On-line determination of animal cell concentration in two industrial high-density culture processes by dielectric spectroscopy.
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 x 10(11) cell per kg of disk carrier, and to quantify the increase of specific protein productivity induced by the production phase, from 5.14 x 10(-8) microg x cell(-1) x h(-1) to 4.24 x 10(-7) microg x cell(-1) x h(-1).
Ducommun
P
P
Institute of Chemical Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland.
Kadouri
A
A
von Stockar
U
U
Marison
I W
IW
D000818:Animals; D019149:Bioreactors; D016466:CHO Cells; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods*; D018914:Cells, Immobilized; D006224:Cricetinae; D008954:Models, Biological; D013057:Spectrum Analysis / Q000379:methods*