On the effect of flow reversal during crossflow microfiltration of a cell and protein mixture

tAlternating tangential flow (ATF) filtration is a cell retention technique of increasing impor-tance in continuous biomanufacturing. Despite its frequent application, the role of flowreversal in fouling mitigation remains unclear this far. We implemented a customized pilotplant comprising a low-shear centrifugal pump and fast switching valves, which enablesus to create alternating crossflow, where crossflow velocities and cycle times can be variedindependently, as well as conventional steady forward and pulsatile forward crossflow. Wethen used a model feed containing yeast cells and bovine serum albumin (BSA) in orderto simulate a fermentation broth and investigated the impact of alternating crossflow onmicrofiltration performance at this customized filtration plant. By comparing the resultswith filtration trials conducted at forward only pulsatile crossflow as well as steady cross-flow using the same plant, we observed the true effect of flow reversal, corrected for effectsinduced by crossflow velocity, transmembrane pressure as well as transmembrane pressurefluctuations. We found that alternating crossflow, i.e. crossflow with flow reversal, leadsto a reduced fouling resistance and a higher solute transmission in comparison to steadycrossflow filtration. However, the flux increase is lower than for pulsatile crossflow filtra-tion, which might be attributed to length dependency effects. The transmission of BSA, onthe other side, is even higher at alternating crossflow filtration than for pulsatile crossflow.Thus, we conclude that flow reversal plays a part in fouling mitigation, but a greater part ofthe anti-fouling effect of alternating crossflow, however, is caused by the transmembranepressure fluctuations.     «

tAlternating tangential flow (ATF) filtration is a cell retention technique of increasing impor-tance in continuous biomanufacturing. Despite its frequent application, the role of flowreversal in fouling mitigation remains unclear this far. We implemented a customized pilotplant comprising a low-shear centrifugal pump and fast switching valves, which enablesus to create alternating crossflow, where crossflow velocities and cycle times can be variedindependently, as well as conventional steady fo...     »