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NMR探头兼容的新型毫米波DNP/EPR前端 摘要 具有魔角的动态核极化（DNP）研究近年来受到了广泛的关注 自旋（MAS）在过去五年中，因为它已经证明了S/N增益超过两个数量级， 与生物样品的常规MAS-NMR和非旋转NMR相比， 大分子在其超分子组装体中在环境条件下。信号的减少 捕获时间高达四个订单是有希望的广泛的应用，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适应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，这主要是因为 昂贵的回旋管，因为需要一个特殊的核磁共振磁铁， 超导扫描线圈（因为回旋管的带宽非常窄）。 我们初步模拟了一种新型毫米波DNP腔， MAS自旋器设计已经显示出实现所需的电子自旋饱和的潜力， 对于类似体积的样品，微波功率比现有的MAS-DNP探针低几个数量级 (1-15μL）和其他条件。随着毫米波谐振腔设计的进步，沿着， 宽带固态InP毫米波功率放大器在过去五年中的巨大进展 （放大器现在高达850 GHz），它可以成为可能，以消除回旋管和需要一个特殊的 具有超导扫描线圈的NMR磁体，即使在NMR频率达到1200 MHz（800 GHz EPR）时也是如此。 这些变革性的进步可以允许将MAS-DNP引入到一个新的系统中的成本的巨大降低。 ssNMR实验室，从而使得几乎所有当前的NMR组开始发展成为可能， 应用强有力的新方法对不溶性刚性蛋白质进行结构测定和功能阐明 和其他大分子，这是关键的进展，在开发治疗阿尔茨海默氏症和癌症。 然而，除了需要有效的MAS-DNP毫米波旋转腔，一种新型的低成本EPR 毫米波前端（桥）是迫切需要的，以便EPR实验可以首先在高， 场核磁共振磁体上制备的样品，以促进必要的校准和优化，为随后的 MAS-DNP实验。不幸的是，所需的毫米波前端硬件是不可用的， 如果要广泛实施DNP，新的方法似乎是必要的。 这一阶段，我将设计，开发和表征一个独特的微电子毫米波电路的初始 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，最终可达800 GHz，用于现有的高场ssNMR光谱仪。模拟分析 和硬件测试将建立潜在的一个数量级减少系统成本和两个 与以前发表的高场方法相比，EPR灵敏度增加了几个数量级 EPR。此外，该新方法将与商业上可行的H/X/Y MAS-DNP探针兼容， 的设计.