Capacitance Sensor as a Robust Tool for Cell Culture Monitoring in Process Development and Manufacturing

Abstract

During the last decades, capacitance sensors have been reported to be very promising and were extensively evaluated in our labs.

Our contribution reports on-line as well as conventional at-line process data of several cell culture processes using recombinant CHO cell lines in bioreactors. It demonstrates that, in the case of mammalian cells, dual-frequency dielectric measurement with the Biomass System is a reliable determination of the biovolume.

In addition, our data show that scanning dielectric spectroscopy provides, through spectral parameters, information on cell size and its distribution and on the membrane capacitance, both of which often vary during cell culture processes. The proposed method enables monitoring of the viable cell number even in cell size changing conditions.

With a single probe, 6 different process parameters are obtained in real-time, enabling detailed characterization of the process dynamics. Biomass spectrometers in Process Development has proven a valuable technology to enable process understanding, and leads to applications in large scale manufacturing, including identification of process deviations and optimal harvesting time, and possibly PAT applications.