# US 11,077,415 B2 · Methods for forming mixed droplets

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- Number: US 11,077,415 B2
- Document ID: US11077415B2
- Status: Granted
- Kind: B2
- Application number: 16/181,256
- Filed: 2018-11-05
- Published: 2019-05-09
- Granted: 2021-08-03
- Earliest claimed: 2011-02-11
- Assignees: Bio-Rad Laboratories, Inc.
- Applicants: Bio-Rad Laboratories, Inc.
- Inventors: Yevgeny Yurkovetsky; Darren Roy Link; Jonathan William Larson
- Web page: https://patentgrep.com/patent/US11077415B2

## CPC

- B01F 33/3031: using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
- B01F 23/405: {Methods of mixing liquids with liquids (B01F23/4105 takes precedence)}
- B01F 23/451: by injecting one liquid into another
- B01F 25/14: {Mixing drops, droplets or bodies of liquid which flow together or contact each other (micromixers using where the materials to be mixed are in the form of droplets B01F33/302)}
- B01F 25/314: wherein additional components are introduced at the circumference of the conduit
- B01F 25/3141: {with additional mixing means other than injector mixers}
- 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 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}
- B01L 3/502784: {specially adapted for droplet or plug flow, e.g. digital microfluidics}
- B01L 7/525: {with physical movement of samples between temperature zones}
- B01F 2101/23: Mixing of laboratory samples e.g. in preparation of analysing or testing properties of materials
- B01L 2200/0652: Sorting or classification of particles or molecules
- B01L 2200/0673: Handling of plugs of fluid surrounded by immiscible fluid
- B01L 2300/0867: Multiple inlets and one sample wells, e.g. mixing, dilution
- B01L 2400/0415: electrical forces, e.g. electrokinetic
- B01L 2400/0487: fluid pressure, pneumatics
- B01F: MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING (mixing paints B44D3/06)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

## Abstract

The invention generally relates to methods for forming mixed droplets. In certain embodiments, methods of the invention involve forming a droplet, and contacting the droplet with a fluid stream, wherein a portion of the fluid stream integrates with the droplet to form a mixed droplet.

## Claims

### Claim 1

A microfluidic device comprising:
a substrate comprising at least a first channel, a second channel, and a merge area at a junction of the first channel with the second channel, the first channel comprising a droplet track configured to steer a droplet of a first fluid flowing therethrough away from a center streamline of the first channel and towards an emerging bolus of a second fluid on entering the merge area at the junction with the second channel to form a mixed droplet comprising the first fluid and the second fluid, wherein the microfluidic device does not include electrodes positioned to create an electric field in the junction.

### Claim 2 (depends on 1)

The microfluidic device of claim 1, wherein the first channel and the second channel are substantially perpendicular to each other.

### Claim 3 (depends on 1)

The microfluidic device of claim 1, wherein the first channel comprises at least one droplet comprising the first fluid.

### Claim 4 (depends on 3)

The microfluidic device of claim 3, wherein the first channel comprises an immiscible carrier fluid surrounding the droplet.

### Claim 5 (depends on 4)

The microfluidic device of claim 4, wherein the immiscible carrier fluid is an oil.

### Claim 6 (depends on 5)

The microfluidic device of claim 5, wherein the oil comprises a surfactant.

### Claim 7 (depends on 3)

The microfluidic device of claim 3, wherein the second channel comprises a fluid stream of the second fluid.

### Claim 8 (depends on 1)

The microfluidic device of claim 1, wherein the bolus protrudes into the first channel.

### Claim 9 (depends on 7)

The microfluidic device of claim 7, wherein the first fluid comprises nucleic acid templates.

### Claim 10 (depends on 9)

The microfluidic device of claim 9, wherein the second fluid comprises reagents for a polymerase chain reaction.

### Claim 11 (depends on 7)

The microfluidic device of claim 7, wherein the droplet comprises a single nucleic acid template.

### Claim 12 (depends on 7)

The microfluidic device of claim 7, wherein the second fluid comprises one or more of Taq polymerase, deoxynucleotides, and forward and reverse primers.