Research Initiation Award Grant: Ultrasensitive Plasmonic Nanoprobes for Monitoring of Intracellular Labile Iron Pools

这项研究将开发一种微创的新传感方法，解决在单细胞水平上理解细胞内不稳定铁池（LIP）的化学性质，分布和合作性的突出挑战。近年来，已经尝试测量细胞中的LIP;然而，LIP的精确测定仍然难以捉摸。用于LIP监测的超灵敏和潜在细胞器特异性等离子体纳米探针的开发将提高对细胞内铁动力学和分布的理解，从而对铁障碍的现有螯合和补充疗法的优化产生影响。这项研究还将为非裔美国本科生和研究生提供研究培训机会，在纳米技术研究的最前沿。该项目将开发一种独特的方法，使用等离子体纳米结构为基础的表面增强拉曼散射（Sers）的选择性传感的LIP，与纳摩尔的灵敏度。这项工作涉及生物模板辅助纳米图案化的二维超晶格构造的银纳米晶体，这些纳米结构的物理化学性质将使用各种分析工具，如TEM，SEM，紫外-可见光谱，FT-IR，和拉曼光谱。LIP的等离子体检测的灵敏度和选择性将使用来自数百万细胞的裂解物进行优化和评估，该项目的最终目标是将最佳等离子体纳米结构整合到光纤的小平面上，因此它可以插入到单个细胞隔室，并用作超灵敏的纳米探针，用于体外实时监测LIP。预计通过开发超灵敏的脂蛋白特异性等离子体纳米探针，将在阐明细胞内铁转运和动力学方面取得相当大的进展。

This study will develop a minimally invasive new sensing approach that addresses outstanding challenges of understanding the chemical nature, distribution and cooperativeness of the intracellular labile iron pool (LIP), at the single-cell level. In recent years, attempts have been made to measure the LIP in cells; however, the precise determination of the LIP remains elusive. The development of ultrasensitive and potentially organelle-specific plasmonic nanoprobes for LIP monitoring will improve the understanding of intracellular iron dynamics and distribution, and will thus have an impact on the optimization of existing chelation and supplementation therapies for iron disorders. The study will also provide research training opportunities for African American undergraduate and graduate students at the forefront of nanotechnology research. The project will develop a unique approach using plasmonic nanostructure-based surface-enhanced Raman scattering (SERS) for selective sensing of the LIP, with nanomolar sensitivity. The work involves biotemplate-assisted nanopatterning of two-dimensional superlattices constructed from silver nanocrystals, and the physicochemical properties of these nanostructures will be characterized using a variety of analytical tools such as TEM, SEM, UV-Vis spectrometry, FT-IR, and Raman spectroscopy. The sensitivity and selectivity for the plasmonic detection of the LIP will be optimized and evaluated using lysates from millions of cells, and the eventual goal of the project is to integrate the optimal plasmonic nanostructures onto the facet of an optical fiber, so it can be inserted to individual cellular compartments, and used as an ultrasensitive nanoprobe for real-time monitoring of the LIP in vitro. It is expected that considerable progress in the elucidation of intracellular iron trafficking and dynamics will be achieved by the development of ultrasensitive LIP-specific plasmonic nanoprobes.