Use of cell cycle analysis in early state estimation and process control

[摘要] The purpose of this project was to develop mathematical models which could predict the behaviour of Chinese Hamster Ovary cells (CH0320) many hours ahead by using their cell cycle profile. Experiments were carried out to study the growth kinetics of CH0320 cells. The initial concentration of glucose in the medium did not appear to have any effect on growth and cell cycle profile of CH0320. However, variation of the initial concentration of glutamine led to decreases in total cell number at concentration of 1 and 0.5 mmol in comparison to the standard medium concentration of 2 mmol. Glucose uptake rates were also found to be lower in batches with 1 and 0.5 mmol concentrations of glutamine. Batch culture studies of CH0320 cells having different cell cycle populations at the start of the culture were also made. Variations in viable, non-viable, substrate consumption and mean relative size and mass in these cultures were observed, but they were found to be largely accountable by reference to their corresponding cell cycle profiles. Variations and similarities in the patterns of cell cycle progression in these cultures were found mainly to be due to the presence or absence of specific period(s) e.g. lag period. Short and long term dynamic mathematical models were constructed. The best performing estimator of short term data was found to be that of models where transition between the phases of cell cycles is based on a predator-prey type of relationship and those with oscillatory rate coefficients. Physiological models based on molecular mechanism of cell cycle transition for prediction of short or long term data were found to be inadequate. As far as the longer term models were concerned, those with substrate dependent G 1-S transition and death terms were found to be the most plausible option.

[发布机构] University:University of Birmingham;Department:School of Chemical Engineering

[关键词] T Technology;TP Chemical technology