High resolution SECM for live sciences.

我们开发了一种新形式的扫描离子电导显微镜(SICM)，它使用精细的纳米管，允许对高度复杂的细胞样本的形貌进行高分辨率成像，并使用相同的探针使用纳米级分析进行功能成像，以将试剂输送到细胞表面或执行电生理测量。这是活细胞成像的一大进步，我们现在的目标是将SICM与扫描电化学显微镜(SECM)相结合，以敏感的纳米尺度绘制化学物种的图谱，从而将其扩展到对化学物种进行成像。SICM/SECM组合探针将设计得足够小，以成像微绒毛或细小神经元树突(50-200 nm)等细胞结构，以便适合于高分辨率SECM/SICM无损伤成像。在我们已经进行的概念验证实验的基础上，我们建议实现对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，我们首先需要设计和优化同时进行SICM/SECM的纳米探针，并修改我们当前的SICM设置和扫描协议。然后，同步的SICM/SECM将被用来显示记录神经介质释放、绘制呼吸活动图以及在活细胞和组织中检测NO的可行性。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.