Size-exclusion ion-exchange particles

• US 20040018559A1
• Filed: 04/14/2003
• Published: 01/29/2004
• Est. Priority Date: 07/26/2002
• Status: Abandoned Application

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applera Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Harrold, Michael P., Lau, Aldrich N.K.
• Application Number:
  US10/414,179
• Publication Number:
  US 20040018559A1
• Time in Patent Office: Days
• US Class Current: 435/7.1
• CPC Class Codes: B01D 15/34 Size selective separation, e.g. size exclusion chromatography, gel filtration, permeation
• CPC Class Codes: B01D 15/361 Ion-exchange
• CPC Class Codes: B01J 20/3293 Coatings on a core, the core being particle or fiber shaped, e.g. encapsulated particles, coated fibers
• CPC Class Codes: B01J 47/018 Granulation; Incorporation of ion-exchangers in a matrix; Mixing with inert materials
• CPC Class Codes: G01N 1/405 by adsorption or absorption
• CPC Class Codes: Y10T 428/2991 Coated
• CPC Class Codes: Y10T 428/2998 including synthetic resin or polymer

Abstract

A size-exclusion ion-exchange particle and a device using the particle are provided wherein the particle includes an ion-exchange core micro-encapsulated by a shell, and the shell includes a polymerization product of a reactive monomer. The shell can be an at least partially cross-linked polymer. The shell can be capable of excluding molecules of a size equal to or larger than a 10 nt ssDNA molecule or molecules of a size equal to or larger than a 100 nt ssDNA molecule, for example, and the core can be capable of ion-exchange. Methods of making size-exclusion ion-exchange particles are also provided, as are methods of purification using the particles.

Claims

1. A size-exclusion ion-exchange particle comprising a core and a shell, wherein the core comprises ion-exchange material, and the shell comprises size-exclusion material.

2. The size-exclusion ion-exchange particle of claim 1, wherein the shell comprises an at least partially cross-linked polymer.

3. The size-exclusion ion-exchange particle of claim 2, wherein the polymer is at least partially covalently cross-linked.

4. The particle of claim 1, wherein the ion-exchange core comprises a solid core material.

5. The particle of claim 4, wherein the solid core material comprises at least one of macroporous silica, controlled pore glass, microporous polymer microspheres, mesoporous polymer microspheres, and macroporous polymer microspheres.

6. The particle of claim 4, wherein the solid core material is capable of ion-exchange.

7. The particle of claim 6, wherein the solid core material comprises at least one of tertiary ammonium groups, quartemary ammonium groups, carboxylic acid groups, and sulfonic acid groups.

8. The particle of claim 4, wherein the solid core material is porous.

9. The particle of claim 4, wherein the solid core material has an average diameter of 500 μ

m or less.

10. The particle of claim 4, wherein the solid core material is coated with an ion-exchange material.

11. The particle of claim 1, wherein the core includes a neutral, water-soluble polymer or an organic soluble polymer.

13. The particle of claim 1, wherein the ion-exchange core is surface-activated.

14. The particle of claim 1, wherein the ion-exchange core comprises an agglomeration.

15. The particle of claim 1, wherein the shell comprises a cross-linked polymerization product of a water-soluble monomer.

16. The size-exclusion ion-exchange particle of claim 1, wherein the shell comprises at least one of a poly((meth)acrylamide material, a poly(N-methyl (meth)acrylamide) material, a poly(N,N-dimethylacrylamide) material, a poly(N-ethyl (meth)acrylamide material, a poly(N-n-propyl (meth)acrylamide) material, a poly(N-iso-propyl (meth)acrylamide) material, a poly(N-ethyl-N-methyl (meth)acrylamide) material, a poly(N,N-diethyl (meth)acrylamide) material, a poly(N-vinylformamide) material, a poly(N-vinylacetamide) material, a poly(N-methyl-N-vinylacetamide) material, a poly(vinylalcohol) material, a poly(2-hydroxyethyl (meth)acrylate) material, a poly(3-hydroxypropyl (meth)acrylate) material, a poly(vinylpyrrolidone) material, a poly(ethylene oxide) material, a poly(vinyl methyl ether) material, a poly(N-(meth)acrylylcinamide) material, a poly(vinyloxazolidone) material, a poly(vinylmethyloxazolidone) material, a poly(2-methyl-2-oxazoline) material, a poly(2-ethyl-2-oxazoline)material, a water-soluble polysaccharide material, a polymer of poly(ethylene glycol) acrylate, a polymer of poly(ethyleneglycol) methacrylate, a water-soluble polysaccharide material, and a combination thereof.

17. The particle of claim 1, wherein the shell comprises a cross-linked hydrogel.

18. The particle of claim 1, wherein the shell comprises the reaction product of acrylamide and N,N′

-methylenebisacrylamide.

19. The size-exclusion ion-exchange particle of claim 1, wherein the shell comprises the reaction product of acrylamide and 2,2-bis(acrylamido)acetic acid.

20. The size-exclusion ion-exchange particle of claim 1, wherein the shell comprises the reaction product of poly(ethylene glycol) (meth)acrylate and poly(ethylene glycol) diacrylate.

21. The particle of claim 1, wherein the shell comprises a plurality of pores, and wherein at least 50% of the pores are capable of excluding molecules of a size equal to or greater than 10 nt ssDNA.

22. A mixture comprising ion-exchange materials including the size-exclusion ion-exchange particle of claim 1, wherein the mixture includes a cationic ion-exchange material, and an anionic ion-exchange material.

23. The mixture of claim 22, wherein the size-exclusion ion-exchange particle is cationic, and the mixture includes an anionic size-exclusion ion-exchange particle.

24. The mixture of claim 22, wherein the mixture is in the form of a mixed bed.

25. The mixture of claim 22, wherein the cationic ion-exchange material and the anionic ion-exchange material are present in stoichiometrically equivalent amounts.

26. A purification device comprising a receptacle, and the size-exclusion ion-exchange particle of claim 1 disposed in the receptacle.

27. A purification device comprising a receptacle, and the mixture of claim 22 disposed in the receptacle.

28. A microfluidic device comprising one or more columns, and the particle of claim 1 disposed in at least one of the one or more columns.

29. The device of claim 28, wherein each of the one or more columns comprises an inlet and an outlet.

30. A microfluidic device comprising one or more columns and the mixture of claim 22 disposed in at least one of the one or more columns.

58. The size-exclusion ion-exchange particle of claim 1, wherein the shell comprises a reaction product of acrylamide and N,N′

-di(meth)acryloylpiperazine.

59. The size-exclusion ion-exchange particle of claim 1, wherein the shell comprises a reaction product of acrylamide and tri(meth)acryloylperhydro-s-triazine.

60. The size-exclusion ion-exchange particle of claim 1, wherein the shell comprises a reaction product of at least two of acrylamide, N,N′

-methylenebisacrylamide, 2,2-bis(acrylamido)acetic acid, poly(ethylene glycol) (meth)acrylate, poly(ethylene glycol) diacrylate, N,N′

-di(meth)acryloylpiperazine, tri(meth)acryloylperhydro-s-triazine.

12. The particle of 11, wherein the core includes one or more of a poly(N-vinylpyrrolidone) polymer material, a poly(vinyl acetate-co-vinyl alcohol) material, a polyacrylamide material, a poly(N,N-dimethyl acrylamide) material, a poly(N-vinylamide) material, a poly(ethyleneoxide-co-propyleneoxide) material, an amphiphilic diblock copolymer, and an amphiphilic block copolymer.

31. A method of forming a size-exclusion ion-exchange particle comprising:

providing an ion-exchange core; and

micro-encapsulating the ion-exchange core with a size-exclusion material.

32. The method of claim 31, wherein micro-encapsulating the ion-exchange core comprises:

forming an aqueous water jacket including at least one monomer, pre-polymer, or co-polymer around the ion-exchange core; and

forming a shell around the ion-exchange core by inverse emulsification of the at least one monomer, pre-polymer, or co-polymer in the aqueous water jacket.

33. The method of claim 31, wherein providing a core comprises:

providing a solid core material comprising an external surface;

binding a first monomer to the external surface; and

contacting the bound first monomer with a second monomer to form an ion-exchange material on at least part of the external surface.

34. The method of claim 33, wherein the solid core further comprises an internal surface, wherein binding further comprises binding the first monomer on the internal surface, and wherein contacting the bound first monomer with a second monomer further comprises forming an ion-exchange material on at least part of the internal surface.

35. The method of claim 31, wherein providing the core comprises:

providing a solid core material comprising an external surface; and

coating the external surface with an ion-exchange material.

36. The method of claim 35, wherein the solid core further comprises an internal surface, and wherein coating further comprises coating an ion-exchange material on at least part of the internal surface.

37. The method of claim 31, wherein providing the core comprises surface-activating the core.

38. The method of claim 37, wherein surface-activating the core comprises adsorbing a neutral, water-soluble polymer or an organic soluble polymer on a surface of the core.

39. The method of claim 38, wherein the surface-activating core comprises one or more of a poly(N-vinylpyrrolidone) polymer material, a poly(vinyl acetate-co-vinyl alcohol) material, a polyacrylamide material, a poly(N,N-dimethyl acrylamide) material, a poly(N-vinylamide) material, a poly(ethyleneoxide-co-propyleneoxide) material, an amphiphilic diblock copolymer, and an amphiphilic block copolymer.

40. The method of claim 31, wherein providing the core comprises agglomerating core material.

41. The method of claim 31, wherein micro-encapsulating the ion-exchange core comprises contacting the core with a polymerizable monomer, and reacting the monomer to form the size-exclusion material.

42. The method of claim 41, wherein contacting the core with the polymerizable monomer comprises:

heating the core;

contacting the core with at least one of an initiator and a catalyst; and

contacting the core with at least one of acrylamide and N, N′

-methylenebisacrylamide.

43. The method of claim 31, wherein micro-encapsulating the ion-exchange core comprises:

positioning the core in an emulsion comprising a polymerizable monomer; and

polymerizing the monomer to micro-encapsulate the core.

44. The method of claim 43, wherein polymerizing comprises inverse-emulsion polymerization.

45. The method of claim 43, wherein the polymerizable monomer is water-soluble.

46. The method of claim 43, wherein the polymerizing comprises contacting a cross-linker with the monomer, wherein the cross-linker is present in an amount of from 1 to 95 weight percent based on the weight of the monomer.

47. The method of claim 43, wherein the polymerizing comprises covalently cross-linking the monomer.

48. A method of forming a size-exclusion ion-exchange particle, comprising:

providing an ion-exchange core;

contacting the core with an emulsion, wherein the emulsion comprises a polymerizable monomer; and

polymerizing the monomer to micro-encapsulate the core, wherein the polymerizing comprises forming a shell comprising a plurality of pores, wherein the plurality of pores exclude material larger than a predetermined size.

49. The method of claim 48, wherein the shell is at least partially covalently cross-linked.

50. The method of claim 48, wherein the predetermined size is equal or greater than 10 nt ssDNA.

51. A method of purifying a sample, comprising:

providing a plurality of size-exclusion ion-exchange particles, wherein each particle comprises a core for ion-exchange and a shell for size-exclusion;

contacting the sample with the particles to form a purified sample; and

separating the purified sample from the particles.

52. The method of claim 51, wherein the purified sample comprises material having a molecular size of 10 nt ssDNA or greater.

53. The method of claim 51, wherein the purified sample comprises material having a molecular size of 100 nt ssDNA or greater.

54. The method of claim 51, wherein the contacting comprises moving the sample through the plurality of particles using centripetal force.

55. The method of claim 51, wherein the plurality of size-exclusion ion-exchange particles comprise a first volume, the biological sample comprises a second volume, and the first volume is less than or equal to the second volume.

56. The method of claim 51, wherein the purified sample has a salt concentration less than or equal to 50 μ

M.

57. The method of claim 51, wherein the plurality of size-exclusion ion-exchange particles comprises stoichiometrically equivalent amounts of size-exclusion anion-exchange particles and size-exclusion cation-exchange particles.