See also graft chains and ionic functional groups attached to membranes (under “chromatography” and “graft chains”)

Types of Materials Used

Hollow fiber: In ultrafiltration applications, one very common membrane form for industrial and laboratory uses is the hollow fiber. Hollow fiber membranes are mounted, usually in cartridges, with the open ends of the fibers potted at each end in an adhesive plug sealed to the cylindrical cartife walls at either end thereof. The membrane barrier layer or “skin” is usually on the inside of the hollow fiber or “lumen”. The process feed usually enters one end of the hollow fiber and a concentrated solution exists at the other end (US 4,990,252).

Mircroporous:

–ceramic: Couto (US 20050260672) teaches that membranes which which separate a desired species from undersirable species without substantial clogging problems and at a rate sufficient for continuous operation of the system include microporous membranes with pore sizes typically from 0.1 to 10 micrometers and are prefeably ceramic. 

–Positively Charged Microporous membranes

Wu (US 7,223,341) discloses a positively charged microporous membrane ahving a protien binding capacity of aobut 25 mg/ml or greater that includes a hydrophilic porous substrate and a crosslinked coating that provides a fixed positive charge to the membrane. The coating can be prepared by crosslinking a composition that includes a diallylamine copolymer haivng epoxy grounds and pendant cationic groups, a polyamine such as a polyakyleneamine, and an amin reactive compoudn having a cationic group. In some bodiments, the psotively charged microporous membrane includes a hydrophilic porous substrate and a coating preapred by crosslinking a composition that includes diallylamine, a diallyldiakylammonium halide, an acrylic monomer having a quaternary ammonium group and a crosslinking agetn. 

Polysulfone type: polymers have been exensively used in the manufacture of ultrafiltration membranes becuase of excellent hydrolytic stability and high temperautre properties. Commercially avilalbe polysulfone polymers include UDEL polysulfone manufactured by Union Carbide Corp and Victrex polyethersulfone manufactured by Victrex (ICI) (US 4,990,252). Couto (US 20050260672) teaches that UF membranes which have smaller pores and are characterized by the size of the protein that will be retained are available in increments from 1000 to 1 million Dalton NMW and are commonly made of polysulfone.

Hydrophilic microporous membranes:

It is well known that membranes with hydrophilic surface are usually less prone to fouling and cake formation. Numerous attempts have been undertaken to hydrophilize UF membrane surface by blending orignal polymers with hydrophilic polymers, by sorption of hydrophilic macromolecules, by pretreatment of polysulfone (PS) membranes with poly(N-vinylpyrrolidone) (PVP), poly(vinyl alchol) or methylcellulose and by introducing ionogenic groupons onto the membrane surface. Surface charge of the membrane has also an influence on membrane fouling. If functional group swith the same charge sign as the seaprated components are introduced on the surface of polymer membranes, membrane foulind decreases. (Tischchenko “Purificaiton of polymer nanoparticles by diafiltration with polysulfone/hydrophilic polymer blend membranes” Separation and purification technology, 22(23), 2001)

–cellulose:

Cellulose is the most hydrophilic filter material in use, and this natural property of cellulose maximizes the yield of protein recovery by minimizing protein adsorption . In addition, cellulose maintains high output over long filtration times and is minimally affected by detergent. (see AsahiKasei, “PLANOVA filters” “Virus removal for biotherapeutic products).

The virus removal filter PLANOVA is composed of the hollow fibre membrane BMM made of a cuprammonium regenerated cellulose, is able to remove particles effectively, mianly based on their size. (Manabe, “Removal of virus through novel membrane filtration method” pp. 81-90).  PLANOVA filters are commercially available from Asahi Chemical Ind. Co. Ltd. 

WO01/14047 describes a filtration membrane for physiologically active substances wherein the logarithmic removing ratio for parovivus is 3 or more. The main membrane comprises hollow fibers made of cellulose. It has been described as disadvantageous in that when it is wet with water, the mechanical strenght is low, filtration pressure cannot be made higher and thus it is difficult to achieve a high permeation rate.

—-Cuprammonium Regnerated Cellulose

AsahiKasei sells Planova filters which utilize a hollow-fiber microporous membranemposed of naturally hydrophilic cuprammonium-regenerated cellulose inside a polycarbonate housing. The filters are sold under the tradenames Planova 15N, 20N, 35N and 75N. The 75N filter is designed to remove impurities or aggregated proteins prior to final virus filtration.

–Synthetic Polymers

—-Polyvinylidene fluoride (PVDF):

Koguma (US2006/0016748 and EP1552878A1) discloses a hydrophilic microporous membrane comprising a thermoplastic resin such as polyolefin and fluoride resins (e.g., polyvinylidene fluoride). The vinyl group is graft polymerized to impart the surface of the micropores with hydrophilicity thereby reducing adsorption of physiologically active substances such as protein.

Yanagida (12/993512) discloses that many methods for hydrophilizing a membrane formed of a synthetic polymer, such as a method of graft polymerizing a hydrophilic vinyl monomer with one vinyl group onto the pore surface of a microporous membrane at a graft ratio of 3 to 50% (WO2004/035180), a method of bonding a polymer formed of a polyfunctional acrylate or methacrylate to a membrane via a crosslinking agent (JP-A-2000-1548), or a method of impregnating a membrane with a solution incluidng a polymerization initiator and a hydrophilic monomer, and polymerizing the monomer inside the pores of the membrane (WO91/16968). The purpose is to imrorve filterability of the membrane formed of a hydrophboic synthetic polymer with respect to the intermediate protein product.

ASAHI KASEI BIOPROCESS sells hydrophilic modified polyvinylidene fluoride (PVDF) hollow fiber membranes under the trademark Plnova BioEX.

–Polyether sulfone (PES): is reported by the manufacturers (Millipore, Bedformd MA) to filter large volumes of sample without protein binding. PES membranes are cheaper than those made of PVDF and larger volume of sewage sample was reportedly filtered with the same PES filter unit. PES membranes are also cheaper than PVDF membranes (Moce-Llivina (J. Virological Methods, 109, 2003, 99-101).

 

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