(402d) A General Graphical Design Method for Affinity Chromatography

In affinity chromatography, an adsorbent with a high selectivity for a target solute is used to isolate the target molecule from other impurities.  Once captured, the target molecule can be eluted from the column in a purified state.  Common applications of affinity chromatography include Protein A chromatography for antibody purification, Immobilized Metal Affinity Chromatography (IMAC) for protein purification, and many other capture processes based on high affinity sorbents. The well-known design method based on constant-pattern mass transfer zone analysis does not apply to small feed batches, which are insufficient to form constant-pattern frontal waves. Other literature design methods rely on simulation or experimental trials can be time-consuming and costly.  In addition, it can be difficult to optimize the process to achieve desired purity, yield, and throughput. In this study, a convenient graphical design method based on intrinsic adsorption and mass transfer parameters and dimensionless groups is developed for affinity chromatography systems with Langmuir isotherms. Only a small number of experiments are needed to obtain the intrinsic parameters. The method is tested with literature data for Protein A chromatography for antibody purification. Close agreement is obtained. One can easily visualize from the graph the effects of material properties, capture yield, and throughput on column utilization. In addition, it can easily adjust to meet various design requirements and can take into account variations in the intrinsic parameters. Various sorbents can be evaluated for cost effectiveness based on the intrinsic parameters. This method is applicable to a broad range of affinity chromatography systems.