Multimodal ligands bind proteins by a combination of ionic interactions, hydrophobic interactions and/or hydrogen bonding. Multimodal resin chromatography is gaining popularity as a purification tool for biologics, as it can accommodate purification needs for challenging feedstocks where single mode methods fail. The novelty of the proposed concept is that multimodal ligands are used to develop advanced membrane adsorbers. Using a membrane support is appealing because dynamic protein binding capacities of these materials will 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. Performance testing will demonstrate that the multimodal functionality can expand the loading operating space for chromatographic separations beyond what is possible with single mode materials.
The program will employ and further advance the strategies developed in our lab to design membrane adsorbers with dynamic binding capacities that exceed traditional materials. Specifically, the multimodal membrane adsorbers will be prepared using an advancement called surface-initiated AGET (activators generated by electron transfer) ATRP (atom transfer radical polymerization), which simplifies the modification procedure and enhances membrane manufacturability. This method of polymerization is unique for this application because it gives us molecular-level control over the nanostructure of the modification layer. Fundamental studies on multimodal polymer nanolayers will be done in parallel to understand how the structural properties of these modification layers impact protein binding capacities, adsorption isotherms, and adsorption kinetics. Adsorption data will be used to build a predictive model for protein breakthrough on multimodal membrane adsorbers and compare predictions to experimental breakthrough curves for various proteins under a range of operating conditions. Finally, performance parameters will be compared to commercial products, which currently are limited to resin-based materials.
Development of efficient bioseparation processes is recognized as an urgent need facing the pharmaceutical and biotechnology industries, particularly for high dose chronic therapies. The proposed use-inspired basic research program will develop multimodal membranes for high productivity protein chromatography. The integration of advanced multimodal functionality and a membrane adsorber platform will provide a new class of chromatography materials to accomplish selective separations with minimal load conditioning at high volumetric throughput. Considering that a high percentage of the total cost of bioprocesses is due to downstream recovery and purification, our membrane materials are a potentially transformative new purification tool to help the pharmaceutical and biotechnology industries provide lower cost therapeutic products for the US consumer. Societal benefits from research require dissemination to potential users in formats beyond the scholarly journal article. Thus, in addition to disseminating findings through publications and presentations, our program will test a new virtual platform for timely dissemination of research findings. The virtual poster conference will allow face-to-face discussions among researchers in the US and internationally without the associated time and cost for travel to a common physical location.
