Fluorocarbon emulsion stabilizing surfactants

• US 9,498,761 B2
• Filed: 04/15/2015
• Issued: 11/22/2016
• Est. Priority Date: 08/07/2006
• Status: Active Grant

• Current Assignee: Bio-Rad Laboratories Incorporated, President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: Raindance Technologies Incorporated (Bio-Rad Laboratories Incorporated), President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Holtze, Christian, Weitz, David A., Hutchison, John Brian
• Primary Examiner(s): Buie-Hatcher, Nicole M
• Assistant Examiner(s): ASDJODI, MOHAMMADREZA
• Application Number:
  US14/687,388
• Publication Number:
  US 20150217246A1
• Time in Patent Office: 587 Days
• Field of Search: 435/120, 564/159, 516/27
• US Class Current: 1/1
• CPC Class Codes: C08G 2650/48 containing fluorine, e.g. perfluropolyethers
• CPC Class Codes: C08G 65/007 containing fluorine
• CPC Class Codes: C08G 65/332 containing carboxyl groups, or halides, or esters thereof
• CPC Class Codes: C08G 65/337 containing other elements organic compounds containing halogens only as halides of a carboxyl group C08G65/332
• CPC Class Codes: C08G 81/00 Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers involving only carbon-to-carbon unsaturated bond reactions C08F299/00 ; polyester-amides C08G69/44; polyester-imides C08G73/16; polyamides-imides C08G73/14; block- or graft polymers containing polysiloxane sequences C08G77/42
• CPC Class Codes: C08L 2201/52 Aqueous emulsion or latex, e.g. containing polymers of a glass transition temperature (Tg) below 20°C
• CPC Class Codes: C08L 2205/05 containing polymer components which can react with one another
• CPC Class Codes: C08L 71/00 Compositions of polyethers obtained by reactions forming an ether link in the main chain of polyacetals C08L59/00; of epoxy resins C08L63/00; of polythioether-ethers C08L81/02; of polyether-sulfones C08L81/06; Compositions of derivatives of such polymers
• CPC Class Codes: C09K 23/007 Organic compounds containing halogen
• CPC Class Codes: C09K 23/16 Amines or polyamines

Abstract

Surfactants (e.g., fluorosurfactants) for stabilizing aqueous or hydrocarbon droplets in a fluorophilic continuous phase are presented. In some embodiments, fluorosurfactants include a fluorophilic tail soluble in a fluorophilic (e.g., fluorocarbon) continuous phase, and a headgroup soluble in either an aqueous phase or a lipophilic (e.g., hydrocarbon) phase. The combination of a fluorophilic tail and a headgroup may be chosen so as to create a surfactant with a suitable geometry for forming stabilized reverse emulsion droplets having a disperse aqueous or lipophilic phase in a continuous, fluorophilic phase. In some embodiments, the headgroup is preferably non-ionic and can prevent or limit the adsorption of molecules at the interface between the surfactant and the discontinuous phase. This configuration can allow the droplet to serve, for example, as a reaction site for certain chemical and/or biological reactions. In another embodiment, aqueous droplets are stabilized in a fluorocarbon phase at least in part by the electrostatic attraction of two oppositely charged or polar components, one of which is at least partially soluble in the dispersed phase, the other at least partially soluble in the continuous phase. One component may provide colloidal stability of the emulsion, and the other may prevent the adsorption of biomolecules at the interface between a component and the discontinuous phase. Advantageously, surfactants and surfactant combinations of the invention may provide sufficient stabilization against coalescence of droplets, without interfering with processes that can be carried out inside the droplets.

Claims

1. A surfactant, comprising a block copolymer including a perfluorinated polyether (PFPE) block coupled to a polyethylene glycol (PEG) block via an amide bond, wherein the PFPE block comprises a formula of F(CF(CF₃)CF₂O)_x—

CF(CF₃)CONH—

, wherein x is an integer greater than or equal to 8; and

the PEG block comprises a formula of—

(C_nH_2n O)_y—

or —

(C_nH_2nO)_y—

CH₃, wherein n is a positive integer and y is an integer greater than or equal to 10.

2. The surfactant of claim 1, wherein the surfactant comprises one block of PFPE and one block of PEG.

3. The surfactant of claim 1, wherein the surfactant comprises two blocks of PFPE and one block of PEG.

4. A composition comprising the surfactant of claim 1.

5. The composition of claim 4, further comprising a hydrophobic liquid.

6. The composition of claim 4, further comprising an aqueous liquid.

7. The composition of claim 4, further comprising a fluorinated oil and an aqueous liquid.

8. The composition of claim 7, wherein the aqueous liquid additionally comprises biological molecules.

9. The composition of claim 8, wherein the biological molecules comprise nucleic acids.

20. A method of forming aqueous droplets, comprising:

providing a microfluidic device;

providing an aqueous liquid to the microfluidic device;

providing a fluorinated liquid to the microfluidic device;

providing a surfactant of claim 1, and

forming aqueous droplets in the fluorinated liquid in the presence of the surfactant.

10. A method of forming aqueous droplets, comprising:

providing a microfluidic device;

providing an aqueous liquid to the microfluidic device;

providing a fluorinated liquid to the microfluidic device;

providing a surfactant comprising a block copolymer that includes a perfluorinated polyether (PFPE) block coupled to a polyethylene glycol (PEG) block via an amide bond, and comprises a formula —

(C_nF_2nO)_x—

(C_mF_2m)_y—

CONH—

wherein n, m, x, and y are positive integers; and

forming aqueous droplets in the fluorinated liquid in the presence of the surfactant.

11. The method of claim 10, wherein the microfluidic device comprises a first channel intersecting a second channel at a junction.

12. The method of claim 11, wherein the aqueous liquid flows in the first channel and the fluorinated liquid flows in the second channel.

13. The method of claim 12, wherein the aqueous droplets are formed at the junction.

14. The method of claim 13, wherein the microfluidic device includes a nozzle, and the droplets form after the aqueous and fluorinated liquids pass through the nozzle.

15. The method of claim 10, wherein the aqueous droplets comprise biological molecules.

16. The method of claim 15, wherein the biological molecules comprise nucleic acids.

17. The method of claim 10, wherein the aqueous droplets comprise buffers, salts, nutrients, therapeutic agents, drugs, hormones, antibodies, analgesics, anticoagulants, anti-inflammatory compounds, antimicrobial compositions, cytokines, growth factors, interferons, lipids, polymers, polysaccharides, polypeptides, protease inhibitors, cells, RNA, DNA, vasoconstrictors, vasodilators, vitamins, minerals, or stabilizers.

18. The method of claim 10, wherein the aqueous droplets comprise fluorescent molecules.

19. The method of claim 10, wherein the surfactant comprises the formula —

(CF(CF₃)CF₂O)_x—

CF(CF₃)CONH—

, wherein x is greater than or equal to 8.