Device and method for making discrete volumes of a first fluid in contact with a second fluid, which are immiscible with each other

• US 10,450,604 B2
• Filed: 09/03/2015
• Issued: 10/22/2019
• Est. Priority Date: 08/22/2005
• Status: Active Grant

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Inventors: Wiyatno, Willy, Lee, Linda, Cox, David, Nurse, James, Greiner, Douglas, Lehto, Dennis, Wojtowicz, Janusz, Woo, Sam, Reel, Richard
• Primary Examiner(s): Gordon, Brian R
• Application Number:
  US14/844,279
• Publication Number:
  US 20160097087A1
• Time in Patent Office: 1,510 Days
• CPC Class Codes: B01J 2219/00353 Pumps
• CPC Class Codes: B01J 2219/0036 Nozzles
• CPC Class Codes: B01J 2219/00364 Pipettes
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00619 using hydrophilic or hydrophobic regions
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00657 One-dimensional arrays
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/0293 for liquids
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502784 : specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: B01L 7/52 : with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: C12Q 1/6806 : Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6869 : Methods for sequencing
• CPC Class Codes: C12Q 1/6874 : involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: C12Q 2535/101 : Sanger sequencing method, i.e. oligonucleotide sequencing using primer elongation and dideoxynucleotides as chain terminators
• CPC Class Codes: F15C 5/00 : Manufacture of fluid circuit elements; Manufacture of assemblages of such elements integrated circuits
• CPC Class Codes: F16K 2099/0084 : Chemistry or biology, e.g. "lab-on-a-chip" technology
• CPC Class Codes: F16K 99/0001 : Microvalves microdevices B81B1/00; manufacture or treatment of devices or systems in or on a substrate B81C1/00; microfluidic structures B01L3/5027; micropumps F04B19/006
• CPC Class Codes: F16K 99/0011 : Gate valves or sliding valves
• CPC Class Codes: F16K 99/0013 : Rotary valves
• CPC Class Codes: G01N 1/14 : Suction devices, e.g. pumps; Ejector devices
• CPC Class Codes: G01N 27/44743 : Introducing samples
• CPC Class Codes: G01N 27/44769 : Continuous electrophoresis, i.e. the sample being continuously introduced, e.g. free flow electrophoresis [FFE]
• CPC Class Codes: G01N 35/08 : using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
• CPC Class Codes: Y10T 137/0318 : Processes
• CPC Class Codes: Y10T 137/4259 : With separate material addition
• CPC Class Codes: Y10T 137/85978 : With pump
• CPC Class Codes: Y10T 137/85986 : Pumped fluid control
• CPC Class Codes: Y10T 137/86863 : Rotary valve unit
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

A method for generating, within a conduit, discrete volumes of one or more fluids that are immiscible with a second fluid. The discrete volumes can be used for biochemical or molecular biology procedures involving small volumes, for example, microliter-sized volumes, nanoliter-sized volumes, or smaller. The discrete volumes are separated from one another by a liquid that is immiscible with the fluid(s) of the discrete volumes, for example, aqueous immiscible-fluid-discrete volumes separated by an oil.

Claims

1. A method comprising:

suctioning discrete volumes of aqueous fluid and a spacing liquid into a first conduit such that the discrete volumes of aqueous fluid are carried and separated by the spacing liquid, the spacing liquid being disposed between the discrete volumes of aqueous fluid in the first conduit, and the spacing liquid being immiscible with the discrete volumes of aqueous fluid;

transferring a first set and a second set of the discrete volumes of aqueous fluid separated by the spacing liquid from the first conduit to a second conduit;

transferring the first set of discrete volumes of aqueous fluid separated by the spacing liquid from the second conduit to a third conduit;

processing the first set of discrete volumes of aqueous fluid in the third conduit;

holding in the second conduit the second set of the discrete volumes of aqueous fluid transferred to the second conduit while the first set of discrete volumes of aqueous fluid is transferred to and processed in the third conduit;

after holding in the second conduit, transferring the second set of discrete volumes of aqueous fluid from the second conduit to the third conduit; and

processing the second set of discrete volumes of aqueous fluid in the third conduit.

2. The method according to claim 1, wherein the processing comprises thermally cycling the first set and the second set of discrete volumes of aqueous fluid in a thermal cycling nucleic acid sequence amplification process.

3. The method according to claim 2, wherein the processing further comprises detecting a fluorescence of the first set and the second set of discrete volumes of aqueous fluid in a fluorescence detection process.

4. The method according to claim 1, wherein the processing comprises detecting a fluorescence of the first set and the second set of discrete volumes of aqueous fluid in a fluorescence detection process.

5. The method according to claim 1, wherein the discrete volumes of aqueous fluid and the spacing liquid are suctioned from a vessel into the first conduit.

6. The method according to claim 1, wherein suctioning the discrete volumes of aqueous fluid and the spacing liquid into the first conduit comprises filling an inner cross-sectional area of the first conduit with the spacing liquid disposed between discrete volumes of aqueous fluid.