IP Library Granted Patent US 10,832,404
Granted Patent B2
US 10,832,404 · App. 16/000,385 · Granted Nov 10, 2020

Automated detection and repositioning of micro-objects in microfluidic devices

Inventors: Fenglei Du (Fremont, CA); Paul M. Lundquist (San Francisco, CA); John A. Tenney (Piedmont, CA); Troy A. Lionberger (Berkeley, CA)
Assignee: Berkeley Lights, Inc.
G06T7/0012G01N15/1434G01N15/1463G01N15/1484G01N21/6456G01N27/453G06T5/50B01L3/502761G01N15/1475G01N2015/0038G01N2015/0065G01N2015/1006G01N2015/1445G01N2015/1486G01N2015/1493G01N2015/1497G01N2021/056G01N2021/1765G01N2201/0635G01N2201/127G06T2207/30024G06T2207/30101
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Quick Facts
Patent No.
US 10,832,404
App. No.
16/000,385
Granted
Nov 10, 2020
Kind
B2
Abstract

Methods are provided for the automated detection of micro-objects in a microfluidic device. In addition, methods are provided for repositioning micro-objects in a microfluidic device. In addition, methods are provided for separating micro-objects in a spatial region of the microfluidic device.

Claims (54)

1. A method of re-positioning a micro-object in a microfluidic device comprising a plurality of sequestration pens, the method comprising:

identifying a first micro-object of a set of micro-objects disposed within the microfluidic device;

computing one or more trajectories for the first micro-object, each trajectory comprising a path connecting the first micro-object, at a first location with a second location within the microfluidic device, wherein the first or second location is located in a sequestration pen of the plurality of sequestration pens disposed within the microfluidic device;

selecting a trajectory from the one or more trajectories computed for the first micro-object, wherein the length of the selected trajectory is minimized; and

re-positioning the micro-object by moving the micro-object along its selected trajectory.

2. The method of claim 1 , further comprising:

identifying a second micro-object of the set of micro-objects disposed within the microfluidic device;

computing one or more trajectories for the second micro-object, each trajectory comprising a path connecting the second micro-object, at a first location with a second location within the microfluidic device, wherein the first or second location is located in a sequestration pen of the plurality of sequestration pens disposed within the microfluidic device;

selecting a trajectory from the one or more trajectories computed for the second micro-object; and

re-positioning the second micro-object by moving the second micro-object along the selected trajectory from the one or more trajectories computed for the second micro-object.

3. The method of claim 2 , wherein the movement of the first micro-object and the second micro-object is synchronized.

4. The method of claim 2 , further comprising identifying the micro-object using machine learning techniques.

5. The method of claim 1 , further comprising:

computing a density value associated with the set of micro-objects; and

computing the one or more trajectories based, at least in part, on the density value associated with the set of micro-objects.

6. The method of claim 5 , further comprising:

determining if the density value exceeds a threshold value; and

computing, for at least one micro-object of the set of micro-objects, one or more trajectories connecting the micro-object with one or more sequestration pens of the set of sequestration pens.

7. The method of claim 5 , further comprising:

determining that the density value does not exceed a threshold value; and

computing, for at least one sequestration pen of the set of sequestration pens, one or more trajectories connecting the sequestration pen with one or more micro-objects of the set of micro-objects.

8. The method of claim 1 , wherein the second location is located in a sequestration pen of the plurality of sequestration pens disposed within the microfluidic device.

9. The method of claim 8 , further comprising identifying a set of sequestration pens, wherein said identifying comprises identifying empty sequestration pens amongst the plurality of sequestration pens.

10. The method of claim 8 , wherein the sequestration pen comprises an isolation region and a connection region which connects the isolation region to a microfluidic channel of the microfluidic device.

11. The method of claim 10 , wherein the selected trajectory moves from the microfluidic channel, through the connection region, and ends in the isolation region of the sequestration pen.

12. The method of claim 1 , further comprising: calculating a sum of lengths of one or more trajectories computed for the first micro-object; and minimizing the sum of the lengths of the one or more trajectories wherein minimizing the sum of the lengths comprises using at least one of the following: a greedy algorithm, a heuristics-based algorithm, a non-linear algorithm, and a constrained search.

13. The method of claim 1 , wherein selecting a trajectory of the one or more trajectories computed for the first micro-object, further comprises determining whether a trajectory of the one or more computed trajectories exceeds a pre-determined length.

14. The method of claim 1 , wherein re-positioning the micro-object comprises accelerating the micro-object from an initial velocity to a traveling velocity over a first time period.

15. The method of claim 14 , wherein re-positioning the micro-object comprises decelerating the micro-object from the traveling velocity to a final velocity over a second time period.

16. The method of claim 1 , wherein the first or second location is within a microfluidic channel of the microfluidic device.

17. The method of claim 16 , wherein the first location is within a sequestration pen of the plurality of sequestration pens and the second location is within the microfluidic channel of the microfluidic device.

18. The method of claim 1 , wherein the first location is within a first sequestration pen of the microfluidic device and the second location is within a second sequestration pen of the microfluidic device.

19. The method of claim 1 , wherein the microfluidic device comprises a dielectrophoresis (DEP) configuration.

20. The method of claim 19 , wherein re-positioning the micro-object comprises activating patterns of DEP electrodes within the microfluidic device, thereby generating DEP forces that move the at least one micro-object.

21. A method of re-positioning a first micro-object in a microfluidic device comprising a plurality of sequestration pens, the method comprising:

identifying a first micro-object disposed within the microfluidic device;

computing one or more trajectories for the first micro-object, each trajectory of the one or more trajectories comprising a path connecting the first micro-object at a first location with a second location within the microfluidic device, wherein the first or second location is located in a sequestration pen of the plurality of sequestration pens;

selecting a trajectory from the one or more trajectories for the first micro-object by determining whether the trajectory exceeds a pre-determined maximum length; and

re-positioning the first micro-object by moving the first micro-object along its selected trajectory.

22. The method of claim 21 , further comprising:

identifying a second micro-object disposed within the microfluidic device;

computing one or more trajectories for the second micro-object, each trajectory comprising a path connecting the second micro-object at a first location with a second location within the microfluidic device, wherein the first or second location is located in a sequestration pen of the plurality of sequestration pens disposed within the microfluidic device;

selecting a trajectory from the one or more trajectories computed for the second micro-object; and

re-positioning the second micro-object by moving the second micro-object along its selected trajectory.

23. The method of claim 22 , wherein the first micro-object and the second micro-object are moved such that the movement is synchronized.

24. The method of claim 21 , further comprising:

computing a density value associated with a set of micro-objects comprising the first micro-object and the second micro-object; and

computing the one or more trajectories based, at least in part, on the density value associated with the set of micro-objects.

25. The method of claim 21 , further comprising selecting a trajectory for the first micro-object so that the length of the selected trajectory of the one or more computed trajectories is minimized.

26. The method of claim 25 , wherein minimizing the length of the selected trajectory comprises using a greedy algorithm, a heuristics-based algorithm, a non-linear algorithm, a constrained search, or a combination thereof.

27. The method of claim 21 , wherein the first or second location is within a microfluidic channel of the microfluidic device.

28. The method of claim 21 , wherein the microfluidic device comprises a dielectrophoresis (DEP) configuration.

29. The method of claim 28 , wherein re-positioning the first micro-object comprises activating patterns of DEP electrodes within the microfluidic device, thereby generating DEP forces that move the micro-object.

30. The method of claim 21 , wherein selecting the trajectory from the one or more trajectories for the first micro-object further comprises determining that the trajectory does not exceed a pre- determined maximum length.

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 Dec 9, 2019
From: DU, FENGLEI; LUNDQUIST, PAUL M.; TENNEY, JOHN A.; LIONBERGER, TROY A.
To: BERKELEY LIGHTS, INC.
Reel/Frame 051221/0647 →