HFSS Modeling in Aqueous Biological Samples for EPR

描述（由申请人提供）：本提案是器械设计驱动的。其中两个目标集中于开发用于电子顺磁共振（EPR）光谱的新型样品谐振器，其提供比目前使用的高得多的信噪比（SNR）。EPR共振器被设计用于在生理温度下使用氮氧自由基自旋标记来增强动态分子结构测定研究。第三个目标是发展一种新型的双模共振器，用于动态核极化增强核磁共振信号。Aim 3的目标是为高分辨率NMR开辟新的机会。这是第一个竞争性的更新建议，是非常强烈的基础上，在最初的供资期的进展。该方法利用有限元建模的电磁场谐振器的设计和放电加工（EDM）和激光铣削制造。目标1提出在X波段（10 GHz）开发第二代环隙谐振器（LGR），以取代20多年来广泛用于定点自旋标记（SDSL）的谐振器。在上一个资助期发现的统一场（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，它能够直接耦合到波导取代以前的同轴耦合器配置。该目标的目标是将SNR增加5倍。目标2提出开发一种UF TE 011空腔谐振器，以优化Q波段（35 GHz）的浓度灵敏度。这是一个新颖的设计目标，在Q波段。除了UF腔技术外，聚四氟乙烯（PTFE）挤出样品比色皿的定制制造经验也是技术驱动力。谐振器将针对使用多达10 <l样品的特定挤出量进行定制。一个子目标将探索利用多达60 μ l的水性样品增强浓度灵敏度的额外机会。Aim 3是与德国法兰克福大学的托马斯普里斯纳博士进行的国际合作的一部分，旨在将液相DNP技术扩展到260 GHz的微波泵浦频率和400 MHz的NMR频率。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用于微波的腔和用于射频的LGR。已经使用有限元建模进行了相当多的分析，但仍有许多工作要做，包括开发精确的制造方法。在EPR中，使用位点特异性突变将自旋标签引入蛋白质，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，这令人非常兴奋。DNP项目的总体目标是改进NMR，这可能会影响包括NMR作为关键词的近1，000个NIH赠款中的许多。

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.