Microfluidic metering systems and methods

• US 7,077,152 B2
• Filed: 05/06/2002
• Issued: 07/18/2006
• Est. Priority Date: 07/07/2001
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Nanostream, Inc.
• Inventors: Karp, Christoph D.
• Primary Examiner(s): Chambers, A. Michael
• Application Number:
  US10/141,011
• Publication Number:
  US 20030005967A1
• Time in Patent Office: 1,534 Days
• Field of Search: 137/806, 137/15.18, 137/833, 137/825, 137/827, 137/557, 137/828, 204/601, 422/100
• US Class Current: 137/15.18
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2300/028 Graduation
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0638 membrane valves, flap valves
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• 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: G01F 13/00 Apparatus for measuring by volume and delivering fluids or fluent solid materials, not provided for in the preceding groups
• CPC Class Codes: Y10T 137/0491 Valve or valve element assembling, disassembling, or replacing
• CPC Class Codes: Y10T 137/2076 Utilizing diverse fluids
• CPC Class Codes: Y10T 137/2185 To vary frequency of pulses or oscillations
• CPC Class Codes: Y10T 137/2224 Structure of body of device

Abstract

Systems and methods for metering microfluidic volumes are provided. A discrete plug may be separated from a larger volume of first fluid by injecting a second fluid, such as a gas, into a channel containing the first fluid. The injection of the second fluid to isolate the desired amount of the first fluid may be controlled through timing of flows, visual indicators and/or automated control systems using optical or electrical sensors.

Claims

1. A method for generating a plurality of discrete plugs of fluid, the method comprising the steps of:

providing a microfluidic channel in fluid communication with a first fluid inlet and a second fluid inlet;

supplying a first fluid into the channel at the first fluid inlet; and

supplying a second fluid into the channel at the second fluid inlet;

wherein the supply conditions of the first fluid and the second fluid are selected to generate the discrete plugs of fluid in the channel.

2. The method of claim 1 wherein the first fluid and the second fluid are substantially immiscible.

3. The method of claim 1 wherein the first fluid or the second fluid is supplied intermittently to the channel.

4. The method of claim 1 wherein the flow rate of the first fluid or the second fluid is varied with time.

5. The method of claim 1 wherein the first fluid is a liquid and the second fluid is a gas.

6. The method of claim 5 wherein the liquid is substantially pure.

7. The method of claim 5 wherein the second fluid inlet comprises a gas-permeable membrane.

8. The method of claim 1 wherein the microfluidic channel, the first fluid inlet, and the second fluid inlet are defined in a multi-layer microfluidic device made with sandwiched stencil layers.

9. A method for metering a plug of fluid from a larger fluidic volume, the method comprising the steps of:

providing a primary microfluidic channel segment in fluid communication with a first fluid inlet and a second fluid inlet;

supplying a first fluid through the first fluid inlet into the primary channel segment; and

introducing a second fluid through the second fluid inlet into the primary channel segment;

wherein the first fluid is supplied before the second fluid is introduced, the pressure of the second fluid exceeds the pressure of the first fluid, and the introduction of the second fluid divides the first fluid to generate a first fluid plug.

10. The method of claim 9 wherein a volumetric indicator for the primary channel segment is provided.

11. The method of claim 9 wherein the indicator comprises a transition between one or more channel segments and/or a chamber.

12. The method of claim 9 wherein the primary channel segment is in fluid communication with a reduced channel segment, the primary and reduced channel segments each having a nominal cross-sectional area, the nominal area of the reduced channel segment being significantly smaller than the nominal area of the primary channel segment, the method further comprising the steps of:

sensing the presence of fluid in the reduced channel segment; and

responsive to the sensing step, introducing the second fluid into the primary channel segment.

13. The method of claim 12 wherein the sensing and introducing steps are automated.

14. The method of claim 12 wherein the nominal area of the reduced channel segment is less than about one-half of the nominal area of the primary channel segment.

15. The method of claim 12 wherein the nominal area of the reduced channel segment is less than about one-fourth of the nominal area of the primary channel segment.

16. The method of claim 12 wherein the nominal area of the reduced channel segment is less than about one-eighth of the nominal area of the primary channel segment.

17. The method of claim 9 wherein fluid is provided to the primary channel segment through an inlet channel segment, the primary and inlet channel segments each having a nominal cross-sectional area, and the nominal area of the inlet channel segment is smaller than the nominal area of the primary channel segment.

18. The method of claim 17 wherein the first fluid inlet is located along the inlet channel segment.

19. The method of claim 17 wherein the second fluid inlet is located along the inlet channel segment.

20. The method of claim 17 wherein the nominal area of the reduced channel segment is less than about one-half of the nominal area of the primary channel segment.

21. The method of claim 17 wherein the nominal area of the reduced channel segment is less than about one-fourth of the nominal area of the primary channel segment.

22. The method of claim 17 wherein the nominal area of the reduced channel segment is less than about one-eighth of the nominal area of the primary channel segment.

23. The method of claim 9 wherein the first fluid is a liquid and the second fluid is a gas.

24. The method of claim 23 wherein the liquid is substantially pure.

25. The method of claim 9 wherein the first fluid inlet comprises a first valve, and the second fluid inlet comprises a second valve.

26. The method of claim 9 wherein the second fluid inlet comprises a gas-permeable membrane.

27. The method of claim 9 wherein the primary channel segment, the first fluid inlet, and the second fluid inlet are defined in a multi-layer microfluidic device made with sandwiched stencil layers.

28. A device for metering a plug of fluid from a larger fluidic volume, the device comprising:

a primary microfluidic channel segment;

a first fluid inlet and a second fluid inlet each in fluid communication with the primary channel segment; and

means for indicating fluidic volume contained in the primary channel segment;

wherein a first fluid is supplied through the first fluid inlet into the primary channel segment, and responsive to the indicating means a second fluid is supplied through the second fluid inlet into the primary channel segment to divide the first fluid.

29. The device of claim 28 wherein the indicating means includes a mark disposed in or along the primary channel segment.

30. The device of claim 28 further comprising a reduced channel segment having a nominal cross-sectional area and in fluid communication with the primary channel segment;

wherein the primary channel segment has a nominal cross-sectional area greater than the nominal area of the reduced channel segment, and the indicating means includes means for sensing the presence of fluid in the reduced channel segment.

31. The device of claim 28 wherein the nominal area of the reduced channel segment is less than about one-half of the nominal area of the primary channel segment.

32. The device of claim 28 wherein the nominal area of the reduced channel segment is less than about one-fourth of the nominal area of the primary channel segment.

33. The device of claim 28 wherein the nominal area of the reduced channel segment is less than about one-eighth of the nominal area of the primary channel segment.

34. A device for metering a plug of fluid from a larger fluidic volume, the device comprising:

a primary microfluidic channel segment having a nominal cross-sectional area;

an inlet channel segment having a nominal cross-sectional area and in fluid communication with the primary channel segment; and

a first fluid inlet and a second fluid inlet each in fluid communication with the inlet channel segment;

wherein the nominal area of the inlet channel segment is smaller than the nominal area of the primary channel segment, a first fluid is provided to the primary channel segment, and a second fluid is supplied through the to the inlet channel segment to divide the first fluid to yield a plug.

35. The device of claim 34 wherein the nominal area of the reduced channel segment is less than about one-half of the nominal area of the primary channel segment.

36. The device of claim 34 wherein the nominal area of the reduced channel segment is less than about one-fourth of the nominal area of the primary channel segment.

37. The device of claim 34 wherein the nominal area of the reduced channel segment is less than about one-eighth of the nominal area of the primary channel segment.