Formation and control of fluidic species

• US 9,038,919 B2
• Filed: 10/07/2005
• Issued: 05/26/2015
• Est. Priority Date: 04/10/2003
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Link, Darren Roy, Weitz, David A., Marquez-Sanchez, Manuel, Cheng, Zhengdong
• Primary Examiner(s): BOECKMANN, JASON J
• Application Number:
  US11/246,911
• Publication Number:
  US 20060163385A1
• Time in Patent Office: 3,518 Days
• Field of Search: 239/3, 239/8, 239/704, 239/423, 239/424, 239/428, 239/10, 239/433, 239/434
• US Class Current: 239/3
• CPC Class Codes: B01F 2215/0431 Numerical size values, e.g. diameter of a hole or conduit, area, volume, length, width, or ratios thereof
• CPC Class Codes: B01F 25/45 Mixers in which the materials to be mixed are pressed together through orifices or interstitial spaces, e.g. between beads B01F25/44 takes precedence
• CPC Class Codes: B01F 33/3011 using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
• 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: B01F 33/3031 using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
• CPC Class Codes: B01J 2/04 in a gaseous medium if combined with suspending the material in a gas, e.g. fluidised beds B01J2/16
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/02 Drop detachment mechanisms of single droplets from nozzles or pins
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0424 Dielectrophoretic forces
• 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: B05B 5/03 characterised by the use of gas , e.g. electrostatically assisted pneumatic spraying B05B5/04, B05B5/043, B05B5/047 take precedence
• CPC Class Codes: B05B 7/061 with several liquid outlets discharging one or several liquids
• CPC Class Codes: B29B 2009/125 Micropellets, microgranules, microparticles
• CPC Class Codes: B29B 9/10 by moulding the material, i.e. treating it in the molten state

Abstract

This invention generally relates to systems and methods for the formation and/or control of fluidic species, and articles produced by such systems and methods. In some cases, the invention involves unique fluid channels, systems, controls, and/or restrictions, and combinations thereof. In certain embodiments, the invention allows fluidic streams (which can be continuous or discontinuous, i.e., droplets) to be formed and/or combined, at a variety of scales, including microfluidic scales. In one set of embodiments, a fluidic stream may be produced from a channel, where a cross-sectional dimension of the fluidic stream is smaller than that of the channel, for example, through the use of structural elements, other fluids, and/or applied external fields, etc. In some cases, a Taylor cone may be produced. In another set of embodiments, a fluidic stream may be manipulated in some fashion, for example, to create tubes (which may be hollow or solid), droplets, nested tubes or droplets, arrays of tubes or droplets, meshes of tubes, etc. In some cases, droplets produced using certain embodiments of the invention may be charged or substantially charged, which may allow their further manipulation, for instance, using applied external fields. Non-limiting examples of such manipulations include producing charged droplets, coalescing droplets (especially at the microscale), synchronizing droplet formation, aligning molecules within the droplet, etc. In some cases, the droplets and/or the fluidic streams may include colloids, cells, therapeutic agents, and the like.

Claims

1. A method of producing a plurality of droplets, comprising:

flowing a first liquid in a first microfluidic channel and a second liquid in a second microfluidic channel such that the first and the second liquids meet at a junction of the first and second microfluidic channels; and

producing a plurality of regularly-spaced, single-file droplets comprising the first liquid at the junction by applying an electric field to the first and second liquids as they meet at the junction, wherein the droplets are surrounded by the second liquid and flow within at least one of the microfluidic channels.

2. The method of claim 1, wherein said first liquid is an aqueous liquid and said second liquid is a liquid that is immiscible in said aqueous liquid.

3. The method of claim 1, wherein said droplets have an average diameter of less than about 60 microns.

4. The method of claim 1, wherein said first microfluidic channel and said second microfluidic channel are contained on a device comprising a location for expelling said droplets.

5. The method of claim 1, further comprising the step of conducting a reaction in said droplets.

6. The method of claim 1, wherein said first liquid forms a Taylor cone when expelled from an outlet in said first microfluidic channel.

7. The method of claim 6, wherein the first and second liquids flow through a dimensional restriction that stabilizes the Taylor cone.

8. The method of claim 1, wherein the droplets comprise a homogeneous distribution of diameters.