Ion Channel Probes for Scanning Ion Conductance Microscopy

通过该奖项，化学部门的化学测量和成像项目资助印第安纳大学的Lane Baker教授开发化学/生化传感器，该传感器由脂质双分子层和悬浮在玻璃毛细管顶端的离子通道组成，称为离子通道探针（或icp）。该传感器将结合扫描离子电导显微镜（SICM），一种探针成像平台，使传感器的空间定位在50-100纳米量级。通过将离子通道与选择性响应相结合，将开发出对独特分析物响应的传感器。可定位的ICP将在多孔膜上进行测试，并将能够在亚细胞尺度上测量小分子和离子，并将能够对细胞通信进行新的研究。因此，期望在这项工作中开发的工具将在化学生物学中有广泛的应用。在这个项目中接受培训的学生将学习最先进的制造、测量和表征协议，为他们毕业后的当前劳动力提供高水平的技术技能。此外，将努力提高化学教师对循证教学方法的参与度。提出的研究将提供新的途径，化学选择性成像方法，甚至在单分子水平，扫描离子电导显微镜。这克服了扫描离子电导显微镜的一个显著缺点；即缺乏化学信息的收集。使用固有的选择性和敏感的离子通道将赋予化学感应能力，扫描离子电导显微镜。如上所述，ICP-SICM有望增加嗅探器贴片的可靠操作、信号和时间响应，这反过来又将为它们通常用于研究的生化过程提供信息。

With this award, the Chemical Measurement and Imaging program of the Chemistry Division is funding Professor Lane Baker at Indiana University to develop chemical/biochemical sensors which consist of lipid bilayers and ion channels suspended at the tip of a glass capillary, called ion channel probes (or ICPs). The sensor will be combined with scanning ion conductance microscopy (SICM), a probe imaging platform, to enable spatial location of the sensor on the order of 50-100 nm. By incorporating ion channels with selective responses, sensors that respond to unique analytes will be developed. The positionable ICP will be tested on porous membranes and will enable measurement of small molecules and ions at subcellular scales and will enable new studies of cellular communication. As such, it is expected that the tools developed in this work that will have broad application in chemical biology. Students trained in this project will learn state-of-the-art fabrication, measurement and characterization protocols, providing them with high level technical skills for the current workforce upon their graduation. In addition, efforts will be made to improve chemistry faculty engagement in evidence-based teaching methods. The proposed research will provide new routes to chemically selective imaging methods, even at single molecule levels, with scanning ion conductance microscopy. This overcomes a significant drawback of scanning ion conductance microscopy; namely, the lack of chemical information collected. The use of inherently selective and sensitive ion channels will impart chemical sensing abilities to scanning ion conductance microscopy. As described, ICP-SICM promises to increase the reliable operation, signal and time response of sniffer patches, which will, in turn, inform the biochemical process they are commonly used to study.