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In Situ Microscopy for Real-time Determination of Single-cell Morphology in Bioprocesses
Published on: December 5, 2019
Soft sensor for monitoring biomass subpopulations in mammalian cell culture processes
Paul Kroll1,2, Ines V Stelzer1,2, Christoph Herwig3,4
1Research Area Biochemical Engineering, Institute of Chemical Engineering, TU Wien, Gumpendorfer Straße 1a, 1060, Vienna, Austria.
Objectives:
Biomass subpopulations in mammalian cell culture processes cause impurities and influence productivity, which requires this critical process parameter to be monitored in real-time.
Results:
For this reason, a novel soft sensor concept for estimating viable, dead and lysed cell concentration was developed, based on the robust and cheap in situ measurements of permittivity and turbidity in combination with a simple model. It could be shown that the turbidity measurements contain information about all investigated biomass subpopulations. The novelty of the developed soft sensor is the real-time estimation of lysed cell concentration, which is directly correlated to process-related impurities such as DNA and host cell protein in the supernatant. Based on data generated by two fed-batch processes the developed soft sensor is described and discussed.
Conclusions:
The presented soft sensor concept provides a tool for viable, dead and lysed cell concentration estimation in real-time with adequate accuracy and enables further applications with respect to process optimization and control.
