Method and device for separating immiscible liquids to effectively isolate at least one of the liquids

• US 10,118,173 B2
• Filed: 10/09/2015
• Issued: 11/06/2018
• Est. Priority Date: 10/09/2014
• Status: Active Grant

• Current Assignee: Illumina Incorporated
• Original Assignee: Illumina Incorporated
• Inventors: Vermaas, Eric Hans, Hage, Matthew
• Primary Examiner(s): Sines, Brian J.
• Application Number:
  US14/879,930
• Publication Number:
  US 20160101420A1
• Time in Patent Office: 1,124 Days
• Field of Search: 422 681, 422502, 422503, 422504, 422534, 436 43, 436177, 436180, 436175, 436178, 210644, 210645, 210649, 210650
• CPC Class Codes: B01D 17/02 Separation of non-miscible liquids
• CPC Class Codes: B01D 17/0202 by ab- or adsorption
• CPC Class Codes: B01D 17/0214 with removal of one of the phases
• CPC Class Codes: B01D 17/085 with membranes
• CPC Class Codes: B01D 2239/0428 Rendering the filter material hydrophobic
• CPC Class Codes: B01D 2325/38 Hydrophobic membranes
• CPC Class Codes: B01D 63/088 Microfluidic devices comprising semi-permeable flat membranes
• CPC Class Codes: B01D 69/02 characterised by their properties
• CPC Class Codes: B01D 71/36 Polytetrafluoroethene
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/12 Specific details about materials
• CPC Class Codes: B01L 2300/165 Specific details about hydrophobic, oleophobic surfaces
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 3/50255 Multi-well filtration
• 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: C12Q 1/6806 Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence

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

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.

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

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

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

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

6. 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.

7. 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.

8. 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.

9. 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.

10. 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°

.

11. 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.

12. 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.

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

14. The method of claim 1, wherein the porous membrane has a pore size that is between and 10 μ

m and 50 μ

m and wherein the porous membrane has a porosity that is between 40% and 70%.

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

16. 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.

17. 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.

18. 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.

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

20. 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.

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