Microfluidic sub-millisecond mixers

• US 5,921,678 A
• Filed: 02/05/1998
• Issued: 07/13/1999
• Est. Priority Date: 02/05/1997
• Status: Expired due to Fees

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Mayo, Stephen, Marzluff, Elaine, Bockenkamp, Dirk, Tai, Yu-Chong, Desai, Amish, Yang, Xing
• Primary Examiner(s): SOOHOO, TONY GLEN
• Application Number:
  US09/019,071
• Time in Patent Office: 523 Days
• Field of Search: 366/173.1, 366/336, 366/150.1, 366/158.5, 366/162.4, 366/167.1, 366/174.1, 366/175.2, 366/177.1, 366/181.5, 366/182.1, 366/262, 366/337, 366/340 , 366/348, 366/349
• US Class Current: 366/336
• CPC Class Codes: B01F 2025/916 Turbulent flow, i.e. every point of the flow moves in a random direction and intermixes
• CPC Class Codes: B01F 25/23 Mixing by intersecting jets
• CPC Class Codes: B01F 25/42 in which the mixing is affected by moving the components jointly in changing directions, e.g. in tubes provided with baffles or obstructions
• CPC Class Codes: B01F 25/4317 Profiled elements, e.g. profiled blades, bars, pillars, columns or chevrons
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00783 Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00797 Concentric tubes
• 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 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/084 Passive control of flow resistance
• 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: Y10S 366/03 Micromixers: variable geometry from the pathway influences mixing/agitation of non-laminar fluid flow

Abstract

A micromachined, high Reynolds number, sub-millisecond liquid mixer for the study of chemical reaction kinetics. This bulk micromachined silicon mixer is capable of initiating and quenching chemical reactions in intervals as short as 100 μs. The mixer chip contains two tee mixers connected by one channel which serves as a reaction chamber. Each tee mixer consists of opposing channels where liquids meet head-on and exit into a third channel forming the base of a "T".

Claims

1. A method of mixing liquids, comprising:

obtaining a first and second liquid;

obtaining a micro-machined chip, with a substrate that has a first mixer integrated with a second mixer;

mixing said first and second liquid at a Reynolds number greater than 2000 and at a flow rate greater than 250 μ

L/s.

2. An apparatus for mixing, comprising:

a support substrate;

a first reactant inlet area formed on said support substrate;

a second reactant inlet area formed on said support substrate;

a inhibitor inlet area formed on said support substrate;

a reservoir outlet hole formed in said support substrate;

a system of fluid channels formed on said support substrate, wherein said fluid channels include a first reactant channel extending from said first reactant inlet area to said inhibitor inlet area, a second reactant channel extending from said second reactant channel to said inhibitor inlet area, a delay channel, an inhibitor channel, and a reservoir channel, said delay channel is positioned at a first intersection of said first reactant channel and said second reactant channel, said inhibitor channel is positioned to feed liquid out of said inhibitor inlet area, said reservoir channel is positioned at a second intersection of said inhibitor channel and said delay channel;

a first mixer, positioned at said first intersection having a shape to mix fluids;

a second mixer positioned at said second intersection having a shape to mix fluids;

a cover layer having a first hole corresponding to said first reactant inlet area, a second hole corresponding to said second reactant inlet area, and a third hole corresponding to said inhibitor inlet area, said cover layer being bonded to said support layer.

3. An apparatus as in claim 2, wherein said support substrate is made of silicon.

4. An apparatus as in claim 2, wherein said support substrate is made of a material that can tolerate flow rates of 1 mL/s.

5. An apparatus as in claim 2, wherein said first reactant inlet area functions to contain a first reactant sample.

6. An apparatus as in claim 2, wherein said second reactant inlet area functions to contain a second reactant sample.

7. An apparatus as in claim 2, wherein said inhibitor inlet area functions to contain an chemical reaction inhibitor.

8. An apparatus as in claim 2, wherein said reservoir outlet hole functions to allow fluids out of said mixer chip.

9. An apparatus as in claim 2, wherein said cover layer is made of PYREX(™

) glass.

10. An apparatus for mixing on a substrate, comprising:

a first mixer formed in said silicon substrate;

a second mixer also formed in said silicon substrate;

a system of fluid channels each formed in said silicon substrate including a delay fluid channel, connecting said first mixer to said second mixer.

11. An apparatus as in claim 10, further comprising a glass cover, covering said first mixer, said second mixer, and said system of fluid channels.

12. An apparatus as in claim 11, wherein said support substrate is silicon.

13. An apparatus as in claim 11, wherein said support substrate is a material that can tolerate flow rates of 1 mL/s.

14. An apparatus as in claim 10, wherein said delay channel is 5.33 mm.

15. An apparatus as in claim 10, wherein said delay channel is 10.66 mm.

16. An apparatus as in claim 10, wherein said delay channel is 20.66 mm.

17. An apparatus comprising:

a mixer chip, wherein said mixer chip having a system of fluid channels connecting a plurality of mixers on a common substrate;

a flow regulation device, wherein said mixer chip is positioned to interface with said flow regulation device.

18. An apparatus as in claim 17, wherein said mixer chip is held in position by a combination of several o-rings and kel-f blocks.

19. An apparatus as in claim 18, wherein said kel-f blocks are machined to have an area to imbed said mixer chip.

20. An apparatus as in claim 18, wherein said o-rings form seals between said flow regulation device and said mixer chip that can tolerate high flow velocities.

21. A mixer apparatus comprising:

a mixer chip, wherein said mixer chip having a system of fluid channels connecting a plurality of mixers, said mixers operating at Reynolds number greater than 2000, said mixers capable of initiating and quenching chemical reactions in intervals of shorter than 100 microseconds.

22. A method of characterizing a mixer, comprising:

performing a first order chemical reaction with a specified time constant; and

characterizing said mixer based on a result of said performing.

23. A method as in claim 22, wherein said time constant is 3 ms.

24. A method as in claim 22, wherein said time constant is 9 ms.

25. A method of characterizing a mixer, comprising:

performing visualization techniques using a visual indicator; and

using said visualization techniques to characterize said mixer.

26. A method as in claim 25, wherein said visual indicator is a dye.

27. A method as in claim 25, wherein said visual indicator is an acid-base indicator.

28. A method for mixing, comprising:

first obtaining a first fluid sample;

second obtaining a second fluid sample;

forming a fluid channel with an intersection on a support substrate;

injecting said first and second fluid sample into said fluid channel wherein said first and second fluid samples meet head-on at said intersection forming a fluid flow;

forming sharp-edged structures in said fluid channel;

breaking said fluid flow with said sharp-edged structures thereby increasing turbulence.

29. An apparatus for mixing, comprising:

a fluid channel having a channel roof and a channel floor;

a plurality of sharp-edged structures positioned within said fluid channel with at least one end connected to said channel roof or said channel floor.

30. An apparatus as in claim 29, wherein said sharp-edged structures are triangular pillars.

31. A method for mixing, comprising:

forming a first fluid channel, a second fluid channel, and a third fluid channel wherein said first, second, and third fluid channel forms an intersection;

first injecting a first liquid sample at a first fluid velocity in said first fluid channel;

second injecting a second liquid sample at a second fluid velocity in said second fluid channel, wherein said first liquid sample and said second liquid sample meet at said intersection;

flowing said first liquid sample and said second liquid sample out of said intersection into said third fluid channel at an angle.

32. A method as in 31, wherein said first fluid velocity and said second fluid velocity are similar.

33. A method as in 32, wherein said angle is 90 degrees.