Single molecule localization microscopy via angstrom-scale three-dimensional imaging of electron spin labels
通过电子自旋标记的埃级三维成像进行单分子定位显微镜
基本信息
- 批准号:10280393
- 负责人:
- 金额:$ 29.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-01 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAntibodiesArchitectureBackBiologicalBiological ProcessBiologyCaliberCellsCollectionComplexDataDetectionDevelopment PlansDiseaseElectronsExplosionFreezingFrequenciesGenetic TranscriptionGoalsImageIndividualLabelLocationLocomotionMagnetic ResonanceMagnetic Resonance ImagingMagnetismMapsMechanicsMicroscopeMicroscopyMolecular MachinesMotionNoiseNucleic AcidsOpticsOrganellesPhysiologic pulsePositioning AttributeProteinsProtocols documentationResolutionRoleSamplingSchemeSignal TransductionSourceSpin LabelsStructureSurfaceTechnologyTemperatureThree-Dimensional ImagingTimeTranslationsVacuumWorkcantilevercold temperaturecryogenicsdensitydetectorexperimental studyimprovedinnovationirradiationmagnetic fieldmicrowave electromagnetic radiationmicrowave imagingnanometernew technologynovelprotein complexpublic health relevancereconstructionsimulationsingle moleculetechnology developmenttheoriestherapy design
项目摘要
Summary
The ability to determine the three-dimensional location of fluorescently labeled biomolecules in cells with 10 to 70
nm resolution has led to an explosion of discoveries in biology. Super-resolution optical microscopy has led to recent
dramatic breakthroughs in our understanding of the organization of molecules in a wide variety of protein assemblies
and has led to discoveries of new supramolecular architectures present in organelles. The spatial resolution typically
achieved by super-resolution optical microscopy remains, frustratingly, considerably larger than most biomolecules.
The goal of this technology development proposal is to create a technology for localizing individual biomolecules
with angstrom precision. We propose a technology for localizing molecules using spin labels. The proposed work
will employ a magnetic resonance force microscope, in which an attonewton-sensitivity cantilever with a 100
nanometer diameter magnetic tip is operated near a sample surface in high vacuum at cryogenic temperatures.
The magnet-tipped cantilever serves two roles. It acts as a force-gradient detector, enabling the observation of
magnetic resonance from individual electron spins as a shift of the cantilever's mechanical resonance frequency. It
furthermore provides a source of magnetic field gradient, 5 gauss/angstrom or larger, that makes possible the three
dimensional magnetic resonance imaging of individual electron spin labels with angstrom spatial resolution. Proof-
of-concept data has been acquired demonstrating the ability to detect magnetic resonance from 100's of nitroxide
spin labels and to spatially resolve electron spin density at a resolution 100 times smaller than the diameter of the
magnetic tip.
We present a stepwise technology development plan — backed by theory, simulations, and preliminary data
— for achieving the detection of individual nitroxide spin labels and imaging their locations in three dimensions
with angstrom precision. Proposed innovations include achieving near-unity spin polarization by operating at high
magnetic field and low temperature using novel cryogenic chip-scale microwave sources, employing better inter-
ferometric cantilever position detectors and spin modulation schemes to evade sample-related noise, harnessing
synchronized cantilever and spin excitation pulse sequences to achieve high fidelity spin modulation, developing
robust Bayesian image collection and reconstruction protocols, and fabricating improved cantilevers and magnetic
tips for increased per-spin sensitivity. The technology will be validated using well characterized nucleic-acid rulers,
biomolecules, protein complexes, and antibodies. Proof-of-concept experiments will be carried out to demonstrate
the applicability of the technology to flash frozen biological samples and the ability to carry out correlative fluo-
rescent localization experiments. Taken together the proposed work represents a new technology for localizing an
individual (spin-labeled and fluorescently labeled) biomolecule in a flash-frozen cell with angstrom precision.
总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JOHN A MAROHN其他文献
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{{ truncateString('JOHN A MAROHN', 18)}}的其他基金
Single molecule localization microscopy via angstrom-scale three-dimensional imaging of electron spin labels
通过电子自旋标记的埃级三维成像进行单分子定位显微镜
- 批准号:
10477321 - 财政年份:2021
- 资助金额:
$ 29.5万 - 项目类别:
Single molecule localization microscopy via angstrom-scale three-dimensional imaging of electron spin labels
通过电子自旋标记的埃级三维成像进行单分子定位显微镜
- 批准号:
10707059 - 财政年份:2021
- 资助金额:
$ 29.5万 - 项目类别:
A cryo-electron microscopy training and sample-preparation research proposal
冷冻电子显微镜培训和样品制备研究计划
- 批准号:
8457701 - 财政年份:2013
- 资助金额:
$ 29.5万 - 项目类别:
Cantilever Magnetic Resonance Microscopy of Biomolecules
生物分子的悬臂磁共振显微镜
- 批准号:
7071865 - 财政年份:2004
- 资助金额:
$ 29.5万 - 项目类别:
Cantilever Magnetic Resonance Microscopy of Biomolecules
生物分子的悬臂磁共振显微镜
- 批准号:
7442122 - 财政年份:2004
- 资助金额:
$ 29.5万 - 项目类别:
Cantilever Magnetic Resonance Microscopy of Biomolecules
生物分子的悬臂磁共振显微镜
- 批准号:
6898294 - 财政年份:2004
- 资助金额:
$ 29.5万 - 项目类别:
Cantilever Magnetic Resonance Microscopy of Biomolecules
生物分子的悬臂磁共振显微镜
- 批准号:
6710808 - 财政年份:2004
- 资助金额:
$ 29.5万 - 项目类别:
Cantilever Magnetic Resonance Microscopy of Biomolecules
生物分子的悬臂磁共振显微镜
- 批准号:
7234446 - 财政年份:2004
- 资助金额:
$ 29.5万 - 项目类别:
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