid in a microfluidic channel;

b) moving the stack of boluses into a chamber of a diaphragm valve, wherein the chamber, when open, has a volume greater than the volume of at least four boluses; and

c) closing the diaphragm valve, wherein closing pumps the liquids out of the valve, thereby mixing the liquids.

20. The method of claim 3, wherein the valve pumps the first liquid and the second liquid into a second microfluidic channel.

18. A method of mixing fluids in a microfluidic device comprising:

a) stacking alternating boluses of a first liquid and a second liquid in a microfluidic channel, wherein the number of alternating boluses in the stack of boluses is at least four; and

b) moving the stack of boluses through the channel, wherein the channel is configured so that moving the boluses increases an area of surface contact between the boluses, thereby promoting mixing of the first and second liquids, wherein the boluses are created using successive strokes of a diaphragm pump comprising three diaphragm valves in the microfluidic device.

19. The method of claim 18, wherein the stack of boluses moves through the channel under laminar flow conditions.