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.

该建议将建立严格的基本工程理解，了解流体动态对多个过程步骤的影响，以实现更安全，更健壮的个性化医学制造，并能够设计超规模下降的设备，从而加快下一代处理的发展，同时提高产量和降低治疗成本。工程理解将用于设计新型Ultra Scaledown工具的组合，以评估和建模T细胞扩展和随后的过程步骤的3D剪切环境的效果。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，该项目将以迭代设计思维过程为指导。模仿关键过程交互的USD工具组合将是无价的，可以在小规模上优化该过程，以关键成本驱动力的目标，从而从一开始就建立了更强大的过程，并允许在后期开发阶段节省。工程表征实验将基于基于激光的技术，高速相机成像和自动图像分析的使用。粒子图像速度计（PIV）系统将用于获取有关流动模式，停滞区域，平均和湍流速度特征的信息以及在特定位置的层流/过渡流的程度。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规模翻译模型的基础，并从工程/流体动力学的角度彻底完整地了解操作机理。工程洞察力将为随后的T细胞种植实验的设计提供信息。