Specific heat flow rate: An on-line monitor and potential control variable of specific metabolic rate in animal cell culture that combines microcalorimetry with dielectric spectroscopy

On-line monitoring of responses to nutrient feed additions by multi-frequency permittivity measurements in fed-batch cultivations of CHO cells

“…One feed addition per day was then performed over a period of 9 days. The maximum in viable cell density of 3.5 9 10 6 c/ml was reached after *100 h. The viable cell count then remained constant over a period of 3 days until viability decreased significantly after *170 h. The total cell count, however, kept increasing and this was most likely the reason why De Fogale showed an increase until the beginning of death phase at *170 h. Stained cells can, depending on cell line and bioreactor system, contribute significantly to the permittivity which seemed to have been the case for cell line CHO II (Table 1; Davey 1993;Guan et al 1998;Ducommun et al 2002;Cannizzaro et al 2003;Ansorge et al 2007a). …”

Process control in cell culture technology using dielectric spectroscopy

“…[Davey et al, 1997] CHO 320 Stirred aerobic batch culture Combination of DS with microcalorimetric measurements. [Guan et al, 1998] …”

On-line Measurements and Control of Viable Cell Density in Cell Culture Manufacturing Processes using Radio-frequency Impedance

“…The application of the Biomass Monitor (BM) to animal cell culture monitoring has only occurred in earnest in the last few years Degouys et al 1993;Beving et al 1994;Davey et al 1997a;Guan and Kemp 1997;Guan et al 1998;Zeiser et al 1999;Ducommun et al 2002a, b;Dowd et al 2003) for studying the growth of a wide variety of animal cells, whether in suspension or in an immobilized state. Cerkel et al (1993) investigated the dielectric properties of Chinese Hamster Ovary (CHO 320) cells and HeLa cells grown in suspension culture at a concentration of 0.5 À 3 · 10 6 cells/ml and scanned at frequencies between 0.2 and 10 MHz using a BM.…”

“…This is important, as the conventional means of assessing biomass are not possible with immobilized cells. Guan et al (1998) combined on-line BM and microcalorimetric measurements to control a stirred aerobic batch culture of CHO 320 cells that had been genetically modified to produce human interferon-c. This approach was chosen as cell growth is associated with an enthalpy change which is a direct reflection of metabolic rate.…”