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

在工程和科学中使用生物过程已经带来了破坏性的医学进步，从个性化细胞疗法（CAR-T细胞疗法）到大规模生产疫苗，这两者都有助于延长人类生命。目前的疫苗市场预计到2020年将达到500亿美元，因此显然需要高效、大规模的疫苗生产。用于疫苗生产的生物工艺通常依赖于生物反应器的设计、操作和优化。然而，生物反应器是非常复杂的单元操作，它结合了多相（气-液-固）多组分流体动力学、相间质量传递和代谢反应。赛诺菲巴斯德是全球最大的疫苗制造商，使用生物工艺/生物反应器为加拿大和全球市场开发和生产疫苗。他们的内部研究和开发设施将受益于理论模型和计算模拟的发展，以改善他们的设计过程和操作。他们处于一个理想的位置，可以利用这些领域的进步，并最终实现同步设计/控制过程，以改善他们的制造运营。拟议的研究项目旨在通过开发多相多物理场模型，将先进的多变量控制方案集成到使用这些模型的模拟中，并与赛诺菲巴斯德的研发团队合作，应用这些方法来提高生产效率。拟议工作的结果将大大有助于我们对生物反应器多物理场过程的理解，并使赛诺菲和疫苗行业能够以最小的资本成本和时间支出来预测多变量控制下生物反应器和其他生物过程的性能和动态。

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.