Microscale stirred-cell filtration for high-throughput evaluation of separation performance

Abstract

Membrane filtration is a key separations technique in downstream bioprocessing applications: for a commercial bioprocess operation, 10–20 membrane-related steps are typically required. At the laboratory scale, the evaluation of membrane separation performance often involves a ‘stirred cell device’; however, this simple tool is poorly suited for conducting high-throughput studies of separation performance. Here, we designed a high-throughput stirred cell (HTSC) device which is ideally suited for conducting optimization studies, especially at the early stages of bioprocess development when small volumes of feed material are available. The HTSC allows for up to six filtration experiments to be run simultaneously with continuous mixing above each membrane facilitated by suspended magnetic stir elements. Using fluorescently-labeled dextrans as model biomolecules and commercial ultrafiltration membranes, it was shown that the HTSC device gave the same separation performance as a traditional stirred cell, but with the added benefits of operating at a faster pace (due to its parallel nature) and requiring nearly an order of magnitude lower sample volumes. Furthermore, the utility of the HTSC was demonstrated by concurrently evaluating the performance of four different ultrafiltration membranes for the same model biomolecule and the membrane selectivity for a mixture of two model bio-macromolecules.