Microfluidic system and method for arranging objects

Patent metadata

Field	Value
Publication number	US-11045805-B2
Application number	US-201816178300-A
Country	US
Kind code	B2
Filing date	Nov 1, 2018
Priority date	Nov 1, 2017
Publication date	Jun 29, 2021
Grant date	Jun 29, 2021

Abstract

Microfluidic systems and methods for arranging a set of objects. In an exemplary method, the set of objects may be transported in carrier fluid along a microfluidic channel structure having a reformatting zone including an object-accessible region and at least one object-excluding region. A portion of the carrier fluid may be moved from the object-accessible region to the at least one object-excluding region in an upstream section of the reformatting zone, to reduce a spacing of objects of the set. The portion of the carrier fluid may be directed into the object-accessible region from the at least one object-excluding region in a downstream section of the reformatting zone, to increase a spacing of objects of the set. The steps of moving and directing in combination may increase the spacing between objects disproportionately for a subset of the objects that are closest to one another.

First claim

We claim:

1. A method of arranging objects, the method comprising:
transporting a set of objects in carrier fluid along a microfluidic channel structure having a reformatting zone including an object-accessible region and at least one object-excluding region;
moving a portion of the carrier fluid from the object-accessible region to the at least one object-excluding region in an upstream section of the reformatting zone, to reduce a spacing of objects of the set in the upstream section; and
directing the portion of the carrier fluid into the object-accessible region from the at least one object-excluding region in a downstream section of the reformatting zone, to increase a spacing of objects of the set in, and/or downstream of, the downstream section.

2. The method of claim 1 , wherein at least one pair of objects of the set are in sufficiently close proximity to one another in the reformatting zone that the objects of the at least one pair mutually obstruct a closer approach to one another encouraged by the step of moving.

3. The method of claim 1 , wherein a spacing between a subset of the objects of the set that are closest together is increased disproportionately by the steps of moving and directing in combination.

4. The method of claim 1 , wherein objects of the set leave the reformatting zone in single file.

5. The method of claim 1 , wherein the reformatting zone has an outlet, further comprising arranging objects of the set in single file in the channel structure upstream of the outlet of the reformatting zone.

6. The method of claim 5 , wherein objects of the set are arranged in single file by an alignment region of the channel structure located in the upstream section.

7. The method of claim 5 , wherein objects of the set are arranged in single file by an alignment region of the channel structure that tapers from the upstream section to the downstream section of the reformatting zone.

8. The method of claim 7 , wherein the alignment region tapers to a width that is less than twice an average diameter of the objects.

9. The method of claim 1 , wherein the object-accessible region is deeper than each object-excluding region of the at least one object-excluding region.

10. The method of claim 9 , wherein the at least one object-excluding region has a depth that is less than an average diameter of the objects of the set.

11. The method of claim 9 , wherein the object-accessible region and each object-excluding region of the at least one object-excluding region are formed by a same channel of the channel structure.

12. The method of claim 11 , wherein each object-excluding region of the at least one object-excluding region is continuously contiguous with the object-accessible region between the upstream section and the downstream section.

13. The method of claim 9 , wherein the object-accessible region includes an object-accessible groove, and wherein the at least one object-excluding region includes one or more wings located adjacent the object-accessible groove.

14. The method of claim 9 , wherein the at least one object-excluding region includes a pair of object-excluding regions that are separated from one another by the object-accessible region.

15. The method of claim 1 , wherein the object-accessible region is formed by a primary channel of the channel structure, wherein the at least one object-excluding region includes one or more by-pass channels defined by the channel structure, and wherein the step of moving includes a step of moving at least part of the portion of the carrier fluid to the one or more by-pass channels.

16. The method of claim 1 , wherein the objects are selected from the group consisting of beads, droplets, and biological cells.

17. The method of claim 1 , further comprising partitioning a stream including the carrier fluid and carrying objects of the set at a position downstream of the downstream section to form isolated volumes, wherein partitioning includes encapsulating the isolated volumes with a liquid that is immiscible with the carrier fluid.

18. The method of claim 17 , wherein the objects include biological cells, wherein the stream includes beads, and wherein each isolated volume of a plurality of the isolated volumes contains only one of the beads and only one of the biological cells.

19. A system for arranging a set of objects, comprising:
a microfluidic channel structure having a reformatting zone including an object-accessible region and at least one object-excluding region; and
at least one source of positive/negative pressure operatively connected to the channel structure and configured to form a stream of carrier fluid transporting objects of the set in the channel structure;
wherein the channel structure is configured such that a portion of the carrier fluid is moved from the object-accessible region to the at least one object-excluding region in an upstream section of the reformatting zone, to reduce a spacing between objects of the set in the upstream section, and such that the portion of the carrier fluid is directed into the object-accessible region from the at least one object-excluding region in a downstream section of the reformatting zone, to increase a spacing between objects of the set in, and/or downstream of, the downstream section.

Assignees

• Bio Rad Laboratories

Inventors

• Hung Lung-Hsin
• Meltzer Robert
• Frenz Lucas

Classifications

• B01L3/502784 Primary

  specially adapted for droplet or plug flow, e.g. digital microfluidics · CPC title

• C12Q1/6869

  Methods for sequencing · CPC title

• B01L2200/0647

  Handling flowable solids, e.g. microscopic beads, cells, particles · CPC title

• B01L2200/143

  Quality control, feedback systems · CPC title

• B01L2400/0487

  fluid pressure, pneumatics · CPC title