Microfluidic branch metering systems and methods

• US 6,481,453 B1
• Filed: 06/27/2002
• Issued: 11/19/2002
• Est. Priority Date: 04/14/2000
• Status: Expired due to Term

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Nanostream, Inc.
• Inventors: Dantsker, Eugene, Pezzuto, Marci, Karp, Christoph D., OʼConnor, Stephen D.
• Primary Examiner(s): CHAMBERS, A MICHAEL
• Application Number:
  US10/185,860
• Publication Number:
  US 20020166582A1
• Time in Patent Office: 145 Days
• Field of Search: 137/833, 137/240, 137/15.18, 137/561.A, 137/15.04, 137/15.05, 204/601, 422/101, 422/103
• US Class Current: 137/15.04
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• 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 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 3/0241 Drop counters; Drop formers making arrays for combinatorial libraries B01J19/0046; automation of dispensing for analysis G01N35/10
• 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: C40B 60/14 for creating libraries
• CPC Class Codes: F15C 1/02 Details , e.g. special constructional devices for circuits with fluid elements, such as resistances, capacitive circuit elements; devices preventing reaction coupling in composite elements servomotor systems adapted for maintaining constant speed F15B11/05; Switch boards; Programme devices hydraulic programme control F15B21/02
• CPC Class Codes: F15D 1/02 in pipes or conduits
• CPC Class Codes: F16K 2099/0074 using photolithography, e.g. etching
• CPC Class Codes: F16K 2099/008 Multi-layer fabrications
• 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 99/0025 Valves using microporous membranes
• CPC Class Codes: F16K 99/0028 Valves having multiple inlets or outlets
• CPC Class Codes: F16K 99/0057 the fluid being the circulating fluid itself, e.g. check valves
• 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 137/0419 : Fluid cleaning or flushing
• CPC Class Codes: Y10T 137/0491 : Valve or valve element assembling, disassembling, or replacing
• CPC Class Codes: Y10T 137/2224 : Structure of body of device
• CPC Class Codes: Y10T 137/4259 : With separate material addition
• CPC Class Codes: Y10T 137/85938 : Non-valved flow dividers

Abstract

Microfluidic devices and methods for metering discrete plugs of fluid are provided. The microfluidic devices include a trunk channel and a branch channel having an impedance region. A fluid is supplied to the trunk channel and fills the branch channel to the impedance region. The fluid is then flushed from the trunk channel leaving the branch channel filled. Because the branch channel has a volume, a discrete plug of the fluid having a volume substantially equal to that of the branch channel is formed.

Claims

1. A method for metering a plurality of microfluidic plugs from a larger fluidic volume, the method comprising the steps of:

providing a trunk channel having a fluidic outlet;

providing a plurality of microfluidic branch channels, each having an associated fluidic impedance region, wherein each branch channel of the plurality of branch channels is in fluid communication with the trunk channel;

supplying a first fluid volume to the trunk channel;

filling, directly from the trunk channel, each branch channel of the plurality of branch channels to each fluidic impedance region with a portion of the first fluid volume; and

flushing, with a second fluid, a remaining portion of the first fluid from the trunk channel through the fluidic outlet while each branch channel of the plurality of branch channels remains substantially filled.

2. The method of claim 1 wherein each branch channel of the plurality of branch channels is in independent, direct fluid communication with the trunk channel.

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

4. The method of claims 1 wherein the second fluid is a gas.

5. The method of claim 1 wherein any branch channel of the plurality of branch channels has a volume of less than about two microliters.

6. The method of claim 1 wherein any branch channel of the plurality of branch channels has a volume of less than about one microliter.

7. The method of claim 1 wherein any branch channel of the plurality of branch channels has a volume of less than about five hundred nanoliters.

8. The method of claim 1 further comprising the step of expelling the portions of the first fluid from the plurality of branch channels by generating a pressure differential.

9. The method of claim 1 wherein at least one fluidic impedance region includes a valve.

10. The method of claim 1 wherein at least one fluidic impedance region includes an overlap region.

11. The method of claim 1 wherein at least one fluidic impedance region includes a porous membrane.

12. The method of claim 11 wherein the porous membrane includes a plurality of porous regions.

13. The method of claim 1 wherein any branch channel of the plurality of branch channels has an associated gas-permeable vent.

14. The method of claim 1 wherein the trunk channel is a microfluidic channel.

15. The method of claim 1 wherein the trunk channel is in fluid communication with a reservoir, the method further comprising the step of receiving the first fluid flushed from the trunk channel in the reservoir.

16. The method of claim 15 wherein the reservoir comprises a microfluidic channel.

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

providing a trunk channel having a fluidic outlet;

providing a microfluidic branch channel having an associated fluidic impedance region, wherein the branch channel is in fluid communication with the trunk channel;

supplying a first fluid volume to the trunk channel;

filling, directly from the trunk channel, the branch channel to the fluidic impedance region with a portion of the first fluid volume; and

flushing, with a second fluid, a remaining portion of the first fluid from the trunk channel through the fluidic outlet while the branch channel remains substantially filled.

18. The method of claim 17 wherein the branch channel includes a plurality of microfluidic sub-branch channels, each having an associated sub-branch fluidic impedance region, wherein each sub-branch channel of the plurality of sub-branch channels is in fluid communication with the branch channel, the method further comprising the step of:

filling, from the branch channel, each sub-branch channel of the plurality of sub-branch channels to each sub-branch fluidic impedance region with a sub-portion of the portion of the first fluid volume.

19. The method of claim 17 wherein the first fluid and the second fluid are substantially immiscible.

20. The method of claims 17 wherein the second fluid is a gas.

21. The method of claim 17 wherein the branch channel has a volume of less than about two microliters.

22. The method of claim 17 wherein the branch channel has a volume of less than about one microliter.

23. The method of claim 17 wherein the branch channel has a volume of less than about five hundred nanoliters.

24. The method of claim 17 further comprising the step of expelling the portion of the first fluid from the branch channel by generating a pressure differential.

25. The method of claim 17 wherein the fluidic impedance region includes a valve.

26. The method of claim 17 wherein the fluidic impedance region includes an overlap region.

27. The method of claim 17 wherein the fluidic impedance region includes a porous membrane.

28. The method of claim 27 wherein the porous membrane includes a plurality of porous regions.

29. The method of claim 17 wherein the branch channel has an associated gas-permeable vent.

30. The method of claim 17 wherein the trunk channel is a microfluidic channel.

31. The method of claim 17 wherein the trunk channel is in fluid communication with a reservoir, the method further comprising the step of receiving the first fluid flushed from the trunk channel in the reservoir.

32. The method of claim 31 wherein the reservoir comprises a microfluidic channel.

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

a trunk channel having a fluidic inlet and a fluidic outlet; and

a microfluidic branch channel in direct, independent fluid communication with the trunk channel, the branch channel having a fluidic impedance region;

wherein the trunk channel, branch channel, fluidic inlet, fluidic outlet, and fluidic impedance are arranged to permit a first fluid to be supplied through the trunk channel to fill the branch channel to the fluidic impedance region, and thereafter to permit the fluidic contents of the trunk channel to be flushed through the fluidic outlet while the branch channel remains substantially filled.

34. The device of claim 33, further comprising a plurality of sub-branch channels in fluid communication with the microfluidic branch channel.

35. The device of claim 33, further comprising a plurality of microfluidic branch channels, each in direct, independent fluid communication with the trunk channel.

36. The device of claim 33 wherein the microfluidic branch channel has a volume of less than about two microliters.

37. The device of claim 33 wherein the microfluidic branch channel has a volume of less than about one microliter.

38. The device of claim 33 wherein the microfluidic branch channel has a volume of less than about five hundred nanoliters.

39. The device of claim 33 wherein the fluidic impedance region comprises a passive valve.

40. The device of claim 33 wherein the fluidic impedance region comprises an active valve.

41. The device of claim 33 wherein the fluidic impedance region comprises an overlap region.

42. The device of claim 33 wherein the fluidic impedance region includes a porous membrane.

43. The device of claim 42 wherein the porous membrane includes a plurality of porous regions.

44. The device of claim 33 wherein the branch channel has an associated gas-permeable vent.

45. The device of claim 33 wherein the trunk channel is a microfluidic channel.

46. The device of claim 33, further comprising multiple microfluidic branch channels each in independent, direct fluid communication with the trunk channel.

47. The device of claim 33 wherein the device is fabricated with a plurality of device layers.

48. The device of claim 33 wherein any device layer of the plurality of device layers is a stencil layer.

49. The device of claim 33 wherein any device layer of the plurality of device layers is fabricated with a polymeric material.

50. The device of claim 33 wherein any device layer of the plurality of device layers is fabricated with a self-adhesive tape material.