Device And Method For Making Discrete Volumes Of A First Fluid In Contact With A Second Fluid, Which Are Immiscible With Each Other

• US 20160097087A1
• Filed: 09/03/2015
• Published: 04/07/2016
• 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, Greiner, Douglas, Lehto, Dennis, Wojtowicz, Janusz, Woo, Sam, Reel, Richard, Nurse, James
• Granted Patent: US 10,450,604 B2
• Time in Patent Office: Days
• 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

1-38. -38. (canceled)

39. A method comprising:

forming a first droplet of a second fluid in a first fluid, wherein the first fluid and the second fluid are immiscible with respect to one another and have different densities;

moving at least one of the first droplet and an intake tip of a conduit relative to one another such that the first droplet is disposed adjacent the intake tip; and

drawing the first droplet and an amount of the first fluid through the intake tip and into the conduit.

40. The method of claim 39, further comprising:

forming in the first fluid a second droplet of a third fluid that is miscible with the second fluid; and

merging the second droplet with the first droplet, thereby forming a merged droplet of first and third fluid, before the drawing step, wherein the drawing comprises drawing the merged droplet through the intake tip and into the conduit.

41. The method of claim 39, wherein the first fluid is disposed in a container having a bottom, and the second fluid is less dense than the first fluid, and further comprising;

ejecting a volume of the second fluid from a through-hole in the bottom, thereby forming the first droplet, which rises in the first fluid.

42. The method of claim 39, wherein the second fluid has a greater density than the first fluid, the droplet of the second fluid is formed on a film, and the method further comprises submersing the film in the first fluid.

43-51. -51. (canceled)

52. A method comprising:

applying a negative pressure to a conduit system comprising an intake tip;

contacting the intake tip with a first fluid and a second fluid that is immiscible with the first fluid, while applying the negative pressure, to draw the first fluid and the second fluid into the conduit system and form a set of discrete volumes of the first fluid spaced apart from one another by the second fluid, the set moving in a first direction in the conduit system; and

thereafter, applying a positive pressure to the conduit system to push the set of discrete volumes in the conduit system.

53. The method of claim 52, wherein the applying a positive pressure causes the set to move in the first direction.

54. The method of claim 52, wherein the applying a positive pressure causes the set to move in the conduit system a second direction that is opposite the first direction.

55. The method of claim 52, wherein the negative pressure is applied to the conduit system until the set moves past a first diverter and the method comprises then changing a position of the diverter before applying the positive pressure.

56. The method of claim 52, wherein the negative pressure is applied to the conduit system until the set moves past a valve and a port, and the method comprises then closing the valve, and wherein the applying positive pressure comprises applying a positive pressure through the port.

57. The method of claim 52, comprising applying the negative pressure with a reversible pump, and reversing the action of the reversible pump to apply the positive pressure.

58. The method of claim 52, wherein the contacting further comprises applying an electrowetting force to move at least one of the first fluid and the second fluid to a location adjacent the intake tip.