CTS-9416921 Cramer RPI The performance of non-linear gradient and displacement chromatography techniques for the separation of proteins will be evaluated and optimized. At present, the optimization of protein purification by chromatography is mainly empirical. A multicomponent equilibrium model has been recently developed for non-linear ion-exchange chromatography. Based on a steric mass transport (SMA) approach, this model has good predictive capabilities. A systematic evaluation of gradient and displacement chromatography will be performed using the SMA approach. Representative classes of model protein separation problems will be defined. Experiments will be conducted with appropriate combinations of proteins, stationary phase materials and pH conditions. Tests will be conducted with novel displacing agents, including some unusual low MW compounds, which are inexpensive and non-toxic. The resolution and merits of gradient and displacement chromatography will be compared. The productivity of these techniques will be analyzed and optimized using numerical techniques. The development of efficient ion-exchange chromatographic techniques for process scale purification has the potential of a significant impact on bioprocessing technology.
