Flow control in microfluidic systems

• US 9,849,455 B2
• Filed: 02/27/2017
• Issued: 12/26/2017
• Est. Priority Date: 04/25/2008
• Status: Active Grant

• Current Assignee: Opko Diagnostics, LLC (Opko Health, Inc.)
• Original Assignee: Opko Diagnostics, LLC (Opko Health, Inc.)
• Inventors: Linder, Vincent, Steinmiller, David
• Primary Examiner(s): MARTINEZ, REBECCA L
• Application Number:
  US15/443,426
• Publication Number:
  US 20170165665A1
• Time in Patent Office: 302 Days
• Field of Search: None
• 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.

Claims

1. A method of operating a microfluidic system, comprising:

applying a pressure drop across an inlet and an outlet of a microfluidic system, while carrying out the following steps;

flowing a first fluid at a first flow rate;

flowing a second fluid in the microfluidic system, wherein the first and second fluids have different viscosities, and wherein the first fluid and the second fluid are separated by a separation fluid that is substantially immiscible with the first and second fluids;

flowing the first fluid from a first channel portion to a second channel portion positioned between the inlet and the outlet of the 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;

causing a volumetric flow rate of the first fluid to decrease by a factor of at least 50 in the microfluidic system; and

preventing any of the first fluid from exiting the microfluidic system via the outlet during operation of the microfluidic system.

2. A device comprising:

a microfluidic system comprising;

a first plug comprising a first fluid and a second plug comprising a second fluid contained in the microfluidic system, wherein the first and second plugs are separated by a separation fluid comprising a gas, and wherein the first plug, the second plug, and the separation fluid are present in the microfluidic system prior to first use of the device;

an inlet and an outlet;

an analysis region positioned between the inlet and the outlet;

a microfluidic channel in fluid communication with the analysis region, the microfluidic channel comprising a first channel portion having a first cross-sectional area; and

a flow constriction region positioned downstream of the first channel portion and upstream of the outlet, wherein the flow constriction region has a second cross-sectional area, the second cross-sectional area being at least 10 times smaller than the first cross-sectional area, wherein the flow constriction region has a height and/or a width of less than 75 microns, and wherein the flow constriction region has a length of at least 1 cm.

3. A device as in claim 2, wherein the second cross-sectional area is less than 50 μ

m².

4. A device as in claim 2, wherein the second cross-sectional area is less than 100 μ

m².

5. A device as in claim 2, wherein the second cross-sectional area is at least 25 times smaller than the first cross-sectional area.

6. A device as in claim 2, wherein the flow constriction region has a length of at least 2 CM.

7. A device as in claim 2, wherein the flow constriction region comprises a serpentine configuration.

8. A device as in claim 2, comprising a liquid containment region positioned downstream of the flow constriction region, wherein the liquid containment region comprises an absorbent material.

9. A device as in claim 2, wherein the first channel portion having the first cross-sectional area is upstream of the analysis region.

10. A device as in claim 2, wherein the first and second plugs of fluid are stored and sealed in a reagent storage area of the device.

11. A device as in claim 10, wherein the first and second plugs of fluid are liquids.

12. A device as in claim 2, wherein the first and second plugs are stored and sealed in a microfluidic channel of the device.

13. A device as in claim 12, wherein the first and second plugs of fluid are liquids.

14. A device as in claim 2, wherein the first and/or second fluid is a buffer solution.

15. A device as in claim 2, wherein the first and/or second fluid comprises a reagent for a chemical and/or biological reagent.

16. A device as in claim 9, wherein the analysis region is a reaction area comprising physisorbed molecules.

17. A device as in claim 2, comprising an optical detection region associated with the flow constriction region.

18. A device as in claim 17, comprising a detector associated with the optical detection region, wherein the detector is adapted and arranged to detect a fluid flowing in the flow constriction region.

19. A device as in claim 2, wherein the second cross-sectional area is at least 25 times smaller than the first cross-sectional area, wherein the flow constriction region has a length of at least 2 cm, and wherein the flow constriction region comprises a serpentine configuration.

20. A device as in claim 2, wherein the first and second plugs of fluid are stored and sealed in a microfluidic channel of the device, and wherein the first and second plugs of fluid are liquids.

21. A device as in claim 2, wherein the analysis region is a part of the microfluidic channel comprising the first channel portion.

22. A device as in claim 2, wherein the analysis region is a part of the constriction region.