SURFACTANT

Abstract

A surfactant of formula (I):

A-(L.sub.1).sub.a-(C.sub.2).sub.b-(L.sub.2).sub.c-X (I)

wherein

A is a perfluoropolyether;

L.sub.1 is CONR', wherein R is selected from H and C.sub.1-6 alkyl;

a is 0 or 1;

b is 0 or an integer between 1 and 10;

L.sub.2 is a linking group;

c is 0 or 1; and

X is a charged group.

Claims

1. A surfactant of formula (I):
A-(L.sub.1).sub.a-(CH.sub.2).sub.b-(L.sub.2).sub.c-X (I) wherein A is a perfluoropolyether; L.sub.1 is CONR, wherein R is selected from H and C.sub.1-6 alkyl; a is 0 or 1; b is 0 or an integer between 1 and 10; L.sub.2 is a linking group; c is 0 or 1; and X is a charged group.

2. A surfactant as claimed in claim 1, wherein said perfluoropolyether comprises any one of (a) a repeat unit of the formula [CF(CF.sub.3)CF.sub.2O].sub.m, wherein m is a positive integer, (b) a unit of the formula [CF.sub.2CF.sub.2O].sub.n[CF (CF.sub.3)CF.sub.2O].sub.m, wherein m and n are each 0 or a positive integer, with the proviso that m and n are not both 0; and (c) CF.sub.3CF.sub.2CF.sub.2O[CF(CF.sub.3)CF.sub.2O].sub.mCF(CF.sub.3), wherein m is a positive integer.

3. (canceled)

4. (canceled)

5. A surfactant as claimed in claim 2, wherein m is an integer from 1 to 100.

6. A surfactant as claimed in claim 1, wherein a is 0.

7. A surfactant as claimed in claim 1, wherein a is 1 and L.sub.1 is CONH or CONCH.sub.3.

8. A surfactant as claimed in claim 1, wherein b is an integer from 1 to 10, more preferably 2 to 3.

9. A surfactant as claimed in claim 1, wherein c is 0.

10. A surfactant as claimed in claim 1, wherein X is a positively charged group.

11. A surfactant as claimed in claim 10, wherein X is selected from: a) any one of ##STR00057## wherein R.sup.1 and R.sup.2 are independently selected from H and C.sub.1-6 alkyl, preferably methyl; R.sup.3 is selected from C.sub.1-6 alkyl, and (CH.sub.2).sub.dO(CH.sub.2CH.sub.2O).sub.eR.sup.x, wherein R.sup.x is H or C.sub.1-6 alkyl, d is a positive integer from 2 to 6, and each e is 0 or a positive integer from 1 to 100, preferably 5 to 50 and more preferably 10 to 30; R.sup.4 is selected from C.sub.1-6 alkyl; and W.sup. is a counter ion; b) X comprises ##STR00058## wherein R.sup.1 and R.sup.2 are inde endentl selected from H and C.sub.1-6 alkyl, preferably methyl; R.sup.4 is selected from C.sub.1-6 alkyl; and W.sup. is a counter ion; and d) any one of ##STR00059## wherein R.sup.1 and R.sup.2 are inde endentl selected from H and C.sub.1-6 alkyl, preferably methyl; R.sup.4 is selected from C.sub.1-6 alkyl; Z is selected from an organic group and (CH.sub.2).sub.rO(CH.sub.2CH.sub.2O).sub.a(CH.sub.2).sub.sY-(L.sub.2).sub.c-(CH.sub.2).sub.b-(L.sub.1).sub.a-A, wherein r is a positive integer from 2 to 6, g is 0 or a positive integer, s is 0 or a positive integer from 2 to 6, Y is as defined as X in subpart b) above, and L.sub.2, L.sub.1, A, c, b and a are as defined in claim 1; and W.sup. is a counter ion.

12. (canceled)

13. (canceled)

14. (canceled)

15. A surfactant as claimed in claim 1, wherein said surfactant is selected from: ##STR00060## ##STR00061## wherein m is preferably an integer from 1 to 100 (e.g. 1 to 50), more preferably an integer from 5 to 50 and particularly preferably an integer from 10 to 25, e is 0 or a positive integer from 1 to 100, preferably 5 to 50 and still more preferably 10 to 30; and g is 0 or a positive integer from 1-100, preferably 5 to 50 and still more preferably 10 to 30.

16. A surfactant as claimed in claim 1, wherein X comprises a zwitterionic group.

17. A surfactant as claimed in claim 16, wherein X is selected from: a) ##STR00062## wherein R.sup.5 is selected from H and C.sub.1-6 alkyl; R.sup.6 is an C.sub.1-6 alkyl group substituted by a COO.sup. or SO.sub.3.sup. group; and R.sup.7 is selected from H, C.sub.1-6 alkyl, and (CH.sub.2).sub.dO(CH.sub.2CH.sub.2O).sub.e0R.sup.x, wherein R.sup.x is independently H or C.sub.1-6 alkyl, d is a positive integer from 2 to 6, and e is 0 or a positive integer from 1 to 100, preferably 5 to 50 and more preferably 10 to 30; or R.sup.5 and R.sup.6 are each independently selected from H and C.sub.1-6 alkyl; and R.sup.7 is (CH.sub.2).sub.o(CHQ)(CH.sub.2).sub.p(H.sup.x),(CH.sub.2CH.sub.2O).sub.4R.sup.x wherein Q is a COO.sup. or SO.sub.3.sup. group, H.sup.x is S or SO.sub.2, each of o and p is 0 or an integer from 1 to 6 with the proviso that both of o and p cannot be 0, q is 1 or 0, R.sup.x is independently H or C.sub.1-6 alkyl, and e is 0 or a positive integer from 1 to 100, preferably 5 to 50 and more preferably 10 to 30; b) X comprises ##STR00063## wherein R.sup.5 is selected from H and C.sub.1-6 alkyl; and R.sup.6 is an alkyl group substituted by a COO.sup. or SO.sub.3.sup. group; or ##STR00064## wherein R.sup.5 and R.sup.6 are each independently selected from H and C.sub.1-6 alkyl; Q is a COO.sup. or SO.sub.3.sup. group; H.sup.x is S or SO.sub.2; each of o and p is 0 or an integer from 1 to 6, with the proviso that both of o and p cannot be 0; q is 1 or 0; g is 0 or a positive integer from 1 to 100; and s is 0 or a positive integer from 2 to 6; c) ##STR00065## wherein R.sup.5 is selected from H and C.sub.1-6 alkyl; R.sup.6 is an alkyl group substituted by a COO.sup. or SO.sub.3.sup. group; and Z is selected from an organic group and (CH.sub.2).sub.rO(CH.sub.2CH.sub.2O).sub.g(CH.sub.2).sub.sY-(L.sub.2).sub.c-(CH.sub.2).sub.b-(L.sub.1).sub.a-A, wherein r is a positive integer from 2 to 6, g is 0 or a positive integer, s is 0 or a positive integer from 2 to 6, Y is as defined as X in subpart b) above, and L.sub.2, L.sub.1, A, c, b and a are as defined in claim 1.

18. (canceled)

19. (canceled)

20. (canceled)

21. A surfactant as claimed in claim 17, wherein said surfactant is selected from: ##STR00066## wherein m is preferably an integer from 1 to 100 (e.g. 1 to 50), more preferably an integer from 5 to 50 and particularly preferably an integer from 10 to 25, e is 0 or a positive integer, more preferably a positive integer from 1 to 100, still more preferably 5 to 50 and yet more preferably 10 to 30; and g is 0 or a positive integer from 1-100, preferably 5 to 50 and still more preferably 10 to 30.

22. A surfactant as claimed in claim 1, wherein X comprises a negatively charged group.

23. A surfactant as claimed in claim 22, wherein X is selected from: a) any one of ##STR00067## wherein R.sup.8 is selected from H, C.sub.1-6 alkyl and (CH.sub.2).sub.dO(CH.sub.2CH.sub.2O).sub.eR.sup.x, wherein R.sup.x is independently H or C.sub.1-6 alkyl, d is a positive integer from 1 to 6, and e is a positive integer from 1 to 100, preferably 5 to 50 and more preferably 10 to 30; and W.sup.+ is a counter ion; b) X comprises ##STR00068## wherein W.sup.+ is a counter ion; and c) ##STR00069## wherein Z is selected from an organic group, (CH.sub.2),O(CH.sub.2CH.sub.2O).sub.g(CH.sub.2).sub.sY-(L.sub.2).sub.c(CH.sub.2).sub.b-(L.sub.1),-A; and (CH.sub.2).sub.tCH.sub.u[(CH.sub.2).sub.rO(CH.sub.2CH.sub.2O).sub.gR.sup.x].sub.w[(CH.sub.2).sub.tY-(L.sub.2).sub.c-(CH.sub.2).sub.b-(L.sub.1).sub.a-A].sub.y, wherein r is a positive integer from 2 to 6, t is a positive integer from 1 to 6, u is 0 or 1, w and y are each 1 or 2, the sum of u, w and y equals to 3, g is 0 or a positive integer, s is 0 or a positive integer from 2 to 6, R.sup.x is independently H or C.sub.1-6 alkyl, Y is as defined as X in subpart b) above, and L.sub.2, L.sub.1, A, c, b and a are as defined in claim 1; and W+ is a counter ion.

24. (canceled)

25. (canceled)

26. (canceled)

27. A surfactant as claimed in claim 23, wherein said surfactant is selected from: ##STR00070## wherein m is preferably an integer from 1 to 100 (e.g. 1 to 50), more preferably an integer from 5 to 50 and particularly preferably an integer from 10 to 25, e is 0 or a positive integer, more preferably a positive integer from 1 to 100, still more preferably 5 to 50 and yet more preferably 10 to 30; and g is 0 or a positive integer from 1-100, preferably 5 to 50 and still more preferably 10 to 30.

28. A surfactant as claimed in claim 1, wherein said surfactant is of formula (I), wherein X is selected from: ##STR00071## wherein R.sup.1 and R.sup.2 are independently selected from H and C.sub.1-6 alkyl, preferably methyl; R.sup.3 is selected from C.sub.1-6 alkyl, and (CH.sub.2).sub.dO(CH.sub.2CH.sub.2O).sub.eR.sup.x, wherein R.sup.x is H or C.sub.1-6 alkyl, d is a positive integer from 2 to 6, and each e is 0 or a positive integer from 1 to 100, preferably 5 to 50 and more preferably 10 to 30; R.sup.4 is selected from C.sub.1-6 alkyl; R.sup.5 is selected from H and C.sub.1-6 alkyl; R.sup.6 is an C.sub.1-6 alkyl group substituted by a COO.sup. or SO.sub.3.sup. group; and R.sup.7 is selected from H, C.sub.1-6 alkyl, and (CH.sub.2).sub.dO(CH.sub.2CH.sub.2O).sub.eR.sup.x, wherein R.sup.x is independently H or C.sub.1-6 alkyl, d is a positive integer from 2 to 6, and e is 0 or a positive integer from 1 to 100, preferably 5 to 50 and more preferably 10 to 30; or R.sup.5 and R.sup.6 are each independently selected from H and C.sub.1-6 alkyl; and R.sup.7 is (CH.sub.2).sub.o(CHQ) (CH.sub.2).sub.p(H.sup.x).sub.q(CH.sub.2CH.sub.2O).sub.eR.sup.x wherein Q is a COO.sup. or SO.sub.3.sup. group, H.sup.x is S or SO.sub.2; each of o and p is 0 or an integer from 1 to 6 with the proviso that both of o and p cannot be 0, q is 1 or 0, R.sup.x is independently H or C.sub.1-6 alkyl, and e is 0 or a positive integer from 1 to 100, preferably 5 to 50 and more preferably 10 to 30; R.sup.8 is selected from H, C.sub.1-6 alkyl and (CH.sub.2).sub.dO(CH.sub.2CH.sub.2O).sub.eR.sup.x, wherein R.sup.x is independently H or C.sub.1-6 alkyl, d is a positive integer from 2 to 6, and e is a positive integer from 1 to 100; preferably 5 to 50 and more preferably 10 to 30; and W.sup. and W+ are counter ions.

29. A surfactant as claimed in claim 1, wherein said surfactant is of formula (Ia),
A-(L.sub.1).sub.a-(CH.sub.2).sub.b-(L.sub.2).sub.c-XBX-(L.sub.2).sub.c-(CH.sub.2).sub.b-(L.sub.1).sub.a-A (Ia) wherein: A is a perfluoropolyether; B is a polyalkylene oxide unit; each L.sub.1 is independently CONR, wherein R is selected from H and C.sub.1-6 alkyl; each a is independently 0 or 1; each b is independently 0 or an integer between 1 and 6; each L.sub.2 is independently a linking group; each c is independently 0 or 1; and each X is independently selected from: ##STR00072## wherein R.sup.1 and R.sup.2 are independently selected from H and C.sub.1-6 alkyl, preferably methyl; R.sup.4 is selected from C.sub.1-6 alkyl; R.sup.5 is selected from H and C.sub.1-6 alkyl; R.sup.6 is an alkyl group substituted by a COO.sup. or SO.sub.3.sup. group; and W.sup. and W+ are counter ions.

30. A method for making a surfactant of formula (I),
A-(L.sub.1).sub.a-(CH.sub.2).sub.b-(L.sub.2).sub.c-X (I) wherein A is a perfluoropolyether; L.sub.1 is CONR, wherein R is selected from H and C.sub.1-6 alkyl; a is 0 or 1; b is 0 or an integer between 1 and 6; L.sub.2 is a linking group; c is 0 or 1; and X is ##STR00073## wherein R.sup.1 and R.sup.2 are independently selected from H and C.sub.1-6 alkyl, preferably methyl; R.sup.3 is selected from C.sub.1-6 alkyl and (CH.sub.2).sub.dO(CH.sub.2CH.sub.2O).sub.eR.sup.x, wherein R.sup.x is H or C.sub.1-6 alkyl, d is a positive integer from 2 to 6, and e is 0 or a positive integer from 1 to 100, preferably 5 to 50 and more preferably 10 to 30; R.sup.4 is selected from C.sub.1-6 alkyl; and W.sup. is a counter ion, comprising: reacting a compound of formula (a): A-(L.sub.1).sub.a-(CH.sub.2).sub.b-(L.sub.2).sub.c-X (a) wherein A is a perfluoropolyether; L.sub.1 is CONR, wherein R is selected from H and C.sub.1-6 alkyl; a is 0 or 1; b is 0 or an integer between 1 and 6; L.sub.2 is a linking group; c is 0 or 1; and X is: ##STR00074## wherein R.sup.1 and R.sup.2 are independently selected from H and C.sub.1-6 alkyl, preferably methyl; and R.sup.4 is selected from C.sub.1-6 alkyl; with R.sup.3-W, wherein R.sup.3 is selected from C.sub.1-6 alkyl, and (CH.sub.2).sub.dO(CH.sub.2CH.sub.2O).sub.eR.sup.x, wherein R.sup.x is H or C.sub.1-6 alkyl, d is a positive integer from 2 to 6, and e is 0 or a positive integer from 1 to 100, preferably 5 to 50 and more preferably 10 to 30; or with W(CH.sub.2),O(CH.sub.2CH.sub.2O).sub.g(CH.sub.2).sub.sW, wherein r is a positive integer from 2 to 6, g is 0 or a positive integer (e.g. 1 to 100), s is 0 or a positive integer from 2 to 6; and W is a leaving group,

31. A method for making a surfactant of formula (I),
A-(L.sub.1).sub.a-(CH.sub.2).sub.b-(L.sub.2).sub.c-X (I) wherein A is a perfluoropolyether; L.sub.1 is CONR, wherein R is selected from H and C.sub.1-6 alkyl; a is 0 or 1; b is 0 or an integer between 1 and 6; L.sub.2 is a linking group; c is 0 or 1; and X is ##STR00075## wherein R.sup.5 is selected from H and C.sub.1-6 alkyl; R.sup.6 is an C.sub.1-6 alkyl group substituted by a COO.sup. or SO.sub.3.sup. group; R.sup.7 is selected from H, C.sub.1-6 alkyl and (CH.sub.2).sub.dO(CH.sub.2CH.sub.2O).sub.eR.sup.x, wherein R.sup.x is independently H or C.sub.1-6 alkyl, d is a positive integer from 2 to 6, and e is 0 or a positive integer from 1 to 100, preferably 5 to 50 and more preferably 10 to 30; and Z is (CH.sub.2).sub.rO(CH.sub.2CH.sub.2O).sub.g(CH.sub.2).sub.sY-(L.sub.2).sub.c-(CH.sub.2).sub.b-(L.sub.1).sub.a-A, wherein r is a positive integer from 2 to 6, g is 0 or a positive integer, s is 0 or a positive integer from 2 to 6, Y is ##STR00076## wherein R.sup.5 is selected from H and C.sub.1-6 alkyl; and R.sup.6 is an alkyl group substituted by a COO.sup. or SO.sub.3.sup. group; or ##STR00077## wherein R.sup.5 and R.sup.6 are each independently selected from H and C.sub.1-6 alkyl; Q is a COO.sup. or SO.sub.3.sup. group; H.sup.x is S or SO.sub.2; each of o and p is 0 or an integer from 1 to 6, with the proviso that both of o and p cannot be 0; q is 1 or 0; g is 0 or a positive integer from 1 to 100; and s is 0 or a positive integer from 2 to 6, and L.sub.2, L.sub.1, A, c, b and a are as defined in claim 1, comprising: reacting a compound of formula (a): A-(L.sub.1).sub.a-(CH.sub.2).sub.b-(L.sub.2).sub.c-X (a) wherein A is a perfluoropolyether; L.sub.1 is CONR, wherein R is selected from H and C.sub.1-6 alkyl; a is 0 or 1; b is 0 or an integer between 1 and 6; L.sub.2 is a linking group; c is 0 or 1; and X is: ##STR00078## wherein R.sup.5 is selected from H and C.sub.1-6 alkyl; and .sup.7 is selected from H, C.sub.1-6 alkyl, (CH.sub.2).sub.dO(CH.sub.2CH.sub.2O).sub.eR.sup.x, wherein R.sup.x is independently H or C.sub.1-6 alkyl, d is a positive integer from 2 to 6, and e is 0 or a positive integer from 1 to 100, preferably 5 to 50 and more preferably 10 to 30; Z is (CH.sub.2).sub.rO(CH.sub.2CH.sub.2O).sub.g(CH.sub.2).sub.sY-(L.sub.2).sub.c-(CH.sub.2).sub.b-(L.sub.1).sub.a-A, wherein r is a positive integer from 2 to 6, g is 0 or a positive integer, s is 0 or a positive integer from 2 to 6, Y is ##STR00079## wherein R.sup.5 is selected from H and C.sub.1-6 alkyl; and R.sup.6 is an alkyl group substituted by a COO.sup. or SO.sub.3.sup. group; or ##STR00080## wherein R.sup.5 and R.sup.6 are each independently selected from H and C.sub.1-6 alkyl; Q is a COO.sup. or SO.sub.3.sup. group; Fix is S or SO.sub.2; each of o and p is 0 or an integer from 1 to 6, with the proviso that both of o and p cannot be 0; q is 1 or 0; g is 0 or a positive integer from 1 to 100; and s is 0 or a positive integer from 2 to 6, and L.sub.2, L.sub.1, A, c, b and a are as defined in claim 1; with R.sup.6W, wherein R.sup.6 is selected from a C.sub.1-6 alkyl group substituted by a COOH or SO.sub.3H group; and W is a leaving group.

32. A method for making a surfactant of formula (I):
A-(L.sub.1).sub.a-(CH.sub.2).sub.b-(L.sub.2).sub.c-X (I) wherein A is a perfluoropolyether; L.sub.1 is CONR, wherein R is selected from H and C.sub.1-6 alkyl; a is 0 or 1; b is 0 or an integer between 1 and 6; L.sub.2 is a linking group; c is 0 or 1; and X is ##STR00081## wherein R.sup.8 is selected from H, C.sub.1-6 alkyl and (CH.sub.2CH.sub.2O).sub.eR.sup.x, wherein R.sup.x is independently H or C.sub.1-6 alkyl and e is a positive integer from 1 to 100, preferably 5 to 50 and more preferably 10 to 30; Z is selected from (CH.sub.2).sub.rO(CH.sub.2CH.sub.2O).sub.g(CH.sub.2).sub.sY-(L.sub.2).sub.c-(CH.sub.2).sub.b-(L.sub.1).sub.a-A and (CH.sub.2).sub.tCH.sub.u[(CH.sub.2).sub.rO(CH.sub.2CH.sub.2O).sub.gR.sup.x].sub.w[(CH.sub.2).sub.tY-(L.sub.2).sub.c-(CH.sub.2).sub.b-(L.sub.1).sub.a-A].sub.y, wherein r is a positive integer from 2 to 6, t is a positive integer from 1 to 6, u is 0 or 1, w and y is 1 or 2, the sum of u, w and y equals to 3, g is 0 or a positive integer, s is 0 or a positive integer from 2 to 6, R.sup.x is independently H or C.sub.1-6 alkyl, Y is ##STR00082## wherein W.sup.+ is a counter ion, and L.sub.2, L.sub.1, A, c, b and a are as defined in any one of claims claims 1; and W.sup.+ is a counter ion, comprising: reacting a compound of formula A-(L.sub.1).sub.a(CH.sub.2).sub.b-(L.sub.2).sub.c-OH with POCl.sub.3, followed by hydrolysis, wherein A is a perfluoropolyether; L.sub.1 is CONR, wherein R is selected from H and C.sub.1-6 alkyl; a is 0 or 1; b is 0 or an integer between 1 and 6; L.sub.2 is a linking group; and c is 0 or 1; and optionally reacting the resulting compound with C.sub.1-6 alcohol or HO (CH.sub.2CH.sub.2O).sub.eR.sup.x, HO(CH.sub.2).sub.rO(CH.sub.2CH.sub.2O).sub.g(CH.sub.2).sub.sOH or HO(CH.sub.2).sub.tCH.sub.u[(CH.sub.2).sub.rO(CH.sub.2CH.sub.2O).sub.gR.sup.x].sub.w[(CH.sub.2).sub.tOH].sub.y, wherein R.sup.x is independently H or C.sub.1-6 alkyl, r is a positive integer from 2 to 6, t is a positive integer from 1 to 6, u is 0 or 1, w and y is 1 or 2, the sum of u, w and y equals to 3, s is 0 or a positive integer from 2 to 6 and e and g is a positive integer from 1 to 100, preferably 5 to 50 and more preferably 10 to 30.

33. A composition comprising a surfactant as claimed in claim 1, preferably wherein said composition further comprises a multicharged compound or polymer, and more preferably, wherein said multicharged compound or polymer is oppositely charged to said surfactant.

34. (canceled)

35. (canceled)

36. (canceled)

37. (canceled)

38. The composition as claimed in claim 33, wherein the composition is an emulsion, preferably comprising a discontinuous aqueous phase and a continuous oil phase.

39. (canceled)

40. A method of preparing an emulsion as claimed in claim 38 comprising: (i) providing an aqueous phase; (ii) providing an oil phase; and (iii) mixing said aqueous phase, said oil phase and a surfactant of formula (I):
A-(L.sub.l).sub.a-(CH.sub.2).sub.b-(L.sub.2).sub.c-X (I) wherein A is a perfluoropolyether; L.sub.1 is CONR wherein R is selected from H and C.sub.1-6 alkyl; a is 0 or 1. b is 0 or an integer between 1 and 10; L.sub.2 is a linking group; c is 0 or 1; and X is a charged group, to form said emulsion, preferably wherein said mixing is by a flow focus junction, a T-junction or step emulsification nozzles of a microfluidic device.

41. (canceled)

42. A method comprising performing one or more chemical and/or biological reactions, and/or biological processes in the discontinuous aqueous phase of an emulsion as claimed in claim 38.

43. A method for sorting, coalescing, introducing a fluid into, or splitting droplets in a microfluidic device or extracting a molecule from a fluid, the method comprising any one of methods (A) to (F), wherein sorting method (A) comprises: (i) providing a stream of aqueous droplets in an emulsion as claimed in claim 38 in a channel of the microfluidic device; (ii) illuminating the stream from a first direction; (iii) detecting light from analytes within the droplets in a second direction; and (iv) sorting the droplets into one of a plurality of differentiated streams in response to the detected light or a measurable signal:, wherein coalescing method (B) comprises: (i) providing at least two aqueous droplets in an emulsion as claimed in claim 38 in a channel of the microfluidic device; and (ii) forcing said aqueous droplets to contact, thereby causing coalescence of the at least two aqueous droplets into a single droplet; wherein method of introducing a fluid (C) comprises: (i) providing an aqueous droplet in an emulsion as claimed in claim 38 in a channel of the microfluidic device; and (ii) contacting the aqueous droplet with a stream of fluid, thereby introducing said fluid into the aqueous droplet; wherein splitting method (D) comprises: (i) providing a microfluidic device comprising a microfluidic junction, said microfluidic junction comprising a first microfluidic channel, a second microfluidic channel and a third microfluidic channel; (ii) providing an aqueous droplet in an emulsion as claimed in claim 38 in said first microfluidic channel; and (iii) passing the aqueous droplet through the microfluidic junction, thereby splitting said aqueous droplet into at least a first daughter droplet and a second daughter droplet, the first daughter droplet in the second microfluidic channel and the second daughter droplet in the third microfluidic channel; wherein sorting method (E) comprises: (i) providing a microfluidic device comprising a microfluidic junction, said microfluidic junction comprising a first microfluidic channel, a second microfluidic channel and a third microfluidic channel; (ii) providing an aqueous droplet in an emulsion as claimed in claim 38 in said first microfluidic channel; (iii) passing the aqueous droplet through the microfluidic junction, thereby splitting said aqueous droplet into at least a first daughter droplet and a second daughter droplet, the first daughter droplet in the second microfluidic channel and the second daughter droplet in the third microfluidic channel; (iv) detecting said first daughter droplet by mass spectroscopy; and (v) sorting said second daughter droplets into one of a plurality of differentiated streams responsive to the mass spectroscopy wherein extracting method (F) comprises: (i) dissolving a surfactant of formula (I) :
A-(L.sub.l).sub.a-(CH.sub.2).sub.b-(L.sub.2).sub.c-X (I) wherein A is a perfluoropolyether; L.sub.1 is CONR wherein R is selected from H and C.sub.1-6 alkyl; a is 0 or 1 b is 0 or an integer between 1 and 10; L.sub.2 is a linking group; c is 0 or 1; and X is a charged group, in carbon dioxide to form a carbon dioxide/surfactant mixture; and (ii) adding a fluid comprising the molecule to the carbon dioxide/surfactant mixture, thereby extracting the molecule from the fluid into the carbon dioxide.

44. (canceled)

45. (canceled)

46. (canceled)

47. (canceled)

48. (canceled)

49. (canceled)

50. (canceled)

Description

BRIEF DESCRIPTION OF FIGURES

[0361] These and other aspects of the invention will now be further described, by way of example only, with reference to the accompanying figures in which:

[0362] FIG. 1 shows a fluorescence microscopy image of a control emulsion comprising the non-ionic surfactant Pico-Surf;

[0363] FIG. 2 shows a fluorescence microscopy image of an emulsion comprising a zwitterionic surfactant of the present invention;

[0364] FIG. 3 shows a fluorescence microscopy image of an emulsion comprising a zwitterionic surfactant of the present invention;

[0365] FIG. 4 shows a fluorescence microscopy image of a control emulsion comprising the polyanionic additive PSS (0.5%) in addition to the non-ionic surfactant Pico-Surf;

[0366] FIG. 5 shows a fluorescence microscopy image of an emulsion comprising a zwitterionic surfactant of the present invention in addition to the polyanionic additive PSS (0.5%);

[0367] FIG. 6 shows a fluorescence microscopy image of a control emulsion comprising the non-ionic surfactant Pico-Surf; and

[0368] FIG. 7 shows a fluorescence microscopy image of an emulsion comprising a cationic surfactant of the present invention in addition to the polyanionic additive PSS (0.5%).

EXAMPLES

[0369] All starting materials and solvents used were commercially available.

1. Synthesis of N-(4-[1-carboxymethylpyridin-1-ium inner salt]methyl) Krytox amide (4)

[0370] ##STR00040##

Synthesis of Krytox Acyl Chloride (2)

[0371] In a 1 litre round bottom flask fitted with a magnetic stirrer bar and a 50 mL dropping funnel fitted with a septum, 385.76 grams (172.8 mmol) of Krytox 157 FS(L)(1) was degassed by applying vacuum and replaced with nitrogen three times. Dry Novec 7100 (stored over anhydrous Na.sub.2SO.sub.4, 320 mL) was injected with a syringe into the dropping funnel and emptied into the flask in 50 mL aliquots. Once all Krytox was dissolved up into a homogenous solution, 45 mL of oxalyl chloride (524.7 mmol) was syringed into the dropping funnel and slowly added over 10 minutes. Finally, 100 L of anhydrous DMF was added by syringe directly into the reaction mixture. The resultant mixture was stirred at room temperature overnight, decanted into a clean 1 litre round bottom flask, concentrated at 40 C. and 270 mbar on a rotary-evaporator, and further dried on at 50 C. at 0-5 mbar for 30 minutes yielding krytox acyl chloride (2) as a clear oil (387.44 grams, 99.6%). IR (cm.sup.1): 1808 (sm).

Synthesis of N-(4-Pyridiniummethyl) Krytox amide (3)

[0372] To a stirred solution of 4-(aminomethyl)pyridine (21.475g, 20.11 mL, 198.6 mmol) in anhydrous THF (30 mL), at 50 C. under nitrogen, was added solution of krytox acid chloride (2, 66.11 g, 28,37 mmol) in Novel 7500 (70 mL) dropwise from a dropping funnel. Then stirred at 50 C. under nitrogen for 48 hours and cooled to RT. The reaction was filtered to remove a dark red coloured solid and washed with a little Novec 7500 (25 mL). The filtrate was stirred with methanol (75 ml) and then the the two phases were separated and the bottom fluorous layer was collected. The fluorous layer was then washed with methanol (350 mL) each time retaining the bottom fluorous layer. The fluorous layer was then evaporated to dryness in vacuo to yield (3) as a pale yellow oil (58.70 g, 86.1%). IR (cm.sup.1): 1709.5 (sm). .sup.1H NMR (400 MHz, 5% C.sub.6D.sub.12 in FC72 ;vol:vol): 9.90 (1H, bs, NH), 8.194 (2H, d, pyridyl-Ha), 7.018 (2H, bs, pyridyl-Hb), 4.51 (1H, bd, benzylic CH.sub.2), 4.395 (1H, bd, benzylic CH.sub.2).

Synthesis of N-(4[1-carboxymethylpyridin-1-ium inner salt]methyl) Krytox amide (4)

[0373] The pale yellow oil of N-(4-Pyridiniummethyl) Krytox amide (3, 11.074 g, 4.609 mmol) was dissolved in Novec 7500 (25.0 mL), and warmed to 35 C. On addition of the solution of iodoacetic acid (1.071 g, 5.671 mmol) and Hunig's base (1.054 mL, 6.049 mmol) in THF, the solution went from yellow to pale green. The reaction temperature was ramped up to 65 C., and maintained at this temperature overnight. The reaction mixture was concentrated in vacuo to remove THF, and the remaining washed with a mixture of methanol (30 mL) and DCM (30 mL). The bottom layer was separated off, washed with 15% methanol/DCM (30 mL) 6 times followed with pure DCM (40 mL) 2 times, and dried in vacuo to give dark oil (4, 8.929 g, 78.7%). IR (cm.sup.1): 1731.4.). .sup.1H NMR (400 MHz, 5% C.sub.6D.sub.12 in FC72 ;vol:vol): 9.406 (1H, bs, NH), 8.253 (2H, bs, pyridyl-Ha), 7.054 (2H, bs, pyridyl-Ha), 5.0-4.0 (4H, bd, benzylic CH.sub.2 and CH.sub.2 of inner salt).

2. Synthesis of N-(4-[1-(y-methoxy PEG-pyridin-1-ium bromide]methyl) Krytox amide (5)

[0374] ##STR00041##

[0375] To a stirred solution of O-[1-bromo-2-ethyl]-O-methyl-polyethylene glycol (3.767g, 4.442 mmol) in THF under nitrogen at heating block temperature of 60 C., was added a solution of N-(4-Pyridiniummethyl) Krytox amide (3, 9.606 g, 3.998 mmol) in Novec 7500 (30 mL) from a dropping funnel dropwise over 30 minutes. The reaction temperature was ramped up to 80 C., and maintained at this temperature for 2 days. The reaction mixture was concentrated in vacuo to remove THF, and the remaining washed with a mixture of methanol (25 mL). The bottom layer was separated off, washed with methanol (25 mL) 6 times, and dried in vacuo to give dark oil (5, 5.595 g). IR (cm.sup.1): 1716.5. .sup.1H NMR (400 MHz, 5% C.sub.6D.sub.12 in FC72 ;vol:vol): 10.366 (1H, bs, NH), 9.296 (2H, bs, pyridyl Ha), 8.103 (2H, bs, pyridyl Ha), 4.295 (2H, bs, pyridyl N4-CH.sub.2), 4.093 (2H, bm, benzylic CH.sub.2), 3.53 (31.0H, CH.sub.2(OCH.sub.2CH.sub.2).sub.6.5OMe).

3. Synthesis of N-[3-(Trimethylammonium iodide)propyl] Krytox amide (7)

[0376] ##STR00042##

Synthesis of N-[3-(Dimethylamino)propyl] Krytox amide (6)

[0377] To a stirred solution of 3-(dimethylamino)-1-propylamine (50.61 g, 62.3 mL, 495 mmol) in anhydrous THF (60 mL),), at 50 C. under nitrogen, was added a solution of krytox acid chloride (2, 192.39 g, 82.55 mmol) in Novec 7500 (203 mL) dropwise over 1 H, via canula. After stirring the mixture at 50 C. under nitrogen for 48 hours the mixture was cooled to RT and a yellow solid removed by filtration and washed with Novec 7500 (30 ml). The filtrate was stirred with methanol (4100 mL), each time the bottom flouorous phase was separated in a separating funnel. The fluorous layer was then evaporated to dryness in vacuo to yield (6) as a pale yellow oil (189.7 g, 95.9%). IR (cm.sup.1): 2955.5 (bw), 2832.0 (bw), 1729.6 (sm). .sup.1H NMR (400 MHz, 5% C.sub.6D.sub.12 in FC72 ;vol:vol): 9.506 (1H, bs, NH), 3.493(2H, m, CONHCH.sub.2), 2.488 (2H, t, CH.sub.2NMe.sub.2), 2.246 (6H, s, NMe.sub.2), 1.692 (2H, m, CH.sub.2CH.sub.2NMe.sub.2).

Synthesis of N-[3-(Trimethylammonium iodide)propyl] Krytox amide (7)

[0378] To a stirred solution of N-[3-(Dimethylamino)propyl] Krytox amide (6, 8.05 g, 3.36 mmol) in Novec 7100 (16.0 mL) and anhydrous acetonitrile, at 40 C. under nitrogen, was added methyl iodide (0.42 mL, 6.72 mmol) via syringe. Immediately the solution went clear, then block temperature was raised to 50 C. and stirred for 60 H. After cooling the solution to RT the solution was evaporated to dryness to thick pale yellow oil (8.73 g, 98.2%). IR (cm.sup.1): 1705.2 cm-.sup.1. .sup.1H NMR (400 MHz, 5% C.sub.6D.sub.12 in FC72 ;vol:vol): 9.575 (1H, bs, NH), 3.667 (4H, bs, CH.sub.2N+Me.sub.3 and NHCH.sub.2), 3.349 (9H, bs, N.sup.+Me.sub.3).

4. Synthesis of N-[3-Dimethyl-3-carboxymethyl ammonium inner salt)propyl] Krytox amide (8)

[0379] ##STR00043##

[0380] To a stirred solution of N-[3-(Dimethylamino)propyl] Krytox amide (6, 12.74 g, 5.32 mmol) in Novec 7100 (25.0 mL), at RT under nitrogen, was added a solution of iodoacetic acid (1.44g, 7.72 mmol) in anhydrous THF (20.0 mL, plus 5.0 ml wash) to which had been added Hunig's base (1.39 mL, 7.98 mmol) via syringe. Then raise the block temperature to 35 C. After 20 H the reaction was cooled to RT and filtered and the filtrate evaporated to dryness. The resultin oil was dissolved in Novec 7500 (25 mL) and washed with methanol (325 mL) each time carefully separating off the lower fluorous layer. The resulting fluorous layer was evaporated to dryness in vacuo to give (8, 11.54 g, 88.4%). IR (cm.sup.1): 1754.7 (w), 1709.7 (m). 1623.2 (m). .sup.1H NMR (400 MHz, 5% C.sub.6D.sub.12 in FC72 ;vol:vol): 10.169 (1H, s, NH), 5.0-3.0 (6H, bm, NHCH.sub.2, CH.sub.2N+Me2 and CH.sub.2CO.sub.2.sup.), 2.342 (2H, bs, CH.sub.2CH.sub.2CH.sub.2).

5. Synthesis of N-[3-Dimethyl-3-y-methoxy-PEG ammonium iodide)propyl] Krytox amide (9)

[0381] ##STR00044##

[0382] To a stirred solution of N-[3-(Dimethylamino)propyl] Krytox amide (6, 3.92 g, 1.64 mmol) in Novec 7100 (8.0 mL), at RT under nitrogen, was added a solution of O-[1-bromo-2-ethyl]-O-methyl-polyethylene glycol (2.79g, 2.45 mmol) in anhydrous acetonitrile (8.0 mL, plus 1.5 mL wash) and the block temperature set to 50 C. After 60 H the reaction was cooled to RT and the top layer was carefully removed with a Pasteur pipette. The solution was evaporated to dryness and redissolved in Novec 7500 (10 mL) and was stirred with methanol (215 mL). Each time the two layers were separated and the bottom fluorous layer was washed with methanol. The resulting fluorous layer was evaporated to dryness in vacuo to give (9, 3.32 g, 58.9%) as an orange oil. IR (cm.sup.1): 1693.4.

6. Synthesis of N-[3-Dimethyl-3-(1-hydroxypropyl) ammonium iodide)propyl] Krytox amide (10)

[0383] ##STR00045##

[0384] To a solution of N-[3-(Dimethylamino)propyl] Krytox amide (6, 10.425 g, 4.351 mmol) in Novec 7100 (12.0 mL) and THF (12.0 mL), was added a solution of 3-iodo-1-propanol (1 g, 5.376 mmol) in THF (6.0 mL). The dark brown solution went lighter on addition and was stirred overnight under nitrogen with the heating block temperature set to 35 C. The reaction mixture was evaporated to dryness, the residue re-dissolved in Novec 7500 (25 mL) and methanol (25 mL), and the solution stirred on a rotary evaporator at 50 C. for 5 minutes. This was repeated for another 3 times, and evaporated to dryness (10, 7.141 g, 66.86%) as an orange oil orange oil. IR (cm.sup.1): 1712.3. .sup.1H NMR (400 MHz, 5% C.sub.6D.sub.12 in FC72 ;vol:vol): 10.404 (1H, bs, NH, 4.0-3.7 (4H, bs, NHCH.sub.2 and CH.sub.2O), 3.7-3.1 (10H, bs, CH.sub.2N+Me.sub.2CH.sub.2), 2.5-2.0 (4H, bs, CH.sub.2CH.sub.2CH.sub.2NMe.sub.2.sup.+CH.sub.2CH.sub.2CH.sub.2OH), 1.694 (1H, bs, OH).

7. Synthesis of Ammonium salt of Krytox (11)

[0385] ##STR00046##

[0386] Krytox (50.00 grams, 21.63 mmol) was placed in a 250 mL round bottom flask fitted with magnetic stirrer bar and septum. The flask was degassed by applying vacuum and refilled with nitrogen 3 times. Novec 7100 (70 mL) was added by syringe to dissolve Krytox, followed by 7 molar ammonia in methanol (20 mL) by syringe. The reaction was stirred at room temperature for three days. The solvent was evaporated under vacuum to leave an amber coloured waxy residue of (11).

8. Synthesis of Quaternary ammonium salt (13)

[0387] ##STR00047##

[0388] Anhydrous tetrahydrofuran (15 mL) was placed in a 20 mL vial and fitted with a stirrer bar. Triethylenetetramine (12, 0.989 g, 6.76 mmol) was added, followed by iodomethane (4.00 g, 28.18 mmol) at room temperature, upon which a precipitate formed. The reaction was stirred for 3 hours at room temperature and then evaporated to dryness to give quaternary ammonium salt (13).

9. Synthesis of Quaternary ammonium salt (15)

[0389] ##STR00048##

[0390] Anhydrous tetrahydrofuran (15 mL) was placed in a 20 mL vial and fitted with a stirrer bar. 1-(2-Aminoethyl)piperidine (1.770 g, 13.81 mmol) was added, followed by iodomethane (4.00 g, 28.18 mmol) at room temperature, upon which a precipitate formed. The reaction was stirred for 3 hours at room temperature and then evaporated to dryness to give quaternary ammonium salt (15).

10. Synthesis of Quaternary ammonium salt (17)

[0391] ##STR00049##

[0392] Anhydrous tetrahydrofuran (15 mL) was placed in a 20 mL vial and fitted with a stirrer bar. Tris(2-aminoethyl)amine (0.989 g, 6.76 mmol) was added, followed by iodomethane (4.00 g, 28.18 mmol) at room temperature, upon which a precipitate formed. The reaction was stirred for 3 hours at room temperature and then evaporated to dryness to give quaternary ammonium salt (17).

11. Proposed Synthesis of cationic triblock surfactant (18)

[0393] ##STR00050##

12. Proposed Synthesis of Zwitterionic diblock polymeric surfactant (23), (24) and (25)

[0394] ##STR00051##

13. Proposed Synthesis of Zwitterionic triblock polymeric surfactant (26), (27) and (28)

[0395] ##STR00052##

14. Proposed Synthesis of anionic surfactant (29) and (30)

[0396] ##STR00053##

15. Proposed Synthesis of anionic triblock polymeric surfactant (31)

[0397] ##STR00054##

16. Proposed Synthesis of anionic 3-armed star polymeric surfactant (35)

[0398] ##STR00055##

17. Proposed Synthesis of anionic 4-armed star polymeric surfactant (38)

[0399] ##STR00056##

[0400] 18. Droplet Generation:

[0401] In order to generate droplets with volumes between 300-400 pL, fluorous oil containing 0.5% (w/w) of one of the surfactants of the invention was used as the continuous carrier oil phase, whilst a PBS solution with various additives was used as the dispersed aqueous phase. The two phases were infused using a Cetoni GmbH syringe pump connected via polythene tubing (ID: 0.38mm) to a PDMS microfluidic chip, containing a single flow-focusing nozzle (nozzle dimensions: 6060 m). Typical flow rates ranged between 1700-2500 L/hr for the fluorous phases and were kept constant at 600 L/hr for aqueous phases. Droplets were collected for 6 minutes in each case, generating 60L of emulsion.

[0402] 19. Resorufin Leakage Test:

[0403] To investigate the ability of the surfactants of the present invention to circumvent the issue of inter-droplet molecular exchange, Resuorufin (sodium salt; 10 M) was added to the aqueous phase, and droplets were generated as described in step 18. The positive emulsions (with Resorufin) were carefully pipetted into an Eppendorf tube containing the corresponding negative emulsions (without Resorufin). The tube was rotated slowly in order to fully mix the emulsions, and left to stand at room temperature overnight. The droplets were then imaged using fluorescence microscopy. Control emulsion samples were also made using phosphate buffered saline (PBS) without additives and a non-ionic surfactant Pico-Surf (Sphere Fluidics Limited).

[0404] The results for the comparative emulsion are shown in FIG. 1 wherein the droplets are uniformly bright indicating resorufin leakage and equilibration across the droplets.

[0405] The results for zwitterionic surfactants (4 and 8) are shown in FIGS. 2 and 3. The for zwitterionic surfactants (4 and 8) showed the capability to stabilize the emulsion of PBS as the aqueous phase, and reduced inter-droplet molecular exchange of resorufin compared to the control emulsion sample stabilized by Pico-Surf, as shown by fluorescent microscopy that Image 2 of emulsion stabilized by zwitterionic surfactant 4 and Image 3 of emulsion stabilized by zwitterionic surfactant 8.

[0406] Addition of the polyanionic additive PSS (0.5%) had little or no positive benefit with the non-ionic surfactant Pico-Surf (Sphere Fluidics Limited)see the fluorescent image in FIG. 4. Again, the picodroplets are almost uniformly bright, indicating significant inter-droplet molecular exchange of resorufin. In contrast, with the addition of the polyanionic additive PSS (0.5%), the zwitterionic surfactant (4) still exhibited the presence of two populations of dropletssee FIG. 5.

[0407] Cationic surfactant (9) was tested by the same methodology. Cationic surfactant (9) also showed the capability to stabilize the emulsion of PBS as the aqueous phase, and reduced inter-droplet molecular exchange of resorufin when compared with the control emulsion sample stabilized by Pico-Surf. This is clear by comparing the fluorescent images in FIGS. 6 (comparative surfactant not containing polyanionic polymer additive PSS (0.5%) and FIG. 7 (cationic surfactant (9) containing polyanionic polymer additive PSS (0.5%)).