S18: Bioprocess Control in Shaken Microfluidic Well Plates

Biotechnological processes are gaining increasingly more importance not only in the biopharmaceutical market, but also in the (bio-)chemical and (bio-)fuel market. Thus, constantly growing numbers of fermentation processes have to be developed. Up to now, several micro bioreactor concepts have been established in industry to fulfill the demand of high-throughput and ease of sample processing. Nevertheless, these concepts currently only offer batch processing of fermentations even though most industrial fermentation processes are operated in fed-batch mode. This was the motivation to develop a new advanced micro bioreactor concept based on the BioLector^® technology. Basically, the BioLector is a fiber-optic online-monitoring system which allows to detect biomass concentration, pH and DO as well as fluorescent proteins in continuously shaken microtiter plates (MTPs). Here, the BioLector was combined with a microfluidic bioprocess control to further improve the features of this micro bioreactor system. To realize a user-friendly system for routine laboratory work, disposable microfluidic MTPs were developed and applied on a user-friendly hardware with pneumatic actuation.

This novel micro fermentation system was tested in pH-controlled batch as well as in fed-batch fermentations of Escherichia coli. Finally, the scale-up potential of the microscale fermentation was evaluated by comparing the obtained results to that of fully controlled fermentation in a 2 L laboratory-scale fermenter. In conclusion, a user-friendly and disposable microfluidic system was established which allows scalable, fully controlled and fully monitored fermentations at microscale.