Charged filtration membranes and uses therefor

• US 20030178368A1
• Filed: 04/16/2003
• Published: 09/25/2003
• Est. Priority Date: 07/30/1999
• Status: Active Grant

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: van Reis, Robert D.
• Granted Patent: US 7,001,550 B2
• Time in Patent Office: Days
• US Class Current: 210/649
• CPC Class Codes: B01D 61/145 Ultrafiltration
• CPC Class Codes: B01D 67/00933 by addition of a layer chemically bonded to the membrane
• CPC Class Codes: B01D 69/02 characterised by their properties
• CPC Class Codes: B01D 71/10 Cellulose; Modified cellulose
• CPC Class Codes: B01D 71/22 Cellulose ethers
• CPC Class Codes: C07K 1/34 by filtration, ultrafiltration or reverse osmosis

Abstract

The invention relates to charged filtration membranes and their use for separation of a protein from solvent, low molecular weight solutes or a mixture of proteins. Modification of the membranes to generate charge includes modification of membrane pores to alter charge within a pore and alter the size of a pore. Consequently, the protein is separated from other solutes in a mixture based on size as well as net protein charge and membrane charge.

Claims

1. A filtration membrane comprising a covalently attached charged compound,

wherein membrane sieving for a solute is improved by at least 1.5 fold relative to the membrane lacking the charged compound,

wherein a sieving versus permeability curve is shifted to lower sieving values relative to a curve obtained with a membrane lacking the charged compound, and

wherein the filtration membrane comprises a cellulose polymer.

2. The membrane of claim 1, wherein the membrane is a composite regenerated cellulose membrane.

3. The membrane of claim 1, wherein membrane permeability is substantially the same for the membrane lacking the charged compound.

4. The membrane of claim 1, wherein permeability is reduced less than sieving is improved relative to a membrane lacking the charged compound.

5. The filtration membrane of claim 1, wherein membrane pore size distribution is reduced relative to the membrane lacking the charged compound.

6. The filtration membrane of claim 1, the compound comprising a linker.

7. The filtration membrane of claim 6, wherein the linker comprises a heteroatom selected from the group consisting essentially of N, O, S, and P.

8. The filtration membrane of claim 6, wherein the linker is selected from the group consisting essentially of an alkyl chain of from 1 to 20 carbon atoms, a branched alkyl chain of from 1 to 20 carbon atoms, a ring structure, a carbohydrate, a saccharide, a dextran, and an amino acid.

9. The filtration membrane of claim 1, wherein the charge is positive.

10. The filtration membrane of claim 9, wherein the compound comprises a charged moiety selected from the group consisting of an amine and a quaternary ammonium ion.

11. The filtration membrane of claim 1, wherein the charge is negative.

12. The filtration membrane of claim 11, wherein the compound comprises a charged moiety selected from the group consisting of an acid, a sulfonic acid, and a carboxylic acid.

13. The filtration membrane of claim 1, wherein the membrane is selected from the group consisting of cellulose, composite regenerated cellulose (CRC), cellulose diacetate and triacetate, cellulose nitrate, and cellulose diacetate/cellulose nitrate blends.

14. The filtration membrane of claim 11, wherein the covalently attached charged compound is attached by an ether linkage.

15. A method of preparing a charged filtration membrane of claim 1, the method comprising:

contacting the membrane with a reactive charged compound; and

reacting surface reactive groups on the membrane with a reactive group of the charged compound such that the charged compound is covalently attached to the membrane.

16. The method of claim 15, wherein during the contacting, the reactive charged compound passes through a plurality of membrane pores.

17. The method of claim 16, wherein the membrane comprises a first side and a second side, the reactive compound passes from the first membrane side to the second membrane side through a plurality of membrane pores, and the contacting further comprises recirculating the reactive compound from the second membrane side to the first membrane side at least once.

18. The method of claim 17, wherein the membrane surface reactive groups are on the exterior membrane surface and on the surface of a plurality of pores of the membrane.

19. A method of preparing a charged filtration membrane of claim 1, the method comprising:

contacting the membrane with a first compound comprising a reactive group;

reacting surface reactive groups on the membrane with the reactive group of the first compound such that the first compound is covalently attached to the membrane;

reacting the attached first compound with a second compound, the second compound comprising a charged group, such that the charged group is covalently attached to the first compound.

20. The method of claim 19, wherein during the contacting, the first and second compounds pass through a plurality of membrane pores.

21. The method of claim 20, wherein the membrane comprises a first side and a second side, and wherein during the contacting the first and second reactive compounds pass from the first membrane side to the second membrane side through a plurality of membrane pores, and the contacting further comprises recirculating the reactive compound from the second membrane side to the first membrane side at least once.

22. The method of claim 21, wherein the membrane surface reactive groups are on the exterior membrane surface and on the surface of a plurality of pores of the membrane.

23. A method of separating a desired protein from at least one other protein of a mixture of proteins in an aqueous buffered solution, the method comprising:

altering the pH of the solution such that the desired protein has a net charge and a protein to be separated from it is neutral or has a net charge that is opposite the net charge of the desired protein;

contacting the protein mixture with the charged filtration membrane of claim 1, wherein the desired protein and the membrane have like net charges;

separating the desired protein from the neutral protein and the oppositely charged protein by retaining the desired protein upstream of the membrane and filtering the neutral or oppositely charged protein through the membrane;

repeating the altering, contacting, and separating steps until the desired protein is separated from at least one other protein of the mixture.

24. A method of separating a desired protein from at least one protein of a mixture of proteins in an aqueous buffered solution, the method comprising:

altering the pH of the solution such that the desired protein is neutral and a protein to be separated from it has a net charge that is the same as the net charge of the filtration membrane;

contacting the protein mixture with the charged filtration membrane of claim 1;

separating the desired protein from the charged protein by retaining the charged protein upstream of the membrane and filtering the desired protein through the membrane;

repeating the altering, contacting, and separating steps until the desired protein is separated from a chosen number of proteins of the mixture.