MICROFLUIDIC CHAOTIC MIXING SYSTEMS AND METHODS

• US 20070054293A1
• Filed: 08/30/2006
• Published: 03/08/2007
• Est. Priority Date: 08/30/2005
• Status: Abandoned Application

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Quake, Stephen, Liu, Jian, Williams, Brian, Wold, Barbara
• Application Number:
  US11/468,642
• Publication Number:
  US 20070054293A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01F 25/431 Straight mixing tubes with baffles or obstructions that do not cause substantial pressure drop; Baffles therefor
• CPC Class Codes: B01F 25/4317 Profiled elements, e.g. profiled blades, bars, pillars, columns or chevrons
• CPC Class Codes: B01F 25/53 in which the mixture is discharged from and reintroduced into a receptacle through a recirculation tube, into which an additional component is introduced
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: C12Q 1/6813 Hybridisation assays

Abstract

Microfluidic nucleic acid hybridization systems are described that include a first reaction chamber to hold an analyte solution comprising nucleic acids, and a first mixing channel in fluid communication with the chamber. The mixing channel includes a textured surface to mix the analyte solution. The systems may also include pump coupled to the mixing channel to circulate the analyte solution through the reaction chamber and the mixing channel, and an input port in fluid communication with the mixing channel and the reaction chamber to supply the analyte solution to the microfluidic system. The input port can be closed to create a closed circulation path for the analyte solution through the reaction chamber and the mixing channel.

Claims

1. A microfluidic nucleic acid hybridization system comprising:

a first reaction chamber to hold an analyte solution comprising nucleic acids;

a first mixing channel in fluid communication with the chamber, wherein the channel includes a textured surface to mix the analyte solution;

a pump coupled to the mixing channel to circulate the analyte solution through the reaction chamber and the mixing channel;

an input port in fluid communication with the mixing channel and the reaction chamber to supply the analyte solution to the microfluidic system, wherein the input port can be closed to create a closed circulation path for the analyte solution through the reaction chamber and the mixing channel.

2. The microfluidic nucleic acid hybridization system of claim 1, wherein the system comprises analyte binding sites present in the chamber.

3. The microfluidic nucleic acid hybridization system of claim 2, wherein the analyte binding sites comprise a nucleic acid microarray.

4. The microfluidic nucleic acid hybridization system of claim 2, wherein the analyte binding sites are formed on an interior surface of the chamber.

5. The microfluidic nucleic acid hybridization system of claim 2, wherein the analyte binding sites are formed on a removable substrate positioned inside the chamber.

6. The microfluidic nucleic acid hybridization system of claim 1, wherein the textured surface of the mixing channel comprises a plurality of groves or protrusions with orientations that form angles relative to a principle direction of fluid flow.

7. The microfluidic nucleic acid hybridization system of claim 1, wherein the textured surface comprises chevron-shaped groves or protrusions.

8. The microfluidic nucleic acid hybridization system of claim 1, wherein the turbulence generating pattern comprises a herring-bone pattern.

9. The microfluidic nucleic acid hybridization system of claim 1, wherein the pump is a peristaltic pump.

10. The microfluidic nucleic acid hybridization system of claim 1, wherein the system comprises a distribution manifold coupled between the chamber and the mixing channel, wherein the manifold comprises a plurality of branches to divide the analyte solution flowing through the manifold.

11. The microfluidic nucleic acid hybridization system of claim 10, wherein the distribution manifold comprises a bifurcation channel with a first and second branch that divides the analyte solution flowing through the channel.

12. The microfluidic nucleic acid hybridization system of claim 10, wherein the distribution manifold comprises a first subdividing bifurcation channel coupled to the first branch, which further divides the analyte solution between at least two more branches, and a second subdividing bifurcation channel coupled to the second branch, which further divides the analyte solution between at least two more branches.

13. The microfluidic nucleic acid hybridization system of claim 1, wherein the input port is in fluid communication with a closable rubber gasket or elastomeric valve that reversibly closes the port.

14. The microfluidic nucleic acid hybridization system of claim 1, wherein the system comprises a output port in fluid communication with the reaction chamber to remove analyte solution from the system.

15. The microfluidic nucleic acid hybridization system of claim 1, wherein the system comprises:

two or more reaction chambers containing analyte binding sites, wherein each chamber is connected to another chamber via a mixing channel so that fluid can circulate in a closed loop through said chambers and channels.

16. The microfluidic nucleic acid hybridization system of claim 15, wherein the system comprises one or more additional ports to supply or remove the analyte solution from the microfluidic system, wherein said ports can be closed to isolate the system and form a closed loop through which fluid can circulate.

17. The microfluidic nucleic acid hybridization system of claim 15, wherein the system comprises a plurality of pumps coupled to the mixing channels to circulate the analyte solution through the system.

18. The microfluidic nucleic acid hybridization system of claim 1, wherein the system further comprises:

a second reaction chamber in fluid communication with the first mixing channel; and

a second mixing channel in fluid communication with the first and second reaction chambers,

wherein the first and second channels and reaction chambers form a fluid flow path to mix and circulate the analyte solution between the first and second reaction chambers.

19. The microfluidic nucleic acid hybridization system of claim 18, wherein the second mixing channel includes a textured surface to facilitate the chaotic mixing of the analyte solution.

20. The microfluidic nucleic acid hybridization system of claim 19, wherein the textured surface in the second channel comprises a plurality of groves or protrusions with orientations that form angles relative to a principle fluid flow direction.

21. The microfluidic nucleic acid hybridization system of claim 19, wherein the textured surface in the second mixing channel comprises a herring-bone pattern.

22. The microfluidic nucleic acid hybridization system of claim 1, wherein the first mixing channel comprises an elastomeric material.

23. The microfluidic nucleic acid hybridization system of claim 1, wherein the first reaction chamber comprises an elastomeric material.

24. A method of chaotically mixing and hybridizing a nucleic acid solution in a microfluidic system, the method comprising:

providing the nucleic acid solution to a first reaction chamber, wherein the reaction chamber contains nucleic acid hybridization sites;

circulating the nucleic acid solution a plurality of times through a mixing channel coupled to the reaction chamber, wherein the solution is mixed as it flows across a textured surface of the mixing channel to mix the solution; and

hybridizing nucleic acids in the solution to one of the hybridization sites.

25. The method of claim 24, wherein the method comprises circulating the nucleic acid solution from the first reaction chamber to a second reaction chamber through the mixing channel.

26. The method of claim 24, wherein the method comprises binding the nucleic acids to hybridization sites in both the first and second analyte chambers.

27. The method of claim 24, wherein the textured surface comprises a plurality of groves or protrusions with orientations that form angles relative to a principle fluid flow direction.

28. The method of claim 27, wherein the textured surface comprises a herring-bone pattern.

29. The method of claim 24, wherein the nucleic acid solution is circulated with a peristaltic pump coupled to the mixing channel.

30. A microfluidic nucleic acid hybridization system comprising:

a glass substrate having an array of nucleic acids on a top surface of the substrate;

a first elastomeric layer attached to the top surface of the glass substrate, wherein the elastomeric layer has a first and second reaction chamber formed therein, and wherein the top surface of the substrate forms an inside surface of each reaction chamber;

a mixing channel that is also formed in the first elastomeric layer, where the mixing channel is in fluid communication with the first and second reaction chamber, and wherein the mixing channel has a textured surface with a herring-bone pattern to mix a nucleic acid solution flowing through the channel;

a second elastomeric layer formed on the first elastomeric layer, wherein the second elastomeric layer has a series of control channels that activate a microfluidic peristaltic pump in the mixing channel; and

an input port in fluid communication with the mixing channel and the reaction chamber to supply the nucleic acid solution to the microfluidic system, wherein the input port is coupled to a closable microvalve that creates a closed circulation path for the nucleic acid solution between the reaction chamber and the mixing channel.