Functionalization of a porous membrane with an adsorbed polyacid

Patent metadata

Field	Value
Publication number	US-9459188-B2
Application number	US-201313799380-A
Country	US
Kind code	B2
Filing date	Mar 13, 2013
Priority date	Mar 16, 2012
Publication date	Oct 4, 2016
Grant date	Oct 4, 2016

Abstract

The disclosure relates to a process and related article for functionalizing a porous membrane by contacting the membrane with a polyacid polymer at low pH to stably adsorb a polyacid layer on the membrane pore surface. The resulting functionalized membrane is characterized by a high density of free acid groups, resulting in a higher specific capacity for its intended application. The process allows functionalization of porous membranes in a very simple, one-step process. Such functional membranes may find multiple uses, including rapid, selective binding of proteins for their purification or immobilization.

First claim

What is claimed is:

1. A method for functionalizing a porous membrane, the method comprising:
(a) providing a porous membrane substrate comprising a plurality of membrane pores; and
(b) contacting the membrane pores with an aqueous fluid mixture (i) having a pH value less than 3.8 and (ii) comprising a polyacid polymer comprising free acid groups selected from the group consisting of carboxylic acid groups, carboxylate groups, and combinations thereof for a time sufficient to adsorb a polyacid layer on surfaces of the membrane pores, thereby forming a polyacid-coated porous membrane comprising the free acid groups;
wherein the polyacid-coated porous membrane substrate comprises a plurality of polyacid layers, wherein (i) a first polyacid layer is adsorbed directly on the porous membrane substrate and (ii) one or more further polyacid layers are adhered to adjacent polyacid layers via one or more intervening polycation layers.

2. The method of claim 1 , wherein the plurality of membrane pores has an average pore size ranging from 0.02 μm to 50 μm.

3. The method of claim 1 , wherein the porous membrane substrate comprises a synthetic polymeric membrane material selected from the group consisting of cellulose acetates, nitrocelluloses, cellulose esters, polysulfones, polyether sulfones, polyacrylonitriles, polyamides, polyimides, polyethylenes, polypropylenes, polytetrafluoroethylenes, polyvinylidene fluorides, polyvinylchlorides, hydroxylated derivatives of the foregoing, and combinations thereof.

4. The method of claim 1 , wherein the pH value of the aqueous fluid mixture ranges from 1 to 3.5.

5. The method of claim 1 , wherein the polyacid-coated porous membrane has a free acid group content ranging from 1.25 to 10 times that of an analogous polyacid-coated porous membrane in which the aqueous fluid mixture had pH value of 4, but which has been otherwise prepared equivalently to the polyacid-coated porous membrane.

6. The method of claim 1 , wherein at least 50% of the polyacid free acid groups in the aqueous fluid mixture are in the form of carboxylic acid groups.

7. The method of claim 1 , wherein the polyacid layer is stably adsorbed on the surfaces of the membrane pores due to one or more of hydrophobic interactions and hydrogen bonding interactions.

8. The method of claim 1 , wherein the aqueous fluid mixture is in the form of an aqueous solution comprising the polyacid polymer and further comprising an electrolyte in solution in the aqueous solution.

9. The method of claim 1 , wherein the polyacid polymer comprises repeating units having one or more pendent free acid groups.

10. The method of claim 1 , wherein the polyacid polymer comprises polyacrylic acid.

11. The method of claim 1 , wherein the polyacid comprises repeating units comprising a metal-binding ligand group.

12. The method of claim 1 , wherein the polyacid-coated porous membrane has a monolayer of the polyacid polymer adsorbed directly on the porous membrane substrate and comprising the free acid groups.

13. The method of claim 1 , wherein the method comprises performing a layer-by-layer polyelectrolyte adsorption process to deposit alternate layers of (i) the polyacid at a pH value less than 3.8 and (ii) the polycation.

14. The method of claim 1 , further comprising:
(c) derivatizing the free acid groups of the polyacid-coated porous membrane to attach protein affinity tag-binding ligands thereto at surfaces exposed to membrane pore void volumes.

15. The method of claim 14 , wherein part (c) comprises:
(c-1) derivatizing the free acid groups of the polyacid-coated porous membrane to attach metal-binding ligands thereto at surfaces exposed to membrane pore void volumes; and
(c-2) contacting the metal-binding ligands with metallic ions to form metal-ligand complexes at the surfaces exposed to membrane pore void volumes.

16. The method of claim 15 , wherein the metallic ions comprise Ni 2+ .

17. The method of claim 15 , wherein the metallic ions comprise one or more of Cu 2+ , Co 2+ , Fe 3+ , and Ga 3+ .

18. The method of claim 15 , wherein the metal-binding ligands comprise one or more of nitrilotriacetic acid groups, iminodiacetic acid groups, and salts thereof.

19. The method of claim 14 , wherein the protein affinity tag-binding ligands are selected from the group consisting of glutathione, glutathione-S-transferase (GST) tag-binding derivatives thereof, amylose, maltose binding protein (MBP) tag-binding derivatives thereof, chitin, and chitin binding protein (CBP) tag-binding derivatives thereof.

20. A polyacid-coated porous membrane formed according to claim 1 .

21. A method for binding a positively charged target analyte, the method comprising:
(a) providing the polyacid-coated porous membrane formed according to claim 1 ;
(b) providing a feed fluid sample comprising a positively charged target analyte; and
(c) passing the feed fluid sample through the polyacid-coated porous membrane, thereby (i) binding at least some of the target analyte with the free acid groups and (ii) providing a permeate fluid with at least some of the target analyte removed.

22. The method of claim 21 , further comprising:
(d) eluting the bound target analyte from the polyacid-coated porous membrane, thereby forming a purified permeate fluid comprising the target analyte.

23. The method of claim 22 , wherein (i) the feed fluid sample further comprises non-positively charged non-target analytes and (ii) the purified permeate fluid is substantially free from the non-target analytes.

24. A method for binding an affinity-tagged target protein, the method comprising:
(a) providing the polyacid-coated porous membrane formed according to claim 14 ;
(b) providing a feed fluid sample comprising a target protein comprising an affinity tag; and
(c) passing the feed fluid sample through the polyacid-coated porous membrane, thereby (i) binding at least some of the target protein via the affinity tag with the immobilized protein affinity tag-binding ligands and (ii) providing a permeate fluid with at least some of the target protein removed.

25. The method of claim 24 , wherein (i) the affinity tag is a polyhistidine tag and (ii) the protein affinity tag-binding ligands comprise one or more of Ni 2+ -ligand complexes and Co 2+ -ligand complexes.

26. The method of claim 24 , wherein (i) the affinity tag is a glutathione-S-transferase (GST) tag and (ii) the protein affinity tag-binding ligands are selected from the group consisting of glutathione, glutathione-S-transferase (GST) tag-binding derivatives thereof, and combinations thereof.

27. The method of claim 24 , wherein (i) the affinity tag is a maltose binding protein (MBP) tag and (ii) the protein affinity tag-binding ligands are selected from the group consisting of amylose, maltose binding protein (MBP) tag-binding derivatives thereof, and combinations thereof.

28. The method of claim 24 , wherein (i) the affinity tag is chitin binding protein (CBP) tag and (ii) the protein affinity tag-binding ligands are selected from the group consisting of chitin, chitin binding protein (CBP) tag-binding derivatives thereof, and combinations thereof.

29. The method of claim 24 , further comprising:
(d) eluting the bound target protein from the polyacid-coated porous membrane, thereby forming a purified permeate comprising the target protein.

Assignees

• Univ Michigan State

Inventors

• Bruening Merlin L
• Baker Gregory L
• Bhattacharjee Somnath
• Ma Yiding

Classifications

• B01J20/22

  comprising organic material · CPC title

• C07K1/22

  Affinity chromatography or related techniques based upon selective absorption processes · CPC title

• B01D15/3828

  Ligand exchange chromatography, e.g. complexation, chelation or metal interaction chromatography · CPC title

• B01D67/0088 Primary

  Physical treatment with compounds, e.g. swelling, coating or impregnation · CPC title

• G01N1/34 Primary

  Purifying; Cleaning {(processes or apparatus for extracting or separating nucleic acids from biological samples C12N15/1003)} · CPC title