Screening of media supplements for high-performance perfusion cultures by design of experiment

Abstract

Perfusion is considered as the preferable unit operation mode for fully integrated continuous bioprocessing. However, the inherent complex process control, long process development times, and lack of suitable scale-down models for high-throughput screening are reasons why perfusion processes are still not routinely applied in cell culture technology. Advantages of perfusion are maintenance of a consistent cellular environment, a constant high-quality product flow, enhanced volumetric bioreactor productivity, and small lab footprint. Here, we provide guidelines for screening different proprietary but commercially available HyClone™ Cell Boost™ supplements in a Design of Experiment (DoE) approach to spike the HyClone™ CDM4NS0 basal media for enhanced product titers in small-scale TubeSpin models. These surrogate semi-perfusion cultures were successfully realized by a daily complete media exchange routine resulting in high viable cell densities for extended time periods at minimal media consumption. This technique was leveraged to define the potential of different perfusion media formulations.