Multiphase systems and uses thereof

Patent metadata

Field	Value
Publication number	US-10732167-B2
Application number	US-201715657951-A
Country	US
Kind code	B2
Filing date	Jul 24, 2017
Priority date	Aug 20, 2010
Publication date	Aug 4, 2020
Grant date	Aug 4, 2020

Abstract

A multi-phase system includes a phase-separated solution comprising at least two phases, each phase having a phase component selected from the group consisting of a polymer, a surfactant and combinations thereof, wherein at least one phase comprises a polymer, wherein the phases, taken together, represent a density gradient. Novel two-phase, three-phase, four-phase, five-phase, or six-phase systems are disclosed. Using the disclosed multi-phase polymer systems, particles, or other analyte of interest can be separated based on their different densities or affinities.

First claim

The invention claimed is:

1. A method of analyzing or separating a sample comprising:
providing a phase-separated system comprising at least two phases, wherein
a) the at least two phases each comprises a phase component selected from the group consisting of a polymer, a surfactant and combinations thereof, wherein at least one phase comprises a polymer;
each said phase has an upper and a lower phase boundary; and
each of the two or more phases has a different density and the phases, taken together, represent a density gradient; and

b) introducing a sample comprising one or more analytes of interest to the phase-separated system without disrupting the phase boundaries of the phase-separated solution; and
c) allowing each of the analytes to migrate to a location in the phase-separated system that is characteristic of its density, wherein during migration the sample contacts one or more of the two or more phases sequentially;
wherein the phase-separated system is supported along a filament or on a sheet.

2. The method of claim 1 , wherein greater than 80% of the analyte is located at one or more of the phase boundaries.

3. The method of claim 1 , wherein greater than 90% of the analyte is located at one or more of the phase boundaries.

4. The method of claim 1 , wherein the sample comprises a plurality of analytes and each analyte migrates to a different location in the phase-separated system.

5. The method of claim 1 , wherein after migration, the analyte resides at a boundary location.

6. The method of claim 1 , wherein the boundary location is at an interface between a phase with a density greater than the density of the analyte and a phase with a density that is less than the density of the analyte.

7. The method of claim 1 , wherein after migration, the analyte resides within a phase of the phase-separated system whose density matches the density of the analyte.

8. The method of claim 1 , wherein the phase-separated system is centrifuged to accelerate migration of the analyte.

9. The method of claim 1 , wherein the analyte migrates under gravitational forces.

10. The method of claim 1 , wherein the analyte migrates under buoyancy forces.

11. The method of claim 1 , wherein the phase-separated system is provided as dispersion or emulsion in another carrier phase.

12. The method of claim 1 , wherein the analyte of interest has a size of more than 200 nm.

13. The method of claim 1 , wherein after analyte migration the phases and the analyte are in thermodynamic equilibrium.

14. The method of claim 1 , wherein the phase separated system comprises three or more phases.

15. The method of claim 1 , wherein the two or more phases comprise a common solvent which is an aqueous solvent.

16. The method of claim 1 , wherein the two or more phases comprise a common solvent which is an organic solvent.

17. The method of claim 1 , wherein the two or more phases comprise a common solvent which is a non-aqueous solvent selected from the groups consisting of liquid polymer, non-polar organic solvent, polar aprotic or protic solvent, supercritical fluid, fuel, oils, and fluorinated solvents, and combinations thereof.

18. The method of claim 17 , wherein the common solvent comprises dichloromethane.

19. The method of claim 1 , wherein the phase separated system comprises three or more phases including the two or more phases comprising a common solvent which is water and additional phase separated phases selected from the group consisting of organic solutions.

20. The method of claim 15 , wherein the aqueous solvent is selected from the group consisting of water, sea water, isotopes of water, buffered water, irrigation water, mine effluent, colloidal solutions, emulsions, and a combination thereof.

21. The method of claim 1 , wherein the analyte is selected from the group consisting of solid particles, an aggregate of particles, a liquid or gel immiscible in the solvent, a liquid crystal, and crystalline materials.

22. The method of claim 1 , wherein the analyte is selected from the group consisting of gem, bead, metal, glass, rock, mineral, crystal, plastic, bone, rubber, paper, fabric, coal, polymer particles, and gases.

23. The method of claim 1 , wherein the polymer is selected from the group consisting of homopolymers, random copolymers, block copolymers, graft copolymers, ter-polymers, dendrimers, star polymers and combinations thereof.

24. The method of claim 23 , wherein the polymer is linear, branched and/or cross-linked.

25. The method of claim 1 , wherein the polymer is selected from the group consisting of dextran, dextran sulfate, chondroitin sulfate A, polysucrose, diethylaminoethyl-dextran, poly(2-vinylpyridine-N-oxide), polysucrose, poly(vinyl alcohol), poly(2-ethyl-2-oxazoline), poly(methacrylic acid), poly(ethylene glycol), polyacrylamide, polyethyleneimine, hydroxyethyl cellulose, polyvinylpyrrolidone, carboxy-polyacrylamide, poly(acrylic acid), poly(2-acrylamido-2-methyl-1-propanesulfonic acid), poly(diallyldimethyl ammonium chloride), poly(styrene sulfonic acid), polyallylamine, alginic acid, poly(bisphenol A carbonate), polydimethylsiloxane, polystyrene, poly(4-vinylpyridine), polycaprolactone, polysulfone, poly(methyl methacrylate-co-methacrylic acid), poly(methyl methacrylate), poly(tetrahydrofuran), poly(propylene glycol), and poly(vinyl acetate) and copolymers or terpolymers thereof.

26. The method of claim 1 , wherein the surfactant is selected from the group consisting of polysorbate, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, polyoxyethylene-polyoxypropylene, 1-O-octyl-β-D-glucopyranoside, nonylphenol polyoxyethylene, 4-(1,1,3,3-Tetramethylbutyl)phenyl-polyethylene glycol, 2-(Perfluoroalkyl)ethyl methacrylate, N,N-dimethyldodecylamine N-oxide, polyethylene glycol dodecyl ether, sodium dodecyl sulfate, sodium cholate, benzylalkonium chloride and dodecyltrimethylammonium chloride.

27. The method of claim 1 , wherein one or more phases further comprise an additive selected from the group consisting of a co-solvent, an acid, a base, a miscible polymer, vitamin, drug, antibiotic, small molecule, dye, and fluorophore.

28. The method of claim 1 , wherein the sample is selected from the group consisting of a forensics study sample, a sample indicative of animal health, a sample indicative of human identity used for border control, homeland security, or intelligence, a sample from food processing, a sample indicative of product quality, a sample indicative of environmental safety, a sample containing different crystal polymorphs, and a combination thereof.

29. The method of claim 1 , further comprising collecting the analyte from the boundary location.

Assignees

• Harvard College

Inventors

• Mace Charles R
• Halatci Ozge Akbulut
• Kumar Ashok A
• Shapiro Nathan D
• Whitesides George M

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• B03D3/00

  Differential sedimentation · CPC title

• G01N33/491 Primary

  by separating the blood components (G01N15/05 takes precedence) · CPC title

• B03B5/442

  composition of heavy media · CPC title

• B03B5/28

  by sink-float separation · CPC title