Ultrafiltration membranes and methods of making and use of ultrafiltration membranes

Abstract

An inherently hydrophobic polymer membrane substrate having its surface rendered hydrophilic with a hydroxyalkyl cellulose and having a throughput greater than about 1500 L/m 2 is provided. A process for making the membrane also is provided which includes a step of autoclaving in boiling water and/or steam or submerging in boiling water. The membrane is useful for removing virus from a protein solution.

1 . A virus-retentive ultrafiltration membrane having a hydrophilic surface and an initial LRV of at least 4.0 for PhiX174 which comprises an ultrafiltration substrate membrane having a surface, said surface being rendered hydrophilic with a hydroxyalkyl cellulose, said hydrorophilic surface being treated to a step selected from the group consisting of (a) autoclaving in the presence of steam or water; and (b) submerging in boiling water; said ultrafiltration membrane having a throughput greater than about 1000 L/m 2 .  
   
   
       2 . The ultrafiltration membrane of  claim 1  comprising a multilayer membrane including a microfiltration layer having an inherently hydrophobic surface which is rendered hydrophilic with a hydroxyalkyl cellulose  
   
   
       3 . The ultrafiltration membrane of  claim 1 , wherein said hydroxyalkyl cellulose is hydroxypropyl cellulose.  
   
   
       4 . An ultrafiltration membrane having a hydrophilic surface which comprises a substrate membrane having at least one support layer formed from a first sulfone polymer having a first outside surface, an ultrafiltration layer formed from a second sulfone polymer having a second outside surface, said first outside surface and said second outside surface being rendered hydrophilic with a hydroalkyl cellulose, said hydrophilic surface being treated to a step selected from the group consisting of (a) autoclaving in the presence of steam or water; and (b) submerging in boiling water; said multilayer ultrafiltration membrane having a throughput greater than about 1000 L/m 2 .  
   
   
       5 . The multilayer ultrafiltration membrane of  claim 4  wherein said first sulfone polymer and said second sulfone polymer are the same sulfone polymer.  
   
   
       6 . The multilayer ultrafiltration membrane of  claim 5 , wherein said sulfone polymer is polysulfone.  
   
   
       7 . The multilayer ultrafiltration membrane of  claim 5 , wherein said sulfone polymer is polyethersulfone.  
   
   
       8 . The multilayer ultrafiltration membrane of  claim 4 , wherein either said first sulfone polymer of said second sulfone polymer is polysulfone.  
   
   
       9 . The multilayer ultrafiltration membrane of  claim 4 , wherein either said first sulfone polymer of said second sulfone polymer is polyethersulfone.  
   
   
       10 . The multilayer ultrafiltration membrane of  claim 4 , having a throughput greater than about 1500 L/m 2 .  
   
   
       11 . The multilayer ultrafiltration membrane of  claim 4 , wherein the hydroxyalkyl cellulose is hydroxypropyl cellulose.  
   
   
       12 . The multilayer ultrafiltration membrane of  claim 10 , wherein the hydroxyalkyl cellulose is hydroxypropyl cellulose.  
   
   
       13 . The process for forming an ultrafiltration membrane having a throughput greater than about 1000 L/m 2  which comprises: 
 (a) providing a substrate membrane having at least one microporous layer formed from a first polymer having a first outside surface, and an ultrafiltration layer formed from a second polymer having a second outside surface,    (b) contacting the first outside surface and said second outside surface with a solution of a hydroxyalkyl cellulose to adsorb said hydroxyalkyl cellulose onto or into said first outside surface and said second outside surface,    (c) optionally removing excess hydroxyalkyl cellulose from said substrate membrane to produce a surface modified substrate membrane.    (d) optionally drying said surface modified substrate membrane to form a dry modified substrate membrane and    (e) subjecting the surface modified substrate membrane from either step b, step (c) or step (d), to a step selected from the group consisting of (1) autoclaving in the presence of steam or water; and (2) submerging in boiling water.    
   
   
       14 . The process of  claim 13 , wherein step (e) is conducted with boiling water.  
   
   
       15 . The process of  claim 13 , wherein step (e) is conducted with steam.  
   
   
       16 . The process of  claim 1 , wherein step (e) is by submerging in boiling water.  
   
   
       17 . The process of  claim 13 , wherein the hydroxyalkyl cellulose is hydroxypropyl cellulose.  
   
   
       18 . The process for forming a multilayer ultrafiltration membrane having a throughput greater than about 1000 L/m 2  which comprises: 
 (a) providing a substrate membrane having at least one microporous layer formed from a first sulfone polymer having a first outside surface, and an ultrafiltration layer formed from a second sulfone polymer having a second outside surface,    (b) contacting the first outside surface and said second outside surface with a solution of a hydroxyalkyl cellulose to adsorb said hydroxyalkyl cellulose onto or into said first outside surface and said second outside surface,    (c) optionally removing excess hydroxyalkyl cellulose from said substrate membrane to produce a surface modified substrate membrane,    (d) optionally drying said surface modified substrate membrane to form a dry modified substrate membrane and    (e) subjecting the surface modified substrate membrane from step b, step (c) or step (d), to a step selected from the group consisting of    (1 )autoclaving in the presence of steam or water; and (2) submerging in boiling water.    
   
   
       19 . The process of  claim 18 , wherein step (e) is conducted with boiling water.  
   
   
       20 . The process of  claim 18 , wherein step (e) is conducted with steam.  
   
   
       21 . The process of  claim 10 , wherein the step (e) is by submerging in boiling water.  
   
   
       22 . The process of  claim 18 , wherein a solvent for the solution in step (b) is water and between about 5 and 100 vol. % isopropanol.  
   
   
       23 . The process of  claim 18 , wherein the hydroxyalkyl cellulose is hydroxylpropyl cellulose.  
   
   
       24 . The process of  claim 22 , wherein the hydroxyalkyl cellulose is hydroxylpropyl cellulose.  
   
   
       25 . The process of  claim 18 , wherein said first sulfone polymer and said second sulfone polymer are the same sulfone polymer and said same sulfone polymer is polysulfone.  
   
   
       26 . The process of  claim 18 , wherein said first sulfone polymer and said second sulfone polymer are the same sulfone polymer and the same sulfone polymer is polyethersulfone.  
   
   
       27 . The process of  claim 18 , wherein either said first sulfone polymer or said second sulfone polymer is polysulfone.  
   
   
       28 . The process of  claim 18 , wherein either said first sulfone polymer or said second sulfone polymer is polyethersulfone.  
   
   
       29 . The process of removing virus from a protein solution which comprises contacting the protein solution with the ultrafiltration membrane of  claim 1  under conditions to effect retention of said virus on said membrane and to effect passage of protein in solution through said membrane.  
   
   
       30 . The process of removing virus from a protein solution which comprises contacting the protein solution with the ultrafiltration membrane of  claim 4  under conditions to effect retention of said virus on said membrane and to effect passage of protein in solution through said membrane.  
   
   
       31 . The process of removing virus from a protein solution which comprises contacting the protein solution with the ultrafiltration membrane of  claim 13  under conditions to effect retention of said virus on said membrane and to effect passage of protein in solution through said membrane.  
   
   
       32 . The process of removing virus from a protein solution which comprises contacting the protein solution with the ultrafiltration membrane of  claim 18  under conditions to effect retention of said virus on said membrane and to effect passage of protein in solution through said membrane.