Fluid mixing and delivery in microfluidic systems

• US 8,567,425 B2
• Filed: 11/24/2010
• Issued: 10/29/2013
• Est. Priority Date: 11/24/2009
• Status: Active Grant

• Current Assignee: Opko Diagnostics, LLC (Opko Health, Inc.)
• Original Assignee: Opko Diagnostics, LLC (Opko Health, Inc.)
• Inventors: Tan, Enqing, Linder, Vincent, Taylor, Jason, Steinmiller, David
• Primary Examiner(s): Fristoe, Jr., John K
• Assistant Examiner(s): Sanchez-Medina, Reinaldo
• Application Number:
  US12/953,771
• Publication Number:
  US 20110120562A1
• Time in Patent Office: 1,070 Days
• Field of Search: 137/597, 137/806, 137/897, 137/869, 137/896, 137/3, 137/7
• US Class Current: 137/3
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0694 vents used to stop and induce flow, backpressure valves
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502723 characterised by venting arrangements
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: C12M 23/16 Microfluidic devices; Capillary tubes integrated microfluidic structures B01L3/5027; microreactors B01J19/0093
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: Y10T 137/0318 Processes
• CPC Class Codes: Y10T 137/0329 Mixing of plural fluids of diverse characteristics or conditions
• CPC Class Codes: Y10T 137/86292 System with plural openings, one a gas vent or access opening
• CPC Class Codes: Y10T 137/87652 With means to promote mixing or combining of plural fluids

Abstract

The specification generally discloses systems and methods for mixing and delivering fluids in microfluidic systems. The fluids can contain, in some embodiments reagents that can participate in one or more chemical or biological reactions. Some embodiments relate to systems and methods employing one or more vent valves to controllably flow and/or mix portions of fluid within the microfluidic system. Advantageously, fluid control such as a sequence of fluid flow and/or a change in flow rate, can be achieved by opening and closing one or more vent valves and by applying a single source of fluid flow (e.g., a vacuum) operated at a substantially constant pressure. This can simplify the operation and use of the device by an intended user.

Claims

1. A method, comprising:

providing a device comprising;

a first microfluidic branching channel having a cross-sectional dimension of less than 1 mm and containing a first fluid;

a second microfluidic branching channel having a cross-sectional dimension of less than 1 mm and containing a second fluid;

a main microfluidic channel having a cross-sectional dimension of less than 1 mm and containing a third fluid, wherein the first and second microfluidic branching channels connect at an intersection and are fluidically connected to the main microfluidic channel; and

a vent valve positioned between a portion of the first microfluidic branching channel and a portion of the main microfluidic channel;

flowing the third fluid without substantially flowing the first or second fluids;

actuating the vent valve;

causing the first and second fluids to flow into the intersection substantially simultaneously; and

mixing at least portions of the first and second fluids to produce a mixed fluid.

2. A method as in claim 1, wherein the intersection of the first and second microfluidic branching channels comprises a mixing region, the mixing region having a larger cross-sectional area than either of the first or second microfluidic branching channels.

3. A method as in claim 2, wherein the mixing region comprises a vent valve.

4. A method as in claim 1, wherein at least one of the fluids contains a reagent for a chemical and/or biological reaction.

5. A method as in claim 4, wherein the reagent participates in a heterogeneous affinity reaction.

6. A method as in claim 1, wherein causing the first and/or second fluids to flow comprises applying a vacuum to one end of the channel containing the first fluid and/or second fluids.

7. A method as in claim 1, wherein the first fluid is a liquid.

8. A method as in claim 1, wherein the second fluid is a liquid.

9. A method as in claim 1, wherein the first fluid is stored in the device prior to first use, and wherein the first and second microfluidic branching channels are in fluid communication with the main microfluidic channel during storage of the first fluid.

10. A method as in claim 1, wherein the first fluid comprises a metal solution.

11. A method as in claim 1, wherein the second fluid comprises a reducing agent.

12. A method as in claim 1, wherein the first and second fluids are separated by a fourth fluid substantially immiscible with both the first and second fluids.

13. A method as in claim 1, wherein the valve is positioned between the first fluid and the second fluid.

14. A method as in claim 1, further comprising contacting the mixed first and second fluids with a reaction area w/in 10 minutes of mixing the first and second fluids.

15. A method as in claim 1, wherein the mixing of at least portions of the first and second fluids includes turbulent mixing.

16. A method as in claim 1, further comprising a binding partner disposed in a reaction area downstream of the intersection.

17. A method as in claim 1, wherein the first fluid contains a first reagent for a chemical and/or biological reaction, and the second fluid contains a second reagent for the chemical and/or biological reaction that is different from the first reagent.

18. A method as in claim 1, wherein the cross-sectional areas of at least one of the first microfluidic branching channel and the second microfluidic branching channel are selected such that, when equal pressures are applied to the first and second microfluidic branching channels, the first and second fluids flow into the intersection substantially simultaneously.

19. A method as in claim 1, wherein a substantially constant vacuum is applied at the outlet of the main channel and timing of the flow of the third, second, and first fluids is accomplished by timing of actuation of the vent valve.

20. A method as in claim 1, comprising waiting a predetermined time after actuating the vent valve in order to allow for a predetermined amount of mixing of the at least portions of the first and second fluids and then opening the vent valve to stop the flow of the first and second fluids remaining in the first and second microfluidic branching channels, respectively, thereby delivering a predetermined mixed amount of the first and second fluids to the main microfluidic channel.

21. A method as in claim 1, comprising closing the vent valve thereby causing the first fluid and/or second fluid to flow.

22. A method as in claim 1, wherein the vent valve is adapted and arranged to allow the first fluid and/or second fluid to flow when the vent valve is in a closed position.

23. A method as in claim 1, wherein the first fluid in the first microfluidic branching channel and the second fluid in the second microfluidic branching channel are liquids and are separated by a gas.

24. A method as in claim 1, wherein the device is sealed so as to store the first and second fluids in the device prior to the flowing step, the method comprising unsealing the device and then performing the flowing step.

25. A method as in claim 1, wherein the first fluid is stored in the first microfluidic branching channel, and the second fluid is stored in the second microfluidic branching channel.

26. A method, comprising:

providing a device comprising;

an upstream microfluidic channel portion having a cross-sectional dimension of less than 1 mm;

a first fluid stored in the upstream microfluidic channel portion, wherein the first fluid is a liquid;

a downstream microfluidic channel portion having a cross-sectional dimension of less than 1 mm;

a second fluid stored in the downstream microfluidic channel portion, wherein the second fluid is different from the first fluid and wherein the second fluid is a liquid; and

a vent valve positioned between the upstream and downstream microfluidic channel portions;

while the first and second fluids are in fluid communication with one another, flowing the second fluid in the downstream microfluidic channel portion without substantially flowing the first fluid; and

flowing the first fluid from the upstream microfluidic channel portion to the downstream microfluidic channel portion after the flowing of the second fluid.

27. A method as in claim 26, wherein the device comprises a first microfluidic branching channel and a second microfluidic branching channel, and wherein the upstream microfluidic channel portion is part of one of the first or second microfluidic branching channels.

28. A method as in claim 27, wherein the first fluid is stored in the first microfluidic branching channel, and the device comprises a third fluid stored in the second microfluidic branching channel.

29. A method as in claim 28, comprising mixing at least portions of the first fluid and the third fluid to form a mixed fluid prior to contacting the mixed fluid with a reaction area.

30. A method as in claim 26, wherein the first fluid comprises a metal solution.

31. A method as in claim 30, wherein the second fluid comprises a rinse solution.

32. A method as in claim 26, wherein at least one of the first and second fluids contains a reagent for a chemical and/or biological reaction.

33. A method as in claim 32, wherein the reagent participates in a heterogeneous affinity reaction.

34. A method as in claim 26, wherein the upstream microfluidic channel portion contains a third fluid stored therein, wherein the third fluid is a liquid, and wherein the first and third fluids are separated by a fluid substantially immiscible with both the first and third fluids.

35. A method as in claim 34, wherein at least one of the first and third fluids contains a reagent for a chemical and/or biological reaction.

36. A method as in claim 35, wherein the first fluid comprises a metal solution and the third fluid comprises a reducing agent.

37. A method as in claim 36, wherein the downstream microfluidic channel portion comprises multiple rinse solutions separated by a gas.

38. A method as in claim 26, wherein the device comprises a second vent valve positioned along the upstream microfluidic channel portion or the downstream microfluidic channel portion.

39. A method as in claim 26, wherein the first and second fluids are separated by a third fluid substantially immiscible with both the first and second fluids.

40. A method as in claim 26, wherein a substantially constant vacuum is applied at the outlet in fluid communication with the downstream microfluidic channel portion and timing of the flow of the second and first fluids is accomplished by timing of actuation of the vent valve.

41. A method as in claim 26, wherein the vent valve is adapted and arranged to allow the first fluid to flow when the vent valve is in a closed position.