FLOW CONTROL IN MICROFLUIDIC SYSTEMS

• US 20090266421A1
• Filed: 04/22/2009
• Published: 10/29/2009
• Est. Priority Date: 04/25/2008
• Status: Active Grant

• Current Assignee: Opko Diagnostics, LLC (Opko Health, Inc.)
• Original Assignee: Claros Diagnostics, Inc. (Opko Health, Inc.)
• Inventors: Steinmiller, David, Linder, Vincent
• Granted Patent: US 8,222,049 B2
• Time in Patent Office: Days
• US Class Current: 137/1
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/082 Active control of flow resistance, e.g. flow controllers
• CPC Class Codes: B01L 2400/084 Passive control of flow resistance
• 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: B01L 3/502784 specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: Y10T 137/0318 Processes
• CPC Class Codes: Y10T 137/0324 With control of flow by a condition or characteristic of a fluid

Abstract

Microfluidic systems and methods including those that provide control of fluid flow are provided. Such systems and methods can be used, for example, to control pressure-driven flow based on the influence of channel geometry and the viscosity of one or more fluids inside the system. One method includes flowing a plug of a low viscosity fluid and a plug of a high viscosity fluid in a channel including a flow constriction region and a non-constriction region. In one embodiment, the low viscosity fluid flows at a first flow rate in the channel and the flow rate is not substantially affected by the flow constriction region. When the high viscosity fluid flows from the non-constriction region to the flow constriction region, the flow rates of the fluids decrease substantially, since the flow rates, in some systems, are influenced by the highest viscosity fluid flowing in the smallest cross-sectional area of the system (e.g., the flow constriction region). This causes the fluids to flow at the same flow rate at which the high viscosity fluid flows in the flow constriction region. Accordingly, by designing microfluidic systems with flow constriction regions positioned at particular locations and by choosing appropriate viscosities of fluids, a fluid can be made to speed up or slow down at different locations within the system without the use of valves and/or without external control.

Claims

1. A method, comprising:

flowing a first fluid from a first channel portion to a second channel portion in a microfluidic system, wherein a fluid path defined by the first channel portion has a larger cross-sectional area than a cross-sectional area of a fluid path defined by the second channel portion;

flowing a second fluid in a third channel portion in the microfluidic system in fluid communication with the first and second channel portions, wherein the viscosity of the first fluid is different than the viscosity of the second fluid, and wherein the first and second fluids are substantially incompressible;

without stopping the first or second fluids, causing a volumetric flow rate of the first and second fluids to decrease by a factor of at least 3 in the microfluidic system as a result of the first fluid flowing from the first channel portion to the second channel portion, compared to the absence of flowing the first fluid from the first channel portion to the second channel portion; and

effecting a chemical and/or biological interaction involving a component of the first or second fluids at a first analysis region in fluid communication with the channel portions while the first and second fluids are flowing at the decreased flow rate.

2. A method as in claim 1, wherein the first and second fluids are positioned immediately adjacent to one another.

3. A method as in claim 1, wherein the first and second fluids are separated by a third fluid.

4. A method as in claim 3, wherein the third fluid is compressible.

5. A method as in claim 1, wherein the first analysis region is a part of the second channel portion.

6. A method as in claim 1, wherein the first analysis region is a part of the third channel portion.

7. A method as in claim 1, wherein the first fluid comprises the component, and the method comprises effecting a chemical and/or biological interaction involving the component of the first fluid at the first analysis region.

8. A method as in claim 1, wherein the second fluid comprises the component, and the method comprises effecting a chemical and/or biological interaction involving the component of the second fluid at the first analysis region.

9. A method as in claim 1, wherein the first fluid has a higher viscosity than the second fluid.

10. A method as in claim 1, wherein the second fluid has a higher viscosity than the first fluid.

11. A method as in claim 1, wherein the viscosities of the first and second fluids differ by at least a factor of 40.

12. A method as in claim 1, wherein a cross-sectional area of the fluid path defined by the third channel portion is the same as the cross-sectional area of the fluid path defined by the second channel portion.

13. A method as in claim 1, wherein a cross-sectional area of the fluid path defined by the third channel portion is greater than the cross-sectional area of the fluid path defined by the second channel portion.

14. A method as in claim 1, wherein the second channel portion is positioned upstream of the first analysis region.

15. A method as in claim 1, comprising allowing the interaction involving the component to occur at least 3 times longer in the first analysis region as a result of the first fluid flowing from the first channel portion to the second channel portion, compared to the absence of the flowing of the first or second fluids from the first channel portion to the second channel portion.

16. A method as in claim 15, comprising allowing the interaction involving the component to occur for at least 60 seconds in the first analysis region.

17. A method as in claim 1, wherein the volumetric flow rate decreases at a rate of at least 3%/s as a result of the first fluid flowing from the first channel portion to the second channel portion, as measured by taking the difference between the flow rate at a first time point just prior to the first fluid entering the second channel portion, and the flow rate at a second time point when the flow rate has decreased by at least 90% while the first fluid is flowing in the second channel portion, and dividing the difference in the flow rates by the amount of time between the first and second time points.

18. A method as in claim 1, wherein the volumetric flow rate decreases by 90% in less than 3 seconds as a result of the first fluid flowing from the first channel portion to the second channel portion.

19. A method as in claim 1, wherein the volumetric flow rate of the first and/or second fluids decreases by a factor of at least 40 in the first analysis region as a result of the first fluid flowing from the first channel portion to the second channel portion.

20. A method as in claim 1, comprising applying a substantially constant, non-zero pressure drop across an inlet and an outlet of the microfluidic system.

21. A method as in claim 1, further comprising causing the volumetric flow rate of the first fluid to increase as a result of the first fluid flowing out of the second channel portion.

22. A method as in claim 1, wherein the second channel portion has a length of at least 1 cm.

23. A method as in claim 1, wherein the component is a cell.

24. A method as in claim 1, wherein the component is part of an enzyme-linked immunosorbent assay.

25. A method as in claim 1, where in the microfluidic system does not include a bypass channel connected to the first and second channel portions.

26. A method as in claim 1, wherein the microfluidic system includes no greater than 1 channel intersection.

27. A method as in claim 1, wherein the microfluidic system does not include any channel intersections.

28. A method as in claim 1, wherein flowing does not take place predominately by capillary forces.

29. A method as in claim 1, wherein the volumetric flow rates of the fluids are not controlled by an actuating valve.

30. A method as in claim 1, comprising determining a product of a chemical and/or biological reaction involving the component at the first analysis region while the first and/or second fluid is flowing.

31. A method as in claim 1, wherein the chemical and/or biological interaction involves interacting the component of the first or second fluids with a second component disposed on a surface of the first analysis region.

32. A method as in claim 1, further comprising flowing a fluid across the first analysis region at the first flow rate after the effecting step.

33. A method as in claim 1, wherein the first channel portion has a larger width than the width of the second channel portion.

34. A method as in claim 1, wherein the first channel portion has a larger width and height than the width and height of the second channel portion.

35. A method as in claim 1, wherein the cross section of at least one channel portion resembles a trapezoid.

36-59. -59. (canceled)