IP Library Granted Patent US 12,168,231
Granted Patent B2
US 12,168,231 · App. 17/486,804 · Granted Dec 17, 2024

Method of analysis

Inventors: Billy W. Colston, Jr. (San Ramon, CA); Benjamin J. Hindson (Livermore, CA); Kevin D. Ness (Pleasanton, CA); Donald A. Masquelier (Tracy, CA)
Assignee: Bio-Rad Laboratories, Inc.
B01L3/502784B01F23/41B01F33/3011B01F35/10B01L3/0241B01L3/502715B01L7/525B29C45/0053B29C45/006C12Q1/686G01N21/3563G01N21/49G01N21/6428G01N21/6486B01F23/4143B01F23/4145B01F2101/23B01L7/52B01L2200/0673B01L2200/0689B01L2200/10B01L2200/12B01L2300/041B01L2300/0654B01L2300/0816B01L2300/0819B01L2300/0858B01L2300/0867B01L2300/1822B01L2400/0478B01L2400/0487B01L2400/049B01L2400/0622B29C2045/0079B29L2031/752G01N2021/6439Y02A90/10
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Quick Facts
Patent No.
US 12,168,231
App. No.
17/486,804
Filed
Sep 27, 2021
Granted
Dec 17, 2024
Kind
B2
Art Unit
1799
USPC
435/6.12
Abstract

Method of analysis. In the method, a microfluidic device defining a flow path extending from an inlet to an outlet may be selected. A sample-containing fluid may be introduced into the flow path via the inlet. Volumes of the sample-containing fluid may be isolated from one another on the flow path. A two-dimensional monolayer of the volumes may be imaged. The two-dimensional monolayer may be formed along the flow path between the inlet and the outlet.

Claims (26)

1. A method of analysis, the method comprising:

selecting a microfluidic device defining a flow path extending from an inlet to an outlet;

introducing a sample-containing fluid into the flow path from a sample port via the inlet;

isolating volumes of the sample-containing fluid from one another on the flow path; and

imaging a two-dimensional monolayer of the volumes, the two-dimensional monolayer being formed along the flow path between the inlet and the outlet, wherein the flow path includes a chamber having an upper surface and a lower surface, and a height, a width, and an area, wherein the height corresponds in size to the volumes such that the two-dimensional monolayer of the volumes is formed in the chamber when the sample-containing fluid flows into the chamber, wherein the width is at least about ten times the height, and wherein the area is larger than the sample port.

2. The method of claim 1 , further comprising placing the sample-containing fluid as a continuous phase into a well of the microfluidic device, and driving the sample-containing fluid along the flow path from the well.

3. The method of claim 1 , wherein the volumes of the two-dimensional monolayer are isolated from one another by an immiscible fluid.

4. The method of claim 3 , wherein the volumes are droplets.

5. The method of claim 1 , wherein at least one of the upper surface and the lower surface of the chamber is transparent.

6. The method of claim 1 , wherein imaging is performed through the upper surface or the lower surface of the chamber.

7. The method of claim 1 , wherein introducing a sample-containing fluid includes creating a pressure differential between the inlet and the outlet.

8. The method of claim 1 , further comprising amplifying a nucleic acid target in the volumes of the two-dimensional monolayer.

9. The method of claim 8 , wherein amplifying includes thermally cycling the two-dimensional monolayer to promote a polymerase chain reaction in the volumes of the two-dimensional monolayer.

10. The method of claim 1 , wherein imaging includes detecting fluorescence from the two-dimensional monolayer.

11. The method of claim 1 , wherein the volumes of the two-dimensional monolayer contain an intercalating dye or a probe that includes an oligonucleotide labeled with a fluorophore, and wherein imaging includes detecting fluorescence from the intercalating dye or the fluorophore.

12. The method of claim 1 , wherein only a subset of the volumes of the two-dimensional monolayer contains an analyte, further comprising determining whether individual volumes of the two-dimensional monolayer contain the analyte based on imaging the two-dimensional monolayer.

13. The method of claim 12 , further comprising enumerating volumes of the two-dimensional monolayer containing the analyte.

14. A method of analysis, the method comprising:

selecting a microfluidic device defining a flow path extending from an inlet to an outlet;

introducing a sample-containing fluid into the flow path from a sample port via the inlet;

isolating volumes of the sample-containing fluid from one another on the flow path, wherein only a subset of the volumes contain a nucleic acid target;

amplifying the nucleic acid target in the volumes while the volumes are arranged in a two-dimensional monolayer along the flow path;

imaging the two-dimensional monolayer; and

determining whether individual volumes of the two-dimensional monolayer contain the nucleic acid target based on imaging the two-dimensional monolayer, wherein the flow path includes a chamber having an upper surface and a lower surface, a height, a width, and an area, wherein the height corresponds in size to the volumes such that the two-dimensional monolayer of the volumes is formed in the chamber when the sample-containing fluid flows into the chamber, wherein the width is at least about ten times the height, and wherein the area is larger than the sample port.

15. The method of claim 14 , wherein imaging includes detecting fluorescence from the two-dimensional monolayer.

16. The method of claim 14 , wherein amplifying includes thermally cycling the two-dimensional monolayer.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 24, 2024
From: COLSTON, BILLY WAYNE, JR.; HINDSON, BENJAMIN JOSEPH; NESS, KEVIN DEAN; MASQUELIER, DONALD ARTHUR; MILANOVICH, FRED PAUL; MODLIN, DOUGLAS N.; RIOT, VINCENT; BURD, SAMUEL; MAKAREWICZ, ANTHONY JOSEPH, JR.; BELGRADER, PHILLIP; BRIGHT, ISAAC J.; LUCERO, MICHAEL Y.
To: QUANTALIFE, INC.
Reel/Frame 067524/0850 →
MERGER Recorded May 24, 2024
From: QUANTALIFE, INC.
To: BIO-RAD QL, INC.
Reel/Frame 067524/0923 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 24, 2024
From: BIO-RAD QL, INC.
To: BIO-RAD LABORATORIES, INC.
Reel/Frame 067524/0941 →
Continuity (15)
Continuation 16404659 · May 6, 2019
Continuation 15365894 · Nov 30, 2016
Continuation 12962511 · Dec 7, 2010
Continuation 12586626 · Sep 23, 2009
Provisional Application 61277270 · Sep 22, 2009
Provisional Application 61277204 · Sep 21, 2009
Provisional Application 61277203 · Sep 21, 2009
Provisional Application 61277216 · Sep 21, 2009
Provisional Application 61277249 · Sep 21, 2009
Provisional Application 61277200 · Sep 21, 2009
Provisional Application 61275731 · Sep 1, 2009
Provisional Application 61271538 · Jul 21, 2009
Provisional Application 61206975 · Feb 5, 2009
Provisional Application 61194043 · Sep 23, 2008
Related Publication 20220008928A1 · Jan 13, 2022
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