A validated model for the simulation of convective affinity chromatography processes

Affinity chromatography represents one of the most important and widely used unit operation in the biotechnology industry. Traditional packed bead columns suffer from several limitations such as high pressure drop, slow mass transfer through the diffusive pores and strong dependence of the binding capacity on flow rate. One possible alternative to overcome these drawbacks is represented by convective media columns packed with affinity membrane or monoliths. To promote their application in large scale processes, it is imperative to have a reliable simulation tool suitable to predict the process performance at all scales. This work presents and validates an effective model for convective affinity chromatography processes. The model accounts for axial convection, longitudinal dispersion in the micro-porous matrix and affinity binding, and includes also extra-column effects associated to mixing volumes and delay times of the circuit. The mathematical description takes into account all the different chromatographic steps: adsorption, washing and elution. Model validation is accomplished by comparing simulation results with an extensive set of experimental data obtained using affinity membranes and monoliths. The good agreement with experimental data for the different supports considered, demonstrates the model accuracy in describing all the relevant transport mechanisms involved. The simulation model was able to predict the chromatographic cycle of IgG capture from a cell culture supernatant based on data obtained for pure IgG solutions. Furthermore, a proper study of the model parameters for the two convective media is addressed, elucidating the main operative differences between the membrane and monolithic columns for protein affinity chromatography.