Multimodal membrane adsorbers for the purification of therapeutic proteins at high ionic strength (Husson)

Development of efficient separation processes for biologics has been highlighted as one of the most pressing challenges facing the pharmaceutical and biotechnology industries (Chung et al., 2010). Demand for biologics is high, and it is estimated that eight out of the top ten drugs will be biologics in 2016 (Coker, 2012). Without intervention to improve the downstream manufacturing capacity, there will be increasing shortages of these products, especially for those used in high doses to treat chronic diseases. To improve process economics and meet market demand, manufacturers will require higher productivity and higher resolution separation techniques.  The Husson Research Group at Clemson has made tremendous advances in the development of adsorptive membranes to address these needs. His lab pioneered the use of controlled graft polymerization to coat the internal membrane pore surfaces of membranes with polymer nanolayers that provide a large number of protein binding sites (Singh et al., 2008). The nanolayers comprise a field of polymeric ‘tentacles’ with adsorptive functionality that extend into the membrane pore volume, providing a scaffold for protein molecules to adsorb. The strategy allows fine control over the nanolayer structure to avoid pore blocking and hindered transport of large adsorptive compounds, such as proteins. Work by his group has dispelled two common misperceptions by showing that (1) membrane adsorbers can have higher capacities than chromatography resins used in the purification of biologics, and (2) membrane chromatography can be a higher resolution process than resin chromatography in the purification of biologics from cell lysate (Bhut et al., 2010). Most recently, his group developed a new class of multimodal membrane adsorbers for protein purifications at high ionic strength (Wang et al., 2014), substantially improving their tolerance of feedstock conditions relative to conventional ion-exchange media. The complete body of work has provided a training ground for numerous PhD students and undergraduate researchers, a number of whom have received national recognition for their work.

The REU student will work on multimodal membrane adsorbers, a new class of materials developed in the Husson lab for the purification of biologics. The goal of this REU project will be to understand how the chemical properties of multimodal membrane coatings impact protein binding capacities and adsorption and desorption kinetics under conditions of high ionic strength. The student will learn how to prepare multimodal membranes with different surface chemistries using graft polymerization strategies developed in the Husson lab. She or he will measure adsorption isotherms and collect kinetic data that are needed to establish the minimum residence time that can be used for flow through a membrane bed without suffering a decrease in dynamic capacity. In addition to learning how to use and analyze data from state-of-the-art equipment, the student will receive high-quality mentoring from a senior PhD student and Dr. Husson.

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