ABSTRACT
The advancement of the technology for large-scale cultivation of animal cells has relied on the implementation of strategies and techniques that can be grouped into four categories: maximization of viable cell concentration, improvement of medium formulation, implementation of high-performance reactor configurations, and maximization of specific production rate. However, the development of optimal-processing schemes has always been hindered by a lack of the equipment necessary for adequate state identification in the bioreaction processes. Most of the monitoring systems available are biochemically based, slow, off-line, and yield only global values for the reaction system. Even on-line analytical systems common in bacterial and fungal fermentations, such as the measurement of oxygen uptake rates and carbon dioxide production rates by off-gas analysis, are problematic in animal cell culture owing to the very low rates to be measured and consequent poor sensitivity.
