In situ and real time monitoring of critical process parameters for automated process control of E.coli Fed-batch cultures

Summary
Biopharmaceutical Biotechnology
Innosuisse
Mettler Toledo AG
Carmen Jungo Rhême
Skills directory
December 2024 - September 2025
This project is a case study which will demonstrate how in situ and real time monitoring with a new glucose-lactate probe from Mettler Toledo and automated process control can be used for advanced bioprocess manufacturing, process modelling by AI and how it will transform the biotech industry.
A recombinant Green Florescent Protein (GFP) expressed with E. coli bacteria serves as a model system for protein expression and optimization in fed-batch cultures. Usually, the feed rate of the substrate is set at defined feed rate, and no process control is implemented to adjust the feed rate during the culture according to the consumption of the substrate by microorganisms. This is a gap and can lead to sub-optimal protein expression. In this project, the aim is to demonstrate that combining in situ real time monitoring of glucose and/or lactate with automated AI-driven process control of the feed rate of glucose is an efficient means to perform fed-batch cultures at optimal process conditions for maximal protein expression.
Different feeding strategies, for example with different residual glucose concentrations, will be tested and evaluated.