Stirred well filtration (SWF) – A high-throughput technique for downstream bio-processing

A high-throughput technique for downstream processing studies was developed by integrating 96-well filter plates with a magnetic tumble stirrer that simultaneously mixes the solution above the membrane in each well akin to the conventional stirred-cell filtration module – thus we call this technique ‘stirred-well filtration’ (SWF). The performance of 30kDa Omega™ ultrafiltration membranes was assessed via hydraulic permeability measurements and protein sieving tests conducted in constant flux mode using a multi-rack syringe pump; individual pressure transducers were used to simultaneously monitor the transmembrane pressure (TMP) in eight wells on the filter plate. The stirring action was found to be critically important in controlling the effects of concentration polarization during protein sieving tests – for example, the maximum TMP in the unstirred wells were on average 7.5, 3.8, and 2.6 times higher than those in the stirred wells at fluxes of 12, 36, and 60LMH respectively. To demonstrate the usefulness of the SWF technique, we simultaneously ran the eight tests for a simple 22 factorial design-of-experiments (DOE) test with duplicates to evaluate the effect of solution pH and salt concentration on protein filtration. The results indicate that combining the SWF technique with statistical methods is a powerful approach for high-throughput testing of filtration processes.