Cantilever Magnetic Resonance Microscopy of Biomolecules

生物分子的悬臂磁共振显微镜

• 批准号: 7442122
• 负责人: JOHN A MAROHN
• 金额: $ 24.61万
• 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/7442122
• 关键词: Biological Process; Biology; Disease; Goals; Image; Image Analysis; Imaging technology; Laboratories; Magnetic Resonance; Magnetic Resonance Imaging; Magnetism; Marriage; Medicine; Methods; Microscope; Microscopy; Molecular; NIH Program Announcements; Nanotechnology; Nuclear; Nuclear Magnetic Resonance; Proteins; Protocols documentation; Protons; Scanning Probe Microscopes; Scanning Probe Microscopy; Silicon; Structure; Students; Surface; Technology; Testing; Universities; Work; base; biological research; cantilever; concept; improved; instrument; macromolecule; nanofabrication; nanoscale; nanoscience; protein structure; research study; response; structural biology; three dimensional structure; tool

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）：本提案旨在开发用于显著提高磁共振成像灵敏度的技术。 其目标是开发一种“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。 迫切需要用于确定大分子和聚集体结构的三维结构的改进工具。 大多数蛋白质不太适合用现有的方法进行分析，因为它们不能以足够大的量分离，或者因为它们不形成晶体。 在这项提案中，我们提出了开发一种基于荧光素的分子显微镜的计划，该显微镜可以确定蛋白质单拷贝的结构，这是目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。 在这个建议中，我们详细介绍了一个逐步的方法来开发一个分子显微镜成像单 基于原子力显微镜和磁共振成像技术的结合的生物分子。 我们的具体目标是：（1）以一种新的方式检测核磁共振，作为磁性尖端微悬臂梁的弹簧常数的变化，（2）制备并表征适合于单质子悬臂梁检测的磁共振的纳米磁体。实验探索最小的力和弹簧常数的变化，可以检测到当一个薄的，超灵敏的，硅微悬臂接近表面，（3）开发和测试磁共振成像协议适合于小合奏的核自旋。