ON-LINE MONITORING OF CELL SIZE DISTRIBUTION IN MAMMALIAN CELL CULTURE PROCESSES

In this work, mammalian cell cultures were monitored on-line by measuring the culture capacitance over a range of excitation frequencies. The data collected during a fed-batch culture were used to build partial least squares (PLS) models for predicting the cell concentration, viability and size distribution. The models were validated on cultures performed in batch and perfusion modes and the predictions agreed well with off-line measurements performed with a Coulter Counter. The capacitance signals can also be used to follow the evolution of the mean cell diameter during a culture. Cell size distribution provides valuable information about the physiological state of cells in culture. Capacitance measurements at multiple frequencies can thus be a useful tool for the development, optimization, monitoring and control of cell culture processes.