Multifrequency microwave powered DNP instrument for MAS NMR

用于 MAS NMR 的多频微波供电 DNP 仪器

• 批准号: 9166814
• 负责人: Songi Han
• 金额: $ 19.98万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9166814
• 关键词: Address; Alzheimer' s Disease; Amyloid Fibrils; Attention; Automobile Driving; Biological; Cells; Characteristics; Collaborations; Detection; Development; Device or Instrument Development; Devices; Diagnostic; Electron Spin Resonance Spectroscopy; Event; Freezing; Frequencies; Funding; Generations; Hand; Helium; Home environment; Label; Laboratories; Liquid substance; Magic; Measurement; Membrane Proteins; Methods; Modification; NMR Spectroscopy; Nitrogen; Nuclear; Optics; Pattern; Peptides; Performance; Physiologic pulse; Power Sources; Proteins; Pump; Research; Research Design; Research Infrastructure; Resolution; Role; Sampling; Signal Transduction; Solid; Solvents; Source; Staging; Structure; System; Techniques; Technology; Temperature; Testing; Time; base; cost; design; improved; innovation; instrument; instrumentation; irradiation; magnetic field; microwave electromagnetic radiation; novel; operation; protein aggregate; protein aggregation; research study; solid state; stem; structural biology; success; tool; transmission process

PROJECT SUMMARY Solid-state dynamic nuclear polarization (ssDNP) is an NMR signal-enhancing technique by on-resonant microwave (MW) irradiation of tailored radical-based DNP agents that is attracting dramatic attention in recent years, given its potential to transform the capability of NMR spectroscopy for structural biology as we know it, in particular of solid-state magic angle spinning (MAS) NMR studies of biological solid samples. The potential of ssDNP stems from the ability of this technique to enhance spin polarization by O(102-103) fold. This signal gain, combined with a thermal polarization gain of O(101) fold from cooling to liquid nitrogen temperatures and O(102) from cooling to liquid helium temperatures, together with high magnetic fields, offers a total signal gain of up to O(105) for ssNMR, and accordingly a reduction in experimental time by up to the square of this signal gain. Such dramatic magnitudes of signal enhancement enable unprecedented ssNMR studies of the types of samples and conditions that have been inaccessible to NMR based structure studies before. Among the ssDNP-enabled research highlights are the study of membrane protein systems in whole cells or the study of inter-strand structure determination of the quaternary structure of amyloid fibrils. A particular focus of our development is to enable transient structure studies of aggregating proteins by ssDNP-enhanced MAS NMR of freeze-quenched proteins at various stages of aggregation. In the well-recognized role of ssDNP to enhance MAS NMR as an ultimate high- resolution structural biology tool to capture transiently evolving structures, we propose to address major technological challenges with our innovative instrument developments. The core of our development will be a compact and versatile quasi-optical MW bridge design with novel two-frequency pump, concurrent DNP and EPR, as well as ELDOR capabilities under MAS operation. While, ssDNP-enhanced MAS NMR is the center of focus of contemporary NMR as it has the potential to transform MAS NMR structure studies of biosolids, only a handful of alternative ssDNP MAS NMR instruments exists in the world to the commercial gyrotron-powered ssDNP MAS NMR instrument operating at >100 Kelvin—our instrumental platform for DNP-enhanced MAS NMR aims to offer an alternative solution with greater versatility and performance.

项目摘要 固态动态核极化（ssDNP）是一种利用共振微波（MW）增强核磁共振信号的技术 定制的基于自由基的DNP试剂的照射近年来引起了极大的关注，因为其具有 改变核磁共振光谱学的能力，为结构生物学，因为我们知道，特别是固态魔角 生物固体样品的旋转（MAS）NMR研究。ssDNP的潜力源于这种技术的能力， 使自旋极化增强O（102-103）倍。该信号增益与O（101）倍的热偏振增益相结合 从冷却到液氮温度和O（102）从冷却到液氦温度，以及高 磁场，为ssNMR提供高达O（105）的总信号增益，因此通过以下方式减少实验时间： 直到该信号增益的平方。如此巨大的信号增强使得前所未有的ssNMR成为可能 研究样品的类型和条件，这些是以前基于NMR的结构研究无法达到的。 ssDNP使能的研究亮点之一是全细胞膜蛋白系统的研究或 淀粉样蛋白原纤维四级结构的链间结构测定。我们发展的一个特别重点是 通过冷冻淬灭蛋白质的ssDNP增强MAS NMR， 在不同的聚合阶段。在ssDNP增强MAS NMR作为最终的高分子的公认作用中， 分辨率结构生物学工具，捕捉瞬态演变的结构，我们建议解决主要的技术 我们的创新工具开发带来的挑战。我们发展的核心将是一个紧凑和多功能的 具有新颖双频泵浦、并发DNP和EPR以及ELDOR能力的准光MW桥设计 在MAS操作下。而ssDNP增强的MAS NMR是当代NMR的焦点，因为它具有 有潜力改变生物固体的MAS NMR结构研究，只有少数替代ssDNP MAS NMR仪器 目前世界上存在的最大的核磁共振仪是以回旋管为动力的ssDNP MAS核磁共振仪，其工作温度>100 K。 DNP增强MAS NMR的仪器平台旨在提供具有更大通用性的替代解决方案， 性能