Ultrafiltration membranes and methods of making

Abstract

The present invention is an integral multilayered composite membrane having at least one ultrafiltration layer made by cocasting or sequentially casting a plurality of polymer solutions onto a support to form a multilayered liquid sheet and immersing the sheet into a liquid coagulation bath to effect phase separation and form a multilayered composite membrane having at least one ultrafiltration layer.

1 .) An unsupported integral multilayer composite ultrafiltration membrane comprised of at least a first porous membrane layer having a first side and an equivalent second side, and at least a second porous membrane layer having an equivalent first side and a second side, the junction of the first layer and the second layer being integral and having a transition zone of porosity from said equivalent first side of said second layer through said equivalent second side of said first layer, wherein at least one of said layers is an asymmetric ultrafiltration membrane. 
     
     
         2 .) The membrane of  claim 1 , wherein the first layer is a skinned asymmetric ultrafiltration membrane layer and the second layer is a microporous membrane layer. 
     
     
         3 .) The membrane of  claim 1 , wherein the first layer is a skinned asymmetric ultrafiltration membrane layer and the second layer is an asymmetric ultrafiltration membrane layer. 
     
     
         4 .) The membrane of  claim 1 , wherein the first layer is a thin microporous ultrafiltration membrane layer and the second layer is asymmetric ultrafiltration membrane layer. 
     
     
         5 .) The membrane of  claim 1 , wherein the first layer is a skinned asymmetric ultrafiltration membrane layer and the second layer is an asymmetric ultrafiltration membrane layer, and wherein the first ultrafiltration membrane layer has a MWCO higher than the second ultrafiltration membrane layer. 
     
     
         6 .) A process for forming an integral multilayered composite ultrafiltration membrane compromising the steps of
 operatingly positioning a polymer solution applying apparatus having at least two dispensing outlets relative to a moving carrier surface, and;   supplying each dispensing outlet with a different polymer solution, and;   applying said solutions onto said moving carrier surface so as to create a multiple layer coating on said carrier, and wherein;   said multiple layers are dispensed with essentially no time interval between successive layers being applied, and;   subjecting said multiple liquid layers to a phase separation process so as to form a wet multilayer ultrafiltration membrane.   
     
     
         7 .) A process for forming an integral multilayered composite ultrafiltration membrane compromising the steps of
 operatingly positioning a polymer solution applying apparatus having at least two dispensing outlets relative to a moving carrier surface, and;   supplying each dispensing outlet with a different polymer solution, and;   applying said solutions onto said moving carrier surface so as to create a multiple layer coating on said carrier, and wherein;   said multiple layers are dispensed sequentially and the previous layer is only partially phase separated before each successive layer is applied, and;   subjecting said multiple liquid layers to a phase separation process to complete phase separation and to form a wet multilayer ultrafiltration membrane.   
     
     
         8 .) The process of  claim 6  wherein the membrane is then dried. 
     
     
         9 .) The process of  claim 6  wherein the membrane is then washed. 
     
     
         10 .) The process of  claim 6  wherein the membrane is then washed and dried. 
     
     
         11 .) The process of  claim 7  wherein the membrane is then dried. 
     
     
         12 .) The process of  claim 7  wherein the membrane is then washed. 
     
     
         13 .) The process of  claim 7  wherein the membrane is then washed and dried. 
     
     
         14 .) A virus removal methodology, suitable for conducting a high-flux fluid separation of a virus from a protein in the course of biopharmaceutical manufacture, the methodology comprising the steps of:
 (a) providing a filtration device comprising a housing having a fluid inlet and a filtrate outlet, and containing at least one multilayered composite membrane having at least one ultrafiltration layer produced from at least two polymer solutions membranes, wherein:
 (i) said composite membranes are each substantially hydrophilic, 
 (ii) said composite membranes are each capable of substantially preventing the passage therethrough of said virus and substantially permitting the passage therethrough of said protein, 
 (iii) said composite membranes have each a tight-side and an open-side, the average surface pore size of said tight-side being less than the average surface pore size of said open-side, and 
 (iv) the foremost composite membrane is oriented such that fluid introduced into said housing through the fluid inlet commences passage through said foremost asymmetric membrane through its open-side; 
   (b) providing a manufactured protein-containing solution, wherein the predominant solute in said solution is said protein, and wherein the solution is prone to contamination by said virus; and   (c) flowing said manufactured protein-containing solution through said filtration device under conditions sufficient to effect substantial passage of said protein through each of said composite membranes and out of said housing through said filtrate outlet, whereby any of said virus contaminating said manufactured protein-containing solution, being substantially prevented from passage through said asymmetric membranes, is substantially removed therefrom.   
     
     
         15 .) The virus removal methodology of  claim 14  wherein the composite membranes form a pleated tube. 
     
     
         16 .) The virus removal methodology of  claim 14  wherein each of said composite membranes are substantially identical in their composition and porosity, and wherein the porosity of each of said asymmetric membranes is defined to enable performance of the virus removal methodology, yielding a log reduction value (LRV) greater than 6 and a protein passage greater than 98%. 
     
     
         17 .) A filtration capsule, suitable for use in virus removal methodologies, comprising a tubular housing though which a fluid process stream can be conducted, the housing having a fluid inlet and a filtrate outlet, and containing a pleated tube composed of one, two or three interfacially-abutting multilayered composite membranes having at least one ultrafiltration layer produced from at least two polymer solutions membranes, wherein the pleated tube is positioned within said process stream between said fluid inlet and said filtrate outlet, and wherein each of said composite membranes is:
 (a) substantially hydrophilic,   (b) capable of substantially preventing the passage therethrough of viruses,   (c) provided with a tight-side and an open-side, the average pore size of said tight-side being less than the average pore size of said open-side, and   (d) oriented such that fluid introduced into said housing through the fluid inlet commences passage through each asymmetric membrane through its open-side.   
     
     
         18 .) The virus removal methodology of  claim 14  wherein the filtration device employed in said methodology is the filtration cartridge of  claim 19 . 
     
     
         19 .) The filtration capsule of  claim 17  wherein the asymmetric membranes are each capable of substantially permitting the passage therethrough of protein. 
     
     
         20 .) The filtration capsule of  claim 17  wherein each asymmetric membrane is composed of polyethersulfone.