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

个性化细胞疗法的工程挑战：应用基础工程、超小型设计和实验流动动力学方法

• 批准号: 2268438
• 金额: --
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2268438
• 关键词: Engineering; challenges; personalised; cell; therapies

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.

该提案将对流体动力学对多个工艺步骤的影响建立严格的基础工程理解，以实现更安全、更稳健的个性化药品制造，并将实现超小型设备的设计，从而加快下一代工艺的开发，同时改进产量并降低治疗成本。工程理解将用于设计一系列新型超缩小工具，以评估和模拟 T 细胞扩增和后续工艺步骤的 3D 剪切环境的影响。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。模仿关键流程交互的美元工具组合对于小规模优化流程、针对关键成本驱动因素非常有价值，从而从一开始就建立更强大的流程，并在开发的后期阶段节省成本。工程表征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) 系统将用于获取有关流动模式、停滞区域的存在、平均和湍流速度特征以及特定位置的层流/过渡流范围的信息。在一系列工业相关操作条件下获得的宏观混合信息将构成开发尺度转换模型的基础，并从工程/流体动力学的角度提供对操作机制的彻底和完整的了解。工程见解将为后续 T 细胞培养实验的设计提供信息。