IDBR: Plasmonic-based electrochemical impedance microscopy for studying molecular binding and cellular processes

摘要技术描述：电阻抗已广泛应用于生物过程的检测和研究，但缺乏空间分辨率和成像能力。实验结果表明，阻抗可以转换为等离子体信号。这种范式转换方法允许光学测量局部阻抗，并导致一种新的基于等离子体的电化学阻抗显微镜（P-EIM），可以对生物样品的电学和电化学响应进行成像。P-EIM可以以微阵列的形式研究小分子和蛋白质的结合亲和力，跟踪单个病毒的结合事件，并以亚微米级的空间分辨率和亚毫秒级的时间分辨率成像各种细胞和亚细胞过程，包括离子通道和G蛋白偶联受体的活性。P-EIM是无标签的，它克服了与基于标签的检测和成像技术相关的限制。该项目将P-EIM与全内反射荧光和表面等离子体共振显微镜相结合，并与不同领域的研究人员合作，包括蛋白质组学，免疫学，神经学和细胞生物学，开发新的应用。具体目标包括开发和展示P-EIM能力：1)测量分子相互作用和动力学，特别是小分子-蛋白质相互作用；2)监测病毒结合动力学和统计数据；3)以毫秒级时间分辨率研究单细胞和亚细胞动力学。非技术描述：光学显微镜使生物学研究取得了许多突破，并成为几乎每个生命科学实验室真正不可或缺的工具。生物学的持续进步将受益于新的成像能力，为当前的显微镜技术提供独特和补充的信息。本项目将引入光学显微镜的阻抗成像模式，允许对生物样品的电学和电化学反应进行光学成像，这是当前光学显微镜所缺乏的能力。为了将新的成像能力转化为生物研究的强大工具，pi将与十多个研究小组合作开发不同的生物应用，通过Youtube，维基百科和专门的网站创建教程材料，并与大学技术转移办公室合作促进商业化。该项目将为跨学科培训和培养下一代科学家和工程师提供独特的机会。除了培养研究生和博士后之外，pi还利用亚利桑那州立大学现有的几个项目和基础设施，提出了新的本科研究教育计划。例如，美国国家科学基金会REU项目、生物设计高中学生实习和亚利桑那州立大学的富尔顿本科生研究计划（FURI），这些项目为招收和支持本科生提供了额外的资源，包括在大学学习的早期阶段，在科学和工程领域代表性不足的群体。该项目还将为学生提供独特的国际和跨学科合作经验。

IDBR: Plasmonic-based electrochemical impedance microscopy for studying molecular binding and cellular processesAbstractTechnical Description: Electrical impedance has been widely used to detect and study biological processes, but it lacks spatial resolution or imaging capability. The PIs have shown that the impedance can be converted into a plasmonic signal. This paradigm shift approach allows the measurement of local impedance optically, and leads to a novel plasmonic-based electrochemical impedance microscope (P-EIM) that can image electrical and electrochemical responses of a biological sample. P-EIM can study binding affinity of small molecules and proteins in microarray format, follow the binding events of single viruses, and image various cellular and subcellular processes, including ion channel and G protein coupled receptor activities, with sub-micron spatial resolution and sub-millisecond temporal resolution. P-EIM is label free, which overcomes limitations associated with label-based detection and imaging technologies. This project will integrate P-EIM with total internal reflection fluorescence and surface plasmon resonance microscopy, and work with researchers in different fields, including proteomics, immunology, neurology and cell biology, to develop new applications. Specific aims include developing and demonstrating P-EIM capabilities to: 1) Measure molecular interactions and kinetics, particularly small molecule-protein interactions; 2) Monitor virus binding kinetics and statistics; 3) Study single cell and sub-cellular kinetics with milliseconds time resolution.Non-technical description: Optical microscopy has enabled many breakthroughs in biological research, and become a truly indispensable tool in nearly every life science lab. Continued advances in biology will benefit from new imaging capabilities that provide unique and complementary information to the current microscopy technologies. The present project will introduce an impedance-imaging mode to optical microscopy, allowing for optical imaging of electrical and electrochemical responses of biological samples, a capability that current optical microscopy lacks. In order to transform the new imaging capability into a powerful tool for biological research, the PIs will collaborate with over ten research groups to develop different biological applications, create tutorial materials via Youtube, Wikipedia, and a dedicated website, and work with the university technology transfer office to facilitate commercialization. The project will provide unique opportunities for interdisciplinary training and nurturing the next generation of scientists and engineers. In addition to training graduate and postdoctoral students, the PIs propose new educational initiatives in undergraduate research taking advantage of several existing programs and infrastructures at ASU. Examples include the NSF REU program, Biodesign high school student internship, and Fulton Undergraduate Research Initiative (FURI) at ASU, which provide additional resources for recruiting and supporting undergraduate students, including groups underrepresented in science and engineering, at the early stages of their studies in the college. The project will also provide students with unique international and interdisciplinary collaboration experience.