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.

与多功能高场 NMR 探头兼容的新型毫米波 (mmw) DNP/EPR 前端 抽象的 人们对魔角动态核极化 (DNP) 的兴趣呈爆炸性增长 过去五年中的旋转（MAS），因为它已证明信噪比增益超过两个数量级 与生物的传统 MAS-NMR 和非自旋 NMR 相比，震级约为 100 K 环境条件下超分子组装体中的大分子信号减弱。 高达四阶的采集时间对于广泛的应用来说是有希望的，特别是结构 生物大分子的测定和功能阐明尽管有巨大的潜在好处， DNP 的适应率将因其高昂的价格（目前为 2-600 万美元）而受到严重限制，这主要是因为 所需要的昂贵的陀螺仪，并且因为需要特殊的核磁共振磁体 超导扫描线圈（因为陀螺仪的带宽非常窄）。 我们对新型毫米波 (mmw) DNP 腔的初步模拟，该腔与新的 MAS 旋转器设计显示了实现所需电子自旋饱和的潜力，最多可以有两个 对于相似体积的样品，微波功率比现有 MAS-DNP 探头低几个数量级 （1-15 μL）和其他条件，随着毫米波腔设计的进步，以及数量级 - 过去五年宽带固态 InP 毫米波功率放大器取得了巨大进展 （放大器现在高达 850 GHz），可以消除陀螺仪并需要特殊的 具有超导扫描线圈的 NMR 磁体，即使 NMR 频率高达 1200 MHz (800 GHz EPR)。 这些变革性的进步可以大大降低将 MAS-DNP 纳入 ssNMR 实验室，使几乎所有当前的 NMR 小组都可以开始开发和 将强大的新方法应用于不溶性刚性蛋白的结构测定和功能阐明 以及其他大分子，它们是开发阿尔茨海默病和癌症治疗方法的关键。 然而，除了需要高效的 MAS-DNP 毫米波旋转腔之外，还需要一种新型的低成本 EPR 迫切需要 mmw 前端（桥），以便 EPR 实验可以首先在高 场 NMR 磁体放在准备好的样品上，以便于后续的必要校准和优化 不幸的是，MAS-DNP 实验所需的毫米波前端硬件不可用，而且根本无法实现。 如果要广泛实施 DNP，就需要采取新的方法。 第一阶段将设计、开发和表征独特的微电子毫米波电路，用于初始 在 200GHz/300MHz 进行演示（在第二阶段期间），这将成为附加 DNP/EPR 前端的基础 终端附件，最终可达 800 GHz，适用于现有的高场 ssNMR 波谱仪模拟、分析、 硬件测试将确定系统成本降低一个数量级的潜力，并且两个 与之前发布的高场方法相比，EPR 灵敏度提高了几个数量级 此外，该新方法将与商业上可行的 H/X/Y MAS-DNP 探针兼容。 设计。