NSF-MRI: Development of Sub-Angstrom Amplitude Atomic Force Microscope for Biological and Liquid Environments

在彼得·霍夫曼博士的指导下，韦恩州立大学获得了一笔赠款，用于设计和建造一种新的、创新的原子力显微镜（AFM），以研究细胞和生物分子。AFM是一种技术，其中安装在悬臂弹簧上的尖锐尖端被扫描穿过或接近表面，以便在纳米尺度下成像和测量机械特性。该技术已被用于测量生物结构超过十年。然而，目前AFM的基本设计问题，限制了它们的实用性。这些包括低灵敏度和固有的非线性。因此，AFM在生物学研究中尚未充分发挥其潜力。这项资助的目的是设计一个完全不同的AFM系统，从一开始就避免这些限制，专门用于对生物样品进行前所未有的高分辨率成像和纳米机械测量。这种新仪器最重要的特点将是使用光纤干涉仪测量悬臂梁的偏转（将灵敏度提高100倍），非接触式操作（用于非侵入性成像），以及使用超小振幅（1埃=单个氢原子的大小），这将使力测量线性化。这种新仪器的开发将对我们对细胞和细胞膜的理解产生巨大影响。将使用这一新工具进行的研究包括：（1）跨膜蛋白的行为（位于细胞膜中的蛋白质），其在细胞信号传导中起重要作用，（2）胎膜的机械性质，解决人类早产的项目的一部分，以及（3）疏水性和模拟细胞膜及其组件的模型系统中的其他力的基础研究，以更好地了解这些基本的构建模块，该仪器将为韦恩州立大学的研究基础设施增加一个重要组成部分，预计将用于从生物学、医学、材料科学到工业应用（纳米摩擦学）的许多突破性的跨学科研究项目。 这项工作的结果将通过底特律地区科学博物馆和学校的计划外展活动传达给公众，这是目前实施的一项计划的一部分，该计划包括为公众举办科学讲座。

A grant has been awarded to Wayne State University under the direction of Dr. Peter Hoffmann to design and construct a new, innovative Atomic Force Microscope (AFM) to study cells and biomolecules. AFM is a technique where a sharp tip mounted on a cantilever spring is scanned across or approached towards a surface in order to image and measure mechanical properties at the nanoscale. The technique has been used for over a decade in measurements of biological structures. However, current AFM's have fundamental design issues that limit their usefulness. These include low sensitivity and inherent non-linearities. As a result, AFM's have not reached their full potential in biological research. The purpose of this grant is to design a radically different AFM system that avoids these limitations from the start and is specifically built to perform unprecedented high-resolution imaging and nano-mechanical measurements of biological samples. The most important features of this new instrument will be the use of a fiber-optic interferometer to measure the deflection of the cantilever (boosting sensitivity by a factor 100), non-contact operation (for non-invasive imaging), and the use of ultra-small amplitudes ( 1 Angstrom = the size of a single hydrogen atom), which will linearize force measurements. The development of this new instrument will have a tremendous impact on our understanding of cells and cell membranes. Research that will be conducted with this new instrument includes: (1) behavior of transmembrane proteins (proteins that are located in the cell membrane), which play important roles in cell signaling, (2) mechanical properties of fetal membranes, part of a project to address prematurity in humans, and (3) basic research of hydrophobicity and other forces in model systems that mimic cell membranes and their components to gain better understanding of these fundamental building blocks of life.The instrument will add a significant component to the research infrastructure here at Wayne State University, and is expected to be used for a number of ground-breaking interdisciplinary research projects ranging from biology, medicine, materials science to industrial applications (nanotribology). Results of the work will be communicated to the general public via planned outreach events in Detroit area science museums and schools, part of a currently implemented program consisting of science lectures for the general public.