This work uses two different techniques for modeling mammalian cell culture: Differential Equation (DE) based Modeling and Agent-Based... Show moreThis work uses two different techniques for modeling mammalian cell culture: Differential Equation (DE) based Modeling and Agent-Based Modeling (ABM). The development of both models was done in free open-source software instead of the traditional software that requires the purchase of licenses. The DE model was developed in Python and can predict total, viable, and dead cell densities, glucose, lactate, glutamine, ammonia, and product titer. To expand on the detail level capabilities of previous DE models it has added temperature, pH, and dissolved oxygen dependence. The ABM can predict viable cell density, glucose, lactate, and the distribution of the three experimentally detectable cell cycle phases G1G0, S, and G2M. The ABM was developed for high-performance computing to improve on a previous ABM and allow for running at a hundred-fold smaller run-time with a much higher capacity for the amount of agents that can be simulated. Show less
This dissertation proposes four different kinetic model frameworks that havebeen developed for optimization and control of monoclonal antibody... Show moreThis dissertation proposes four different kinetic model frameworks that havebeen developed for optimization and control of monoclonal antibody producing mammalian cell cultures to improve biopharmaceutical production by decreasing the costof trial and error experimentation. The developed models mainly describe the transient metabolic behavior of mammalian cell culture under different culture conditionsand predicts cell growth and death, cell metabolism, and monoclonal antibody synthesis, and production. These models are developed via ordinary differential equationsbased on the assumption of well-mixing reactor. All developed models were calibrated, and their predictive capabilities were tested with experimental reports published in the literature. Good agreement was obtained between model predictions and experimental data. The presented results illustrate that the developed models successfully describe and predict the transient behavior of mammalian cell cultures and can be a useful tool for biopharmaceutical production. Show less
