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Title: The mathematical modelling of the cell cycle of a hybridoma cell line
Author: Faraday, David Brian Foster
ISNI:       0000 0001 3457 1707
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1994
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A generic model of cell growth and division cycles (CELCYMUS) is proposed. It is a one dimensional population balance model based on cell age. The model can describe changes in cell age distribution, interactions with a multi-component medium and changes in cytological state. A specific cell cycle model for the mm321 hybridoma cell line, which produces antibody to paraquat, has been developed within CELCYMUS. This specific model is based on the four conventional cell cycle phases, however, a number of modifications have been made to this structure: the division of the G1 phase into two parts, Gla and Glb; the addition of a quiescent phase, GO, and a death phase, D; the probability of transition from Glb to S is a function of the cumulative glutamine content in Glb; the rate of cell death depends on the prevalent ammonia concentration; and consumption and production kinetics of glutamine, glucose, ammonia, lactate and antibody are also cell cycle dependent. This model is successfully fitted to post-synchronisation cultures. The model, thus fitted, is capable of predicting the growth of this cell line in conventional shake-flask and static flask cultures, in a stirred fermenter and in a chemostat. Finally, the model is used to predict the behaviour of this cell line in repeated-batch culture and in continuous culture subjected to periodic perturbations. The objectives of this research have been met; a successful cell cycle model has been developed for the mm321 cell line. In addition, CELCYMUS has proven capable of exhibiting highly non-linear behaviour. It is concluded that an understanding cell cycle kinetics is important for the bioprocess engineer. Finally, it has shown that cyclic propagation strategies are highly cell cycle dependent, however they can produce significant increases in product yield.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Micro-biological systems