Rosalind Franklin Institute: Platform Development Project

该提案旨在为RFI开发一种重要而独特的仪器功能，使其能够在微米长度尺度和亚微秒时间尺度上对物理现象进行改变游戏规则的观察和测量，适用于物理和生命科学中的广泛问题，特别是生物医学成像和治疗。申请资金将用于(1)开发独一无二的超高速成像设备；(2)用于INSIGHT实验室的初始装备，以支持相机以及INSIGHT主题下的未来Hub活动。该系统最初的重点将是了解空化介导的药物传递的物理、化学和生物机制。然而，一旦仪器完成，它可以以多种方式配置，并应用于材料科学，等离子体/冲击物理，声化学，光声学，生物膜动力学，流体动力学，甚至惯性限制核聚变的广泛问题。所涉及的时间和长度尺度的范围提出了一系列艰巨的挑战：-时间分辨率：成像现象，如声空化需要每秒1亿帧（fps）的帧率。相反，成像细胞和生物体对物理刺激的生物反应需要几个小时甚至几天的时间间隔成像。因此，不仅需要出色的光灵敏度（量子效率），而且还需要在成像帧速率方面具有显著的灵活性。它还应该能够按需触发，以捕捉特定现象。-空间分辨率：使用直接或荧光显微镜对亚细胞过程成像对于机制理解至关重要。因此，相机的像素分辨率和光带宽都必须尽可能的大。-生物兼容性：除了相机本身，还需要一个提供真实生物环境的系统，相机和其他仪器可以集成在其中。目前最先进的高速成像系统只能满足这些要求的一部分。新系统将由牛津大学的一个学术团队、一家专门从事高速成像和隐形视觉的英国中小企业、英国/欧盟研究合作伙伴联盟合作开发。一旦投入使用，该系统将作为仪器安装在RFI中心，并以与RAL现有仪器相同的方式作为研究设施使用。

This proposal is to develop a significant and unique instrumentation capability for the RFI that will enable game-changing observations and measurements of physical phenomena at micrometre length scales and sub-microsecond time scales applicable to a broad range of problems in the physical and life sciences in general, and biomedical imaging and therapy in particular. Funds are requested to (1) develop a one-of-a kind very-high-speed imaging facility and (2) for the initial outfitting of the INSIGHT laboratory that will support the camera, as well as future Hub activities within the INSIGHT theme. The initial focus of the system will be understanding the physical, chemical, and biological mechanisms underpinning cavitation mediated drug delivery. However, once the instrument is completed, it can be configured in a variety of ways and applied to broad range of problems in materials science, plasma/shock physics, sonochemistry, photoacoustics, biological membrane dynamics, fluid dynamics, and even inertially-confined nuclear fusion. The range of time and length scales involved poses a series of formidable challenges:-Temporal resolution: imaging phenomena such as acoustic cavitation requires frame rates of the order of 100 million frames per second (fps). Conversely, imaging the biological response of cells and organisms to physical stimuli requires time lapsed imaging over hours or even days. Thus, not only is exceptional light sensitivity (quantum efficiency) required but also significant flexibility in the imaging frame rate. It should also be capable of being triggered on demand to capture specific phenomena.-Spatial resolution: imaging of sub-cellular processes using either direct or fluorescence microscopy is vital for mechanistic understanding. Hence both the pixel resolution of the camera and the optical bandwidth must be as large as possible.-Biological compatibility: in addition to the camera itself, a system providing a realistic biological environment is needed into which the camera and other instrumentation can be integrated.The state of the art high speed imaging systems currently available offer only a subset of these requirements. The new system will be developed through a collaboration between an academic team at Oxford, a UK-SME specialising in high-speed imaging, Invisible Vision and supported by a UK/EU consortium of research partners. Once operational, the system will be installed at the RFI hub as an instrument and accessed as a research facility in the same way as existing instruments at RAL.