Group of Prof. Wiedemann

Process-Monitoring via mass spectrometry (Cooperation with ZAFH ABIMAS, Mannheim Univ. of Applied Sciences)

A disadvantage of today’s standard animal cell monitoring methods is the fact that “cell stress” is predominantly detected by looking at cell membrane integrity. This is correct in the case of quick and complete stress/death processes (e.g. necrosis). Unfortunately, other stress inflicted processes as e.g. apoptosis, the predominant cause of cell death in bioreactors, remain undiscovered for a long time. Much more informative would therefore be a method that directly analyses stress-related biomarkers, e.g. changes in the “protein composition” (proteome) of the cell in order to detect necrosis as well as apoptosis and early signs thereof.

In this work, we investigated for the first time mass spectrometry (MS) as label-free at line analysis tool to detect cell stress based on specific changes in MS fingerprints, i.e. in the protein content of cultivated animal cells.

A condensed signature was identified in mass spectra that enables detection of coming viability changes up to 24 h earlier than with standard methods. Classification models were computed based on this signature that identify cell stress in unknown samples solely based on their mass spectra.

With respect to industrial cell culture processes, the method’s independence from process mode, cultivation format and CHO cell line could be shown. Additionally, method transfer to a compact, more reasonably priced mass spectrometer was achieved.