EAGER: Directionally Aligned Macroporous Ceramics with In-Situ Synthesized Functional Polymer Microgels as a Platform for Next Generation Membrane Chromatography

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A monoclonal antibody is a protein capable of specifically binding a targeted molecule or receptor. Through this specific binding, antibodies become highly active drugs with reduced side effects. The market for biopharmaceuticals, such as monoclonal antibodies, is growing rapidly, with worldwide sales expected to reach $125 billion by 2020. The growing demand for antibodies and related biologics has driven up the cost of treatment using these products. As a result, the biopharmaceutical industry is increasingly under pressure from regulators, healthcare providers, and consumers to decrease production and treatment costs. Purification of monoclonal antibodies during bioprocessing is both slow and costly, representing more than 80% of the manufacturing expense. Membrane adsorbers are emerging as more efficient separation systems compared to conventional resin column beds in downstream biopharmaceutical manufacturing. Membrane adsorbers can be operated with much higher flow rates and throughput and, thus, are ideally suited for reducing processing times and production costs. The overarching goal of the EAGER project is to build the foundation for a new generation of macroporous membrane materials and modules that overcome the capacity, selectivity, and throughput limitations of existing commercial membrane adsorbers. To achieve this goal, functional polymers with high protein binding capacity and selectivity will be coupled with high surface area macroporous ceramic scaffolds, which can be configured into scalable modules for continuous bioprocessing. Within the biopharmaceutical manufacturing community, the desired transition to precisely targeted therapeutics based on monoclonal antibodies (mAb) depends on dramatically increasing manufacturing speed and reducing production costs. Although membrane chromatography has demonstrated advantages over standard column chromatography, including higher throughput and lower cost, it is limited by low protein binding capacity and selectivity of commercial membrane adsorbers as well as complex module configurations and fabrication. Consequently, there is a critical need for a new generation of membrane adsorber materials that can be readily configured into scalable modules with high binding capacity and selectivity. This project seeks to build a foundation for the next generation of scalable membrane adsorber materials and modules for downstream biopharmaceutical manufacturing that overcome the limitations of existing commercial membranes. This EAGER project will focus on achieving two specific objectives: the design, preparation, and characterization of 1) salt-tolerant membrane adsorbers with high protein binding capacity for mAb purification; and 2) membrane adsorbers for selective mAb capture and recovery from bioreactor harvests. The strategy to establish the foundation for these membrane adsorbers relies upon the design of a family of macroporous ceramics with tunable pore size, structure, and morphology using directional solution freeze casting. Building upon the porous scaffolds, a two-pronged approach will be undertaken. Firstly, in-situ polymerization and phase-separation micromolding will be employed to prepare functional polymer microgels inside macroporous ceramic scaffolds that contain high concentrations of ligands with large protein binding capacity and selectivity. Secondly, conformal microgel coatings of highly tortuous dendritic pores will be prepared to provide hydrodynamic trapping and adsorption sites inside macroporous scaffolds. Fundamental understanding of the material preparation and functionalization process and protein binding capacity and selectivity will be developed.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.