Small-scale Membrane-less Perfusion Bioreactor System for High-throughput Cell line Development and Process Optimization

Performance Period: 6/15/2020 to 1/31/2022

The bio manufacturing industry needs a reliable and robust, cell retention device for perfusion that is non fouling and supports the ever-increasing high cell concentration. Existing perfusion culture using hollow fiber membranes (ATF or TFF) is challenging to maintain because it requires much care to change membrane filters regularly and bleed cells, rendering them hard to run many small bioreactors concurrently for optimization / DOE. We aim to develop a fully automated small-scale (<500 mL) membrane-less perfusion bioreactor system for CHO cells at high concentration (50–100E+6 cells/mL) using a novel cell retention device based on inertial sorting.

This simple and low-cost system requires minimal maintenance and no clogging and no product retention problems seen with membranes, therefore conducive to running many parallel small-scale perfusion cultures for process development. Successful completion of this project will enable the first implementation of reliable small-scale perfusion culture for rapid process development and efficient DOE. The project will also rapidly generate various culture parameter data which can be used for large-scale production culture. At the end of 18th month, we will transfer components to commercial manufacturing facilities (MRL 5 or 6) and perform small-scale multiple perfusion cultures.