Microfluidic system

• US 20060094119A1
• Filed: 03/16/2005
• Published: 05/04/2006
• Est. Priority Date: 10/29/2004
• Status: Active Grant

• Current Assignee: University of Chicago The (University of Chicago)
• Original Assignee: University of Chicago The (University of Chicago)
• Inventors: Zheng, Bo, Ismagilov, Rustem F., Gerdts, Cory J.
• Granted Patent: US 7,655,470 B2
• Time in Patent Office: Days
• US Class Current: 436/55
• 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: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• 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 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0433 vibrational forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/06 Crystallising dishes
• CPC Class Codes: B01L 3/502723 characterised by venting arrangements
• 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 3/527 for a plurality of reagents
• CPC Class Codes: C30B 29/58 Macromolecular compounds
• CPC Class Codes: C30B 7/00 Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions from molten solvents C30B9/00; by normal or gradient freezing C30B11/00; under a protective fluid C30B27/00
• 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 436/12 Condition responsive control

Abstract

The present invention provides microfluidic technology enabling rapid and economical manipulation of reactions on the femtoliter to microliter scale.

Claims

1. A microfluidic system, comprising:

a loading component comprising at least one microchannel, wherein the loading component is suitable for forming an array of plugs, wherein each plug comprises a plug fluid and wherein each plug is separated another plug by a carrier and/or spacer that is immiscible with the plug fluid; and

at least one detachable holding component comprising at least one microchannel that is configured to make a fluid connection with the holding component;

wherein when the holding component is loaded with the array of plugs and is detached from the loading component, the plugs do not immediately merge or mix.

2. The microfluidic system of claim 1, wherein the holding component is a capillary tube.

3. The microfluidic system of claim 1, wherein the holding component is a piece of tubing.

4. The microfluidic system of claim 1, wherein the holding component is a chip.

5. The microfluidic system of claim 1, wherein one of the holding component or loading component has a female end and the other has a male end.

6. A kit, comprising:

a holding component comprising a first microchannel with at least one open end, wherein at least one open end is configured for making a fluid connection with another microchannel; and

one or more linear arrays of plugs of plug fluid disposed within the first microchannel of the holding component,

wherein each plug is separated from another by either a carrier and/or a spacer,

wherein the carrier and the spacer are immiscible with the plug fluid and with each other, and

wherein the microchannel is wetted by carrier.

7. The kit of claim 6, which is a capillary tube.

8. The kit of claim 6, which is tubing with a diameter less than 1 mm.

9. The kit of claim 6, wherein each plug in the linear array of fluid plugs comprises at least one solvent and one or more reagents, and wherein each plug comprises a different concentration of the same one or more reagents.

10. The kit of claim 6, wherein each plug in the linear array of fluid plugs comprises at least one solvent and at least one reagent, and wherein at least two plugs in the linear array comprise different reagents.

11. The kit of claim 6, wherein each plug in the linear array of fluid plugs comprises at least one solvent and at least one reagent, and wherein the linear array contains substances whose properties span a region of chemical space.

12. The kit of claim 6, wherein each plug in the linear array of fluid plugs comprises at least one solvent and at least one reagent, and wherein the linear array is suitable for conducting a crystallization screen.

13. The kit of claim 6, wherein every other plug in the linear array comprises at least one solvent and reagent, and the remaining plugs comprise at least one solvent and at least one marker.

14. The kit of claim 6, wherein the linear array of fluid plugs comprises at least 2 fluid plugs.

15. The kit of claim 6, wherein the linear array of fluid plugs comprises at least 10 fluid plugs.

16. The kit of claim 6, wherein each plug in the linear array of fluid plugs comprises at least 1000 fluid plugs.

17. The kit of claim 6, wherein each plug in the linear array of fluid plugs comprises about 0.001 fL to 10 mL of plug fluid.

18. The kit of claim 6, wherein each plug in the linear array of fluid plugs comprises less than about 10 M of reagent.

19. The kit of claim 6, wherein each plug is separated by a carrier.

20. The kit of claim 6, wherein at least two plugs in the linear array are separated by a spacer.

21. The kit of claim 6, wherein the spacer is a liquid, a gas, a gel or a solid.

22. The kit of claim 6, wherein the spacer is a liquid or a gas.

23. A combining component, comprising:

a first microchannel with an inlet and an outlet,

a second microchannel with a reagent inlet and one or more delivery channels in fluid communication with the first microchannel, wherein the delivery channels have substantially similar fluidic resistance.

24. The combining component of claim 23, wherein the inlet is configured for making a fluid connection with a holding component.

25. The combining component of claim 23, wherein the outlet is configured for making a fluid connection with a receiving component.

26. A microfluidic system, comprising:

at least one carrier fluid which comprises a fluorine-containing molecule;

one or more plugs of plug fluid separated by the carrier fluid, wherein the plug fluid is immiscible with the carrier; and

a surfactant that is substantially insoluble in the plug fluid and soluble in the carrier fluid.

27. A microfluidic system, comprising:

a holding component comprising at least one microchannel, wherein the holding component is suitable for storing and transporting an array of plugs comprising plugs of a plug fluid that are separated from one another by a carrier that is immiscible with the plug fluid; and

a combining component comprising (a) a first microchannel with an inlet and an outlet and (b) a second microchannel with a reagent inlet and one or more delivery channels in fluid communication with the first microchannel, wherein the delivery channels have substantially similar fluidic resistance;

wherein the holding component is detachable from the combining component.

28. The microfluidic system of claim 27, further comprising a loading component comprising at least one microchannel, wherein the loading component is suitable for forming the array.

29. The microfluidic system of claim 27, further comprising a receiving component comprising one or more microchannels, wherein the receiving component is suitable for manipulating the array.

30. A method comprising:

(a) introducing a linear array of plugs of a first plug fluid into a first microchannel within a microfluidic device with a first flow rate, wherein plugs of the first plug fluid are separated from each other either by a first carrier and/or by a spacer, and wherein the carrier and the spacer are immiscible with the plug fluid and with each other;

(b) introducing a stream of second plug fluid into a second microchannel within the microfluidic device with a second flow rate, wherein in the first and second microchannels are in fluid communication with each other; and

(c) merging at least one plug of first plug fluid with at least some second plug fluid to form a merged plug, wherein said merging occurs at one or more intersections of the first and second microchannels.

31. The method of claim 30, further comprising (d) monitoring the merged plug.

32. The method of claim 30, wherein the linear array of plugs of first plug fluid is introduced into the first microchannel by attaching a holding component comprising:

a third microchannel with two open ends, wherein at least one open end is configured for making a fluid connection with the first microchannel within the device; and

the linear array of plugs of first plug fluid.

33. The method of claim 30, wherein the second microchannel is split into multiple delivery channels that intersect the first microchannel.

34. A method comprising the steps of:

offering an inventory of reagents, carrier and plug fluids;

receiving from the customer a desired subset of reagents, a carrier and plug fluids, and

delivering a holding component to the customer that contains an array of plugs of plug fluids separated from each other with a carrier and/or spacer, wherein the carrier and the spacer are immiscible with the plug fluid and with each other, and where each plug contains an element of the desired subset of reagents.

35. The method of claim 34, further comprising the step of calculating a price for the subset of desired reagents.

36. A kit comprising:

a receiving component comprising a receiving microchannel with at least one open end, wherein the open end is configured for making a fluid connection with another microchannel and for receiving a linear array of fluid plugs; and

a measuring device for identifying the placement of a fluid plug within the first microchannel.

37. A kit comprising:

a combining component comprising (a) a first microchannel with an inlet and an outlet and (b) a second microchannel with a reagent inlet and one or more delivery channels in fluid communication with the first microchannel, wherein the delivery channels have substantially similar fluidic resistance; and

a pump.

38. The kit of claim 38, further comprising a reservoir configured to make a fluid connection with the reagent inlet of the second microchannel.

39. A receiving component comprising a first microchannel with at least one open end, wherein the open end is configured for making a fluid connection with another microchannel and wherein the first microchannel contains one or more physical marks for identifying the placement of a plug within the microchannel.