High resolution SECM for live sciences.

我们已经开发出一种新形式的扫描离子电导显微镜（SICM），它使用精细的纳米移液管，允许高度复杂的细胞样品的形貌的高分辨率成像，以及使用纳米级测定的功能成像，使用相同的探针将试剂递送到细胞表面或进行电生理测量。这是活细胞成像的一个重大进展，我们的目标是通过将SICM与扫描电化学显微镜（SECM）相结合，对化学物质进行灵敏的纳米级映射，将其扩展到化学物质的图像。组合的SICM/SECM探针将被设计为足够小以成像细胞结构，例如微绒毛或精细神经元树突（50-200 nm），以便适用于高分辨率SECM/SICM成像而不损伤。基于我们已经进行的概念验证实验，我们建议实现复杂细胞结构和组织样本的高分辨率SECM/SICM成像，这目前是一个巨大的技术挑战。要做到这一点，我们需要首先设计和优化纳米探针，同时SICM/SECM和修改我们目前的SICM设置和我们的扫描协议。同时SICM/SECM将被用来显示的可行性，记录神经介质的释放，映射呼吸活动和检测NO在活细胞和组织。这项新技术应该在生物、医学和物理科学中有广泛的应用。

We have developed a new form of scanning ion conductance microscopy (SICM) that uses a fine nanopipette that allows the high resolution imaging of the topography of highly complex cellular samples and also functional imaging using the nanoscale assays using the same probe to deliver reagents to the cell surface or to perform electrophysiological measurements. This is a major advance in live cell imaging and we aim to now extend this to image chemical species by combining SICM with scanning electrochemical microscopy (SECM) for sensitive nanoscale mapping of chemical species. The combined SICM/SECM probes will be designed to be small enough to image cellular structure such as microvilli or fine neuronal dendrites (50-200 nm) in order to be suitable for high resolution SECM/SICM imaging without damage. Building on proof of concept experiments that we have performed, we propose to achieve high resolution SECM/SICM imaging of complex cellular structures and tissue samples which currently present a great technical challenge. To do this we need to firstly design and optimize nanoprobes for simultaneous SICM/SECM and modify our current SICM set-up and our scanning protocols. Simultaneous SICM/SECM will then be used to show the feasibility to record neuromediator release, map respiratory activity and detect NO in live cells and tissue. This novel technology should have widespread application in the biological, medical and physical sciences.