An Improved Atomic Force Microscope for Biomedical Applications

描述（由申请人提供）：原子力显微镜（AFM）可以在生理条件下以纳米分辨率对生物样品进行成像和操作。尽管其操作非常缓慢（有时每张图像超过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AFM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机械特性的新见解。然而，AFM可以成像的生物过程的范围受到AFM当前的低时间分辨率的严重限制，这是由于基于具有100微米量级尺寸的杠杆的当前一代AFM中固有的基本限制。这种新一代的用户友好的（2小时的培训），高速（2图像/秒）的AFM被提出开发的基础上的基本创新的设计，特别是通过基于新的AFM的尺寸为10微米量级的杠杆，以提高时间和力的分辨率探测分子和成像速度的数量级或更多。该项目的具体目标是：i）开发一种高速AFM，可以以512 x512分辨率，每秒2张图像成像; 2）开发一种用户友好的AFM，其中大部分设置AFM和调整反馈参数的过程都是自动化的; 3）开发一种新的AFM，将高速与自动化相结合。希望并期望这些新的AFM可以作为原型来指导未来商业AFM的开发，这可以为更广泛的生物医学研究人员带来高速和自动化的优势。新一代的AFM将是快速和易于使用，并提高了调谐和力的分辨率。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有利影响。长期目标是将AFM从一种专门的研究工具转变为一种通用的医疗仪器。

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.