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）：该提案旨在开发技术，以显着提高磁共振成像的敏感性。 目的是开发一个“分子显微镜”来检测与生物医学相关的纳米级实体。 确定蛋白质结构的工具对于生物学研究至关重要。 迫切需要改进的工具来确定大型大分子和聚集结构的三维结构。 大多数蛋白质不太适合通过当前方法进行分析，因为它们不能大量足够大，也不能因为它们不形成晶体而被隔离。 在此提案中，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的单个副本的结构，这是当前技术无法实现的任务。这种工具将彻底改变结构生物学，从而极大地影响广泛的生物学过程，疾病和疾病。 在此提案中，我们详细介绍了开发用于成像单个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的婚姻的生物分子。 我们的具体目的是：（1）以一种新的方式检测核磁共振，作为磁性倾斜的微型管理器的弹簧常数的变化，（2）制造和表征适合单蛋白悬臂检测到的磁共振的纳米磁性。在实验上探索最小力和弹簧常数变化，这些变化可以检测到当将薄，超敏感的微敏感性微型磁管带到表面附近时，并且（3）开发和测试适合于核自旋小型团的磁共振成像方案。