Engineering challenges in personalised cell therapies: applying fundamental engineering, ultra scale-down design and experimental flow dynamics approa

该提案将建立对流体动力学对多个过程步骤的影响的严格的基础工程理解，以实现更安全和更强大的个性化药物制造，并将使超尺寸设备的设计成为可能，这将加速下一代工艺的发展，同时提高产量并降低治疗成本。工程知识将用于设计一系列新型超缩小工具，以评估和模拟三维剪切环境对t细胞膨胀和后续工艺步骤的影响。该项目将以迭代设计思维过程为指导，从建立目标和规范标准，到综合、分析、制造、测试和最终用户评估。模仿关键过程交互的美元工具组合对于在小范围内优化过程，针对关键成本驱动因素，从而从一开始就建立一个更健壮的过程，并允许在开发的后期阶段节省成本是非常宝贵的。工程特性实验将基于激光技术、高速相机成像和自动图像分析的使用。粒子图像测速（PIV）系统将用于获取流动模式、停滞区域的存在、平均和湍流速度特征以及特定位置层流/过渡流的程度等信息。在一系列与工业相关的操作条件下获得的宏观混合信息，将构成开发尺度平移模型的基础，并从工程/流体动力学的角度提供对操作机制的全面和完整的见解。工程洞察力将告知后续t细胞培养实验的设计。

This proposal will establish a rigorous fundamental engineering understanding of the impact of fluid dynamics on multiple process steps towards safer and more robust personalised medicine manufacture and will enable the design of ultra-scale down devices that will speed the development of the next generation processing while improving yields and reducing cost of therapies. The engineering understanding will be used to design a portfolio of novel ultra scaledown tools to evaluate and model the effect of 3D shear environment of T-cells expansion and subsequent process steps. The project will be guided by an iterative design thought process, from the establishment of objectives and specification criteria, through to synthesis, analysis, fabrication, testing and end-user evaluation. A portfolio of USD tools mimicking critical process interactions would be invaluable to optimise the process at a small scale, targeting key cost drivers, thus establishing a more robust process from the start and allowing for savings at later stages of development. Engineering characterisation experiments will be based on the use of laser-based techniques, high speed camera imaging and automated image analysis. A Particle Image Velocimetry (PIV) system will be used to obtain information on flow pattern, presence of stagnant areas, mean and turbulent velocity characteristics and extent of laminar/transitional flow at specific locations. Macromixing information, obtained under a range of industrially relevant operating conditions, will constitute a basis for developing scale translation models and provide a thorough and complete insight of the mechanism of operation from the engineering/fluid dynamics viewpoint. The engineering insight will inform the design of the subsequent T-cells cultivation experiments.