Mixing in microfluidic devices

• US 7,347,617 B2
• Filed: 08/19/2003
• Issued: 03/25/2008
• Est. Priority Date: 08/19/2003
• Status: Active Grant

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Inventors: Kuo, Hai Hang, Blankenstein, Gert, Pugia, Michael J., Schulman, Lloyd S.
• Primary Examiner(s): SOOHOO, TONY GLEN
• Application Number:
  US10/643,862
• Publication Number:
  US 20050041525A1
• Time in Patent Office: 1,680 Days
• Field of Search: 366/341, 366/DIG.1, 366/DIG.2, 366/DIG.3, 366/DIG.4, 422/100, 422/102
• US Class Current: 366/341
• 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 25/4323 using elements provided with a plurality of channels or using a plurality of tubes which can either be placed between common spaces or collectors
• 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 25/4335 Mixers with a converging-diverging cross-section
• CPC Class Codes: B01F 25/4338 Mixers with a succession of converging-diverging cross-sections, i.e. undulating cross-section
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 35/71725 using centrifugal forces
• CPC Class Codes: B01J 2219/00837 comprising coatings other than catalytically active coatings
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• 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 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: Y10S 366/03 Micromixers: variable geometry from the pathway influences mixing/agitation of non-laminar fluid flow

Abstract

Mixing of liquids in a microfluidic device is accomplished by dispensing the liquids into a first chamber to produce combined liquid. The liquids are thereafter discharged through at least one capillary from the first chamber into a second chamber for complete mixing.

Claims

1. A method of mixing predetermined volumes of two or more liquids in a microfluidic device comprising:

(a) dispensing each of said liquids into a well determining the predetermined volume of said liquid to be mixed;

(b) discharging the predetermined volume from each of said wells through separate capillary passageways into a first chamber to begin said mixing, said first chamber having a volume greater than the sum of said predetermined volumes, thereby providing free space in said first chamber;

(c) discharging the said sum of said predetermined volumes from said first chamber into a second chamber via at least one capillary passageway to complete mixing of said predetermined volumes, said second chamber having a volume greater than said sum of said predetermined volumes, thereby providing free space in said second chamber.

2. A method of mixing liquids of claim 1 wherein said combined liquid volume of (a) is discharged into said second chamber through two or more separated capillary passageways.

3. A method of mixing liquids of claim 2 wherein said combined liquid volume of (a) is discharged into said second chamber through at least three separated capillary passageways.

4. A method of claim 3 wherein three or more separated capillary passageways are in liquid communication between said first and second chambers.

5. A method of mixing liquids of claim 1 wherein said combined liquid volume of (a) discharged into said second chamber is discharged into at least a third chamber through one capillary passageway or via two or more separated capillary passageways.

6. A method of claim 1 wherein said combined liquid volume of (a) is discharged into said second chamber in the form of droplets.

7. A method of claim 1 wherein said first chamber has a volume of at least about twice that of the combined liquid volume of (a), thereby providing free space in said first chamber.

8. A method of claim 1 wherein said second chamber has a volume of at least about twice that of the combined liquid volume of (a), thereby providing free space in said second chamber.

9. A method of claim 1 wherein a space of at least 100 μ

m is provided above the level of the combined liquid volume of (a) in the first chamber, thereby providing sufficient free space to allow liquid entering said first chamber to separate into droplets.

10. A method of claim 1 wherein a space of at least 100 μ

m is provided above the level of the combined liquid volume of (a) in the second chamber, thereby providing sufficient free space to allow liquid entering said second chamber to separate into droplets.

11. A method of claim 1 wherein at least one of said first and second chambers contains steps or ramps to assist mixing of said combined liquids.

12. A method of claim 1 wherein said combined liquid volume of (a) in said at least one capillary passageway is discharged into said second chamber with a velocity of at least 1 mm/sec.

13. A method of claim 1 wherein said first and second liquids are dispensed from said first and second liquid wells at the same time into said first chamber through capillary passageways.

14. A method of claim 1 further comprising moving said completely mixed combined liquid volume of (a) to downstream chambers for further processing.

15. A microfluidic device in which predetermined volumes of liquids are mixed comprising:

(a) a first well having a first predetermined volume and a second well having a second predetermined volume, said wells being adapted to hold said predetermined volumes of liquids before mixing;

(b) a first chamber having a volume larger than the combined volumes said first and second wells, said first chamber being in communication with said first and second wells through separate capillary passageways;

(c) a second chamber for complete mixing of said predetermined volumes of liquids, said second chamber having a volume larger than the combined volumes of said first and second wells and in communication with said first chamber through one capillary passageway or via two or more separated passageways.

16. A microfluidic device of claim 15 wherein said first and second chambers are in communication through two or more separated capillary passageways.

17. A microfluidic device of claim 16 wherein said first and second chambers are in communication through at least three separated capillary passageways.

18. A microfluidic device of claim 16 wherein said two or more capillary passageways have different diameters.

19. A microfluidic device of claim 16 wherein said two or more capillary passageways are disposed so as to cause liquid streams or droplets exiting from said passageways to impinge as said liquid streams or droplets enter said second chamber.

20. A microfluidic device of claim 16 wherein said two or more capillary passageways are manifolded before entering said second chamber.

21. A microfluidic device of claim 15 wherein said second chamber is in communication with at least a third chamber through one capillary passageway or two or more separated capillary passageways.

22. A microfluidic device of claim 15 wherein said first chamber has a volume of at least about twice that of the combined volume of said first and second wells.

23. A microfluidic device of claim 15 wherein said second chamber has a volume of at least about twice that of the combined volume of said first and second wells.

24. A microfluidic device of claim 15 wherein a space of at least 100 μ

m is above the level of said combined first and second wells in the first chamber.

25. A microfluidic device of claim 15 wherein a space of at least 100 μ

m is above the level of said combined first and second wells in the second chamber.

26. A microfluidic device of claim 15 wherein said capillary passageways have cross-sectional dimensions of 1 to 2000 μ

m.

27. A microfluidic device of claim 26 wherein said capillary passageways have cross-sectional dimensions of 200 to 1000 μ

m.

28. A microfluidic device of claim 15 wherein said capillary passageways have lengths of 0.5 to 100 mm.

29. A microfluidic device of claim 28 wherein said capillary passageways have lengths of 1 to 50 mm.

30. A microfluidic device of claim 15 wherein three or more separated capillary passageways are in communication between said first and second chambers.

31. A microfluidic device of claim 15 wherein at least one of said first and second chambers contains microstructures to assist mixing.

32. A microfluidic device of claim 15 wherein said passageways have hydrophilic surfaces.