Methods for Optimizing Bio-Chromatography Processes for Repeated Cyclic Operations

Simple methods for calculating the productivity of chromatography processes are proposed, which consider both the productivity P defined by P = (mass recovered)/[(bed volume)(cycle time)] and the buffer consumption per cycle, V_C. The method was applied to model separation systems (polyphenol separations by polystyrene divinylbenzene resins with the ethanol-water mixture mobile phase, and protein separations by ion-exchange chromatography). The distribution coefficient K was determined as a function of mobile phase concentration I by linear gradient elution experiments. The HETP-mobile phase velocity u curves were determined as a function of I. By using K and HETP, the iso-resolution curve was calculated, from which the productivity was determined as a function of I. It was found that there is an optimum I, where the highest productivity with the minimum amount of mobile phase consumption is obtained.