Date of Award

Fall 2021

Project Type


Program or Major


Degree Name

Master of Science

First Advisor

Paul C Tsang

Second Advisor

Thomas Foxall

Third Advisor

Thaddaeus Webster


The monitoring and control of mammalian cell culture processes are critical for the safe and cost-effective development of biotherapeutics in drug development. Current control using off line sampling is infrequent and can miss important metabolic shifts which can impact product quality and consistency. Raman spectroscopy can provide in-line monitoring of multiple metabolites and critical process parameters to allow automation and process improvements. In this research a generic model was developed for monitoring multiple cell lines with a platform Chinese hamster ovary (CHO) cell process. Parameter estimation was then used for the implementation of feedback control. Two nutrient feeds were added based on the culture needs as measured approximately every hour for viable cell and glucose concentrations without operator intervention. This demonstrated comparable, if not improved, control compared to historically adjusting feeds based on daily off-line sampling.