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

• US 9,140,630 B2
• Filed: 12/21/2012
• Issued: 09/22/2015
• 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, Jim, Greiner, Douglas, Lehto, Dennis, Wojtowicz, Janusz, Woo, Sam, Reel, Richard
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Kingan, Timothy G
• Application Number:
  US13/724,079
• Publication Number:
  US 20130183210A1
• Time in Patent Office: 1,005 Days
• Field of Search: None
• US Class Current: 1/1
• 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

Various embodiments described in the application relate to an apparatus, system, and 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 system can comprise an apparatus comprising at least one conduit operatively connected to one or more pumps for providing discrete volumes separated from one another by a fluid that is immiscible with the fluid(s) of the discrete volumes, for example, aqueous immiscible-fluid-discrete volumes separated by an oil.

Claims

1. An apparatus comprising:

a first conduit having an outer perimeter and a length;

a second conduit having an inner perimeter, wherein at least a portion of the length of the first conduit is inside of the second conduit, thereby defining a space between the outer perimeter of the first conduit and the inner perimeter of the second conduit, and wherein the second conduit comprises a block having a through-hole, wherein the block further comprises a passageway formed therein, the passageway having a first end configured to be in fluid communication with the through-hole and extending away from the through-hole;

a first pump operatively connected to the first conduit, wherein the first pump is configured to flow a first fluid through the first conduit in a first direction;

a second pump operatively connected to the second conduit, wherein the second pump is configured to flow a second fluid through the second conduit in a second direction that is opposite the first direction; and

a conduit positioner configured to axially move one of the first conduit and the second conduit with respect to the other from a first position to a second position, wherein the second position includes the first conduit withdrawn into the second conduit,

wherein, in the first position, the first conduit is configured to draw the first fluid, wherein, in the second position, the first fluid is configured to draw in the second fluid from the second conduit, and wherein the conduit positioned is configured to move the first conduit and the second conduit to the first and second positions to generate slugs of the first fluid in the first conduit.

2. The apparatus of claim 1, further comprising a control unit configured to synchronize actuation of the first pump and the second pump.

3. The apparatus of claim 1, further comprising a control unit configured to synchronize actuation of the first pump, the second pump, and the conduit positioner.

4. The apparatus of claim 1, wherein the first conduit has an end surface, the second conduit has an end surface, and the end surface of the first conduit is beyond the end surface of the second conduit.

5. The apparatus of claim 1, wherein the first conduit comprises an end surface and the end surface is disposed within the through-hole of the block.

6. The apparatus of claim 1, further comprising a third pump operatively connected to the passageway and configured to draw fluid from the through-hole into the passageway.

7. The apparatus of claim 1, wherein the first conduit has a first inner diameter, the first inner diameter is from about 10 microns to about 2000 microns, the second conduit has a second inner diameter, and the second inner diameter is from about 20 microns to about 5000 microns.

8. The apparatus of claim 1, wherein the first conduit comprises a tube.

9. The apparatus of claim 1, wherein the first fluid is immiscible with the second fluid.

10. The apparatus of claim 1, wherein the first fluid is an emulsification.