Characterization of Cell Growth and Recombinant Protein Production in Fermentation for Implementation of Nir Spectroscopy as a Monitoring Technique

Although rarely available, timely process information about fermentation biomass, substrates, intermediates, and products is required to make control decisions. Near infrared (NIR) spectroscopy offers the opportunity to improve the fermentation processes by incorporating rapid, nondestructive, and multi-constituent analysis of fermentation broth media directly into the fermentation monitoring and control strategies. The objective of our research project is to use NIR technology to monitor the cell growth and recombinant protein production of a genetically-modified Escherichia coli strain cultures in fed-batch mode. Various fed-batch fermentation runs were performed in order to measure and detect changes in biomass production. The experimental data obtained from the fermentation process using E. coli showed some significant differences in NIR spectra over time around the wavelengths of 1800 and 2200 nm. It is believed that these differences are due to NIR detection of biomass production. To confirm this theory, chemometrics analysis are needed to analyze the subtle differences in spectra in order to determine which culture medium components influence the spectral results. Future experiments will be conducted to calibrate and validate the NIR equipment and build the models needed to fully validate the NIR as a tool for monitoring cell growth and recombinant protein production. This method would result in an important contribution to bioprocessing in its implication to Process Analytical Technologies (PAT). PAT has been promoted by the FDA as a preferred mode to produce regulated biotechnology products in the future.