(131e) Design Calculation Procedure for Flow-through Chromatography

Flow-through chromatography (FTC) is considered to be an efficient method for separating two components as the flow is continuous. It is also suited for a single-use chromatography operation. Although several papers have been published on the flow-through chromatography process design, it is still not clear especially how the mass transfer affects the separation performance.

In this study, we have demonstrated how to design FTC based on the distribution coefficient as a function of salt concentration K(I) obtained from linear gradient elution experimental data along with the zone spreading (mass transfer) data. We have determined K-I curves of monomer and dimer from linear gradient elution (LGE) experiments. The zone spreading parameter values were evaluated based on the plate number N by using a simplified single-lumped zone spreading parameter model. Curves for monomer and dimer were numerically calculated in order to determine the sample feed volume VF that can allow complete separation. Then, VF values were calculated as a function of I. For low K values, the operation time was short whereas VF was quite small. By increasing K values (which corresponds to lowering I), VF increased. However, the separation time increased markedly. The separation time â?? the sample feed volume curves were found to be useful for designing FTC. It was also found that for difficult separations such as aggregate removal the mass transfer plays a significant role. Flow-velocity must be carefully tuned in order to increase the sample volume. For such cases monoliths or membranes are better choice.