# US 2014/0154695 A1 · Manipulating droplet size

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- Number: US 2014/0154695 A1
- Document ID: US20140154695A1
- Status: Published application
- Kind: A1
- Application number: 14/173,974
- Filed: 2014-02-06
- Published: 2014-06-05
- Earliest claimed: 2011-07-20
- Assignees: Raindance Technologies, Inc.
- Applicants: Raindance Technologies, Inc.
- Inventors: Benjamin J. Miller; Qun Zhong; Darren Roy Link
- Web page: https://patentgrep.com/patent/US20140154695A1

## CPC

- C12Q 1/6806: Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay (C12Q1/6804 takes precedence)
- B01F 23/41: Emulsifying
- 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
- B01F 35/2213: {Pressure}
- B01L 3/502761: {specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules}
- B01L 3/502784: {specially adapted for droplet or plug flow, e.g. digital microfluidics}
- B05B 1/02: designed to produce a jet, spray, or other discharge of particular shape or nature, e.g. in single drops, {or having an outlet of particular shape}(B05B1/26, B05B1/28, B05B1/34 take precedence)
- B05B 1/08: of pulsating nature, e.g. delivering liquid in successive separate quantities
- B05B 1/26: with means for mechanically breaking-up or deflecting the jet after discharge, e.g. with fixed deflectors; Breaking-up the discharged liquid or other fluent material by impinging jets
- B05B 7/0012: {Apparatus for achieving spraying before discharge from the apparatus}
- B01L 7/525: {with physical movement of samples between temperature zones}
- B01L 2200/025: Align devices or objects to ensure defined positions relative to each other
- B01L 2200/0647: Handling flowable solids, e.g. microscopic beads, cells, particles
- B01L 2200/141: Preventing contamination, tampering
- B01L 2200/143: Quality control, feedback systems
- B01L 2200/148: Specific details about calibrations
- B01L 2300/0867: Multiple inlets and one sample wells, e.g. mixing, dilution
- B01L 2300/14: Means for pressure control
- B01L 2400/0487: fluid pressure, pneumatics
- Y10T 436/2575: Volumetric liquid transfer
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- B01F: MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING (mixing paints B44D3/06)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B05B: SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES (spray-mixers with nozzles B01F25/72; processes for applying liquids or other fluent materials to surfaces by spraying B05D)
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

The invention generally relates to methods and systems for manipulating droplet size. In certain aspects, the invention provides methods for manipulating droplet size that include forming droplets of aqueous fluid surrounded by an immiscible carrier fluid, and manipulating droplet size during the forming step by adjusting pressure exerted on the aqueous fluid or the carrier fluid.

## Claims

### Claim at position 1

1-17. (canceled)

### Claim 18

A microfluidic apparatus comprising:
a plurality of microfluidic circuits, each circuit comprising:
a first fluid channel comprising a first resistance and a first fluid;
a second fluid channel, comprising a second resistance and a second fluid that is immiscible with the first fluid;
a junction where the first fluid channel and the second fluid channel meet such that a plurality of droplets are formed; and
an outlet channel that exits the junction and receives the droplets;
wherein the first and second resistances of the microfluidic circuits are configured such that variation in pressure exerted on the first fluid in each circuit results in a change in flow rate of the second fluid and a change in a dimension of the droplets.

### Claim 19 (depends on 18)

The microfluidic apparatus of claim 18, wherein the change in flow rate of the second fluid is an inverse change to the variation in pressure of the first fluid.

### Claim 20 (depends on 18)

The microfluidic apparatus of claim 18, wherein the droplets flow in the second fluid through the outlet channel.

### Claim 21 (depends on 18)

The microfluidic apparatus of claim 18, wherein the change in dimension of the droplets allows for control of coalescence of the droplets from a first microfluidic circuit with droplets from a second microfluidic circuit.

### Claim 22 (depends on 18)

The microfluidic apparatus of claim 18, wherein the junction comprises a nozzle.

### Claim 23 (depends on 18)

The microfluidic apparatus of claim 18, wherein the outlet channel from each of the microfluidic circuits connects to the same main channel.

### Claim 24 (depends on 23)

The microfluidic apparatus of claim 23, wherein the main channel connects to one or more analysis modules.

### Claim 25 (depends on 24)

The microfluidic apparatus of claim 24, wherein the analysis modules comprise a merging module, an amplification module, a detection module, and a sorting module.

### Claim 26 (depends on 18)

The microfluidic apparatus of claim 18, wherein the first fluids in the microfluidic circuits are different from each other.

### Claim 27 (depends on 18)

The microfluidic apparatus of claim 18, wherein the first fluids in the microfluidic circuits are the same.

### Claim 28 (depends on 18)

The microfluidic apparatus of claim 18, wherein the variation in pressure is exerted on the first fluid in all of the microfluidic circuits independently.

### Claim 29

A microfluidic apparatus comprising:
a plurality of microfluidic circuits each configured to produce droplets; and
a regulator operably associated with each microfluidic circuit that controls pressure exerted on a first fluid that causes a change in flow rate of a second fluid, and adjusts a dimension of the droplets from each microfluidic circuit.

### Claim 30 (depends on 29)

The microfluidic apparatus of claim 29, wherein each microfluidic circuit comprises:
a first fluid channel comprising a first resistance and the first fluid;
a second fluid channel comprising a second resistance and the second fluid that is immiscible with the first fluid;
a junction where the first fluid channel and the one or more second fluid channels meet such that a plurality of the droplets are formed; and
an outlet channel that exits the junction and receives the droplets;
wherein the first and second resistances of the microfluidic circuits are configured such that variation in pressure exerted on the first fluid in each circuit results in the change in flow rate of the second fluid and a change in the dimension of the droplets.

### Claim 31 (depends on 29)

The microfluidic apparatus of claim 29, wherein the pressure regulator associated with each circuit controls pressure exerted on the first fluid in each microfluidic circuit.

### Claim 32 (depends on 29)

The microfluidic apparatus of claim 29, wherein a second pressure regulator controls pressure exerted on the second fluid in all of the microfluidic circuits.

### Claim 33 (depends on 29)

The microfluidic apparatus of claim 29, further comprising a pressure source that provides pressure exerted on the first fluid in the microfluidic circuits.

### Claim 34 (depends on 33)

The microfluidic apparatus of claim 33, wherein the pressure source provides pressure exerted on the second fluid in the microfluidic circuits.

### Claim 35 (depends on 30)

The microfluidic apparatus of claim 30, wherein the junction comprises a nozzle.

### Claim 36 (depends on 30)

The microfluidic apparatus of claim 30, wherein the outlet channel from each of the microfluidic circuits connects to the same main channel.

### Claim 37 (depends on 36)

The microfluidic apparatus of claim 36, wherein the main channel connects to one or more analysis modules.

### Claim 38 (depends on 37)

The microfluidic apparatus of claim 37, wherein the analysis modules comprise a merging module, an amplification module, a detection module, and a sorting module.