DEVICE AND METHOD FOR PRESSURE-DRIVEN PLUG TRANSPORT

• US 20120329171A1
• Filed: 07/31/2012
• Published: 12/27/2012
• Est. Priority Date: 05/09/2002
• Status: Active Grant

• Current Assignee: University of Chicago
• Original Assignee: University of Chicago
• Inventors: Ismagliov, Rustem F., Tice, Joshua David, Gerdts, Cory John, Zheng, Bo
• Granted Patent: US 8,822,148 B2
• Time in Patent Office: Days
• US Class Current: 436/172
• CPC Class Codes: B01D 2009/0086 Processes or apparatus therefor
• CPC Class Codes: B01D 9/0072 Crystallisation in microfluidic devices
• CPC Class Codes: B01F 25/433 Mixing tubes wherein the shape of the tube influences the mixing, e.g. mixing tubes with varying cross-section or provided with inwardly extending profiles
• CPC Class Codes: B01F 25/4331 Mixers with bended, curved, coiled, wounded mixing tubes or comprising elements for bending the flow
• CPC Class Codes: B01F 33/3021 the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
• CPC Class Codes: B01J 14/00 Chemical processes in general for reacting liquids with liquids; Apparatus specially adapted therefor B01J8/00, B01J19/08 take precedence
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00599 Solution-phase processes
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00736 Non-biologic macromolecules, e.g. polymeric compounds
• CPC Class Codes: B01J 2219/00756 Compositions, e.g. coatings, crystals, formulations
• CPC Class Codes: B01J 2219/00783 Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00837 comprising coatings other than catalytically active coatings
• CPC Class Codes: B01J 2219/0086 Dimensions of the flow channels
• CPC Class Codes: B01J 2219/00869 Microreactors placed in parallel, on the same or on different supports
• CPC Class Codes: B01J 2219/00889 : Mixing micromixers B01F33/30
• CPC Class Codes: B01J 2219/00891 : Feeding or evacuation
• CPC Class Codes: B01J 2219/00894 : More than two inlets
• CPC Class Codes: B01J 2219/00903 : Segmented flow
• CPC Class Codes: B01J 2219/00975 : Ultraviolet light
• CPC Class Codes: B01J 2219/00977 : Infrared light
• CPC Class Codes: B01L 2200/0673 : Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/12 : Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0867 : Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/0487 : fluid pressure, pneumatics
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 : characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• 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: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C07K 14/43 : Sweetening agents, e.g. thaumatin, monellin
• CPC Class Codes: C12N 9/2462 : Lysozyme (3.2.1.17)
• 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: C12Y 302/01017 : Lysozyme (3.2.1.17)
• CPC Class Codes: C30B 29/54 : Organic compounds
• CPC Class Codes: C30B 29/58 : Macromolecular compounds
• CPC Class Codes: C30B 7/14 : the crystallising materials being formed by chemical reactions in the solution
• CPC Class Codes: G01N 1/28 : Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Qmounting specimens on microscopic slides G02B21/34; means for supporting the objects or the materials to be analysed in electron microscopes H01J37/20 ; laboratory gas handling apparatus B01L5/00
• 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 117/10 : Apparatus
• CPC Class Codes: Y10T 137/0318 : Processes
• CPC Class Codes: Y10T 436/117497 : with a continuously flowing sample or carrier stream
• CPC Class Codes: Y10T 436/143333 : Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/25 : including sample preparation

Abstract

The present invention provides microfabricated substrates and methods of conducting reactions within these substrates. The reactions occur in plugs transported in the flow of a carrier-fluid.

Claims

1. A method comprising the steps of:

providing a microfluidic system comprising one or more channels;

providing within the one or more channels a carrier fluid comprising an oil and at least one plug substantially surrounded by the carrier fluid, wherein the plug comprises reagents sufficient for an autocatalytic reaction including a first species of molecule in a concentration such that the plug contains no more than a single molecule of the first species; and

conducting an autocatalytic reaction such that the single molecule is amplified.

2. The method of claim 1, wherein the single molecule is a single biological molecule.

3. The method of claim 2, wherein the single biological molecule is DNA or RNA and the autocatalytic reaction is a polymerase-chain reaction.

4. The method of claim 1, wherein the conducting step includes heating.

5. The method of claim 1, further comprising the step of providing a detector to detect, analyze, characterize, or monitor one or more properties of the autocatalytic reaction during and/or after it has occurred.

6. The method of claim 5, wherein the properties comprise light emission.

7. The method of claim 6, wherein the reagents include one or more fluorescent labels and the detector detects emissions from the one or more fluorescent labels.

8. The method of claim 5, further comprising the step of directing the plug to a first channel of the one or more channels when the detector detects, analyzes, characterizes, or monitors one or more of a first set of properties and directing the plug to a second channel of the one or more channels when the detector detects, analyzes, characterizes, or monitors one or more property not included in the first set.

9. The method of claim 1, wherein the oil is fluorinated oil.

10. The method of claim 1, wherein the carrier fluid further comprises a surfactant.

11. The method of claim 10, wherein the surfactant is fluorinated surfactant.

12. The method of claim 1, wherein the at least one plug is a merged plug.

13. The method of claim 1, wherein the one or more channels comprises an expansion portion where the at least one plug is trapped for a period of time during or after the reaction.

14. The method of claim 1, wherein the at least one plug is substantially spherical in shape.

15. The method of claim 1, further comprising the step of separating the at least one plug from the carrier fluid.