# US 10,118,173 B2 · Method and device for separating immiscible liquids to effectively isolate at least one of the liquids

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- Number: US 10,118,173 B2
- Document ID: US10118173B2
- Status: Granted
- Kind: B2
- Application number: 14/879,930
- Filed: 2015-10-09
- Published: 2016-04-14
- Granted: 2018-11-06
- Earliest claimed: 2014-10-09
- Assignees: Illumina, Inc.
- Applicants: Illumina, Inc.
- Inventors: Eric Hans Vermaas; Matthew Hage
- Web page: https://patentgrep.com/patent/US10118173B2

## CPC

- B01L 3/502784: {specially adapted for droplet or plug flow, e.g. digital microfluidics}
- B01D 17/02: Separation of non-miscible liquids
- B01D 17/0202: {by ab- or adsorption}
- B01D 17/0214: {with removal of one of the phases}
- B01D 17/085: {with membranes}
- B01D 63/088: {Microfluidic devices comprising semi-permeable flat membranes}
- B01D 69/02: characterised by their properties
- B01D 71/36: Polytetrafluoroethylene
- B01L 3/50255: {Multi-well filtration}
- B01D 2239/0428: Rendering the filter material hydrophobic
- B01D 2325/38: Hydrophobic membranes
- B01L 2200/0673: Handling of plugs of fluid surrounded by immiscible fluid
- B01L 2200/10: Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
- B01L 2300/0681: Filter
- B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions
- B01L 2300/12: Specific details about materials
- B01L 2300/165: Specific details about hydrophobic, oleophobic surfaces
- B01L 2400/0406: capillary forces
- B01L 2400/0409: centrifugal forces
- C12Q 1/6806: Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay (C12Q1/6804 takes precedence)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- 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

## Abstract

Method that includes providing a phase-separation device having a porous membrane with a filter surface. The filter surface has a non-planar contour that forms a receiving cavity. The method also includes providing a liquid mixture into the receiving cavity of the porous membrane. The liquid mixture includes a polar liquid and a non-polar liquid that are immiscible with respect to each other. The filter surface along the receiving cavity has a surface energy that impedes flow of the polar liquid through the filter surface and permit flow of the non-polar liquid into the porous membrane. The method also includes permitting the non-polar liquid to flow into the porous membrane. The polar liquid forms a droplet within the receiving cavity as the non-polar liquid flows into the porous membrane.

## Claims

### Claim 1

A phase-separation method comprising:
providing a phase-separation device including a porous membrane having a filter surface, the filter surface having a non-planar contour that forms a receiving cavity;
depositing a liquid mixture into the receiving cavity of the porous membrane, the liquid mixture including a polar liquid and a non-polar liquid that are immiscible with respect to each other, the filter surface along the receiving cavity configured to impede flow of the polar liquid through the filter surface and permit flow of the non-polar liquid into the porous membrane; and
permitting the non-polar liquid to flow into the porous membrane, the filter surface along the receiving cavity configured so that the polar liquid forms a droplet within the receiving cavity as the non-polar liquid flows into the porous membrane.

### Claim 2 (depends on 1)

The method of claim 1, wherein the polar liquid is denser than the non-polar liquid.

### Claim 3 (depends on 1)

The method of claim 1, wherein the filter surface is hydrophobic.

### Claim 4 (depends on 1)

The method of claim 1, wherein the filter surface contacts the liquid mixture at different depths of the receiving cavity.

### Claim 5 (depends on 1)

The method of claim 1, wherein at least a portion of the filter surface has a radius of curvature.

### Claim 6 (depends on 1)

The method of claim 1, wherein a majority of the filter surface has a slope that changes a depth of the receiving cavity at a linear rate.

### Claim 7 (depends on 1)

The method of claim 1, wherein the receiving cavity has a bottom representing a maximum depth of the receiving cavity, the filter surface having a slope that increases from the bottom to an access opening of the receiving cavity.

### Claim 8 (depends on 1)

The method of claim 1, wherein the receiving cavity has an access opening that is defined by a cavity edge, the receiving cavity having a maximum depth that is less than a maximum diameter of the access opening.

### Claim 9 (depends on 1)

The method of claim 1, wherein the receiving cavity has an access opening that is defined by a cavity edge, the receiving cavity having a maximum depth that is greater than a maximum diameter of the access opening.

### Claim 10 (depends on 1)

The method of claim 1, wherein the droplet forms a contact angle with respect to the filter surface, the contact angle being equal to or greater than 60°.

### Claim 11 (depends on 1)

The method of claim 1, wherein the porous membrane includes an absorption region that is positioned adjacent to the receiving cavity, the absorption region having a volume that is greater than a volume of the receiving cavity.

### Claim 12 (depends on 1)

The method of claim 1, wherein the porous membrane is defined between the filter surface and an outer surface, the outer surface permitting the non-polar liquid to flow out of the porous membrane.

### Claim 13 (depends on 1)

The method of claim 1, wherein the porous membrane comprises polytetrafluoroethylene (PTFE).

### Claim 14 (depends on 1)

The method of claim 1, wherein the porous membrane has a pore size that is between and 10 μm and 50 μm and wherein the porous membrane has a porosity that is between 40% and 70%.

### Claim 15 (depends on 1)

The method of claim 1, wherein at least 85% of the non-polar liquid is removed from the receiving cavity within 20 seconds.

### Claim 16 (depends on 1)

The method of claim 1, wherein a ratio of the corresponding volume of the non-polar liquid to the corresponding volume of the polar liquid is at least 5:1.

### Claim 17 (depends on 1)

The method of claim 1, wherein the phase-separation device includes a plurality of the receiving cavities and the step of depositing the liquid mixture includes depositing the liquid mixture into each of the receiving cavities, wherein the receiving cavities include a first receiving cavity and a second receiving cavity, the polar liquid of the liquid mixture in the first receiving cavity being different than the polar liquid of the liquid mixture in the second receiving cavity.

### Claim 18 (depends on 1)

The method of claim 1, wherein the phase-separation device includes a tube and the porous membrane is sized and shaped to be inserted into the tube.

### Claim 19 (depends on 1)

The method of claim 1, further comprising removing the liquid mixture from a digital fluidics (DF) device prior to depositing the liquid mixture.

### Claim 20 (depends on 19)

The method of claim 19, further comprising generating a biological sample utilizing the DF device, the biological sample being within the polar liquid of the liquid mixture.

### Claim 21 (depends on 20)

The method of claim 20, wherein the biological sample includes a library of fragmented nucleic acids.