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.

一种新型毫米波（MMW）DNP/EPR前端与多功能高场NMR探针兼容 抽象的 对动态核极化（DNP）的兴趣爆炸性增长 在过去五年中旋转（MAS），因为它已显示出S/N的增长超过两个顺序 与传统的MAS-NMR和生物学的非旋转NMR相比，大约100 K的大小幅度 在环境条件下的超分子组件中的大分子。信号的减少 对于广泛的应用，尤其是结构，最多可达四个订单是有希望的 尽管有巨大的潜在利益， DNP的适应率将受到其非常高的价格标签（目前为200至600万美元）的严重限制，主要是因为 需要的昂贵的旋转，并且由于需要特殊的NMR磁铁 超导扫地线圈（因为陀螺仪的带宽非常狭窄）。 我们对新型毫米波（MMW）DNP腔的初步模拟，该腔与新的 MAS Spinner设计显示了实现所需的电子自旋饱和的潜力，最多可达到两个 微波功率的数量级比现有的MAS-DNP问题低的数量级相似。 （1-15μl）和其他条件。随着MMW腔设计的这种进步，以及 在过去五年中，宽带固态INP MMW功率放大器的幅度进展 （现在最大850 GHz的放大器），可以消除陀螺仪和需要特殊的需要 NMR磁铁具有超导扫描线圈，即使在NMR频率为1200 MHz（800 GHz EPR）也是如此。 这些变革性的进步可以使将MAS-DNP的成本大大降低 SSNMR实验室，因此几乎所有当前的NMR组都可以开始开发和 应用强大的新方法来结构不溶性刚性蛋白的确定和功能阐明 以及其他大分子，这些大分子是开发阿尔茨海默氏病和癌症治疗方法的关键的关键。 但是，除了需要有效的MAS-DNP MMW旋转器腔外，一种新型的低成本EPR MMW前端（桥）非常需要，以便首先可以在高中进行EPR实验 准备样品上的现场NMR磁铁，以促进必要的校准和优化后续序列 MAS-DNP实验。不幸的是，所需的MMW前端硬件不可用，并且是根本上的 如果要广泛实施DNP，则似乎有必要新的方法。 该阶段I将设计，开发和表征独特的微电子MMW电路 在200GHz/300MHz的II期间演示（在II期间），这将是附加DNP/EPR前部的基础 结束附件，最终对于现有的高场SSNMR光谱仪最高为800 GHz。模拟，分析， 硬件测试将确定系统成本降低数量级的潜力和两个 与先前公布的高场方法相比，EPR敏感性的数量级增加了 EPR。此外，新颖的方法将与商业上可行的H/X/Y MAS-DNP兼容 设计。