Microbial Cultivation In Different Scales In The CELL-tainer® Rocking Single-Use Bioreactor

By Lexan Lhu, Nico Oosterhuis, Peter Neubauer, and Stefan Junne

Single-use bioreactors are applied in the biopharmaceutical industry for mammalian cell culture processes. The low gas-liquid mass transfer coefficient generally achieved in these systems does not allow for the compatable application of microbial processes in these bioreactor systems. The CELL-tainer® technology combines a vertical and horizontal movement in a rocking bioreactor concept, so that the turbulence and power input is intensified. In this system, mass transfer rates comparable to stirred tank reactors are achievable. Thus, volumetric oxygen transfer rates (kLa) of over 400 h-1 could be achieved. The scale-up of Escherichia coli nutrient-limited fed-batch cultivations from 15L to 150L cultivation scale in the CELL-tainer single-use bioreactor has been conducted sucessfully. A final biomass concentration of 45 gL-1 within 24 hrs was obtained, proving the suitability of this reactor for the application of bacterial processes. The combination of intelligent software sensor control and improving sensors lead to improved control of bacterial fed-batch processes. The availability of single-use bioreactors for microbial cultivations widens their potential, not only in biopharmaceutical processing, but also as a pre-culture bioreactor for large processes and as a tool in bioprocess development.