Understanding and Enhancing Selectivity in Multimodal Chromatography

This research seeks to determine what conditions are required to achieve selective separations of similar protein variants and to provide fundamental insight into the mechanisms underlying these separations.  The retention of protein libraries on several multimodal cation-exchange systems demonstrated that the retention of many proteins proved to be sensitive to subtle changes in the ligand chemistry and geometrical presentation. All-atom explicit Molecular Dynamics (MD) simulations were then carried out to shed light on the multiple weak interactions that resulted in the unique selectivities achieved in these multimodal chromatographic systems. A range of biophysics techniques was also employed to study the energetics, kinetics and thermodynamics of protein binding to self-assembled monolayers (SAMs) of MM ligands. This work provides fundamental understanding of the nature of these interactions at the molecular level and insight into the design of MM ligands, the roles of synergy and the modulation of selectivity using fluid phase modifiers with important implications for addressing challenging problems in downstream bioprocessing.

Steven Cramer , PhD 1986, Yale University, Department of Chemical Engineering is the William Weightman Walker Professor of Chemical and Biological Engineering at Rensselaer Polytechnic Institute (RPI), Troy, New York.  He is currently conducting research on several areas related to protein-surface interactions including: prediction of protein binding affinity and multiscale modeling of chromatographic systems, design of chemically selective displacers, development of efficient antibody separation systems, fundamental studies in multimodal chromatography, novel chromatographic and diode based electrophoretic lab on chip systems, protein unfolding in chromatographic systems, chemometrics for process analytical technology, multilevel automated peptide synthesis/screening system for design of affinity peptides, smart biopolymer affinity precipitation systems, biophysics of protein interactions with surfaces, ligands and proteins, and integrated semi-continuous biomanufacturing processes. Professor Cramer is known worldwide for his expertise in separations in general.  He just stepped down as the Editor-in-Chief of the journal Separation Science and Technology after 18 years. Professor Cramer was the awarded the Alan S. Michaels Award for the Recovery of Biological Products (ACS Division of Biochemical Technology). He was also awarded Rensselaer’s School of Engineering Research Excellence Award, a Presidential Young Investigator award from the National Science Foundation, the Early Career Award from RPI as well as several teaching awards.  Professor Cramer has been elected a fellow of the AIChE, the ACS and the American Institute for Medical and Biological Engineering. He has also chaired several meetings including 2 International HIC/RPC Bioseparation Conferences, the ACS Recovery of Biological Products Meeting and the Gordon Conference on Reactive Polymers. Starting with his dissertation research under the direction of Csaba, Horváth, Prof. Cramer has published over 160 papers in peer-reviewed journals and has 9 patents. Importantly, he has produced 37 Ph.D. students who have gone on to leadership positions in the biotechnology industry and academia.