The direct preparation of amphiphilic graft copolymers from commercial poly(vinylidene fluoride) (PVDF) using atom transfer radical polymerization (ATRP) is demonstrated. Here, direct initiation of the secondary fluorinated site of PVDF facilitates grafting of the hydrophilic comonomer. Amphiphilic comb copolymer derivatives of PVDF having poly(methacrylic acid) side chains (PVDF-g-PMAA) and poly(oxyethylene methacrylate) side chains (PVDF-g-POEM) are prepared using this method. Surface segregation of PVDF-g-POEM additives in PVDF is examined as a route to wettable, foul-resistant surfaces on PVDF filtration membranes. Because of surface segregation during the standard immersion precipitation process for membrane fabrication, a PVDF/5 wt % PVDF-g-POEM membrane, having a bulk POEM concentration of 3.4 wt %, exhibits a near-surface POEM concentration of 42 wt % as measured by X-ray photoelectron spectroscopy (XPS). This membrane displays substantial resistance to BSA fouling compared with pure PVDF and wets spontaneously when placed in contact with water.

Self-organizing blends of an amphiphilic comb polymer having a poly(methyl methacrylate) (PMMA) backbone and poly(ethylene oxide) (PEO) side chains in poly(vinylidene fluoride) (PVDF) have been examined as a means to create foul-resistant, self-healing surfaces on polymer membranes. X-ray photoelectron spectroscopy (XPS) analysis of phase inversion membranes prepared from these blends indicates substantial surface segregation of the amphiphilic component, which occurs both during the coagulation step of the phase inversion process and in subsequent annealing of the membranes in water. With annealing, a near-surface coverage of nearly 45 vol % comb polymer is produced on a membrane with a bulk comb concentration of only 3 vol %. Surface enrichment of the hydrophilic comb polymer is shown to impart significant resistance to the adsorption of bovine serum albumin (BSA). XPS analysis of membranes treated with concentrated acid shows that hydrophilic surface layers removed by acid exposure may be regenerated by further surface segregation during a subsequent heat treatment in water, resulting in partial recovery of protein adsorption resistance.

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Recent progress in mammalian cell culture process has resulted in significantly increased product titers, but also a substantial increase in process-and product-related impurities. Due to the diverse physicochemical properties of these impurities, there is constant need for new technologies that offer higher productivity and improved economics without sacrificing the process robustness required to meet final drug substance specifications. Here, we examined the use of new synthetic adsorptive hybrid filters (AHF) modified with the high binding capacity of quaternary amine (Emphaze TM AEX) and salt-tolerant biomimetic (Emphaze TM ST-AEX) ligands for clearance of process-related impurities like host cell protein (HCP), residual DNA, and virus. The potential to remove soluble aggregates was also examined. Our aim was to develop a mechanistic understanding of the interactions governing adsorptive removal of impurities during filtration by evaluating the effect of various filter types, feed streams, and process conditions on impurity removal. The ionic capacity of these filters was measured and correlated with their ability to remove impurities for multiple molecules. The ionic capacity of AHF significantly exceeded that of traditional adsorptive depth filters (ADF) by 40% for the Emphaze TM AEX and by 700% for the Emphaze TM ST-AEX, providing substantially higher reduction of soluble anionic impurities, including DNA, HCPs and model virus. Nevertheless, we determined that ADF with filter aid provided additional hydrophobic functionality that resulted in removal of higher molecular weight species than AHF. Implementing AHF demonstrated improved process-related impurity removal and viral clearance after Protein A chromatography and enabled a two-step purification process. The consequences of enhanced process performance are far reaching because it allows the downstream polishing train to be restructured and simplified, and chromatographic purity standards to be met with a reduced number of chromatographic steps.