HFSS Modeling in Aqueous Biological Samples for EPR

描述(申请人提供)：本建议书以设备设计为导向。其中两个目标集中在开发用于电子顺磁共振(EPR)光谱的新型样品谐振器，该样品谐振器提供比目前使用的更高的信噪比(SNR)。EPR谐振器旨在增强在生理温度下使用氮氧化物自由基自旋标记进行动态分子结构测定的研究。第三个目标是研制一种用于动态核极化增强核磁共振信号的新型双模谐振器。目标3的目标是在高分辨率核磁共振领域开辟新的机会。这是第一个竞争性延长提案，其基础是最初筹资期间取得的进展。该方法利用电磁场有限元模型进行谐振器设计，同时利用电火花加工(EDM)和激光铣削进行制造。目标1建议开发X波段(10 GHz)的第二代环隙谐振器(LGR)，以取代20多年来广泛使用的位置定向自旋标记(SDSL)。在上一个资助期发现的统一电场(UF)LGR是该项目的主要技术驱动力。另一个驱动器是长槽虹膜，它可以直接耦合到波导，取代了以前的同轴耦合器配置。目标是将信噪比提高5倍。目标2提出了一种为优化Q波段(35 GHz)的浓度灵敏度而量身定做的超滤TE011腔谐振器。这是Q波段的一个新的设计目标。除了UF腔技术，聚四氟乙烯(PTFE)挤出样品试管的定制制造经验也是技术驱动因素。谐振器将为特定的挤出定制，使用多达10&lt；L的样品。一个子目标将探索另一个增强浓度灵敏度的机会，利用多达60&lt；L的水样。AIM 3是与德国法兰克福大学Thomas Prisner博士的国际合作的一部分，目的是将液态DNP技术扩展到微波泵频率的260 GHz和核磁共振频率的400 MHz。这是一个雄心勃勃的高风险、高回报的目标。所提出的双模谐振器是一个用于微波的腔体和一个用于射频的LGR。已经使用有限元模型进行了大量的分析，但仍有许多工作要做，包括开发精密制造方法。在EPR中，使用定点突变将自旋标记引入蛋白质作为一种可能是独特的方式来获得与功能相关的时间尺度上的动态结构信息，这是非常令人兴奋的。DNP项目的总体目标是改进核磁共振，这可能会影响包括核磁共振作为关键字的近1000项NIH拨款中的许多。

DESCRIPTION (provided by applicant): This proposal is device-design driven. Two of the aims focus on development of novel sample resonators for electron paramagnetic resonance (EPR) spectroscopy that provides substantially higher signal-to-noise ratios (SNR) than those currently used. EPR resonators are designed to enhance dynamic molecular structure determination studies using nitroxide radical spin labels at physiological temperatures. The third aim focuses on development of a novel bimodal resonator for nuclear magnetic resonance (NMR) signal enhancement by dynamic nuclear polarization (DNP). The goal of Aim 3 is to open up new opportunities in high-resolution NMR. This first competitive renewal proposal is very strongly based on progress in the initial funding period. The methodology utilizes finite-element modeling of electromagnetic fields for resonator design and both electric discharge machining (EDM) and laser milling for fabrication. Aim 1 proposes development of a second generation loop-gap resonator (LGR) at X-band (10 GHz) to replace the one that has been in widespread usage for site-directed spin labeling (SDSL) for over 20 years. The discovery of the Uniform Field (UF) LGR in the previous funding period is the primary technological driver for this project. Another driver is the long-slot iris, which enables direct coupling to a waveguide replacing the previous coaxial-coupler configuration. The goal of this aim is increase of SNR by a factor of 5. Aim 2 proposes to develop a UF TE011 cavity resonator tailored to optimize concentration-sensitivity at Q-band (35 GHz). This is a novel design objective at Q-band. In addition to UF cavity technology, experience in custom fabrication of polytetrafluoroethylene (PTFE) extruded sample cuvettes is a technology driver. Resonators will be tailored for a specific extrusion utilizing as much as 10 <l of sample. A sub-aim will explore an additional opportunity for enhanced concentration-sensitivity utilizing as much as 60 <l of aqueous sample. Aim 3 is part of an international collaboration with Dr. Thomas Prisner of Frankfurt University, Germany, to extend liquid phase DNP technology to 260 GHz for the microwave pump frequency and 400 MHz for the NMR frequency. This is an ambitious high-risk, high-payoff aim. The proposed bimodal resonator is a cavity for the microwaves and an LGR for the radiofrequency. Considerable analysis has already been carried out using finite-element modeling, but much remains to be done, including development of precision fabrication methods. In EPR there is great excitement in the use of site-specific mutagenesis to introduce spin labels to proteins as a way, perhaps unique, to obtain dynamic structural information on a time scale that is relevant to function. The overall goal of the DNP project is improved NMR that could impact many of the nearly 1,000 NIH grants that include NMR as a keyword.