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

Authors

  • P. Ducommun,

    1. Institute of Chemical Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland; (telephone: +41 21 693 31 94; fax: +41 21 693 36 80
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  • A. Kadouri,

    1. Department of Process Development, Serono Biotech Center, CH-1809 Fenil-sur-Corsier, Switzerland
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  • U. von Stockar,

    1. Institute of Chemical Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland; (telephone: +41 21 693 31 94; fax: +41 21 693 36 80
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  • I. W. Marison

    Corresponding author
    1. Institute of Chemical Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland; (telephone: +41 21 693 31 94; fax: +41 21 693 36 80
    • Institute of Chemical Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland; (telephone: +41 21 693 31 94; fax: +41 21 693 36 80
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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.

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