SINGLE MOLECULAR NANOSCOPIC IMAGING ON LIVING CELLS

摘要 在这项研究中，我们将演示一种超分辨率圆二色纳米成像的概念证明 一种可以在单分子水平上绘制细胞膜光谱的工具。我们将充分利用这一优势 扫描探头技术的空间分辨率与等离子体增强的强局域场现象 手性超材料。我们之前已经分别演示了一种平面手性超材料传感器 可以测量手性分子的圆二向色性，增强了七个数量级；以及 用于从纳米样品中检测手性相关光学力的光学力纳米显微镜工具 空间分辨率。建立在这些先前发现的基础上，但与先前的工作有很大不同，在本提案中 我们将在原子力显微镜(AFM)的尖端上制造一种等离子体超材料，它可以局部增强 手征光场关联力。这种超材料-AFM尖端可以接近细胞膜 近场，由超材料增强的强大光学力与细胞强烈相互作用 膜分子。这些力的变化将被AFM尖端再次检测到 靶向分子的二色性可以去卷曲。从长远来看，这一新工具可以实现 测量膜分子的动态构象变化，如离子通道，进一步我们的 了解活细胞在单分子水平上的基本分子机制。

ABSTRACT In this research, we will demonstrate a proof of concept super-resolution circular dichroism nanoscopy imaging tool that can map the spectrum of cell membranes at single molecule level. We will capitalize on the high spatial resolution of scanning probe technique and strongly localized field phenomena enhanced by plasmonic chiral metamaterials. We have previously separately demonstrated a planar chiral metamaterial sensor that can measure circular dichroism of chiral molecules with seven orders of magnitude enhancement; and an optical force nanoscopy tool to detect chirality related optical forces from nano-specimen with nanometer spatial resolution. Building upon these previous findings, but very different from the prior work, in this proposal we will fabricate a plasmonic metamaterial on an atomic force microscope (AFM) tip that can locally enhance the chiral optical field-associated forces. This metamaterial-AFM tip can approach the cell membrane in the near field, where the strong optical forces enhanced by the metamaterial interact strongly with the cell membrane molecules. The change of these forces will be detected again by the AFM tip where circular dichroism of the targeting molecules can be de-convoluted. In the long term, this new tool can enable measurements of dynamic conformational changes of membrane molecules such as ion channels, further our understanding of fundamental molecular mechanisms at the single molecular level on living cells.