PUB - Publikationen an der Universität Bielefeld

In large-scale bioreactors, gradients in cultivation parameter such as oxygen, substrate and pH result in fluctuating cell environments. pH fluctuations were identified as a critical parameter for bioprocess performance. Traditionally, scale-down systems at the laboratory scale are used to analyze the effects of fluctuating pH values on strain and thus process performance. Here, we demonstrate the application of dynamic microfluidic single-cell cultivation (dMSCC) as a novel scale-down system for the characterization of Corynebacterium glutamicum growth using oscillating pH conditions as a model stress-factor. A detailed comparison between two-compartment reactor (two-CR) scale-down experiments and dMSCC was performed for one specific pH oscillation between reference pH 7 (~ 8 min) and disturbed pH 6 (~2 min). Similar reductions in growth rates were observed in both systems (dMSCC 21% and two-CR 27%) compared to undisturbed cultivation at pH 7. Afterwards, systematic experiments at symmetric and asymmetric pH oscillations between pH ranges of 4–6 and 8–11 and different intervals from 1 minute to 20 minutes, were performed to demonstrate the unique application range and throughput of the dMSCC system. Finally, the strength of the dMSCC application was demonstrated by mimicking fluctuating environmental conditions of a putative large-scale bioprocesse, which is difficult to conduct using two-CRs.