Advanced off-gas measurement using proton transfer reaction mass spectrometry to predict cell culture parameters
© Schmidberger and Huber; licensee BioMed Central Ltd. 2013
Published: 4 December 2013
Mass spectrometry is a well-known technology to detect O2 and CO2 in the off-gas of cell culture fermentations. In contrast to classical mass spectrometers, the proton transfer reaction mass spectrometer (PTR MS) enables the noninvasive analysis of a broad spectrum of volatile organic compounds (VOCs) in real time. The thereby applied soft ionization technology generates spectra of less fragmentation and facilitates their interpretation. This gave us the possibility to identify process relevant compounds in the bioreactor off-gas stream in addition to O2 and CO2. In our study the PTR-MS technology was applied for the first time to monitor volatile organic compounds (VOC) and to predict cell culture parameters in an industrial mammalian cell culture process.
Materials and methods
Summary PLS-R models
Specific glutamine uptake
In our study we showed that the VOC profile obtained with the PTR-MS can be used to predict important cell culture parameters, but compared to other on-line techniques such as near infrared spectroscopy the PLS-R models are currently less robust (expressed by a lower R²). Moreover the most important VOCs in the PLS-R model could be used to get deeper insights into the cellular metabolism. At the moment however, this is limited by the lack of identified VOCs and the small literature basis reporting of pathways including volatile metabolites. Finally, further experiments will be necessary to assess the most influential factors on the VOC production and to fully exploit the potential of the PTR-MS.
We want to thank Rene Gutmann from Ionicon for the installation and support for the PTR-MS and Karl Bayer for the fruitful discussions.
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