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，更强大的个性化药物制造，并将实现超规模缩小设备的设计，这将加快下一代处理的开发，同时提高产量并降低治疗成本。工程理解将用于设计一系列新颖的超大规模工具，以评估和模拟T细胞扩增的3D剪切环境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，从目标和规范标准的建立，到综合，分析，制造，测试和最终用户评估。模拟关键流程交互的USD工具组合对于小规模优化流程非常宝贵，针对关键成本驱动因素，从而从一开始就建立更强大的流程，并在后期开发阶段节省成本。工程表征实验将基于激光技术、高速摄像机成像和自动图像分析的使用。将使用粒子图像测速系统获取关于流型、停滞区的存在、平均和湍流速度特性以及特定位置层流/过渡流的程度的信息。宏观混合的信息，在一系列工业相关的操作条件下获得的，将构成开发规模的翻译模型的基础，并提供一个彻底和完整的洞察力的运作机制，从工程/流体动力学的观点。工程洞察力将为后续T细胞培养实验的设计提供信息。

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.