Enhanced Settling of Mammalian Cells in Tanks with Inclined Plates/Simulation by Fluid Mechanical Model and Experiment.

Abstract

In perfusion culture of mammalian cells, the cells should be separated from the spent medium and retained in the culture vessel. A possible cell separator for this purpose is a multiple inclined plate space in an agitated or air-circulated culture vessel. Local fluid velocity and cell concentration contours in an assumed hybridoma cell suspension, which was held stationary in such a gravitational cell settler consisting of multiple open-ended spaces partitioned by inclined plates, were estimated by numerically solving the momentum and continuity equations. The simulated maximum convection flow velocity was 20 times the Stokes’ velocity of the cells. The flow penetrated into the space below the lower ends of the inclined plates. The model estimated a larger cell settling rate than the Ponder-Nakamura-Kuroda (PNK) formula. In our experiment, the cell suspension of hybridoma 2E3 was held stationary in a vessel containing multiple inclined plates, and the position of the interface between the clear and turbid fluids was observed. The falling rate of the interface was larger than that predicted by the PNK formula. The model can be utilized for designing such cell separators for perfusion culture of suspended mammalian cells, including optimization of the size and interval of the plates.