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

集成多相流体动力学、代谢建模和控制，实现生物反应器的基于仿真的设计

• 批准号: 538642-2019
• 负责人: Abukhdeir, NasserMohieddinNM
• 金额: $ 3.69万
• 依托单位: University of Waterloo
• 依托单位国家: 加拿大
• 项目类别: Collaborative Research and Development Grants
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=746977
• 关键词: Integration; Multiphase; Hydrodynamics; Metabolic; Modelling

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.

生物过程在工程和科学中的使用导致了从个性化的基于细胞的疗法（CAR-T细胞疗法）到大规模生产疫苗的破坏性医学进步，这两种疫苗都有助于延长人类的生命。到2020年，当今的疫苗市场预计将达到500亿美元，这显然需要对高效，大规模的疫苗生产。用于疫苗制造的生物过程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，可将多相（气体固体）多组分流体动力学，相间质量传输和代谢反应结合在一起。 赛诺菲巴斯德（Sanofi Pasteur）是全球疫苗最大的制造商，使用生物处理器/生物反应器为加拿大和全球市场开发和生产疫苗。他们的内部研发设施将受益于理论模型和计算模拟的开发，以改善其设计过程和操作。它们是利用这些领域进步的理想位置，最终是同时设计/控制过程来改善其制造运营。 拟议的研究项目旨在通过开发多相多物理学模型，使用这些模型将高级多变量控制方案整合到模拟中，并与Sanofi Pasteur的研究和开发小组合作应用这些方法，从而提高生产效率。 拟议工作的结果将极大地有助于我们对生物反应器多物理过程的理解，并使SANOFI和疫苗行业能够预测生物反应器和在多变量控制下具有最小资本成本和时间支出的多变量控制下的生物反应器和其他生物处理。