An Improved Atomic Force Microscope for Biomedical Applications

描述（由申请人提供）：原子力显微镜（AFM）可以在纳米分辨率下对生理条件下的生物样品进行成像和操作。尽管AFM的操作非常缓慢（每张图像有时超过30分钟），并且需要特殊的专业知识来克服其使用的复杂性，但它已经促进了重大的生物医学发现，包括对膜蛋白和结构蛋白的机械特性的新见解。然而，AFM可以成像的生物过程范围受到AFM当前低时间分辨率的严重限制，这是由于当前一代基于尺寸为100微米的悬臂梁的AFM固有的基本限制。这新一代用户友好的（2小时的培训），高速（2张图像/秒）AFMs被提出是基于设计的基本创新，特别是通过将新的AFMs建立在10微米的悬臂上，以提高探测分子的时间和力分辨率以及成像速度的数量级或更多。该项目的具体目标是：i)开发能够以512x512分辨率成像，每秒2张图像的高速AFM；2)开发一种用户友好的AFM，其中设置AFM和调整反馈参数的大部分过程都是自动化的；3)开发一种高速与自动化相结合的新型AFM。希望并期待这些新型原子力显微镜可以作为原型，指导未来商用原子力显微镜的发展，为更广泛的生物医学研究人员带来高速和自动化的优势。这种新一代afm将是快速和易于使用，并有改进的调谐和力的分辨率。这将有助于在分子水平上对生物过程进行成像，从而对生物医学研究产生广泛的影响。长期目标是将原子力显微镜从一个专门的研究工具转变为一个通用的医疗仪器。

DESCRIPTION (provided by applicant): The Atomic Force Microscope (AFM) can image and manipulate biological samples under physiological conditions at nanometer resolution. Despite its very slow operation (sometimes over 30 minutes per image) and the special expertise required to overcome its complexity of use, the AFM has already facilitated significant biomedical discoveries including new insights into membrane proteins and the mechanical properties of structural proteins. The range of biological processes the AFM can image is, however, severely limited by the AFM's current low time resolution, which is due to fundamental limits inherent in the current generation of AFMs based on cantilevers with dimensions of order 100 microns. This new generation of user-friendly (2 hours' training), high speed (2 images/second) AFMs is proposed to be developed based on fundamental innovations in design, particularly by basing the new AFMs on cantilevers with dimensions of order 10 microns to improve time and force resolution for probing molecules and speed in imaging by an order of magnitude or more. The Specific Aims of the project are: i) to develop a high-speed AFM that can image at 512x512 resolution, at 2 images/second; 2) to develop a user-friendly AFM in which most of the processes in setting up the AFM and adjusting feedback parameters are automated; 3) to develop a new AFM that combines high-speed with automation. It is hoped and expected that these new AFMs can serve as prototypes to guide the development of future commercial AFMs, which can bring the advantages of high-speed and automation to the broader community of biomedical researchers. This new generation of AFMs will be fast and easy to use and have improved tune and force resolution. This will facilitate imaging of biological processes at the molecular level and thus have a broad enabling impact on biomedical research. The long term goal is to transition the AFM from a specialized research tool to a general use medical instrument.