A Novel Millimeter-wave (mmw) DNP/EPR Front-end Compatible with Versatile High-field NMR Probes

与多功能高场 NMR 探头兼容的新型毫米波 (mmw) DNP/EPR 前端

• 批准号: 9343460
• 负责人: Francis DAVID Doty
• 金额: $ 22.46万
• 依托单位: DOTY SCIENTIFIC, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9343460
• 关键词: Alzheimer' s Disease; Amplifiers; Amyloid Fibrils; Binding; Biological; Biomedical Research; Budgets; Calibration; Communication; Computer software; Databases; Deposition; Detection; Development; Devices; Drops; Electrons; Equipment; Frequencies; Growth; HIV; Laboratories; Liquid substance; Magic; Malignant Neoplasms; Membrane Proteins; Methods; NMR Spectroscopy; Nuclear; Nuclear Magnetic Resonance; Optics; Pharmaceutical Preparations; Phase; Physiologic pulse; Play; Price; Proteins; Publishing; Race; Radar; Rattus; Reporting; Research Personnel; Resolution; Role; Sampling; Scanning Tunneling Microscopy; Side; Signal Transduction; Small Business Innovation Research Grant; Solid; Source; Structure; System; Techniques; Testing; Time; Vertebral column; base; cost; cryogenics; design; detector; experimental study; falls; flexibility; gallium arsenide; improved; instrument; interest; macromolecule; microwave electromagnetic radiation; millimeter; nanosecond; novel; novel strategies; protein function; prototype; simulation; solid state; solid state nuclear magnetic resonance; structural biology; tool; virtual

A Novel Millimeter-wave (mmw) DNP/EPR Front-end Compatible with Versatile High-field NMR Probes Abstract There has been explosive growth in interest in Dynamic Nuclear Polarization (DNP) with Magic Angle Spinning (MAS) over the past five years because it has demonstrated S/N gains exceeding two orders of magnitude at ~100 K compared to conventional MAS-NMR and non-spinning NMR of biological macromolecules in their supramolecular assemblies under ambient conditions. The reduction in signal acquisition time up to four orders is promising for a wide range of applications, and in particular structure determination and function elucidation of biological macromolecules. Despite this enormous potential benefit, the adaptation rate of DNP will be severely limited by its very high price tag (currently $2-6M), largely because of the expensive gyrotron that has been required and because of the need for a special NMR magnet with superconducting sweep coils (as the bandwidth of the gyrotron is very narrow). Our preliminary simulations of a novel millimeter wave (mmw) DNP cavity that is compatible with a new MAS spinner design have shown the potential for achieving the needed electron spin saturation with up to two orders of magnitude lower microwave power than with existing MAS-DNP probes for samples of similar volume (1-15 μL) and other conditions. With such an advance in mmw cavity design, along with the order-of- magnitude progress in broad-band solid-state InP mmw power amplifiers seen over the past five years (amplifiers now up to 850 GHz), it can become possible to eliminate both the gyrotron and need for a special NMR magnet with superconducting sweep coils, even at NMR frequencies to 1200 MHz (800 GHz EPR). These transformational advances can permit an enormous reduction in the cost of bringing MAS-DNP into an ssNMR laboratory, thereby making it possible for virtually all current NMR groups to begin developing and applying powerful new methods to structure determination and function elucidation of insoluble rigid proteins and other macromolecules that are key to progress in developing cures for Alzheimer’s Disease and cancer. However, in addition to the need for efficient MAS-DNP mmw spinner cavities, a novel low-cost EPR mmw front-end (bridge) is critically needed so that EPR experiments can first be carried out within the high- field NMR magnet on the prepared sample to facilitate essential calibration and optimization for the subsequent MAS-DNP experiments. Unfortunately, the needed mmw front-end hardware is not available and a radically new approach appears necessary if DNP is to become widely implemented. This Phase-I would design, develop, and characterize a unique microelectronics mmw circuit for initial demonstration (during the Phase-II) at 200GHz/300MHz that will be the basis for an add-on DNP/EPR front- end accessory, eventually up to 800 GHz for existing high-field ssNMR spectrometers. Simulations, analysis, and hardware tests will establish the potential for an order of magnitude reduction in system cost and two orders of magnitude increase in EPR sensitivity compared to previously published approaches to high-field EPR. Moreover, the novel approach will be compatible with H/X/Y MAS-DNP probes of commercially viable designs.

一种与多功能高场核磁共振探针兼容的新型毫米波DNP/EPR前端 摘要 人们对魔角动态核极化(DNP)的兴趣出现了爆炸性增长 旋转(MAS)在过去五年中，因为它展示了S/N的收益超过两个数量级 生物的常规MAS-核磁共振和非自旋核磁共振在~100K下的大小比较 在环境条件下，大分子在它们的超分子组装中。信号的减少 获取时间高达四个数量级，对于广泛的应用，特别是结构，是很有希望的 生物大分子的测定和功能阐明。尽管有这个巨大的潜在好处， DNP的改编率将受到其非常高的价格标签(目前为200万至600万美元)的严重限制，主要原因是 由于需要昂贵的回旋管，并且需要一种特殊的具有 超导扫描线圈(因为回旋管的带宽很窄)。 我们对一种新型毫米波DNP腔的初步模拟，该腔与新的 MAS旋转器的设计已经显示出实现所需的电子自旋饱和的潜力，最多两个 对于类似体积的样品，微波功率比现有的MAS-DNP探头低数量级 (1-15μL)等条件。随着毫米波腔体设计的如此进步，以及 宽带固态InP毫米波功率放大器在过去五年中的巨大进步 (放大器现在高达850 GHz)，可以同时消除回旋管和需要特殊的 具有超导扫描线圈的核磁共振磁体，即使在核磁共振频率为1200 MHz(800 GHz EPR)时也是如此。 这些变革性进展可以极大地降低将MAS-DNP引入 单核磁共振实验室，从而使几乎所有当前的核磁共振基团都有可能开始开发和 强有力的新方法在难溶刚性蛋白结构测定和功能研究中的应用 以及其他在阿尔茨海默氏症和癌症治疗方面取得进展的关键大分子。 然而，除了需要高效的MAS-DNP毫米波旋转腔外，一种新型的低成本EPR 迫切需要毫米波前端(网桥)，以便EPR实验可以首先在高 在准备好的样品上放置磁场核磁共振磁体，以便于后续的必要校准和优化 MAS-DNP实验。不幸的是，所需的MMW前端硬件不可用，并且根本无法 如果DNP要得到广泛实施，新的方法似乎是必要的。 本阶段将设计、开发和表征一种独特的微电子毫米波电路，用于初始 在200 GHz/300 MHz的演示(在第二阶段)，这将是附加DNP/EPR前端的基础- 终端附件，最终高达800 GHz，用于现有的高场ss核磁共振光谱仪。模拟、分析、 硬件测试将确定将系统成本降低一个数量级的可能性和两个 与以前发表的高场方法相比，EPR灵敏度增加了数量级 EPR。此外，新方法将与商业上可行的H/X/Y MAS-DNP探针兼容 设计。