DEVICE AND METHOD FOR PRESSURE-DRIVEN PLUG TRANSPORT

• US 20110174622A1
• Filed: 02/09/2011
• Published: 07/21/2011
• Est. Priority Date: 05/09/2002
• Status: Active Grant

• Current Assignee: University of Chicago
• Original Assignee: University of Chicago
• Inventors: Gerdts, Cory John, Zheng, Bo, Tice, Joshua David, Ismagilov, Rustem F.
• Granted Patent: US 8,273,573 B2
• Time in Patent Office: Days
• US Class Current: 204/452
• 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:

(a) providing a microfluidic system comprising one or more channels;

(b) providing within the one or more channels a carrier fluid and a plurality of plugs immiscible with the carrier fluid including a first plug and a second plug, wherein;

(i) the first plug includes a marker identifying a characteristic of the first plug when the first plug is formed; and

(ii) the second plug includes a marker identifying a characteristic of the second plug when the second plug is formed.

2. The method of claim 1, wherein the marker is an optically detectable group, moiety or compound.

3. The method of claim 1, wherein the characteristic comprises any one or combination of concentration, identity of chemical species, or elapsed time since droplets were formed.

4. The method of claim 1, wherein the marker comprises a dye.

5. The method of claim 4, wherein the dye is fluorescein.

6. The method of claim 1, wherein the marker has a fluorescence intensity indicative of a concentration of the marker.

7. The method of claim 1, wherein the characteristic comprises a concentration of a component within the plug when it is formed.

8. The method of claim 7, wherein the marker has a fluorescence intensity indicative of a concentration of the marker and identifying the concentration of a component within the plug when it is formed.

9. The method of claim 1, wherein the characteristic of the first plug as applied to the first component comprises a concentration of a first component within the first plug when it is formed and the characteristic of the second plug comprises a concentration of the second component different from the first component within the second plug when it is formed.

10. The method of claim 9, wherein the marker has a fluorescence intensity indicative of a concentration of the marker and identifying the concentration of the first component within the first plug when it is formed and/or the concentration of the second component within the second plug when it is formed.

11. The method of claim 1, wherein the marker is present in the first plug at a first concentration and is present in the second plug at a second concentration.

12. The method of claim 11, wherein the first concentration is suitable for directly or indirectly detecting, analyzing, and/or characterizing a third concentration of at least the first component and the second concentration is suitable for directly or indirectly detecting, analyzing, and/or characterizing a fourth concentration of the first component.

13. The method of claim 11, wherein step (b) further comprises providing dispersion in a pressure-driven flow of a continuous stream of a first plug fluid thereby generating a gradient in the first plug fluid, and fixing the first concentration of the marker within the first plug by the formation of the first plug and fixing the second concentration of the marker within the second plug by the formation of the second plug.

14. The method of claim 11, wherein, at a first time, the first plug fluid comprises a second plug fluid and a third plug fluid in a first ratio and, at a second time, comprises the second plug fluid and the third plug fluid in a second ratio, wherein the second plug fluid comprises the first marker at a third concentration and the third plug fluid comprises the first marker at a fourth concentration, and wherein step (b) further comprises fixing the first concentration by forming the first plug at the first time and fixing the second concentration by forming the second plug at the second time.

15. The method of claim 14, wherein the first ratio is determined by a first flow rate of the second plug fluid and a second flow rate of the third plug fluid, and the second ratio is determined by a third flow rate of the second plug fluid and a fourth flow rate of the third plug fluid.

16. The method of claim 11, wherein the first plug comprises a second marker at a third concentration and the second plug comprises the second marker at a fourth concentration.

17. The method of claim 11, wherein step (b) further comprises providing within the one or more channels a second plug fluid immiscible with the carrier fluid, and further comprising the step of (c) merging the first plug with the second plug fluid thereby forming a first merged plug and (d) merging the second plug with the second plug fluid thereby forming a second merged plug.

18. A product comprising the first plug, second plug, first merged plug, and/or second merged plug produced by the method of claim 17.

19. The method of claim 17, wherein the second plug fluid comprises a third component capable of reacting in the presence of the first plug fluid.

20. The method of claim 19, further comprising the steps of (e) measuring the reaction of the third component, if it occurs, in the first merged plug by measuring a property or characteristic of the first merged plug and directly or indirectly measuring the first concentration, and (f) measuring the reaction of the third component, if it occurs, in the second merged plug by measuring a property or characteristic of the second merged plug and directly or indirectly measuring the second concentration.

21. The method of claim 20, further comprising the steps of (g) comparing the reactions of the third component in the first merged plug and the second merged plug.

22. The method of claim 11, wherein the first concentration is suitable for directly or indirectly identifying or detecting a first chemical species comprising the first component, and the second concentration is suitable for directly or indirectly identifying or detecting a second chemical species comprising the second component.

23. A product comprising a first and a second plug, wherein the product is made by a process comprising the steps of:

(a) providing a microfluidic system comprising one or more channels;

(b) providing within the one or more channels a carrier fluid and a plurality of plugs immiscible with the carrier fluid including the first plug and the second plug, wherein;

(i) the first plug includes a marker identifying a characteristic of the first plug when the first plug is formed; and

(ii) the second plug includes a marker identifying a characteristic of the second plug when the second plug is formed.

24. An apparatus constructed and adapted to provide a plurality of plugs immiscible with a carrier fluid including a first plug and a second plug, wherein:

(i) the first plug includes a marker identifying a characteristic of the first plug when the first plug is formed; and

(ii) the second plug includes a marker identifying a characteristic of the second plug when the second plug is formed.