An Improved Atomic Force Microscope for Biomedical Applications

描述(申请人提供)：原子力显微镜(AFM)可以在生理条件下以纳米分辨率成像和操作生物样品。尽管AFM的操作非常慢(有时每张图像超过30分钟)，而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性能的新见解。然而，AFM可以成像的生物过程的范围受到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。这种新一代的用户友好型(2小时培训)、高速(2图像/秒)原子力显微镜是基于设计上的根本性创新而开发的，特别是基于尺寸为10微米的悬臂梁，以提高探测分子的时间和力的分辨率以及成像速度一个数量级或更多。该项目的具体目标是：i)开发一台能够以512x512分辨率成像的高速AFM，每秒2幅图像；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)开发一种集高速和自动化于一体的新型AFM。人们希望并期待这些新的AFM能够作为原型来指导未来商业AFM的发展，从而将高速和自动化的优势带给更广泛的生物医学研究人员。这一新一代原子力显微镜将是快速和易于使用的，并具有更好的调谐和力分辨率。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有利影响。长期目标是将原子力显微镜从专门的研究工具转变为通用的医疗仪器。

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.