Foam control and in-line cell density monitoring in a laboratory-scale bioreactor

Abstract

To design a feasible bioprocess for modern manufacturing a multitude of process parameters must be considered. One of these parameters is the cell density, which is usually aimed to be increased to achieve high space-time-yields. This often results in excessive foaming, which can have disastrous consequences for the fermentation.Since chemical anti-foaming agents can be detrimental for cell growth and product quality, mechanical solutions for foamy fermentations are demanded. However, commercially designed mechanical foam breakers are not suitable for lab-scale applications due to their spatial and energetic demands. In the first chapter of this thesis, the approach of mechanically breaking foam using an impeller mounted to the main stirrer shaft is critically investigated. 3D-printing is used to prototype and compare different foam breaker designs. We show that this method of defoaming leads to a decrease in bubble size, which stabilizes the foam and can promote foam build-up. Therefore, an alternative approach focussed on foam mitigation is proposed where an alternative submerse impeller configuration is used to keep oxygen transfer high despite reduced agitation and aeration. It is shown that the use of a downward pumping axial impeller close to the surface can improve the volumetric mass transfer coefficient, especially for low agitation and high temperature conditions.As a determining parameter for the foam build-up, and as a key performance indicator for bioprocesses in general, the concentration of biomass needs to be adequately monitored. In the second chapter of this thesis, we investigate optical and dielectric spectroscopy methods to measure cell density in-line, during continuous cultivations of Sulfolobus acidocaldarius. This organism thrives at high temperatures and low pH values. Thus, the performance of three commercially available sensors is examined under these extreme conditions.