Fluid mixing and delivery in microfluidic systems

• US 9,555,408 B2
• Filed: 10/23/2014
• Issued: 01/31/2017
• 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): Sanchez-Medina, Reinaldo
• Application Number:
  US14/521,959
• Publication Number:
  US 20150044760A1
• Time in Patent Office: 831 Days
• Field of Search: 137/3, 137/7, 137/597, 137/605, 137/806, 137/896, 137/897
• US Class Current: 1/1
• 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 device comprising:

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

a first liquid positioned in the upstream microfluidic channel portion;

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

a second liquid positioned in the downstream microfluidic channel portion; and

a component of a vent valve comprising a port positioned between the upstream and downstream microfluidic channel portions,

wherein the device can be configured such that when the port is in an open position, the second liquid in the downstream microfluidic channel portion can be flowed without substantially flowing the first liquid, and when the port is in a closed position, the first liquid from the upstream microfluidic channel portion can be flowed to the downstream microfluidic channel portion.

2. A device as in claim 1, wherein the device is sealed and constructed and arranged for storing the first liquid in the device.

3. A device as in claim 2, wherein the upstream microfluidic channel portion contains a third liquid stored therein, and wherein the first and third liquids are separated by a fluid substantially immiscible with both the first and third liquids.

4. A device as in claim 2, wherein the device is sealed and constructed and arranged for storing the first liquid and the second liquid in the device while the first and second liquids are in fluid communication with one another.

5. A device as in claim 1, comprising 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.

6. A device as in claim 5, wherein the first and second branching channels connect at an intersection and are fluidically connected to the downstream microfluidic channel portion.

7. A device as in claim 5, wherein the first liquid is positioned in the first microfluidic branching channel, and the device comprises a third liquid positioned in the second microfluidic branching channel.

8. A device as in claim 6, 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 a cross-sectional area of the first microfluidic branching channel or the second microfluidic branching channel.

9. A device as in claim 1, wherein the first liquid comprises a metal solution, and wherein the upstream microfluidic channel portion contains a third liquid, the third liquid comprising a reducing agent.

10. A device as in claim 1, wherein the device comprises a second component of a vent valve comprising a port positioned along the upstream microfluidic channel portion or the downstream microfluidic channel portion.

11. A device as in claim 1, wherein the second liquid is different from the first liquid.

12. A device as in claim 1, wherein the second liquid is the same as the first liquid.

13. A device as in claim 1, wherein the downstream microfluidic channel portion comprises multiple rinse solutions separated by one or more gases.

14. A device as in claim 1, wherein the first liquid and/or second liquid comprises a rinse solution.

15. A device as in claim 1, wherein the first and second liquids are separated by a third liquid substantially immiscible with both the first and second liquids.

16. A device as in claim 1, wherein at least one of the first and second liquids contains a reagent for a chemical and/or biological reaction.

17. A device as in claim 16, wherein the reagent participates in a heterogeneous affinity reaction.

18. A device as in claim 1, comprising a valving mechanism adapated and arranged to open and close the port.

19. A device comprising:

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

a first liquid positioned in the upstream microfluidic channel portion;

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

a second liquid positioned in the downstream microfluidic channel portion; and

a port positioned between the upstream and downstream microfluidic channel portions, wherein the port can be configured to be opened and closed in a vent valve arrangement,

wherein the device can be configured such that when the port is in an open position, the second liquid in the downstream microfluidic channel portion can be flowed without substantially flowing the first liquid, and when the port is in a closed position, the first liquid from the upstream microfluidic channel portion can be flowed to the downstream microfluidic channel portion.

20. A device as in claim 19, wherein the device is sealed and constructed and arranged for storing the first liquid in the device.

21. A device as in claim 20, wherein the first and second liquids are separated by a third liquid substantially immiscible with both the first and second liquids.

22. A device as in claim 19, wherein the upstream microfluidic channel portion contains a third liquid stored therein, and wherein the first and third liquids are separated by a fluid substantially immiscible with both the first and third liquids.

23. A device as in claim 19, wherein the device is sealed and constructed and arranged for storing the first liquid and the second liquid in the device while the first and second liquids are in fluid communication with one another.

24. A device as in claim 19, comprising 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.

25. A device as in claim 24, wherein the first and second branching channels connect at an intersection and are fluidically connected to the downstream microfluidic channel portion.

26. A device as in claim 24, wherein the first liquid is positioned in the first microfluidic branching channel, and the device comprises a third liquid positioned in the second microfluidic branching channel.

27. A device as in claim 19, wherein the first liquid comprises a metal solution, and wherein the upstream microfluidic channel portion contains a third liquid, the third liquid comprising a reducing agent.

28. A method, comprising:

in a device comprising an upstream microfluidic channel portion having a cross-sectional dimension of less than 1 mm and containing a first liquid, a downstream microfluidic channel portion having a cross-sectional dimension of less than 1 mm and containing a second liquid, and a component of a vent valve comprising a port positioned between the upstream and downstream microfluidic channel portions, flowing the second liquid in the downstream microfluidic channel portion without substantially flowing the first liquid; and

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