IP Library Granted Patent US 10,799,865
Granted Patent B2
US 10,799,865 · App. 15/336,768 · Granted Oct 13, 2020

Microfluidic apparatus having an optimized electrowetting surface and related systems and methods

Inventors: Randall D. Lowe, Jr. (Emeryville, CA); Shao Ning Pei (Albany, CA); Jian Gong (Danville, CA); Alexander J. Mastroianni (Alameda, CA); Jason M. McEwen (El Cerrito, CA); Justin K. Valley (Berkeley, CA)
Assignee: Berkeley Lights, Inc.
B01L3/50273C12M23/16C12M29/10B01L2200/0647B01L2200/12B01L2300/0816B01L2300/0887B01L2300/12B01L2300/161B01L2400/0427
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Quick Facts
Patent No.
US 10,799,865
App. No.
15/336,768
Granted
Oct 13, 2020
Kind
B2
Abstract

Microfluidic devices having an electrowetting configuration and an optimized droplet actuation surface are provided. The devices include a conductive substrate having a dielectric layer, a hydrophobic layer covalently bonded to the dielectric layer, and a first electrode electrically coupled to the dielectric layer and configured to be connected to a voltage source. The microfluidic devices also include a second electrode, optionally included in a cover, configured to be connected to the voltage source. The hydrophobic layer features self-associating molecules covalently bonded to a surface of the dielectric layer in a manner that produces a densely-packed monolayer that resists intercalation and or penetration by polar molecules or species. Also provided are microfluidic devices having an electrowetting configuration that further include a section or module having a dielectrophoresis configuration; systems that include any of the microfluidic devices in combination with an aqueous droplet and a fluidic medium immiscible with the medium of the aqueous droplet; related kits; and methods of manipulating droplets, optionally containing micro-objects such as biological cells, within the microfluidic devices.

Claims (77)

1. A microfluidic device comprising:

a substrate having at least one electrode configured to be connected to a voltage source;

a cover having at least one electrode configured to be connected to the voltage source; and

at least one spacing element,

wherein the substrate and the cover are substantially parallel to one another and joined together by the at least one spacing element so as to define an enclosure configured to hold a liquid,

wherein the substrate has a droplet actuation surface that defines, in part, the enclosure, the droplet actuation surface having an inner dielectric layer and an outer hydrophobic layer,

wherein the inner dielectric layer comprises two or more sublayers of dielectric material;

wherein the outer hydrophobic layer comprises self-associating molecules covalently bonded to a surface of the inner dielectric layer, to thereby form a densely packed hydrophobic monolayer thereon,

wherein the self-associating molecules of the hydrophobic monolayer each comprise a surface modifying ligand and a linking group that links the surface modifying ligand to the surface of the inner dielectric layer, wherein the droplet actuation surface has a structure of Formula II:

wherein is a surface of the inner dielectric layer;

V is —P(O)(OY)W— or —Si(OZ) 2 W—;

W is —O—, —S—, or —NH— and connects to the surface of the inner dielectric layer;

Z is a bond to an adjacent silicon atom attached to the surface of the inner dielectric layer or is a bond to the surface of the inner dielectric layer;

Y is a bond to an adjacent phosphorus atom attached to the surface of the inner dielectric layer or is a bond to the surface of the inner dielectric layer;

R is hydrogen or fluorine;

M is hydrogen or fluorine;

h is independently an integer of 2 or 3;

j is 1;

k is 0 or 1;

m is 0 or an integer of 1 to 20

n is 0 or an integer of 1 to 20;

the sum of (n+[(h+j)·k]+m) is an integer of 11 to 25;

when k is 1, then m is at least 2 and M is hydrogen; and

when k is 0 and R is fluorine, then m is at least 2 and M is hydrogen, and

wherein, when the at least one electrode of the substrate and the at least one electrode of the cover are connected to opposing terminals of the voltage source, the substrate is capable of applying an electrowetting force to aqueous droplets in contact with the droplet actuation surface of the substrate.

2. The microfluidic device of claim 1 , wherein V is —Si(OZ) 2 W—.

3. The microfluidic device of claim 1 , wherein V is —P(O)(OY)W—.

4. The microfluidic device of claim 1 , wherein n is an integer of 1 to 20, and wherein R is hydrogen.

5. The microfluidic device of claim 4 , wherein m is an integer of 1 to 20, and wherein M is hydrogen.

6. The microfluidic device of claim 5 , wherein m is 2.

7. The microfluidic device of claim 1 , wherein n is an integer of 1 to 20, and wherein R is fluorine.

8. The microfluidic device of claim 7 , wherein m is an integer of 1 to 20, and wherein M is hydrogen.

9. The microfluidic device of claim 8 , wherein m is 2.

10. The microfluidic device of claim 1 , wherein k is 1.

11. The microfluidic device of claim 1 , wherein k is 0.

12. The microfluidic device of claim 1 , wherein the sum of (n+[(h+j)·k]+m) is an integer of 13 to 19.

13. The microfluidic device of claim 1 , wherein the inner dielectric layer of the droplet actuation surface of the substrate comprises a first sublayer of dielectric material and a second sublayer of dielectric material, the first sublayer of dielectric material comprising an oxide.

14. The microfluidic device of claim 13 , wherein the oxide is a metal oxide.

15. The microfluidic device of claim 14 , wherein the metal oxide is aluminum oxide.

16. The microfluidic device of claim 13 , wherein the outer hydrophobic layer is covalently bonded to the first sublayer of dielectric material.

17. The microfluidic device of claim 16 , wherein the second sublayer of dielectric material comprises an oxide or a nitride.

18. The microfluidic device of claim 17 , wherein the second sublayer of dielectric material is selected from the group consisting of silicon dioxide and silicon nitride.

19. The microfluidic device of claim 16 , wherein the first sublayer of dielectric material comprises silicon oxide.

20. The microfluidic device of claim 1 , wherein the inner dielectric layer of the droplet actuation surface of the substrate has a thickness of about 40 nanometers to about 120 nanometers.

21. The microfluidic device of claim 1 , wherein the substrate further comprises a photoresponsive layer having a first side that contacts the inner dielectric layer and a second side that contacts the at least one electrode of the substrate.

22. The microfluidic device of claim 1 , wherein the substrate comprises a plurality of electrodes, each electrode configured to be connected to one or more AC voltage source(s), and wherein each electrode of the plurality is connectable to one of the one or more AC voltage source(s) via a transistor switch.

23. The microfluidic device of claim 1 , wherein the cover has an inward-facing surface that defines, in part, the enclosure, the inward-facing surface of the cover having an inner layer and an outer hydrophobic layer, wherein the outer hydrophobic layer of the cover comprises self-associating molecules covalently bonded to a surface of the inner layer of the cover, to thereby form a densely packed hydrophobic monolayer thereon.

24. The microfluidic device of claim 23 , wherein the self-associating molecules of the hydrophobic monolayer of the cover each comprise a surface modifying ligand and a linking group that links the surface modifying ligand to the surface of the inner layer of the cover, wherein the inward-facing surface of the cover has a structure of Formula II:

wherein is a surface of the inner layer;

V is —P(O)(OY)W— or —Si(OZ) 2 W—;

W is —O—, —S—, or —NH— and connects to the surface of the inner layer;

Z is a bond to an adjacent silicon atom attached to the surface of the inner layer or is a bond to the surface of the inner layer;

Y is a bond to an adjacent phosphorus atom attached to the surface of the inner layer or is a bond to the surface of the inner layer;

R is hydrogen or fluorine;

M is hydrogen or fluorine;

h is independently an integer of 2 or 3;

j is 1;

k is 0 or 1;

m is 0 or an integer of 1 to 20

n is 0 or an integer of 1 to 20;

the sum of (n+[(h+j)·k]+m) is an integer of 11 to 25;

when k is 1, then m is at least 2 and M is hydrogen; and

when k is 0 and R is fluorine, then m is at least 2 and M is hydrogen.

25. The microfluidic device of claim 24 , wherein the self-associating molecules of the hydrophobic monolayer of the cover are the same as the self-associating molecules of the hydrophobic monolayer of the droplet actuation surface of the substrate.

26. The microfluidic device of claim 1 , wherein the at least one spacing element defines one or more microchannels and a plurality of chambers within the enclosure, wherein each chamber opens off of at least one microchannel.

27. A system for transporting micro-objects, biological products, and/or reagents that are compatible with and/or soluble in aqueous media, the system comprising:

a microfluidic device according to claim 1 ;

a first fluidic medium that is immiscible with aqueous media; and

at least one aqueous droplet.

28. A process of operating the microfluidic device of claim 1 , the process comprising:

filling the enclosure, or a portion thereof, with a first liquid medium;

applying an AC voltage potential between the at least one electrode of the substrate and the at least one electrode of the cover;

introducing a first droplet of liquid into the enclosure, wherein the first droplet is immiscible in the first liquid medium; and

moving the first droplet to a desired location within the enclosure by applying an electrowetting force to the first droplet.

29. The microfluidic device of claim 1 , wherein the inner dielectric layer comprises three sublayers of dielectric material.

30. The microfluidic device of claim 29 , wherein the outer hydrophobic layer is in contact with an outermost sublayer of the two or more sublayers of dielectric material, wherein the outermost sublayer comprises an oxide.

31. The microfluidic device of claim 30 , wherein the oxide is silicon oxide.

Assignments (4)
MERGER Recorded Apr 9, 2026
From: BRUKER CELLULAR ANALYSIS, INC.
To: BRUKER SPATIAL BIOLOGY, INC.
Reel/Frame 075375/0517 →
MERGER AND CHANGE OF NAME Recorded Nov 30, 2023
From: PHENOMEX INC.; BIRD MERGERSUB CORPORATION
To: BRUKER CELLULAR ANALYSIS, INC.
Reel/Frame 065726/0624 →
CHANGE OF NAME Recorded Sep 20, 2023
From: BERKELEY LIGHTS, INC.
To: PHENOMEX INC.
Reel/Frame 064961/0794 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 5, 2017
From: LOWE, RANDALL D., JR.; PEI, SHAO NING; GONG, JIAN; MASTROIANNI, ALEXANDER J.; MCEWEN, JASON M.; VALLEY, JUSTIN K.
To: BERKELEY LIGHTS, INC.
Reel/Frame 040859/0910 →
Continuity (6)
Continuation In Part 15135707 · Apr 22, 2016
Provisional Application 62246605 · Oct 27, 2015
Provisional Application 62247725 · Oct 28, 2015
Provisional Application 62342131 · May 26, 2016
Provisional Application 62410238 · Oct 19, 2016
Related Publication 20170173580A1 · Jun 22, 2017
Cited By (2)
US 12,280,370 US 12,467,031