(433a) Environmentally-Responsive Membrane Adsorbers for Hydrophobic Interaction Chromatography

Hydrophobic interaction chromatography (HIC) is a technology capable of purifying high-value products such as proteins and pharmaceuticals with high selectivity.  A feed stream containing the protein product is loaded at conditions which favor interactions between the hydrophobic proteins and the stationary phase (typically resin).  The conditions are then changed, via introduction of a low conductivity solution, reducing these interactions.  The protein which bound in the hydrophobic condition is then collected as a purified product.  Unfortunately, HIC and other types of resin-based chromatography are very slow, yield only small volume of product, and are expensive to operate due to the large volume of chemicals used.  Membrane based chromatography is an emerging protein purification process capable of quickly producing large volume of product.  Specifically, membrane chromatography is appealing for purification of proteins in low concentrations (< 1 mg/mL). 

Responsive membrane adsorbers for HIC were developed by grafting responsive polymer chains onto the surface of hydrophilic membranes, which were used to minimize nonspecific protein binding.  The grafted polymer undergoes a conformational change (hydrophilic to hydrophobic) in the presence of ammonium sulfate salt.  It is shown that the response of the grafted polymer chains yields improved HIC performance, specifically high binding capacities and recoveries.  The effect of grafted polymer chain density on the stimulus response was investigated, and an optimal density determined.  Membranes modified at this optimal density were tested at various loading buffer ionic strengths.  Binding capacities and recoveries for these responsive HIC adsorbers compared  favorably to, and in numerous instances surpassed, published values for industrial resin-based adsorbers.