Methods for sampling a liquid flow

• US 7,329,545 B2
• Filed: 09/24/2002
• Issued: 02/12/2008
• Est. Priority Date: 09/24/2002
• Status: Active Grant

• Current Assignee: Duke University
• Original Assignee: Duke University
• Inventors: Pamula, Vamsee K., Ren, Hong, Paik, Philip Y., Pollack, Michael G., Fair, Richard B.
• Primary Examiner(s): SINES, BRIAN J
• Application Number:
  US10/253,342
• Publication Number:
  US 20040058450A1
• Time in Patent Office: 1,967 Days
• Field of Search: 436/43, 436/47, 436/52, 436/53, 436/63, 436/174, 436/180, 422/50, 422/68.1, 422/81, 422/82, 422/100
• US Class Current: 436/53
• 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: B01F 33/30351 using hydrophilic/hydrophobic surfaces
• CPC Class Codes: B01J 2219/00479 Means for mixing reactants or products in the reaction vessels
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01L 2300/089 Virtual walls for guiding liquids
• CPC Class Codes: B01L 2300/165 Specific details about hydrophobic, oleophobic surfaces
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• 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
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 15/14 Optical investigation techniques, e.g. flow cytometry
• CPC Class Codes: G01N 2035/1046 Levitated, suspended drops
• CPC Class Codes: G02B 26/005 based on electrowetting
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/113332 with conveyance of sample along a test line in a container or rack
• CPC Class Codes: Y10T 436/117497 with a continuously flowing sample or carrier stream
• CPC Class Codes: Y10T 436/118339 with formation of a segmented stream
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/25625 Dilution
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

In a method for sampling a continuous liquid flow, the liquid flow is supplied to a surface along an input flow path. The liquid flow is sampled by forming a sample droplet from a portion of the liquid flow. The sample droplet is moved along an analysis flow path to a processing area of the surface, where the sample droplet is processed. Discrete sample droplets are formed and moved using an electrowetting technique. A binary mixing apparatus and method are also provided. The apparatus comprises an array of electrodes, an electronic controller communicating with the electrodes, a sample droplet supply area communicating with the array, and an additive droplet supply area communicating with the array. The electronic controller alternately energizes and de-energizes selected electrodes to carry out droplet-to-droplet binary mixing operations to obtain one or more droplets having a target mixing ratio.

Claims

1. A method for sampling a liquid flow, comprising the steps of:

(a) supplying a continuous liquid flow from a continuous flow fluid input source to a surface along a first flow path, wherein the surface comprises an array and/or path of electrodes;

(b) sampling the continuous liquid flow by splitting off a sample droplet from a portion of the liquid flow, wherein the splitting off is mediated by the electrodes;

(c) moving the sample droplet along a second flow path to a processing area of the surface; and

(d) processing the sample droplet at the processing area.

2. The method according to claim 1 wherein the conductive element is spaced from the array of electrodes, and the sample droplet, during movement, is disposed between the array of electrodes and the conductive element.

3. The method according to claim 1 wherein the step of sampling the liquid flow comprises biasing a selected set of the electrodes of the array, wherein a first one of the selected electrodes is disposed under the liquid flow along the first flow path, a second one of the selected electrodes is adjacent to the first electrode, and a third one of the selected electrodes is adjacent to the second electrode.

4. The method according to claim 3 wherein the step of sampling the liquid flow comprises biasing the first, second and third electrodes to a first voltage to cause the liquid flow portion to spread over the second and third electrodes from the first electrode, and biasing the second electrode to a second voltage different from the first voltage to cause the sample droplet to form on the third electrode.

5. The method according to claim 3 wherein the second electrode is adjacent to the first flow path, wherein the droplet is formed adjacent to the first flow path.

6. The method according to claim 1 wherein the step of moving the sample droplet along the second flow path comprises biasing a selected set of the electrodes of the array.

7. The method according to claim 6 wherein the step of biasing causes the sample droplet to make a turn as the sample droplet is moved along the second flow path.

8. The method according to claim 1 wherein the step of processing the sample droplet comprises biasing a selected set of the electrodes of the array.

9. The method according to claim 1 wherein the step of moving the sample droplet comprises merging the sample droplet with an additional droplet to form a combined droplet, and moving the combined droplet along the second flow path to the processing area to mix the combined droplet as it moves along the second flow path.

10. The method according to claim 1 wherein the step of processing the sample droplet comprises merging the sample droplet with an additional droplet to produce a combined droplet.

11. The method according to claim 10 wherein the step of merging causes the sample droplet to become diluted.

12. The method according to claim 10 wherein the step of merging causes the sample droplet to react with the additional droplet.

13. The method according to claim 10 comprising the step of linearly oscillating the combined droplet back and forth to mix its contents.

14. The method according to claim 10 comprising the step of moving the combined droplet along a looped path one or more times to mix its contents.

15. The method according to claim 14 wherein the combined droplet is disposed on a two-by-two array of four electrodes of the surface, and the method comprises the step of mixing the combined droplet by biasing each of the four electrodes to rotate the combined droplet.

16. The method according to claim 15 wherein a portion of the combined droplet remains substantially stationary at or near an intersecting region of the four electrodes while the combined droplet is rotating.

17. The method according to claim 10 comprising the step of splitting the combined droplet into first and second split droplets.

18. The method according to claim 17 comprising the step of merging the first and second split droplets to mix their contents.

19. The method according to claim 18 comprising the step of oscillating the first and second split droplets to mix their contents prior to merging the first and second split droplets.

20. The method according to claim 10 wherein the processing area comprises a first electrode, a second electrode adjacent to the first electrode, and a third electrode adjacent to the second electrode, and the sample droplet is merged with the additional droplet by moving the sample droplet from the first electrode to the second electrode and moving the additional droplet from the third electrode to the second electrode, whereby the combined droplet is formed on the second electrode.

21. The method according to claim 20 comprising the step of splitting the combined droplet into first and second split droplets by the first, second and third electrodes to a first voltage to cause the combined droplet to spread to the first and third electrodes, and subsequently biasing the second electrode to a second voltage different from the first voltage, whereby the first split droplet is formed on the first electrode and the second split droplet is formed on the third electrode.

22. The method according to claim 10 wherein the processing area comprises at least two electrodes, the sample droplet is disposed on one of the electrodes and an additional droplet is disposed on the other electrode, and the sample droplet is merged with the additional droplet by moving either the sample droplet or the additional droplet onto the electrode on which the other droplet is disposed.

23. The method according to claim 1 wherein the step of processing the sample droplet comprises analyzing the sample droplet at the processing area.

36. The method according to claim 2 wherein the conductive element is spaced vertically from the array of electrodes.

37. The method according to claim 2 wherein the conductive element is spaced horizontally from the array of electrodes.

38. The method according to claim 10 comprising the step of moving the combined droplet uni-directionally or multi-directionally to mix its contents.

24. A method for sampling multiple droplets from a liquid flow, comprising the steps of:

(a) supplying a continuous liquid flow from a continuous flow fluid input source to a surface along an input flow path, wherein the surface comprises an array and/or path of electrodes;

(b) sampling the continuous liquid flow by splitting off a first sample droplet and a second sample droplet from a portion of the liquid flow, wherein the splitting off is mediated by the electrodes;

(c) moving the first sample droplet along a first transport flow path to a first destination area of the surface; and

(d) moving the second sample droplet along a second transport flow path to a second destination area of the surface.

25. The method according to claim 24 wherein the first droplet is moved at a first movement rate and the second droplet is moved at a second movement rate substantially equal to the first movement rate.

26. The method according to claim 24 wherein the first droplet is moved at a first movement rate and the second droplet is moved at a second movement rate different from the first movement rate.

27. The method according to claim 24 comprising the steps of processing the first sample droplet at the first destination area and processing the second sample droplet at the second destination area.

28. The method according to claim 27 wherein the step of processing the first sample droplet comprises combining the first sample droplet with a first additional droplet.

29. The method according to claim 28 wherein the step of processing the second sample droplet comprises combining the second sample droplet with a second additional droplet.

30. The method according to claim 29 wherein the first additional droplet is different in composition from the second additional droplet.

31. The method according to claim 27 wherein the first and second sample droplets are processed substantially simultaneously.

32. The method according to claim 27 wherein the first and second sample droplets are processed at different rates.

33. The method according to claim 24 wherein the first destination area is adapted to perform a first process and the second destination area is adapted to perform a second process different from the first process.

34. The method according to claim 24 wherein the first and second destination areas are the same area.

35. The method according to claim 24 wherein the first and second sample droplets are formed at two different locations along the input flow path.

39. The method according to claim 24 wherein step (b) is repeated a desired number of times to form a plurality of droplets.