A Novel Waveguide to Enable MAS-DNP-NMR in Standard-bore High-field Magnets
A Novel Waveguide to Enable MAS-DNP-NMR in Standard-bore High-field Magnets
批准号:
10081009
负责人:
Francis DAVID Doty
金额:
$29.72万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-08-01 至 2021-10-31
关键词:
Alzheimer&aposs DiseaseAmyloidAmyloid FibrilsAreaAwarenessBindingBiologicalBiomedical ResearchBudgetsCaliberCellular MembraneCommunicationConfined SpacesCountryCryoelectron MicroscopyDimensionsElectronsFrequenciesFundingFutureHIVLaboratoriesMagicMalignant NeoplasmsMembrane ProteinsMethodsNuclearNuclear Magnetic ResonancePharmaceutical PreparationsPhasePhysiologic pulsePlayPriceProteinsReportingResearchResearch PersonnelResolutionRoleScanningShapesSmall Business Innovation Research GrantSolidSourceSpectrum AnalysisStructureSystemTechniquesTimeWorkattenuationcostdesignexperimental studyimaging systemimprovedin silicomacromoleculemeternovelprotein functionrestraintsimulationsolid statesolid state nuclear magnetic resonancestructural biologytooltransmission process
中文摘要
一种能够实现标准口径高场磁体MAS-DNP-核磁共振的新型波导
摘要
经过近二十年的研究,固体核磁共振(SsNMR)的重要性最近被证明。
密集的努力,产生了第一个原子分辨结构的A40和A42淀粉样纤维,发挥了CRU-
社会在阿尔茨海默病(AD)中的作用。结构确定关键是一种称为动态的技术
核极化(DNP)与魔角旋转(MAS)。而低温电子显微镜,扫描隧道电子未命中。
CRONSPORM(STEM)等方法提供了有用的信息,介绍了MAS-核磁共振方法的最新进展。
可见的基本限制和其他关键信息,包括蛋白质中重要的侧链动力学
它们的作用和对其作用的无数机制的理解。因此,开发变革性广告--
单链核磁共振的VANCES对于结构生物学和生物医学研究都是至关重要的,对于CURR的进展是至关重要的。
ING阿尔茨海默氏病和癌症,并提供特定地区的药物结合信息,使详细
有效药物的作用机制。
到目前为止,MAS-DNP系统都需要专门的大口径(WB)磁体,因为已知的设计
与太赫兹传输兼容的波导和各种相关问题都不能做得足够小
用于标准孔(SB,也称为窄孔,NB)磁体的探头。专业的WB
磁体和所需的波纹太赫兹波导构成了高系统成本的一大部分
MAS-DNP,这让它变得遥不可及,除了少数几个一流实验室。这项拟议的第一阶段SBIR将
展示用于85-1000 GHz范围(AS)的革命性宽带多模波导的可行性
需要3-35T的核磁共振),可以很容易地制造出足够小的直径来制造MAS-DNP
探头适用于现有的Nb高场磁体。据预测,衰减将是两个数量级-
低于400 GHz的基模波导,甚至低于非常昂贵的Corru-Coru。
用于广泛应用的门控过模光导器件。
预计这一进步与正在进行的其他几项技术进步相结合
其他项目,最终将使DNP能够被添加到现有的SS核磁共振高场系统中,而不需要重新-
停止使用专门的磁铁或回旋管。
英文摘要
A Novel Waveguide to Enable MAS-DNP-NMR in Standard-bore High-field Magnets
Abstract
The critical importance of solid-state NMR (ssNMR) was recently demonstrated by, after nearly two decades of
intense efforts, yielding the first atomic-resolution structures of the A40 and A42 amyloid fibrils that play a cru-
cial role in Alzheimer’s Disease (AD). Key to that structure determination was a technique denoted as dynamic
nuclear polarization (DNP) with magic angle spinning (MAS). While Cryo EM, scanning tunneling electron mi-
croscopy (STEM) and other methods provided useful information, recent advances in MAS-NMR methods pro-
vided essential restraints and additional crucial information, including sidechain dynamics important in protein
functions and in understanding of myriad mechanisms of their action. Hence, developing transformational ad-
vances for ssNMR is crucial for both structural biology and biomedical research in general, for progress in cur-
ing Alzheimer’s Disease and cancer, and for providing regio-specific drug binding information enabling detailing
of the mechanism of action for effective drugs.
MAS-DNP systems thus far have all required specialized wide-bore (WB) magnets because known designs of
waveguides compatible with THz transmission and the various relevant issues cannot be made small enough
to work in probes for use in standard-bore (SB, also called narrow-bore, NB) magnets. The specialized WB
magnets and the required corrugated THz waveguides constitute a large portion of the high system cost for
MAS-DNP, which has put it out of reach to all but a few premiere laboratories. This proposed Phase I SBIR will
show feasibility of a revolutionary broad-band multi-mode waveguide for use in the 85-1000 GHz range (as
needed for NMR at 3-35 T) that can easily be manufactured at diameters small enough to make MAS-DNP
probes practical in existing NB high-field magnets. Attenuation is predicted to be two orders of magnitude be-
low that of fundamental-mode waveguides at 400 GHz and even lower than that of the very expensive corru-
gated over-moded waveguides for a wide range of applications.
It is expected that this advance, in combination with several other technological advances being pursued in
other projects, will eventually enable DNP to be added to existing ssNMR high-field systems without the re-
quirement of either a specialized magnet or a gyrotron.
期刊论文(2)
专著(0)
科研奖励(0)
会议论文
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