Flow control in multi-stream microfluidic devices

• US 6,499,499 B2
• Filed: 09/25/2001
• Issued: 12/31/2002
• Est. Priority Date: 04/20/2001
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Nanostream, Inc.
• Inventors: Patel, Paren P., Dantsker, Eugene, Pezzuto, Marci, Hobbs, Steven E., Karp, Christoph D.
• Primary Examiner(s): CHAMBERS, A MICHAEL
• Application Number:
  US09/962,034
• Publication Number:
  US 20020153046A1
• Time in Patent Office: 462 Days
• Field of Search: 137/833, 137/803, 137/828, 137/1, 137/14
• US Class Current: 137/1
• CPC Class Codes: B01L 2300/0681 Filter
• 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 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0418 electro-osmotic flow [EOF]
• 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 2400/084 Passive control of flow resistance
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: F16K 2099/0074 using photolithography, e.g. etching
• CPC Class Codes: F16K 2099/0076 using electrical discharge machining [EDM], milling or drilling
• 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 99/0036 operated by temperature variations
• CPC Class Codes: F16K 99/0057 the fluid being the circulating fluid itself, e.g. check valves
• CPC Class Codes: Y10T 137/0318 Processes
• CPC Class Codes: Y10T 137/206 : Flow affected by fluid contact, energy field or coanda effect [e.g., pure fluid device or system]
• CPC Class Codes: Y10T 137/2196 : Acoustical or thermal energy
• CPC Class Codes: Y10T 137/2224 : Structure of body of device

Abstract

Microfluidic devices for splitting an established fluidic flow through a microfluidic channel among multiple downstream microfluidic channels include a plurality of elevated flow resistance regions to promote precise and predictable splitting. Each elevated resistance region imparts a flow resistance that is substantially greater than the characteristic resistance to established flow of its associated downstream channel. Elevated flow resistance regions may include one or more porous materials and/or alterations to the channel geometry of at least a portion of a downstream channel.

Claims

1. A method for splitting an established flow of liquid among a plurality of microfluidic channels, the method comprising the steps of:

providing a microfluidic upstream channel;

providing at least a first microfluidic downstream channel having a first characteristic resistance to established flow and a second microfluidic downstream channel having a second characteristic resistance to established flow, the first downstream channel and the second downstream channel being in fluid communication with the upstream channel;

permanently elevating the flow resistance of the first downstream channel by at least about two times the first characteristic flow resistance;

permanently elevating the flow resistance of the second downstream channel by at least about two times the second characteristic flow resistance;

passively governing flow of a first portion of the liquid through the first downstream channel with the first elevated flow resistance region; and

passively governing flow of a second portion of the liquid through the second downstream channel with the second elevated flow resistance region.

2. The method of claim 1 wherein the flow resistance of the first downstream channel is elevated by at least about five times the first characteristic flow resistance, and the flow resistance of the second downstream channel is elevated by at least about five times the second characteristic flow resistance.

3. The method of claim 1 wherein, following the permanent elevation steps, the flow resistance of the first downstream channel is substantially equal to the flow resistance of the second downstream channel.

4. The method of claim 1 wherein, following the permanent elevation steps, the flow resistance of the first downstream channel is substantially different from the flow resistance of the second downstream channel.

5. The method of claim 1 wherein the flow resistance of the first downstream channel is permanently elevated using a porous material.

6. The method of claim 5 wherein the upstream channel is defined in a first device layer, the first downstream channel is defined in a second device layer, the porous material comprises a porous layer, and the flow resistance of the first downstream channel is elevated by inserting the porous layer between the first device layer and the second device layer.

7. The method of claim 1 wherein the flow resistance of the first downstream channel is permanently elevated by altering the channel geometry of at least a portion of the first downstream channel.

8. The method of claim 1 wherein the flow resistance of the first downstream channel is permanently elevated by collapsing at least a portion of the first downstream channel.

9. The method of claim 1 wherein the flow resistance of the first downstream channel is permanently elevated by providing a flow-limiting aperture between the upstream channel and the first downstream channel.

10. The method of claim 1 wherein the upstream channel is disposed in a first device layer, the first downstream channel is disposed in a second device layer, and the flow resistance of the first downstream channel is elevated by providing a flow-limiting overlap region between the upstream channel and the first downstream channel.

11. The method of claim 1 further comprising the steps of:

providing a third microfluidic downstream channel having a third characteristic resistance to established flow, the third downstream channel being in fluid communication with the upstream channel;

permanently elevating the flow resistance of the third downstream channel by at least about two times the third characteristic flow resistance; and

passively governing flow of a third portion of the liquid through the third downstream channel with the third elevated flow resistance region.

12. A device for predictably splitting a first established microfluidic liquid stream into a plurality of portions, the device comprising:

an upstream microfluidic channel;

a first downstream microfluidic channel in fluid communication with the upstream channel, the first downstream channel having a first characteristic flow resistance;

a second downstream microfluidic channel in fluid communication with the upstream channel, the second downstream channel having a second characteristic flow resistance;

a first elevated flow resistance region associated with the first downstream channel, the first elevated flow resistance region providing a permanently elevated resistance to established flow that is substantially greater than the first characteristic flow resistance; and

a second elevated flow resistance region associated with the second downstream channel, the second elevated flow resistance region providing a permanently elevated resistance to established flow that is substantially greater than the second characteristic flow resistance;

wherein the first downstream channel and the second downstream channel are adapted to remain completely filled with liquid while the first established liquid stream is present in the upstream channel; and

wherein flow through the first downstream channel is governed by the first elevated flow resistance region and flow through the second downstream channel is governed by the second elevated flow resistance region.

13. The device of claim 12 wherein the first elevated flow resistance region provides a flow resistance at least about two times greater than the first characteristic flow resistance.

14. The device of claim 12 wherein the first elevated flow resistance region provides a flow resistance at least about five times greater than the first characteristic flow resistance.

15. The device of claim 12 wherein the first elevated flow resistance region provides a flow resistance at least about ten times greater than the first characteristic flow resistance.

16. The device of claim 12 wherein at least one of the first elevated flow resistance region and the second elevated flow resistance region includes a porous material.

17. The device of claim 16 wherein the porous material is selected from the group consisting of:

a sandwiched porous device layer, an interference-fit porous element, an in-plane porous element, a porous polymerized material, a porous sol-gel, and a plurality of beads.

18. The device of claim 12 wherein the device is a multi-layer microfluidic device, the upstream channel being disposed in a first device layer and at least one of the first downstream channel and the second downstream channel is disposed in a second device layer.

19. The device of claim 18 wherein:

the first device layer is a first sandwiched stencil layer having a thickness, the upstream channel being defined through the entire thickness of the first stencil layer; and

the second device layer is a second sandwiched stencil layer having a thickness, at least one of the first downstream channel and the second downstream channel being defined through the entire thickness of the second stencil layer.

20. The device of claim 18, further comprising a third device layer disposed between the first device layer and the second device layer.

21. The device of claim 20 wherein the third device layer comprises a porous material.

22. The device of claim 20 wherein the first elevated flow resistance region includes a flow-limiting aperture defined in the third device layer.

23. The device of claim 12 wherein the device is formed with a plurality of device layers, and at least one of the upstream channel, the first downstream channel, and the second downstream channel is formed with a micromachining technique in a surface of at least one device layer of the plurality of device layers.

24. The device of claim 12 wherein the first elevated flow resistance region is formed by altering the channel geometry of at least a portion of the first downstream channel.

25. The device of claim 24 wherein the first elevated flow resistance is characterized by a reduced cross-sectional flow area.

26. The device of claim 12 wherein the first elevated flow resistance region includes a flow-limiting aperture disposed between the upstream channel and the first downstream channel.

27. The device of claim 12 wherein the first elevated flow resistance region includes a capillary.

28. The device of claim 12 wherein the first elevated flow resistance region includes a collapsed channel section.

29. The device of claim 12, further comprising:

a third downstream microfluidic channel in fluid communication with the upstream channel, the third downstream channel having a third characteristic flow resistance; and

a third elevated flow resistance region associated with the third downstream channel, the third elevated flow resistance region providing a permanently elevated resistance to established flow that is substantially greater than the third characteristic flow resistance;

wherein the third downstream channel is adapted to remain completely filled with liquid while the upstream channel contains the first established liquid stream; and

wherein flow through the third downstream channel is governed by the third elevated flow resistance region.

30. A multi-layer microfluidic device for splitting a first established liquid stream into a plurality of portions, the device comprising:

a microfluidic upstream channel defined in a first device layer;

a first and a second microfluidic downstream channel in fluid communication with the upstream channel, the first downstream channel having a first characteristic resistance to established flow and the second downstream channel having a second characteristic resistance to established flow, with at least one of the first and the second downstream channel being defined in a second device layer;

a first permanently elevated flow resistance region associated with the first downstream channel, the first elevated flow resistance region providing a flow resistance substantially greater than the first characteristic flow resistance and governing a portion of the first established liquid stream received by the first downstream channel; and

a second permanently elevated flow resistance region associated with the second downstream channel, the second elevated flow resistance region providing a flow resistance substantially greater than the second characteristic flow resistance and governing a portion of the first established liquid stream received by the second downstream channel;

wherein the first and the second downstream channel are adapted to remain completely filled with liquid while the first established liquid flow is present in the upstream channel.

31. The device of claim 30 wherein the first device layer and the second device layer comprise sandwiched stencil layers.