Monitoring the Cell Size Distribution of Mammalian Cell Cultures Using On-Line Capacitance Measurements

Abstract

Capacitance measurements at one single frequency are already an established tool for the on-line monitoring of the viable and total cell density in animal cell culture processes. Recently available systems allow for the automatic measurement over a wide range of frequencies. As changes in the characteristic fall of capacitance with increasing frequency (β-dispersion) change with the cell size distribution, we hypothesized that we could get information about the cell size distribution from on-line capacitance measurements.

We correlated on-line capacitance measurements performed at several frequencies with changes in the cell size distribution. Using data from a fed-batch cultivation of human 293SF cells as a calibration set, partial least square (PLS) models were built and used to predict the cell concentration, cell viability, cell diameter and size distribution. These models were validated by independent data from other experiments performed in batch and perfusion modes.

We demonstrated that capacitance measurements provide real-time quantitative information about the viable cell count, viability, mean cell diameter and also cell size distribution. As these are important physiological parameters that can be related to cell growth, metabolism and productivity, multi-frequency capacitance systems can provide a useful tool for process development, optimization and control. We applied this concept for the production of adenoviral vectors in which cell size changes are of importance to monitor the infection’s success.

This technology could be used for the on-line prediction of successful viral infections and the optimization of infection processes.