S15: Recent Advances in Application of Shaken Microbioreactors – from Fed-batch Screening to Automated Bioprocessing

Microbioreactors have been used intensively to improve bioprocess development in recent years. While miniature stirred tank reactors and bubble columns found broad application in bioprocess characterization, shaken microplates are widely used in clone screening, media optimization and bioprocess automation exploiting its intrinsic capacity for high-throughput. This presentation will report about recent advances in application of shaken microbioreactors. One key application of shaken microbioreactors is the selection of high producer strains in high-throughput. A new method applying product specific transcription factors and fluorescent reporter proteins will be presented and demonstrated by examples from screening of Corynebacterium glutamicum strains for amino acid production. Another important step in bioprocess design is the media optimization. Due to the high variability of media components it is very useful to apply Design of Experiment (DoE) tools to optimize the culture media. A media optimization study for improved protein expression in Pichia pastoris will be given. Due to the broad dispersion of the fed-batch operation mode in biotechnological manufacturing it is of great interest to apply this operation mode also in the screening scale. Here, a comparison of batch and fed-batch screening with Pichia pastoris will be shown. In addition, an example of feeding rate optimization with Corynebacterium glutamicum will be presented. Finally, the most recent advances of automated upstream bioprocessing including DO-controlled fed-batch mode and induction profiling will be demonstrated. Microbioreactors promise to replace continuously more lab fermenter experiments by enabling scalable and process relevant conditions at microscale and by providing more bioprocess information more easily.