IP Library Granted Patent US 9,132,394
Granted Patent B2
US 9,132,394 · App. 13/072,673 · Granted Sep 15, 2015

System for detection of spaced droplets

Inventors: Anthony J. Makarewicz, Jr. (Livermore, CA); Amy L. Hiddessen (Dublin, CA)
Assignee: Bio-Rad Laboratories, Inc.
B01F3/0807B01F13/0062B01L3/0241B01L3/502784B01L3/563G01N21/645B01L3/502715B01L7/52B01L7/525B01L2200/0689B01L2300/0816B01L2300/0819B01L2300/1822B01L2400/0478B01L2400/0487B01L2400/0622
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Quick Facts
Patent No.
US 9,132,394
App. No.
13/072,673
Granted
Sep 15, 2015
Kind
B2
Abstract

System, including methods and apparatus, for detection of spaced droplets.

Claims (46)

1. A detection system for droplet-based assays, comprising:

a channel network defining a flow path for droplets extending through a confluence region configured to increase an average distance between droplets, and to an examination region disposed downstream of the confluence region; and

a detector operatively connected to the examination region,

wherein the channel network includes a droplet inlet channel configured to carry droplets to the confluence region, wherein the droplet inlet channel forms a tapered region and a neck region extending from the tapered region to the confluence region, wherein the tapered region is sized such that droplets enter the neck region in single file, wherein the flow path has a smaller diameter in the neck region than in the examination region, and wherein at least one dilution inlet channel meets the droplet inlet channel at the confluence region and is configured to provide a dilution fluid that increases the average distance between droplets.

2. The detection system of claim 1 , wherein the length of the neck region is between one and two times the average diameter of the droplets.

3. The detection system of claim 1 , wherein the neck region has a substantially uniform diameter.

4. The detection system of claim 1 , further comprising a droplet outlet channel that extends from the confluence region, and wherein the droplet outlet channel has about a same diameter as the neck region.

5. The detection system of claim 1 , wherein the tapered region of the droplet inlet channel converges from a diameter of two or more average droplet diameters to a diameter of one or less than one average droplet diameters.

6. The detection system of claim 1 , wherein the confluence region is formed at a junction between the droplet inlet channel, the at least one dilution inlet channel, and a droplet outlet channel.

7. The detection system of claim 6 , wherein the at least one dilution inlet channel includes a pair of dilution inlet channels.

8. The detection system of claim 1 , further comprising a light source configured to illuminate the examination region, wherein the detector is configured to detect light received from the examination region.

9. The detection system of claim 1 , further comprising a tip having an open end configured to be placed into a container holding an emulsion such that the open end contacts the emulsion, wherein the flow path for droplets extends from the open end, through the confluence region, and to the examination region.

10. The detection system of claim 9 , wherein the tip extends downward to the open end.

11. The detection system of claim 9 , wherein the tip has a substantially uniform diameter.

12. The detection system of claim 1 , wherein the diameter of the neck region is approximately equal to a diameter of the droplets.

13. A detection system for droplet-based assays, comprising:

a tip extending downward to an open end configured to be placed into a container holding an emulsion such that the open end contacts the emulsion;

a channel network defining a flow path for droplets, the flow path extending from the open end of the tip, through a confluence region configured to increase an average distance between droplets, and to an examination region disposed downstream of the confluence region; and

a detector operatively connected to the examination region,

wherein the channel network includes a droplet inlet channel configured to carry droplets to the confluence region, wherein the droplet inlet channel forms a tapered region and a neck region extending from the tapered region to the confluence region, and wherein the tapered region is sized such that droplets enter the neck region in single file.

14. The detection system of claim 13 , wherein the length of the neck region is between one and two times the average diameter of the droplets.

15. The detection system of claim 13 , wherein the neck region has a substantially uniform diameter.

16. The detection system of claim 13 , further comprising a droplet outlet channel that extends from the confluence region, and wherein the droplet outlet channel has about a same diameter as the neck region.

17. The detection system of claim 13 , wherein the tapered region of the droplet inlet channel converges from a diameter of two or more average droplet diameters to a diameter of one or less than one average droplet diameters.

18. The detection system of claim 13 , wherein the confluence region is formed at a junction between the droplet inlet channel, a droplet outlet channel, and at least one dilution inlet channel configured to provide a dilution fluid.

19. The detection system of claim 18 , wherein the at least one dilution inlet channel includes a pair of dilution inlet channels.

20. The detection system of claim 13 , wherein the tip has a substantially uniform diameter.

21. The detection system of claim 13 , wherein the diameter of the neck region is less than or approximately equal to a diameter of the droplets.

22. The detection system of claim 13 , wherein the diameter of the neck region is approximately equal to the diameter of the droplets.

23. A method of detection for droplet-based assays using the detection system of claim 13 , comprising:

driving droplets along the flow path from the tip, through the confluence region where a dilution fluid is introduced into the flow path, and through the examination region; and

detecting light from the examination region as droplets pass through.

24. The method of claim 23 , further comprising a step of placing the open end of the tip into an emulsion, and a step of drawing droplets of the emulsion into the tip.

25. A detection system for droplet-based assays, comprising:

a channel network defining a flow path for droplets, the flow path extending through a confluence region configured to increase an average distance between droplets, and to an examination region disposed downstream of the confluence region; and

a detector operatively connected to the examination region,

wherein the channel network includes a droplet inlet channel configured to carry droplets to the confluence region, wherein the droplet inlet channel forms a tapered region and a neck region extending from the tapered region to the confluence region, wherein the tapered region is sized such that droplets enter the neck region in single file, and wherein the neck region has a diameter that is approximately equal to an average diameter of the droplets.

26. The detection system of claim 25 , wherein the length of the neck region is between one and two times the average diameter of the droplets.

27. The detection system of claim 25 , wherein the neck region has a substantially uniform diameter.

28. The detection system of claim 25 , further comprising a droplet outlet channel that extends from the confluence region, and wherein the droplet outlet channel has about a same diameter as the neck region.

29. The detection system of claim 25 , wherein the tapered region of the droplet inlet channel converges from a diameter of two or more average droplet diameters to a diameter of one or less than one average droplet diameters.

30. The detection system of claim 25 , wherein the confluence region is formed at a junction between the droplet inlet channel, a droplet outlet channel, and at least one dilution inlet channel configured to provide a dilution fluid.

31. The detection system of claim 30 , wherein the at least one dilution inlet channel includes a pair of dilution inlet channels.

32. The detection system of claim 25 , further comprising a light source configured to illuminate the examination region, wherein the detector is configured to detect light received from the examination region.

33. The detection system of claim 25 , further comprising a tip extending downward to an open end configured to be placed into a container holding an emulsion such that the open end contacts the emulsion, wherein the flow path for droplets extends from the open end, through the confluence region, and to the examination region.

34. The detection system of claim 25 , wherein the flow path has a smaller diameter in the neck region than in the examination region.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 1, 2012
From: MAKAREWICZ, ANTHONY J., JR.; HIDDESSEN, AMY L.
To: BIO-RAD LABORATORIES, INC.
Reel/Frame 029228/0836 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 16, 2012
From: BIO-RAD LABORATORIES
To: LAWRENCE LIVERMORE NATIONAL SECURITY, LLC
Reel/Frame 028800/0910 →
Continuity (14)
Continuation In Part 12586626 · Sep 23, 2009
Provisional Application 61317635 · Mar 25, 2010
Provisional Application 61467347 · Mar 24, 2011
Provisional Application 61194043 · Sep 23, 2008
Provisional Application 61206975 · Feb 5, 2009
Provisional Application 61271538 · Jul 21, 2009
Provisional Application 61275731 · Sep 1, 2009
Provisional Application 61277200 · Sep 21, 2009
Provisional Application 61277203 · Sep 21, 2009
Provisional Application 61277204 · Sep 21, 2009
Provisional Application 61277216 · Sep 21, 2009
Provisional Application 61277249 · Sep 21, 2009
Provisional Application 61277270 · Sep 22, 2009
Related Publication 20110311978A1 · Dec 22, 2011