Understanding Membrane Performance during Combined Tangential Flow and Depth Filtration

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 traditional downstream clarification and purification operations. This is especially true for the initial clarification steps. Depth filtration, centrifugation and tangential-flow filtration (TFF) are used to remove cells, cell debris and other impurities. Depth filters consist of a thick porous bed that can trap particles within the filter matrix. Screen type filters on the other hand largely reject particulate matter by surface filtration. In tangential flow filtration the feed flows parallel to the membrane surface while the filtrate flows perpendicular to the feed. This mode of operation tends to suppress cake growth. The BioOtimal MF-SL from Asahi KASEI represents a hybrid TFF-depth filter. The performance and especially fouling behavior of the BioOptimal filter is not well understood. Here a combined pore blockage and cake filtration model has been developed to describe the fouling behavior of this filter in normal flow mode whereas a resistance in series model has been used to describe the performance in TFF mode. Significant insights have been obtained into the fouling mechanism and optimal operation conditions of this filter.