Advancing mRNA Manufacturing with Mid-Infrared Process Monitoring: From Batch to Fed-Batch

Institute
Lehrstuhl für Bioseparation Engineering (TUM-ED)
Type
Semester Thesis / Master's Thesis /
Content
experimental / theoretical /  
Description

Messenger RNA (mRNA) has become a key technology in modern biotechnology and vaccine manufacturing. Its production relies on in vitro transcription (IVT), a cell-free enzymatic reaction in which nucleoside triphosphates (NTPs) are converted into RNA. Conventional IVT is commonly operated in batch mode, while fed-batch operation can maintain favorable reaction conditions by supplying substrates during the process. A mid-infrared (MIR)-based soft sensor has already been developed for real-time estimation of mRNA and NTP concentrations during batch IVT. In fed-batch operation, however, continuous substrate addition, changing concentrations, dilution, and variable feeding profiles introduce new spectral and modelling challenges. The existing model must therefore be transferred, adapted, and systematically validated under dynamic fed-batch conditions. In this thesis, you will extend and evaluate the existing soft sensor using a Monipa inline MIR system and reference analytics. A central objective is to assess its robustness across different feed strategies and process conditions and to determine whether reliable mRNA and NTP predictions are possible in new fed-batch experiments. The project combines experimental bioprocessing, spectroscopy, and data-driven modelling in a highly relevant field of mRNA process development.

Requirements

Enrolled in a Master’s program in Biotechnology, Chemical Engineering, Bioprocess Engineering, Bioengineering, Data Science, or a related discipline
Interest in mRNA production, process analytical technology, and data-driven modelling
Basic laboratory experience and knowledge of Python or data analysis are advantageous
Independent, structured, and motivated working style

Possible start
sofort
Contact
Marc Müller
Room: 3427
m.r.muellertum.de
Announcement