Enhanced control of cell metabolism

A rather more futuristic aspect of fermentation control is the use of complex parameters, calculated from basic and biochemical parameters (Fenge et aL, 1991  

Glacken, 1991). These include growth rate, uptake and production rates as well as intracellular metabolites. Such parameters directly monitor the physiological state of the cells and would allow very reliable and fast control of the process (Grammatikos, 1997). 

Our own unpublished results show a correlation between glucose uptake rate and monoclonal antibody production rate with a hybridoma. However, due to limited technical resources, it has only become possible recently to use this phenomenon within a production process. Nevertheless, the automatic off-vessel, on-line measurement of glucose, twice per hour, can be established (Ozturk, 1997). An in-line glucose measurement system has been developed recently, based on 

A very interesting task would be automatic measurement of the product and the calculation of production rates. This would allow automatic optimization of the process by a computer program that varies all relevant parameters, probably by multiparameter analysis, to find the best production conditions. As long as there are no product sensors available, the main problem may be the time necessary for the measurement of an automatically taken sample. However, the use of HPLC methods can give accurate results within 20 min, and high-performance capillary electrophoresis (HPCE), with an analysis time of 5 min, could be introduced (Beckman PIACE 2(X)0, E. Wasserbauer, personal communication and James et al, 1994). Nonetheless, further development is necessary before these methods can be used routinely for automatic fermentation analysis. 

Blackie J, Dean A, Konstantinov K Naveh D (1998) Real-time imaging for monitoring of mammalian cell culture processes. In Merten OW Griffiths B (eds) Animal Cell Technology New Developments and New Applications. Kluwer, Dordrecht, in press. 

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