Dielectric spectroscopy in the cultivation of suspended and immobilized hybridoma cells

Abstract

Dielectric spectroscopy, also referred to as capacitance measurement, was evaluated as a tool for on-line and real-time monitoring of hybridoma cell growth in suspension batch culture and in immobilized cell culture in porous glass carriers. The capacitance signal proved to be a lumped parameter influenced by cell concentration, cell size and culture conditions. During a batch culture the cell specific capacitance signal changes by about 45% having a maximum value at the maximum growth rate. An excellent correlation between the specific capacitance and the specific amount of nucleotidetriphosphates in the cells could be shown. Dielectric spectroscopy proved to be a useful tool for on-line monitoring of cell attachment and growth in open porous microcarriers in fluidized bed fermenters. Also, in this system only an approximate correlation with viable cell concentration appeared, whereas an exact correlation with the glutamine consumption rate, a measure of the metabolic activity of the cells, could be shown. This allowed a closed loop control of the medium feed rate, which was directly linked to the capacitance signal during the entire course of a continuous fermentation.