Monitoring of Bioprocesses. Opportunities and challenges: Opportunities and Challenges

The monitoring of bioprocesses is a crucial issue and demand, not yet trivial outside the standard sensors comprising temperature, pH, dissolved oxygen and, in well-quipped laboratories and industries, off-gas analysis. The crucial process parameters such as biomass, substrate and product concentrations are rarely assessable on-line, a fact, that can compromise the reactor efficiency. Hence, this thesis addressed state-of-the art and novel technologies, commercially available but rather uncommonly considered as a monitoring strategy for fermentation processes. Within 4 individual chapters, the work investigated the monitoring of a yeast lab-scale fermentation process by means of:
• a biosensor designed as a small flow-through-cell for the monitoring of glucose;
• infrared (IR) spectroscopy combined with partial-least-squares (PLS) modeling for the monitoring of glucose, ethanol, glycerol, acetic acid, ammonium and phosphate;
• microscopic imaging and image analysis for the detection of growth supplemented with morphological characterization of the growing culture;
• a backscatter sensor for non-invasive monitoring of the microbial growth via the fermenter wall (glass);
It must be highlighted that all technologies could be applied on-line via a recirculation loop or non-invasively via the fermenter wall. The biosensor and the backscatter cell were found to be fast and easy to use as ‘plug and play’ devices, facilitating the monitoring of glucose and biomass, respectively, continuously on-line, during the entire course of the fermentation under study.
IR spectroscopy combined with PLS modelling yielded good results for the modelling of glucose and ethanol, while the monitoring of glycerol, acetic acid, phosphate and ammonium were compromised by e.g. high batch-to-batch variability, low concentration levels inside the broth, low IR-activity and indirect predictions. However, it is considered as a highly powerful approach on a long-term perspective. Imaging an image analysis was found to be an exciting new possibility, suggesting a totally novel, image based monitoring and control strategy. The technology in use was developed in parallel to this work and more research is needed to develop this approach into a final application.
The results achieved within this work were overall very promising. They allowed an integrated insight into the fermentation process under study while outlining the opportunities and challenges connected to the different technologies.