On‐line determination of animal cell concentration in two industrial high‐density culture processes by dielectric spectroscopy

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Abstract
Dielectric spectroscopy was applied to two industrial high cell density culture processes and used to determine on‐line the concentration of CHO cells immobilized on macroporous microcarriers in a stirred bioreactor and in a packed‐bed of disk carriers. The cell concentration predicted from the spectroscopic data was in excellent agreement with off‐line cell counting data for both processes. Deviations between the two counting methods only occurred in the case of a significant decrease of the cell viability, from 93% to 64%, which induced a change of the average cell size in the culture. Results for the packed‐bed process were further confirmed by the application of indirect yield models based on the measurement of glucose, lactate, and the protein of interest. Moreover, dielectric spectroscopy was used as a tool to characterize the packed‐bed process. It was possible to determine both the maximum cell concentration that could be reached in the culture system, 2.0 × 1011 cell per kg of disk carrier, and to quantify the increase of specific protein productivity induced by the production phase, from 5.14 × 10−8 μg cell−1 h−1 to 4.24 × 10−7 μg cell−1 h−1. © 2002 John Wiley & Sons, Inc. Biotechnol Bioeng 77: 316–323, 2002.