Droplet manipulation device

Patent metadata

Field	Value
Publication number	US-10022719-B2
Application number	US-201514935823-A
Country	US
Kind code	B2
Filing date	Nov 9, 2015
Priority date	Sep 24, 2002
Publication date	Jul 17, 2018
Grant date	Jul 17, 2018

Abstract

Methods are provided for manipulating droplets. The methods include providing the droplet on a surface comprising an array of electrodes and a substantially co-planer array of reference elements, wherein the droplet is disposed on a first one of the electrodes, and the droplet at least partially overlaps a second one of the electrodes and an intervening one of the reference elements disposed between the first and second electrodes. The methods further include activating the first and second electrodes to spread at least a portion of the droplet across the second electrode and deactivating the first electrode to move the droplet from the first electrode to the second electrode.

First claim

What is claimed is:

1. A binary mixing process, comprising:
(a) providing a binary mixing apparatus for mixing two droplets comprising a first binary mixing unit,
wherein the first binary mixing unit comprises an electrode array comprising X rows of electrodes and X columns of electrodes to form an electrode array consisting of X 2 matrix electrodes and associated cells EA ij where i is a positive integer that designates 1, 2, . . . X rows of electrodes, and where j is a positive integer that designates 1, 2, . . . X columns of electrodes,
wherein the first binary mixing unit comprises a logic cell matrix comprising a subset of the rows and columns of the electrode array consisting of matrix electrodes and associated cells EA ij in which i and j are both odd integers, and each cell of the logic cell matrix is capable of storing one of a sample droplet, a reagent droplet or an intermediate-mixture droplet,
wherein electrodes situated in rows of the electrode array consisting of matrix electrodes and associated cells EA ij in which i is an even integer comprise electrodes on which merging and/or splitting of the sample droplet, the reagent droplet, and/or the intermediate-mixture droplet occurs, and
wherein electrodes situated in columns of the electrode array consisting of matrix electrodes and associated cells EA ij in which j is an even integer comprise electrodes on which transport of the sample droplet, the reagent droplet, or the intermediate-mixture droplet occurs; and

(b) using the binary mixing apparatus to perform a first mixing phase comprising a row mix, a column mix, or a combination of a series of row mixes and/or column mixes of a sample droplet, a reagent droplet, and/or an intermediate-mixture droplet and to dilute the concentration of the sample droplet to a desired ratio in a series of ratios selected from the group consisting of 1:1, 1:3, 1:7 . . . 1:2 n-1 , wherein n is a positive integer equal to the number of mixing operations performed.

2. The process of claim 1 , wherein the binary mixing apparatus further comprises a second binary mixing unit, and a buffer in fluid communication with the first and second binary mixing units to store intermediate products and transfer intermediate products between the first and second binary mixing units.

3. The process of claim 2 , wherein the second binary mixing unit comprises an electrode array comprising X rows of electrodes and X columns of electrodes to form an electrode array consisting of X 2 matrix electrodes and associated cells EA ij where i is a positive integer that designates 1, 2, . . . X rows of electrodes, and where j is a positive integer that designates 1, 2, . . . X columns of electrodes,
wherein the second binary mixing unit comprises a logic cell matrix comprising a subset of the rows and columns of the electrode array consisting of matrix electrodes and associated cells EA ij in which i and j are both odd integers, and each cell of the logic cell matrix is capable of storing one of a sample droplet, a reagent droplet, or an intermediate-mixture droplet,
wherein electrodes situated in rows of the electrode array consisting of matrix electrodes and associated cells EA ij in which i is an even integer comprise electrodes on which merging and/or splitting of the sample droplet, the reagent droplet, and/or the intermediate-mixture droplet occurs, and
wherein electrodes situated in columns of the electrode array consisting of matrix electrodes and associated cells EA ij in which j is an even integer comprise electrodes on which transport of the sample droplet, the reagent droplet, or the intermediate-mixture droplet occurs.

4. The process of claim 3 , wherein the binary mixing apparatus further comprises a microprocessor capable of executing the instructions of a computer program in communication with the first binary mixing unit, second binary mixing unit, and buffer through one or more communication lines.

5. The process of claim 4 , wherein the binary mixing apparatus further comprises electrode containing droplet-handling regions for each mixing unit which can be sequentially activated to implement one or more mixing operations selected from the group consisting of droplet discarding, droplet merging, droplet splitting, and combinations thereof.

6. The process of claim 5 , wherein first and second binary mixing units are capable of producing a volume of droplets that is equivalent to the number of associated cells in each of the respective logic cell matrices.

7. The process of claim 6 , wherein the first and second binary mixing units further comprise a sample reservoir, a waste reservoir, and a reagent reservoir in fluid communication with the electrode array.

8. The process of claim 7 , wherein the first and second binary mixing units comprises a plurality of transport electrodes and associated cells for transporting droplets to and from the electrode array.

9. The process of claim 8 , wherein the first binary mixing unit comprises a plurality of electrical leads connected to matrix electrodes EA ij and the transport electrodes to control the movement or manipulation of droplets.

10. The process of claim 9 , wherein the binary mixing apparatus is fabricated on a microfluidic chip.

11. The process of claims 1 or 10 , wherein the first and/or second binary mixing units comprise a 7×7 electrode array consisting of 49 matrix electrodes and associated cells EA ij , where i designates 1, 2, . . . , 7 rows of electrodes and j designates 1, 2, . . . , 7 columns of electrodes.

12. The process of claim 11 , wherein the binary mixing apparatus is used to perform a first single row mix by combining a sample droplet S 1 having a concentration of 1 with a reagent droplet R 1 having a concentration of 0 to produce two intermediate-mixture droplets I 1 and I 2 , each intermediate-mixture droplet having ½ of the concentration of sample droplet S 1 .

13. The process of claim 12 , further comprising discarding at least one of intermediate-mixture droplets I 1 or I 2 , and transporting a second reagent droplet R 2 having a concentration of 0 to a logic cell in the same column as, and adjacent to, the remaining intermediate-mixture droplet I 1 or I 2 .

14. The process of claim 13 , further comprising using the binary mixing apparatus to perform a second single row mix by combining the remaining intermediate-mixture droplet I 1 or I 2 and the second reagent droplet R 2 to produce two intermediate-mixture droplets I 3 or I 4 , each intermediate-mixture droplet having ¼ of the concentration of sample droplet S 1 .

15. The process of claim 14 , further comprising transporting a third reagent droplet R 3 and a fourth reagent droplet R 4 , each having a concentration of 0, to logic cells in the same column as, and adjacent to, the intermediate-mixture droplets I 3 and I 4 .

16. The process of claim 15 , further comprising using the binary mixing apparatus to perform a double row mixing operation by combining the intermediate-mixture droplets I 3 and I 4 with the respective reagent droplets R 3 and R 4 to produce four intermediate-mixture droplets I 5 , I 6 , I 7 , and I 8 , each intermediate-mixture droplet having ⅛ of the concentration of sample droplet S 1 .

17. The process of claim 16 , further comprising transporting a fifth reagent droplet R 5 , a sixth reagent droplet R 6 , a seventh reagent droplet R 7 , and an eighth reagent droplet R 8 , each having a concentration of 0, to logic cells in a different column than, and adjacent to, the intermediate-mixture droplets I

Assignees

• Univ Duke

Inventors

• Pollack Michael G
• Pamula Vamsee K
• Fair Richard B

Classifications

• B01L2200/06

  Fluid handling related problems · CPC title

• B01L2300/165

  Specific details about hydrophobic, oleophobic surfaces · CPC title

• B01L2300/161

  Control and use of surface tension forces, e.g. hydrophobic, hydrophilic · CPC title

• B01L3/502792

  for moving individual droplets on a plate, e.g. by locally altering surface tension · CPC title

• B01L2400/0427

  Electrowetting · CPC title