Integration of Multiphase Hydrodynamics, Metabolic Modelling, and Control to enable Simulation-based Design of Bioreactors

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The use of biological processes in engineering and science has resulted in disruptive medical advances ranging from personalized cell-based therapies (CAR-T cell therapy) to large-scale production of vaccines, both of which contribute to prolonging human life. Today's vaccine market is expected to reach $50 billion by 2020, creating a clear need for efficient, large-scale vaccine production. Biological processes used for vaccine manufacturing generally rely on the design, operation, and optimization of bioreactors. However, bioreactors are very complex unit operations that combine multiphase (gas-liquid-solid) multicomponent hydrodynamics, interphase mass transport, and metabolic reactions. Sanofi Pasteur, the largest manufacturer of vaccines worldwide, uses bioprocesses/bioreactors to develop and manufacture vaccines for the Canadian and global markets. Their in-house research and development facilities would benefit from the development of theoretical models and computational simulations to improve their design processes and operations. They are in an ideal position to leverage advances in these areas and, ultimately, a simultaneous design/control process to improve their manufacturing operations. The proposed research project aims to increase production efficiencies by developing multiphase multiphysics models, integrating advanced multivariable control schemes into simulations using these models, and applying these methods in collaboration with Sanofi Pasteur's research and development group. The outcome of the proposed work would significantly contribute to our understanding of bioreactor multiphysics processes and enable Sanofi and the vaccine industry, to predict the performance and dynamics of bioreactors and other bioprocesses under multivariable control with minimal capital costs and time expenditure.