Effect of density variations and buoyancy on flow in small-scale depth filter capsules

Depth filters are widely employed to clarify cell culture fluids in bioprocessing, with cells, cell debris, and intra- and extra-cellular impurities (e.g. DNA and host cell proteins) removed based on their size as well as adsorptive interactions within the depth of the porous media. Some large-scale depth filters are designed to operate with the filter media in a horizontal orientation, while others employ modules arranged with the filters oriented vertically. However, the potential impact of the filter orientation on flow and filtration performance has not previously been examined. In this work, a combination of experimental studies and computational fluid dynamics (CFD) were used to quantitatively evaluate the effect of density differences between the suspending media (buffer/deionized water) and the cell culture broth on the flow distribution and the fouling behavior of the Millistak+® HC Micro 20 depth filter. Dye visualization experiments showed that the flow fields depend significantly on the orientation of the depth filter with respect to gravity. The flow is highly asymmetric when the filter is operated in the vertical orientation (with feed flow directed perpendicular to gravity), while a symmetric flow pattern was found for filters oriented horizontally (feed flow aligned with or against gravity). The CFD analysis was in very good agreement with experimental results in all filter orientations. These results have significant implications in understanding the fouling behavior, scale-up, and separation efficiency of depth filters used in bioprocessing, including the impact of buoyancy-driven flows arising from the density differences between cells / cell debris and supernatant.