Microfluidic devices for fluid manipulation and analysis

• US 20050106066A1
• Filed: 06/17/2004
• Published: 05/19/2005
• Est. Priority Date: 01/14/2003
• Status: Active Grant

• Current Assignee: Revvity Health Sciences Incorporated (Revvity, Inc.)
• Original Assignee: Micronics Inc. (Sony Group Corp.)
• Inventors: Weigl, Bernhard H., Battrell, C. Frederick, Lancaster, Christy A., Houkal, Jeffrey M., Saltsman, Patrick, Shen, Mingchao
• Granted Patent: US 7,419,638 B2
• Time in Patent Office: Days
• US Class Current: 422/57
• CPC Class Codes: B01F 25/3141 with additional mixing means other than injector mixers
• 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 33/30 Micromixers
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/049 vacuum
• CPC Class Codes: B01L 2400/0605 check valves
• CPC Class Codes: B01L 2400/0633 with moving parts
• 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 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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: B01L 3/502753 : characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: F04B 43/043 : Micropumps
• CPC Class Codes: G01N 33/5304 : Reaction vessels, e.g. agglutination plates for solid-phase systems G01N33/543
• CPC Class Codes: G01N 33/80 : involving blood groups or blood types or red blood cells white blood cells G01N33/56972

Abstract

The present invention relates to microfluidic devices and methods for manipulating and analyzing fluid samples. The disclosed microfluidic devices utilize a plurality of microfluidic channels, inlets, valves, filter, pumps, liquid barriers and other elements arranged in various configurations to manipulate the flow of a fluid sample in order to prepare such sample for analysis.

Claims

1. A microfluidic device for analyzing a liquid sample, comprising:

a microfluidic channel having a first end and a second end;

a sample inlet fluidly connected to the first end of the microfluidic channel for receiving the liquid sample;

a filter interposed between the sample inlet and the first end of the microfluidic channel, wherein the filter removes selected particles from the liquid sample;

a bellows pump fluidly connected to the second end of the microfluidic channel; and

a liquid barrier interposed between the bellows pump and the second end of the microfluidic channel, wherein the liquid barrier is gas permeable and liquid impermeable.

2. The microfluidic device of claim 1 wherein the bellows pump comprises a vent hole.

3. The microfluidic device of claim 1, further comprising:

a first check valve interposed between the bellows pump and the liquid barrier, wherein the first check valve permits fluid flow towards the bellows pump; and

a second check valve fluidly connected to the bellows pump, wherein the second check valve permits fluid flow away from the bellows pump.

4. The microfluidic device of claim 1 wherein the filter comprises a membrane.

5. The microfluidic device of claim 1 wherein the microfluidic channel further comprises one or more optical viewing areas.

6. The microfluidic device of claim 1 wherein the selected particles removed from the liquid sample by the filter comprise white blood cells, red blood cells, polymeric beads or bacteria cells.

7. A microfluidic device for analyzing a liquid sample, comprising:

a first microfluidic channel having a first end and a second end;

a sample inlet fluidly connected to the first end of the first microfluidic channel for receiving the liquid sample;

an active valve interposed between the sample inlet and the first end of the first microfluidic channel;

a means for actuating the active valve;

a first bellows pump fluidly connected to the second end of the first microfluidic channel;

a liquid barrier interposed between the first bellows pump and the second end of the first microfluidic channel, wherein the liquid barrier is gas permeable and liquid impermeable;

a second microfluidic channel having a first end and a second end, wherein the first end is fluidly connected to the first microfluidic channel at a location adjacent to the active valve;

a passive valve interposed between the first end of the second microfluidic channel and the first microfluidic channel, wherein the passive valve is open when the fluid pressure in the first microfluidic channel is greater than the fluid pressure in the second microfluidic channel; and

a sample reservoir fluidly connected to the second end of the second microfluidic channel.

8. The microfluidic device of claim 7 wherein the first bellows pump comprises a vent hole.

9. The microfluidic device of claim 7 wherein the means for actuating the active valve comprise a second bellows pump.

10. The microfluidic device of claim 7 wherein the sample reservoir comprises a vent hole.

11. A microfluidic device for analyzing a liquid sample, comprising:

first and second microfluidic channels, each having a first end and a second end;

a sample inlet fluidly connected to the first end of the first microfluidic channel for receiving the liquid sample;

a first bellows pump fluidly connected to, and interposed between, the second end of the first microfluidic channel and the first end of the second microfluidic channel;

a second bellows pump fluidly connected to the second end of the second microfluidic channel, wherein the second bellows pump has a fluid outlet;

a first check valve interposed between the sample inlet and the first end of the first microfluidic channel, wherein the first check valve permits fluid flow towards the first microfluidic channel;

a second check valve interposed between the second end of the first microfluidic channel and the first bellows pump, wherein the second check valve permits fluid flow towards the first bellows pump;

a third check valve interposed between the first bellows pump and the first end of the second microfluidic channel, wherein the third check valve permits fluid flow towards the second microfluidic channel; and

a fourth check valve interposed between the second end of the second microfluidic channel and the second bellows pump, wherein the fourth check valve permits fluid flow towards the second bellows pump.

12. A microfluidic device for analyzing a liquid sample, comprising:

a first microfluidic channel having a first end and a second end;

a sample inlet fluidly connected to the first end of the first microfluidic channel for receiving the liquid sample;

a first reagent inlet fluidly connected to the first end of the first microfluidic channel for receiving a first reagent;

a bellows pump fluidly connected to the second end of the first microfluidic channel; and

a first liquid barrier interposed between the bellows pump and the second end of the first microfluidic channel, wherein the liquid barrier is gas permeable and liquid impermeable.

13. The microfluidic device of claim 12 wherein the bellows pump comprises a vent hole.

14. The microfluidic device of claim 12, further comprising a check valve fluidly connected to the bellows pump, wherein the check valve permits fluid flow away from the bellows pump.

15. The microfluidic device of claim 12 wherein the first microfluidic channel further comprises one or more optical viewing areas.

16. The microfluidic device of claim 12, further comprising:

a second microfluidic channel having a first end, fluidly connected to the sample inlet, and a second end, fluidly connected to the bellows pump;

a second reagent inlet fluidly connected to the first end of the second microfluidic channel for receiving a second reagent; and

a second liquid barrier interposed between the bellows pump and the second end of the second microfluidic channel, wherein the second liquid barrier is gas permeable and liquid impermeable.

17. The microfluidic device of claim 16 wherein the second microfluidic channel further comprises one or more optical viewing areas.

18. The microfluidic device of claim 16, further comprising:

a third microfluidic channel having a first end, fluidly connected to the sample inlet, and a second end, fluidly connected to the bellows pump;

a third reagent inlet fluidly connected to the first end of the third microfluidic channel for receiving a third reagent; and

a third liquid barrier interposed between the bellows pump and the second end of the third microfluidic channel, wherein the third liquid barrier is gas permeable and liquid impermeable.

19. The microfluidic device of claim 18 wherein the liquid sample comprises a blood sample, the first reagent comprises antibody-A, the second reagent comprises antibody-B, and the third reagent comprises antibody-D.

20. The microfluidic device of claim 18 wherein the third microfluidic channel further comprises one or more optical viewing areas.

21. The microfluidic device of claim 18 wherein the first reagent inlet comprises a first blister pouch containing the first reagent, the second reagent inlet comprises a second blister pouch containing the second reagent, and the third reagent inlet comprises a third blister pouch containing the third reagent.

22. A microfluidic device for analyzing a liquid sample, comprising:

a first microfluidic channel having a first end and a second end;

a sample inlet fluidly connected to the first end of the first microfluidic channel for receiving the liquid sample;

a first dried reagent zone, comprising a first reagent printed thereon, fluidly connected to the first end of the first microfluidic channel;

a bellows pump fluidly connected to the second end of the first microfluidic channel; and

a first liquid barrier interposed between the bellows pump and the second end of the first microfluidic channel, wherein the liquid barrier is gas permeable and liquid impermeable.

23. The microfluidic device of claim 22 wherein the bellows pump comprises a vent hole.

24. The microfluidic device of claim 22, further comprising a check valve fluidly connected to the bellows pump, wherein the check valve permits fluid flow away from the bellows pump.

25. The microfluidic device of claim 22 wherein the first microfluidic channel further comprises one or more optical viewing areas.

26. The microfluidic device of claim 22, further comprising:

a second microfluidic channel having a first end, fluidly connected to the sample inlet, and a second end, fluidly connected to the bellows pump;

a second dried reagent zone, comprising a second reagent printed thereon, fluidly connected to the first end of the second microfluidic channel; and

a second liquid barrier interposed between the bellows pump and the second end of the second microfluidic channel, wherein the second liquid barrier is gas permeable and liquid impermeable.

27. The microfluidic device of claim 26 wherein the second microfluidic channel further comprises one or more optical viewing areas.

28. The microfluidic device of claim 26, further comprising:

a third microfluidic channel having a first end, fluidly connected to the sample inlet, and a second end, fluidly connected to the bellows pump;

a third dried reagent zone, comprising a third reagent printed thereon, fluidly connected to the first end of the third microfluidic channel; and

a third liquid barrier interposed between the bellows pump and the second end of the third microfluidic channel, wherein the third liquid barrier is gas permeable and liquid impermeable.

29. The microfluidic device of claim 28 wherein the liquid sample comprises a blood sample, the first reagent comprises antibody-A, the second reagent comprises antibody-B, and the third reagent comprises antibody-D.

30. The microfluidic device of claim 28 wherein the third microfluidic channel further comprises one or more optical viewing areas.

31. The microfluidic device of claim 28, further comprising a hydrating buffer inlet, fluidly connected to the first, second and third dried reagent zones and to the first ends of the first, second and third microfluidic channels, for receiving a hydrating buffer.

32. The microfluidic device of claim 31 wherein the hydrating buffer inlet comprises a hydrating buffer blister pouch containing the hydrating buffer.