Scale-up of controlled-shear affinity filtration using computational fluid dynamics

Controlled shear affinity filtration (CSAF) is an integrated bioprocess that positions a contoured rotor above a membrane affinity chromatography column to permit the capture and purification of a secreted protein product directly from cell culture. Here, computational fluid dynamics (CFD) simulations previously used on a laboratory-scale unit (Francis et al., Biotechnol. Bioeng. 2005, 95, 1207-1217) are extended to study the fluid hydrodynamics and expected filter performance of the CSAF device for rotor sizes up to 140 cm in radius. We show that the fluid hydrodynamics within the rotor chamber of larger-scale CSAF units are complex and include turbulent boundary layers; thus, CFD likely provides the only reliable route to CSAF scale-up. We then model design improvements that will be required for CSAF scale-up to permit processing of industrial feedstock. The result is the in silico design of a preparative CSAF device with an optimized rotor 140 cm in radius. The scaled up device has an effective filtration area of 5.93 m(2), which should allow for complete processing in ca. 2 h of 1000 L of culture harvested from either a perfusion, fed-batch or batch bioreactor. Finally, a novel method for the parallelization of CSAF units is presented for use in bioprocessing operations larger than 1000 L.