(468b) Understanding Membrane Fouling during a Combined Tangential-Flow and Depth Filtration Process

The rapid advancement in upstream cell culture operations has led to a significant increase in product titers. However, this high-level of productivity is accompanied by a rather high cell density which places a significant burden on the traditional downstream clarification and purification operations, especially during the initial clarification and capture steps. Depth filtration, centrifugation and tangential-flow filtration (TFF) have been used to remove cells, cell debris and other impurities. Depth filter consists of a thick porous bed that can trap particles within the filter in contrast to screen type filters that largely reject particulate matter based on surface filtration. On the other hand, the tangential flow of the feed to the membrane surface leads to the suppression of cake growth during TFF operation. BioOptimal MF-SL from Asahi KASEI operates as a hybrid TFF-depth filter. However, the plugging mechanism(s) for BioOptimal MF-SL and other hybrid filters are poorly understood. Here a combined pore blockage and cake filtration model has been able to describe well the fouling mechanism of this hybrid filter in the normal flow mode whereas a resistance in series model has been able to predict performance of the filter operated in the TFF mode. Significant insights have been obtained in understanding the fouling mechanism and optimal operation condition of this hybrid filter.