Microfluidic system and method for arranging objects

Patent metadata

Field	Value
Publication number	US-11857968-B2
Application number	US-202117357860-A
Country	US
Kind code	B2
Filing date	Jun 24, 2021
Priority date	Nov 1, 2017
Publication date	Jan 2, 2024
Grant date	Jan 2, 2024

Abstract

Microfluidic methods of altering the spacing of a stream of objects. In an exemplary method, objects of the object stream may be transported in carrier fluid along a microfluidic channel structure having an inflow region, an outflow region, and an expanded region extending from the inflow region to the outflow region. The expanded region may have a greater cross-sectional area for fluid flow than each of the inflow region and the outflow region. Objects of the object stream may be moved from the inflow region to the expanded region such that at least a subset of such objects are moved closer to one another. Objects of the object stream may be passed from the expanded region to the outflow region to increase a distance between such objects.

First claim

We claim:

1. A method of altering a spacing of a stream of objects, the method comprising:
transporting the objects of the object stream in carrier fluid along a microfluidic channel structure having an inflow region, an outflow region, and an expanded region extending from the inflow region to the outflow region, wherein the expanded region has a greater cross-sectional area for fluid flow than each of the inflow region and the outflow region;
moving objects of the object stream from the inflow region to the expanded region such that at least a subset of such objects are moved closer to one another in the expanded region than in the inflow and outflow regions; and
passing objects of the object stream from the expanded region to the outflow region to increase a distance between such objects in the outflow region;
wherein the expanded region includes an object-accessible groove and at least one object-excluding wing located adjacent the groove.

2. The method of claim 1 , wherein the object stream has a more uniform spacing of objects downstream of the expanded region compared to upstream of the expanded region, and/or wherein a distance between object pairs of the object stream that are closest together upstream of the expanded region is increased disproportionately by moving and passing in combination.

3. The method of claim 1 , wherein moving includes moving a portion of the carrier fluid from a deeper region of the expanded region to at least one shallower region of the expanded region of the channel structure.

4. The method of claim 3 , wherein the moving includes moving the portion of the carrier fluid to a pair of shallower regions of the expanded region of the channel structure that are separated from one another by a deeper, object-accessible groove of the expanded region.

5. The method of claim 3 , wherein moving includes moving the portion of the carrier fluid to at least one shallower region of the expanded region having a depth that is less than a diameter of the objects, such that a majority of objects of the object stream are excluded from the at least one shallower region.

6. The method of claim 1 , wherein a plurality of the objects of the object stream enter the expanded region during moving, and wherein only a subset of the plurality of objects move closer to an adjacent object of the object stream during moving until closer approach is obstructed by a periphery of the adjacent object.

7. The method of claim 1 , wherein at least a pair of the plurality of objects do not move substantially closer to one another during moving due to mutual obstruction.

8. The method of claim 1 , wherein passing objects includes passing a plurality of the objects from the expanded region to the outflow region, and wherein passing causes each object of the plurality of objects to move farther from each adjacent object of the object stream as a result of passing.

9. The method of claim 1 , wherein the objects are formed at least predominantly of liquid that is immiscible with the carrier fluid.

10. The method of claim 1 , wherein the objects are selected from the group consisting of beads, droplets, and biological cells, further comprising forming partitions from a stream including the carrier fluid and carrying a plurality of the objects at a position of the channel structure downstream of the outflow region.

11. The method of claim 10 , wherein each partition of a majority of the partitions contains none or only one of the objects, and wherein forming partitions includes encapsulating volumes of the stream including the carrier fluid using an immiscible liquid.

12. The method of claim 10 , wherein the objects are beads, further comprising adding biological cells to the carrier fluid, wherein each partition of a plurality of the partitions contains only one of the beads and only one biological cell.

13. A method of altering a spacing of a stream of objects, the method comprising:
transporting the objects of the object stream in carrier fluid along a microfluidic channel structure having an inflow region, an outflow region, and an expanded region extending from the inflow region to the outflow region, wherein the expanded region has a greater cross-sectional area for fluid flow than each of the inflow region and the outflow region;
moving objects of the object stream from the inflow region to the expanded region such that at least a subset of such objects are moved closer to one another in the expanded region than in the inflow and outflow regions; and
passing objects of the object stream from the expanded region to the outflow region to increase a distance between such objects in the outflow region;
wherein moving includes moving a portion of the carrier fluid from a deeper region of the expanded region to at least one shallower region of the expanded region of the channel structure.

14. The method of claim 13 , wherein the moving includes moving the portion of the carrier fluid to a pair of shallower regions of the expanded region of the channel structure that are separated from one another by a deeper, object-accessible groove of the expanded region.

15. The method of claim 13 , wherein moving includes moving the portion of the carrier fluid to at least one shallower region of the expanded region having a depth that is less than a diameter of the objects, such that a majority of objects of the object stream are excluded from the at least one shallower region.

16. A method of altering a spacing of a stream of objects, the method comprising:
transporting the objects of the object stream in carrier fluid along a microfluidic channel structure having an inflow region, an outflow region, and an expanded region extending from the inflow region to the outflow region, wherein the expanded region has a greater cross-sectional area for fluid flow than each of the inflow region and the outflow region;
moving objects of the object stream from the inflow region to the expanded region such that at least a subset of such objects are moved closer to one another in the expanded region than in the inflow and outflow regions; and
passing objects of the object stream from the expanded region to the outflow region to increase a distance between such objects in the outflow region;
wherein the objects are selected from the group consisting of beads, droplets, and biological cells, further comprising forming partitions from a stream including the carrier fluid and carrying a plurality of the objects at a position of the channel structure downstream of the outflow region.

17. The method of claim 16 , wherein each partition of a majority of the partitions contains none or only one of the objects, and wherein forming partitions includes encapsulating volumes of the stream including the carrier fluid using an immiscible liquid.

18. The method of claim 16 , wherein the objects are beads, further comprising adding biological cells to the carrier fluid, wherein each partition of a plurality of the partitions contains only one of the beads and only one biological cell.

Assignees

• Bio Rad Laboratories Inc

Inventors

• Hung Lung-Hsin
• Meltzer Robert
• Frenz Lucas

Classifications

• B01L3/502761 Primary

  specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules · CPC title

• B01L3/502784 Primary

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

• C12Q1/6869

  Methods for sequencing · CPC title

• B01L3/502776

  specially adapted for focusing or laminating flows · CPC title

• B01L2200/0647

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