Adsorptive membranes for trapping viruses

Patent metadata

Field	Value
Publication number	US-9375499-B2
Application number	US-77677407-A
Country	US
Kind code	B2
Filing date	Jul 12, 2007
Priority date	Jul 14, 2006
Publication date	Jun 28, 2016
Grant date	Jun 28, 2016

Abstract

A disposable, virus-trapping membrane, and a corresponding method to remove viruses from solution are described. The membrane includes a disposable, micro-porous filter membrane and a ligand immobilized on the membrane. The ligand irreversibly and selectively binds viruses. The ligand also has a pKa sufficiently high to repel antibodies via electrostatic charge repulsion.

First claim

What is claimed is:

1. A disposable, virus-trapping membrane comprising:
a disposable, micro-porous filter membrane; and
a multi-modal anion-exchange ligand immobilized on the membrane, wherein the ligand is dimensioned and configured to:
(a) bind neutral viruses;
(b) have a pKa sufficiently high to repel basic proteins via electrostatic charge repulsion; and
(c) yield a log-reduction value (LRV) of at least 1.0 for the neutral viruses disposed in a solution comprising 50 mM salt.

2. The virus-trapping membrane of claim 1 , wherein the ligand has a positive charge at pH 7.

3. The virus-trapping membrane of claim 1 , wherein the ligand has a pKa of at least 10.0.

4. The virus-trapping membrane of claim 1 , wherein the filter membrane comprises a polymer substrate selected from the group consisting of polyvinylidene difluoride, polytetrafluorethylene, polyamides, polyamide-imides, polysulfones, polyethersulfones, and polyphenylsulfones.

5. The virus-trapping membrane of claim 1 , wherein the ligand is dimensioned and configured to yield a log-reduction value (LRV) of at least 1.0 for neutral viruses disposed in a solution comprising 150 mM salt.

6. The virus-trapping membrane of claim 1 , wherein the ligand is dimensioned and configured to yield a log-reduction value (LRV) of at least 5.0 for neutral viruses disposed in a solution comprising 50 mM salt.

7. The virus-trapping membrane of claim 1 , wherein the ligand is dimensioned and configured to yield a log-reduction value (LRV) of at least 5.0 for neutral viruses disposed in a solution comprising 150 mM salt.

8. The virus-trapping membrane of claim 1 , wherein the ligand is selected from the group consisting of tyrosinol, tryptophanol, octopamine, 2-aminobenzimidazole, 1,3-diamino-2-hydroxypropane, tris(2-aminoethyl)amine, and agmatine.

9. A disposable, virus-trapping membrane comprising:
a disposable, micro-porous filter membrane; and
a ligand immobilized on the membrane, wherein the ligand is selected from the group consisting of tyrosinol, tryptophanol, octopamine, 2-aminobenzimidazole, 1,3-diamino-2-hydroxypropane, tris(2-aminoethyl)amine, and agmatine, and further wherein the ligand:
(a) binds neutral viruses;
(b) is a multi-modal anion-exchange ligand;
(c) has a pKa sufficiently high to repel basic proteins via electrostatic charge repulsion; and
(d) yields a log-reduction value (LRV) of at least 1.0 for the neutral viruses disposed in a solution comprising 50 mM salt.

10. The virus-trapping membrane of claim 9 , wherein the ligand is selected from the group consisting of tryptophanol, 2-aminobenzimidazole, tris(2-aminoethyl)amine, and agmatine, and further wherein the ligand is dimensioned and configured to yield a log-reduction value (LRV) of at least 1.0 for neutral viruses disposed in a solution comprising 150 mM salt.

11. The virus-trapping membrane of claim 9 , wherein the ligand is selected from the group consisting of tris(2-aminoethyl)amine and agmatine, and further wherein the ligand is dimensioned and configured to yield a log-reduction value (LRV) of at least 5.0 for neutral viruses disposed in a solution comprising 50 mM salt.

12. The virus-trapping membrane of claim 9 , wherein the ligand is selected from the group consisting of tris(2-aminoethyl)amine and agmatine, and further wherein the ligand is dimensioned and configured to yield a log-reduction value (LRV) of at least 5.0 for neutral viruses disposed in a solution comprising 150 mM salt.

13. A method of removing viruses from a solution suspected of containing viruses, the method comprising:
contacting a solution suspected of containing viruses with virus-trapping membrane comprising a disposable, micro-porous filter membrane and a multi-modal anion-exchange ligand immobilized on the membrane, wherein the ligand is dimensioned and configured to bind neutral viruses, has a pKa sufficiently high to repel basic proteins present in the solution via electrostatic charge repulsion, and yields a log-reduction value (LRV) of at least 1.0 for the neutral viruses disposed in a solution comprising 50 mM salt.

14. The method of claim 13 , wherein the solution is contacted with the virus-trapping membrane for a time sufficient to yield a log-reduction value (LRV) of at least 1.0 for neutral viruses disposed in the solution when the solution comprises from 0 to about 50 mM salt.

15. The method of claim 13 , wherein the solution is contacted with the virus-trapping membrane for a time sufficient to yield a log-reduction value (LRV) of at least 1.0 for neutral viruses disposed in the solution when the solution comprises from 0 to about 150 mM salt.

16. The method of claim 13 , wherein the solution is contacted with the virus-trapping membrane for a time sufficient to yield a log-reduction value (LRV) of at least 5.0 for neutral viruses disposed in the solution when the solution comprises from 0 to about 50 mM salt.

17. The method of claim 13 , wherein the solution is contacted with the virus-trapping membrane for a time sufficient to yield a log-reduction value (LRV) of at least 5.0 for neutral viruses disposed in the solution when the solution comprises from 0 to about 150 mM salt.

18. The method of claim 13 , wherein the solution is contacted with a disposable, micro-porous filter membrane comprising polyvinylidene difluoride; and the ligand immobilized on the membrane is selected from the group consisting of tyrosinol, tryptophanol, octopamine, 2-aminobenzimidazole, 1,3-diamino-2-hydroxypropane, tris(2-aminoethyl)amine, and agmatine.

19. The method of claim 18 , wherein the ligand immobilized on the membrane is selected from the group consisting of tris(2-aminoethyl)amine and agmatine.

20. A disposable, virus-trapping membrane comprising:
a disposable, micro-porous filter membrane;
a multi-modal exchange ligand immobilized on the membrane, wherein the ligand is selected from the group consisting of tryptophanol, 2-aminobenzimidazole, tris(2-aminoethyl)amine, and agmatine, and further wherein the ligand is dimensioned and configured to:
(a) bind neutral viruses;
(b) have a pKa sufficiently high to repel basic proteins via electrostatic charge repulsion; and
(c) yield a log-reduction value (LRV) of at least 1.0 for the neutral viruses disposed in a solution comprising 150 mM salt.

21. The virus-trapping membrane of claim 20 , wherein the ligand is dimensioned and configured to yield a log-reduction value (LRV) of at least 5.0 for the neutral viruses disposed in a solution comprising 150 mM salt.

22. The virus-trapping membrane of claim 20 , wherein the ligand is selected from the group consisting of tris(2-aminoethyl)amine and agmatine, and is dimensioned and configured to yield a log-reduction value (LRV) of at least 5.0 for the neutral viruses disposed in a solution comprising 150 mM salt.

Assignees

• Etzel Mark R
• Wisconsin Alumni Res Found

Inventors

• Etzel Mark R

Classifications

• B01J20/3248

  the functional group or the linking, spacer or anchoring group as a whole comprising at least one type of heteroatom selected from a nitrogen, oxygen or sulfur, these atoms not being part of the carrier as such · CPC title

• B01J20/28033

  Membrane, sheet, cloth, pad, lamellar or mat · CPC title

• B01J20/2808

  being less than 2 nm, i.e. micropores or nanopores · CPC title

• B01J20/261

  obtained by reactions only involving carbon to carbon unsaturated bonds (macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds per se C08F) · CPC title

• B01J20/3285

  Coating or impregnation layers comprising different type of functional groups or interactions, e.g. different ligands in various parts of the sorbent, mixed mode, dual zone, bimodal, multimodal, ionic or hydrophobic, cationic or anionic, hydrophilic or hydrophobic · CPC title