Ratiometric dilution devices and methods

• US 20030198576A1
• Filed: 02/21/2003
• Published: 10/23/2003
• Est. Priority Date: 02/22/2002
• Status: Abandoned Application

• Current Assignee: Nanostream, Inc.
• Original Assignee: Nanostream, Inc.
• Inventors: Coyne, Courtney L., Flynn, Terence T., Pezzuto, Marci, Hobbs, Steven E., Karp, Christoph D., Levine, Leanna M., Hightower, Adrian
• Application Number:
  US10/372,032
• Publication Number:
  US 20030198576A1
• Time in Patent Office: Days
• US Class Current: 422/400
• CPC Class Codes: B01F 2215/0431 Numerical size values, e.g. diameter of a hole or conduit, area, volume, length, width, or ratios thereof
• CPC Class Codes: B01F 25/433 Mixing tubes wherein the shape of the tube influences the mixing, e.g. mixing tubes with varying cross-section or provided with inwardly extending profiles
• CPC Class Codes: B01F 25/4331 Mixers with bended, curved, coiled, wounded mixing tubes or comprising elements for bending the flow
• CPC Class Codes: B01F 25/4335 Mixers with a converging-diverging cross-section
• CPC Class Codes: B01F 31/65 the materials to be mixed being directly submitted to a pulsating movement, e.g. by means of an oscillating piston or air column
• CPC Class Codes: B01F 31/85 with a vibrating element inside the receptacle
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 33/452 using independent floating stirring elements
• 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 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/049 vacuum
• CPC Class Codes: B01L 2400/06 Valves, specific forms thereof
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• 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: B01L 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

Substantially sealed microfluidic devices for performing pipettorless ratiometric dilution are provided. In one embodiment, valves are disposed between and permit selective fluid communication between multiple chambers of a series of chambers. In another embodiment, a mixing chamber receives fluid from an inlet port and is in donative fluid communication with multiple receiving chambers each having a small volume than the mixing chamber. Active mixing means may be provided, including moveable magnetic elements, sonication, and mixing channels coupled with fluid transport means. A material transport system may be used with a non-electrokinetic pipettorless dilution system for transporting sample, diluent, and combinations thereof within the device.

Claims

1. A substantially sealed microfluidic device for performing pipettorless ratiometric dilution, the device comprising:

a first chamber defining a first discrete volume;

a second chamber defining a second discrete volume;

a third chamber defining a third discrete volume;

a first valve disposed between and permitting selective fluid communication between the first chamber and the second chamber;

a second valve disposed between and permitting selective fluid communication between the second chamber and the third chamber; and

a sample inlet port in selective fluid communication with any of the first, second, or third chamber.

2. The device of claim 1, further comprising a diluent inlet port in selective fluid communication with any of the first, second, or third chamber.

3. The device of claim 1 wherein the device is pressure-driven.

4. The device of claim 1 wherein the device is non-electrokinetic.

5. The device of claim 1 wherein any of the first, second, and third chamber is bounded along at least one surface by a deformable membrane.

6. The device of claim 1 wherein any of the first, second, and third chamber is bounded along at least one surface by a substantially optically transmissive material.

7. The device of claim 1, further comprising:

first mixing means in fluid communication with the second chamber, and

second mixing means in fluid communication with the third chamber.

8. The device of claim 7 wherein any of the first mixing means and the second mixing means includes a contraction region and a mixing channel.

9. The device of claim 7 wherein any of the first mixing means and the second mixing means includes a ferromagnetic or paramagnetic element.

10. The device of claim 7 wherein any of the first mixing means and the second mixing means includes a sonicator.

11. The device of claim 7 wherein the mixing means includes at least one first mixing channel associated with the second chamber, and at least one second mixing channel associated with the third chamber, the device further comprising:

a third valve disposed between the second chamber and the first mixing channel; and

a fourth valve disposed between the third chamber and the second mixing channel.

12. The device of claim 1 wherein the first discrete volume, the second discrete volume, and the third discrete volume are substantially equal.

13. The microfluidic device of claim 1 wherein any of the first discrete volume, the second discrete volume, and the third discrete volume is less than or equal to about one microliter.

14. The device of claim 1 wherein the device comprises a plurality of laminated device layers including a plurality of stencil layers.

15. The device of claim 14 wherein a device layer of the plurality of laminated device layers comprises a gas-permeable porous material.

16. The device of claim 14 wherein the first chamber and the second chamber are defined through the entire thickness of one stencil layer of the plurality of stencil layers.

17. The device of claim 1, further comprising a plurality of valve actuation ports.

18. The microfluidic device of claim 1 wherein the first, second, and third chamber are sized, shaped, and positioned to conform to wells arrayed in a standard ninety-six, three hundred eighty-four, or fifteen hundred thirty-six well plate format.

19. A substantially sealed microfluidic device for pipettorless ratiometric dilution, the device comprising:

a first fluidic inlet port;

a mixing chamber in selective fluid communication with the fluidic inlet port;

a first receiving chamber in selective fluid communication with the mixing chamber;

a second receiving chamber in selective fluid communication with the mixing chamber; and

a third receiving chamber in selective fluid communication with the mixing chamber;

wherein the mixing chamber has a mixing chamber volume, the first receiving chamber has a first volume, the second receiving chamber has a second volume, and the third receiving chamber has a third volume, and the mixing chamber volume is greater than any of the first volume, second volume, and the third volume.

20. The device of claim 19 wherein the device is pressure-driven.

21. The device of claim 19 wherein the device is non-electrokinetic.

22. The device of claim 19, further comprising:

a channel network and a channel junction permitting fluid communication between the mixing chamber and the first, second, and third receiving chamber.

23. The device of claim 19, further comprising fluid mixing means.

24. The device of claim 23 wherein the mixing means includes a ferromagnetic or paramagnetic element.

25. The device of claim 23 wherein the mixing means includes a sonicator.

26. The device of claim 19, further comprising:

a first valve disposed between the mixing chamber and the first receiving chamber;

a second valve disposed between the mixing chamber and the second receiving chamber; and

a third valve disposed between the mixing chamber and the third receiving chamber.

27. The device of claim 19 wherein any of the first, second, and third chamber is bounded along at least one surface by a substantially optically transmissive material.

28. The device of claim 19 wherein any of the first, second, and third chamber is bounded along at least one surface by a deformable membrane.

29. The device of claim 19 wherein the first volume, second volume, and third volume are substantially equal.

30. The device of claim 19 wherein any of the first volume, second volume, and third volume is less than or equal to about one microliter.

31. The device of claim 19 wherein the device comprises a plurality of laminated device layers including a plurality of stencil layers.

32. The device of claim 31 wherein a device layer of the plurality of laminated device layers comprises a gas-permeable porous material.

33. The device of claim 31 wherein the first chamber and the second chamber are defined through the entire thickness of one stencil layer of the plurality of stencil layers.

34. The device of claim 19, further comprising a plurality of valve actuation ports.

35. A system for performing pipettorless ratiometric dilution in a microfluidic device, the system comprising:

a microfluidic device having a plurality of microfluidic chambers and a plurality of valves;

a first sample source in fluid communication with at least one chamber of the plurality of chambers;

a diluent source in fluid communication with at least one chamber of the plurality of chambers;

valve actuation means in sensory communication with the plurality of valves; and

a material transport system for transporting sample, diluent, and combinations thereof within the device.

36. The system of claim 35, further comprising mixing means in fluid or sensory communication with at least one chamber of the plurality of chambers.

37. The system of claim 35 wherein the material transport system is non-electrokinetic.

38. The system of claim 35 wherein the material transport system comprises at least one of a pressure source and a vacuum source.

39. The system of claim 35, further comprising a detector in sensory communication with at least one chamber of the plurality of chambers.

40. The system of claim 35 wherein the detector is an optical detector.

41. The system of claim 35, further comprising a controller in sensory communication with the valve actuation means and material transport system.

42. A non-electrokinetic microfluidic system for mixing a discrete volumes of a plurality of liquids, the system comprising:

a first microfluidic chamber and a second microfluidic chamber being in at least intermittent fluid communication;

a first microfluidic channel disposed between the first microfluidic chamber and the second microfluidic chamber;

a second microfluidic channel in fluid communication with first microfluidic chamber; and

a reversible fluid transport system in fluid communication with the second microfluidic channel.

43. The system of claim 42, further comprising a third microfluidic channel in fluid communication with second microfluidic chamber, wherein the reversible fluid transport system is in fluid communication with the third microfluidic channel.

44. The system of claim 42, further comprising a gas-permeable porous material in fluid communication with the second microfluidic channel.

45. The system of claim 42 wherein the reversible fluid transport system comprises a reversible pump.

46. A method for performing pipettorless ratiometric dilution in a microfluidic device, the method comprising the steps of:

providing a microfluidic device having a plurality of chambers and a plurality of valves;

substantially filling a first chamber of the plurality of chambers with a sample;

substantially filling a series of chambers of the plurality of chambers with diluent;

establishing fluid communication between the first chamber and a second chamber of the series of chambers;

mixing the contents of the first chamber and the second chamber to form a first mixture;

isolating at least two portions of the first mixture;

establishing fluid communication between the second chamber and a third chamber of the series of chambers; and

mixing the contents of the second chamber and the third chamber to form a second mixture.

47. A method for performing pipettorless ratiometric dilution in a microfluidic device, the method comprising the steps of:

providing a microfluidic device having a mixing chamber, a plurality of receiving chambers in selective fluid communication with the mixing chamber, and a plurality of valves;

substantially filling the mixing chamber with a sample;

establishing fluid communication between the mixing chamber and a first receiving chamber, of the plurality of receiving chambers;

supplying diluent to the mixing chamber, thus displacing a portion of the contents of the mixing chamber into the first receiving chamber;

mixing the contents of the mixing chamber;

establishing fluid communication between the mixing chamber and a second receiving chamber of the plurality of receiving chambers;

supplying diluent to the mixing chamber, thus displacing a portion of the contents of the mixing chamber into the second receiving chamber; and

mixing the contents of the mixing chamber.