METHOD AND APPARATUS FOR REAL-TIME FEEDBACK CONTROL OF ELECTRICAL MANIPULATION OF DROPLETS ON CHIP

• US 20100096266A1
• Filed: 11/01/2007
• Published: 04/22/2010
• Est. Priority Date: 11/02/2006
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Gong, Jian, Kim, Chang-Jin
• Granted Patent: US 9,266,076 B2
• Time in Patent Office: Days
• US Class Current: 204/451
• CPC Class Codes: B01F 33/3021 the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
• CPC Class Codes: B01F 33/3031 using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/143 Quality control, feedback systems
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/089 Virtual walls for guiding liquids
• CPC Class Codes: B01L 2400/0427 Electrowetting
• CPC Class Codes: B01L 3/502792 for moving individual droplets on a plate, e.g. by locally altering surface tension

Abstract

A device for generating droplets includes a substrate comprising a reservoir site configured to hold a liquid and including a first electrode, a droplet creation site including a second electrode, and droplet separation site disposed between the reservoir site and the droplet creation site and containing an electrode. The device includes control circuitry operatively coupled to the first, second, and third electrodes. The control circuitry is configured to measure the fluid volume on the electrodes and independently adjust an applied voltage to increase/decrease the quantity of fluid. The device can move fluid onto the creation site or back onto to the reservoir site. When the fluid volume is at the desired value or range, a driving voltage is delivered to the first and second electrodes to form a new droplet. The device may generate droplets having a uniform or user-defined size smaller than the electrode.

Claims

1. A device for generating droplets comprising:

a substrate comprising a reservoir site configured to hold a liquid and comprising a first electrode, a droplet creation site comprising a second electrode, and a droplet separation site comprising a third electrode disposed between the reservoir site and the droplet creation site;

control circuitry operatively coupled to the first, second, and third electrodes, the control circuitry configured to measure the droplet volume on at least the second electrode, the control circuitry further being configured to independently adjust an applied voltage to one or more of the first, second, and third electrodes based at least in part on the measured droplet volume.

2. The device of claim 1, wherein the control circuitry is further configured to apply a voltage to the first and second electrodes to separate a droplet from the liquid in the reservoir site.

3. The device of claim 2, wherein the generated droplet has a size that is substantially equal to or less than the second electrode.

4. The device of claim 2, wherein the generated droplet has a user-controlled volume.

5. The device of claim 1, wherein the control circuitry comprises a capacitance sensing circuit.

6. The device of claim 5, further comprising a microcontroller operatively coupled to an output of the capacitance sensing circuit.

7. The device of claim 6, wherein the microcontroller is operatively coupled to a voltage control circuit, the voltage control circuit being operatively coupled to a voltage amplifier coupled at least to the first and second electrodes.

8. The device of claim 1, wherein the at least one of the reservoir site, droplet creation site, and droplet separation site comprise a plurality of electrodes.

9. The device of claim 7, wherein the voltage controlled by the microcontroller is based in part on control logic stored within the microcontroller.

10. The device of claim 9, wherein the control logic comprises one or more predetermined threshold values corresponding to threshold droplet volumes.

11. The device of claim 10, wherein the control logic comprises a control algorithm selected from the group consisting of proportional control, proportional-integral control, and proportional-integral-derivative control.

12. A device for generating droplets comprising:

a substrate comprising a reservoir site configured to hold a liquid and comprising a first electrode, a droplet creation site comprising a second electrode, and droplet separation site comprising a third electrode, the droplet separation site being disposed between the reservoir site and the droplet creation site;

control circuitry operatively coupled to the first, second, and third electrodes, the control circuitry configured to measure the droplet volume on at least the second electrode while simultaneously being configured to independently adjust an applied voltage to one or more of the first, second, and third electrodes based at least in part on the measured droplet volume, wherein when a driving voltage is applied to the first electrode fluid is drawn onto the first electrode and when a driving voltage is applied to the third electrode fluid is drawn onto the third electrode and when a driving voltage is applied to the second electrode fluid is drawn onto to the second electrode.

13. The device of claim 12, wherein if the measured droplet volume is below a target, the control circuitry drives the second electrode and if the measured droplet volume is above a target, the control circuitry drives the first electrode.

14. The device of claim 13, wherein the target comprises a range of droplet volumes.

15. The device of claim 13, wherein the target comprises a single droplet volume.

16. The device of claim 13, wherein if the measured droplet volume is at the target, the control circuitry applies a driving voltage to both the first and second electrodes so as to form a new drop of liquid on the second electrode.

17. The device of claim 13, wherein the target is adjustable.

18. A method of forming droplets in a microfluidic device comprising a reservoir site configured to hold a liquid and comprising a first electrode, a droplet creation site comprising a second electrode, a droplet separation site comprising a third electrode, and control circuitry operatively coupled to the first, second, and third electrodes, the method comprising:

applying a first set of applied voltages via the control circuitry to one or more of the first, second, and third electrodes, wherein the first set of applied voltages pulls fluid onto the second and third electrodes;

measuring a parameter indicative of the fluid volume on the second electrode using the control circuitry;

comparing the parameter indicative of the fluid volume against a target; and

applying a second set of applied voltages via the control circuitry to at least the first electrode if the parameter indicative of the fluid volume exceeds the target, wherein the second set of applied voltages pulls fluid onto the first electrode;

or

applying a second set of applied voltages via the control circuitry to at least the second electrode if the parameter indicative of the fluid volume is below the target, wherein the second set of applied voltages draws more fluid onto the second electrode; and

repeating the operation of measuring the parameter and comparing the parameter against the target and applying a next set of applied voltages.

19. The method of claim 18, wherein the target comprises a range of droplet volumes.

20. The method of claim 18, wherein the target comprises a single droplet volume.

21. The method of claim 18, further comprising applying a driving voltage to both the first and second electrodes.

22. The method of claim 18, wherein the target is adjustable.

23. A method of mixing solutions in a microfluidic device comprising at least first and second solutions and a plurality of electrodes, the plurality of electrodes being operatively coupled to control circuitry for substantially and simultaneously applying driving voltages and measuring capacitance values, the method comprising:

(a) forming a reduced volume droplet of the first solution on one of the plurality of electrodes, the reduced volume droplet having a size that is less than the size of the electrode;

(b) forming a droplet of the second solution on one or more of the plurality of electrodes, the droplet having a size that is similar to or larger than the size of the electrode;

(c) mixing the reduced volume droplet of the first solution with the droplet of the second solution;

(d) splitting the mixed droplet into multiple split droplets; and

(e) forming a droplet of at least the second solution on one of the plurality of electrodes;

(f) mixing one of the split droplets from operation (d) with the droplet of at least the second solution in operation (e); and

(g) repeating operations (d) through (f) a plurality of times with at least the second solution.

24. The method of claim 23, wherein the mixing comprises dilution of the first solution by the second solution.

25-27. -27. (canceled)