A small-scale bioreactor concept with magnetically levitated stirrer

Bioreactors are the central element in biopharmaceutical drug production processes using microorganisms or animal cell cultures. In recent years, there has been an increasing trend in preliminary process development to carry out cell or strain selection through to process optimisation using scale-down models in ever-shrinking cultivation systems. This allows throughput to be increased through parallel operation, while at the same time saving resources and materials and ensuring a better understanding of the process. Based on the different energy, gas, heat and oxygen requirements of the different types of production organisms, a distinction is made between stirred bioreactors with different geometries, equipment, impeller geometries and drives. To further address this trend towards small-scale bioreactors and to simplify the selection of cultivation systems, a project with Levitronix GmbH was undertaken to develop a universal, seal-less, magnetically driven bottom stirrer and bioreactor concept on the mL scale. Following preliminary process engineering studies using conventional methods and CFD with respect to power input, oxygen transfer, mixing time and system optimisation, microbial and animal cell cultures were successfully cultivated. Optical densities of OD600>80 (>24 g/L dry weight) were achieved in batch operation and OD600>328 (>88 g/L dry weight) in fed-batch operation with Escherichia coli according to DECHEMA guideline. Mass propagation of CHO cells (Chinese Hamster Ovarian Cells) in a chemically defined medium resulted in cell densities and product titres for monoclonal antibodies comparable to other stirred systems.