Exporting a selected group of micro-objects from a micro-fluidic device

Patent metadata

Field	Value
Publication number	US-9617145-B2
Application number	US-201414520510-A
Country	US
Kind code	B2
Filing date	Oct 22, 2014
Priority date	Oct 22, 2013
Publication date	Apr 11, 2017
Grant date	Apr 11, 2017

Abstract

A group of micro-objects in a holding pen in a micro-fluidic device can be selected and moved to a staging area, from which the micro-objects can be exported from the micro-fluidic device. The micro-fluidic device can have a plurality of holding pens, and each holding pen can isolate micro-objects located in the holding pen from micro-objects located in the other holding pens or elsewhere in the micro-fluidic device. The selected group of micro-objects can comprise one or more biological cells, such as a clonal population of cells. Embodiments of the invention can thus select a particular group of clonal cells in a micro-fluidic device, move the clonal cells to a staging area, and export the clonal cells from the micro-fluidic device while maintaining the clonal nature of the exported group.

First claim

What is claimed:

1. A process of exporting micro-objects from a micro-fluidic device having an enclosure which comprises a plurality of holding pens, said processing comprising:
selecting a group of micro-objects located in a holding pen that is one of said plurality of holding pens inside said enclosure of said micro-fluidic device;
moving said selected group of micro-objects to a staging area inside said enclosure; and
exporting ones of said micro-objects of said selected group from said staging area through a passage in said enclosure to a location outside of said enclosure.

2. The process of claim 1 , wherein said moving comprises isolating said group of micro-objects from all other micro-objects disposed in said micro-fluidic device.

3. The process of claim 1 , wherein each holding pen of said plurality comprises an isolation region configured to hold a plurality of micro-objects.

4. The process of claim 1 , wherein each micro-object of said selected group is a biological cell.

5. The process of claim 4 , wherein said selected group is a single biological cell.

6. The process of claim 4 , wherein said selected group is a clonal population of biological cells.

7. The process of claim 1 , wherein:
said selecting comprises determining that said group of micro-objects has a particular activity or physical characteristic.

8. The process of claim 1 , wherein:
said selecting comprises directing a pattern of light into said micro-fluidic device, wherein said pattern of light surrounds said micro-objects of said selected group and activates DEP forces that trap said micro-objects of said selected group; and
said moving comprises moving said pattern of light to said staging area, wherein said micro-objects of said selected group remain trapped by said DEP forces activated by said pattern of light as said pattern of light moves to said staging area.

9. The process of claim 1 , wherein said staging area is located in a channel defined by said enclosure of said micro-fluidic device.

10. The process of claim 1 , wherein said staging area is located within said holding pen.

11. The process of claim 10 , wherein moving said selected group of micro-objects to said staging area comprises allowing gravity to attract said group of micro-objects to said staging area.

12. The process of claim 1 , wherein said exporting comprises drawing said micro-objects of said selected group from said staging area through said passage in said enclosure by drawing said micro-objects of said selected group through an opening in a proximal end of an export device.

13. The process of claim 12 , wherein said drawing comprises generating a pressure differential that draws said micro-objects of said group into said opening at said proximal end of said export device.

14. The process of claim 12 , wherein said exporting further comprises inserting said export device into an export interface disposed over said passage in said enclosure, to thereby place said opening at said proximal end of said export device adjacent to said passage.

15. The process of claim 14 , wherein:
said export interface comprises a self-closing cover disposed over and covering said passage; and
said inserting comprises opening said cover by pressing said proximal end of said export device against a separation in said cover and moving said proximal end of said export device to be adjacent said passage.

16. The process of claim 14 , wherein:
said export interface comprises a self-healing cover disposed over and covering said passage; and
said inserting comprises piercing said cover with said proximal end of said export device and positioning said proximal end of said export device adjacent to said passage.

17. The process of claim 1 , wherein said selected group of micro-objects is exported in a medium or other solution having a volume of 1 μL or less.

18. The process of claim 12 further comprising, after said exporting, inspecting said export device for any un-exported micro-objects of said selected group.

19. The process of claim 18 further comprising removing any un-exported ones of said micro-objects from said export device.

20. The process of claim 1 , wherein:
said passage in said enclosure is a second passage in said enclosure and is disposed adjacent a second end of said staging area,
said moving comprises moving said selected group to a middle portion of said staging area between said second end and an opposite first end of said staging area, and
said exporting comprises:
flowing a liquid from a first export device through a first passage in said enclosure toward said first end of said staging area and thereby generating a flow from said first end of said staging area to said second end of said staging area, and
drawing said micro-objects of said selected group from said second end of said staging area through said second passage in said enclosure into an opening at a proximal end of a second export device disposed adjacent said second passage.

21. A micro-fluidic apparatus comprising:
an enclosure configured to contain a liquid medium, said enclosure comprising a passage through said enclosure;
a channel disposed inside said enclosure, said channel having a plurality of holding pens which open off of said channel, each holding pen of said plurality configured to hold a group of micro-objects and isolate the group of micro-objects from micro-objects in others of said plurality of holding pens; and
an export interface disposed on said enclosure adjacent said passage, said export interface configured to interface an export device such that an opening in a first end of said export device is positioned adjacent to said passage through said enclosure.

22. The apparatus of claim 21 , wherein said enclosure comprises at least one staging area.

23. The apparatus of claim 22 , wherein said at least one staging area is located adjacent to said passage through said enclosure.

24. The apparatus of claim 22 , wherein said at least one staging area is located in said channel.

25. The apparatus of claim 22 , wherein said enclosure comprises a plurality of staging areas, and wherein each holding pen comprises one staging area of said plurality of staging areas.

26. The apparatus of claim 21 , wherein said export interface comprises a cover that covers entirely said passage through said enclosure.

27. The apparatus of claim 26 , wherein:
said cover comprises a separation dividing said cover into contiguous flaps,
said flaps are biased to contact one another to thereby cover entirely said passage through said enclosure, and
said flaps are sufficiently flexible to move apart to form an opening to receive said first end of said export device in response to a force of said first end of said export device being pressed against said separation.

28. The apparatus of claim 26 , wherein said cover comprises a self-healing material that can be pierced by and thus form a hole for receiving said export device but self-heals and thereby closes said hole when said export device is removed from said material.

29. The apparatus of claim 21 further comprising means for trapping a group of said micro-objects in any one of said plurality of holding pens and moving said trapped group of micro-objects to said at least one staging area.

Assignees

• Berkeley Lights Inc

Inventors

• Breinlinger Keith J
• Malleo Daniele
• Mathieu Gaetan L
• Nevill J Tanner
• Slocum Alexander H
• White Mark P

Classifications

• G01N33/54326

  Magnetic particles · CPC title

• B01L2300/044

  pierceable, e.g. films, membranes · CPC title

• B01L2200/0668

  Trapping microscopic beads · CPC title

• G01N35/10

  Devices for transferring samples {or any liquids} to, in, or from, the analysis apparatus, e.g. suction devices, injection devices {(G01N35/0099 takes precedence)} · CPC title

• G01N33/543 Primary

  with an insoluble carrier for immobilising immunochemicals · CPC title