Rapid Calibration of Raman Spectroscopy Models for Bioreactor Monitoring
M. Klaverdijk (TU Delft - BT/Bioprocess Engineering)
M. Ottens – Promotor (TU Delft - BT/Design and Engineering Education)
M.E. Klijn – Copromotor (TU Delft - BT/Bioprocess Engineering)
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Abstract
Bioprocess engineering involves the controlled cultivation of cells for the production of specialized products. These cells function as living factories, and their environment must be carefully controlled to optimize metabolic activity and productivity. Cell cultures are operated in bioreactor systems which aim to maintain optimal environmental conditions and provide optimal mass transfer. Monitoring bioreactor conditions such as nutrient levels or cell growth is typically dependent on manual sampling. This involves an operator extracting a small sample and analysing it on an external device, which provides a delayed and partial view of the process. To overcome the challenges of manual sampling, the bioprocessing industry is adopting Process Analytical Technology (PAT) tools like Raman spectroscopy, which can monitor the molecular composition of the system in real-time. However, accurate monitoring by Raman spectroscopy is dependent on chemometric models that typically require extensive calibration with process data, leading to processspecific models which do not transfer to related processes. This often necessitates repeating the extensive collection of process data for each new process that must be monitored. Therefore, this thesis focuses on investigating alternative approaches to calibration data collection and chemometric model calibration, while studying how varying measurement conditions affect spectral integrity...