Development of Multimodal Membrane Adsorbers for Protein Separations

Development of multimodal membrane adsorbers for protein separations

Juan Wang, Scott M. Husson

Department of Chemical and Biomolecular Engineering, Clemson University, Clemson, SC 29634 USA

Development of efficient bioseparation processes is recognized as an urgent need facing the pharmaceutical and biotechnology industries, particularly for high dose chronic therapies. This presentation will describe our latest research efforts to develop multimodal membranes as a new class of high-productivity chromatographic materials for applications in the purification of therapeutic proteins. Multimodal membranes incorporate ligands that can bind proteins through a combination of columbic interactions, hydrophobic interactions, and/or hydrogen bonding. This advancement has the potential to widen the operation ranges for chromatographic separations. Using a membrane support is appealing because dynamic protein binding capacities of these materials generally do not depend on throughput. Thus, volumetric productivity can be very high compared to more traditional chromatography materials. This will help to alleviate the tradeoff that manufacturers must now make between load processing time and dynamic binding capacity. Membranes were prepared using surface-initiated ATRP (atom transfer radical polymerization) of poly(glycidyl methacrylate) ‘tentacles’ from regenerated cellulose membranes. In a second step, 4-mercaptobenzoic acid was coupled to the membranes by an epoxide ring-opening reaction. ATR-FTIR measurements were carried out to support successful ligand incorporation. Protein binding experiments with bovine immunoglobulin G showed that static binding capacities of the multimodal membranes were dependent on pH and ionic strength. A maximum binding capacity of > 60 mg IgG/mL was found near the isoelectric point of the protein.