Cantilever Magnetic Resonance Microscopy of Biomolecules

生物分子的悬臂磁共振显微镜

• 批准号: 6710808
• 负责人: JOHN A MAROHN
• 金额: $ 24.36万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6710808
• 关键词: atomic force microscopy; bioimaging /biomedical imaging; macromolecule; magnetic resonance imaging; microscopy; nanotechnology; nuclear magnetic resonance spectroscopy; protein structure; structural biology; technology /technique development

DESCRIPTION (provided by applicant): This proposal aims to develop technology for dramatically increasing the sensitivity of magnetic resonance imaging. The goal is to develop a "molecular microscope" to detect, analyze, and image nanoscale entities of relevance to biomedicine. Tools for determining protein structure are central to biological research. Improved tools for determining the three dimensional structure of large macromolecules and aggregate structures are urgently needed. A majority of proteins are not well suited for analysis by current methods because they cannot be isolated in large enough quantities or because they do not form crystals. In this proposal we present plans for developing a cantilever-based molecular microscope that can determine the structure of a single copy of a protein, a task which no current technology can achieve. Such an instrument would revolutionize structural biology, dramatically impacting a broad spectrum of biological processes, disorders, and diseases. In this proposal we detail a stepwise approach to developing a molecular microscope for imaging single biomolecules based on a marriage of atomic force microscope and magnetic resonance imaging technologies. Our specific aims are: (1) To detect nuclear magnetic resonance in a new way, as a change in the spring constant of a magnetically tipped microcantilever, (2) Fabricate and characterize nanomagnets suitable for single-proton cantilever detected magnetic resonance. Explore experimentally the minimum forces and spring constant changes that can be detected when a thin, ultrasensitive, silicon microcantilever is brought close to a surface, and (3) Develop and test magnetic resonance imaging protocols suited to small ensembles of nuclear spins.

描述（由申请人提供）：该提案旨在开发显着提高磁共振成像灵敏度的技术。 目标是开发一种“分子显微镜”来检测、分析和成像与生物医学相关的纳米级实体。 确定蛋白质结构的工具是生物学研究的核心。 迫切需要改进的工具来确定大分子的三维结构和聚集体结构。 大多数蛋白质不太适合通过当前方法进行分析，因为它们无法大量分离或因为它们不形成晶体。 在本提案中，我们提出了开发基于悬臂的分子显微镜的计划，该显微镜可以确定蛋白质单个副本的结构，这是当前技术无法实现的任务。这样的仪器将彻底改变结构生物学，极大地影响广泛的生物过程、紊乱和疾病。 在本提案中，我们详细介绍了开发用于单个图像成像的分子显微镜的逐步方法。 基于原子力显微镜和磁共振成像技术结合的生物分子。 我们的具体目标是：（1）以新的方式检测核磁共振，即磁尖微悬臂梁弹簧常数的变化，（2）制造并表征适合单质子悬臂检测磁共振的纳米磁体。通过实验探索当薄的超灵敏硅微悬臂梁靠近表面时可以检测到的最小力和弹簧常数变化，以及 (3) 开发和测试适合小型核自旋系综的磁共振成像协议。