HFSS Modeling in Aqueous Biological Samples for EPR

描述（由申请人提供）：本提案由设备设计驱动。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，该谐振器提供比目前使用的信噪比（SNR）高得多的信噪比。EPR谐振器设计用于增强动态分子结构测定研究，在生理温度下使用氮氧化物自由基自旋标签。第三个目标是开发一种新型双峰谐振器，用于动态核极化（DNP）增强核磁共振（NMR）信号。Aim 3的目标是为高分辨率核磁共振开辟新的机会。第一个竞争性续期提案很大程度上取决于最初筹资期的进展情况。该方法利用电磁场的有限元建模来设计谐振器，并利用电火花加工和激光铣削来制造谐振器。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）的环隙谐振器。在之前的资助期内，均匀场（UF） LGR的发现是该项目的主要技术驱动力。另一个驱动因素是长槽虹膜，它可以直接耦合到波导上，取代以前的同轴耦合器配置。这个目标的目标是将信噪比提高5倍。目标2提出开发一种UF TE011腔谐振器，以优化q波段（35 GHz）的浓度灵敏度。这是q波段一个新颖的设计目标。除了超滤腔技术，在定制制造聚四氟乙烯（PTFE）挤压样品试管方面的经验也是一个技术驱动因素。谐振器将为使用多达10 <l样品的特定挤出而量身定制。子目标将探索一个额外的机会，以提高浓度敏感性利用高达60 <l的水样。Aim 3是与德国法兰克福大学Thomas Prisner博士国际合作的一部分，旨在将液相DNP技术扩展到260 GHz的微波泵频率和400 MHz的核磁共振频率。这是一个高风险、高回报的雄心勃勃的目标。提出的双峰谐振器是微波腔和射频LGR。使用有限元建模已经进行了大量的分析，但仍有许多工作要做，包括精密制造方法的开发。在EPR中，使用位点特异性诱变将自旋标签引入蛋白质，作为一种可能是独特的方法，在与功能相关的时间尺度上获得动态结构信息，这是非常令人兴奋的。DNP项目的总体目标是改进核磁共振，这可能会影响到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.