Tractable Tandem Ion Mobility Technology using Structures for Lossless Ion Manipulations and Photodissociation
Tractable Tandem Ion Mobility Technology using Structures for Lossless Ion Manipulations and Photodissociation
批准号:
10548229
负责人:
Brian Clowers
金额:
$29.41万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-01-01 至 2024-12-31
关键词:
AddressAdoptionBiologicalCarbohydratesCharacteristicsChargeChemicalsClinicalCommunitiesComplementCost SavingsCouplingDataDiagnosticDiffusionDimensionsDisciplineDiseaseDissociationElectrodesElectronicsEvaluationFoundationsGasesGoalsHealthIntelligenceIon ChannelIonsLasersMass Spectrum AnalysisMeasurementMeasuresMinorModalityModernizationMolecularMolecular ConformationMultidimensional NMR TechniquesNatureNoiseNucleic AcidsOutcomePeptidesPerformancePhasePhotonsPopulationProtein ConformationProteinsProteomicsRadialResearchResearch PersonnelResolutionRoleSamplingSeriesSignal TransductionSpectrometrySpeedStructureSystemTechniquesTechnologyTimeTranscendTravelVariantbiological systemsbiophysical propertiescomparativecostcost effectivedata acquisitiondensityelectric fieldexperienceexperimental studyinnovationinsightinstrumentationion mobilityionizationirradiationlight emissionmanufacturemass analyzermetabolomicsmolecular dynamicsmolecular shapepressureprinted circuit boardprogramspromoterprotein foldingprototypestereochemistrystructural biologysuccesstandem mass spectrometrytechnology developmenttooltransmission processultra high resolutionultraviolet
中文摘要
项目摘要
除了浓度外,蛋白质、碳水化合物、代谢物和
核酸是区分健康和疾病状态的基本特征。事实上,随处可见
具有无与伦比的选择性、速度和灵敏度的质谱学(MS)的进步已经武装起来
研究人员具有新的生物学见解,并提示有关分子和生物物理的其他问题
区分疾病状态但超越MS测量的参数。离子迁移谱(IMS)
是一种气相分离技术,它直接补充了MS测量并扩展了对
关于生物系统中的分子形状和动力学。然而,相对较低的样本利用率
分离效率阻碍了它在生物分析和临床领域的广泛采用。使用
最近,在印刷电路板(PCB)领域广泛可用的技术进步制造了一种新的
实现了一类离子迁移率分离,这在很大程度上缓解了其前身的缺点。这个
无损离子操纵结构(SLIM)框架通过建立动态电学来实现这一目标
能够将电离分子限制更长时间的场,以及一种有效地
细分不同班级前用女士分析当代瘦身实验取得令人印象深刻
气相离子分离的水平,但由于很大程度上的限制,只关注分离的一个维度
由底层的印刷电路板电极布置和控制电子设备施加。将纤细的平台铸造成
多个分离维度并实现生物相关诊断的新水平,目前的努力
旨在开发和传播一个经济的串联IMS平台,该平台集成了一系列创新的、
简化战略。其中包括集成一个低成本的电极开关,以扩大实验范围
超薄平台内的多功能性和一系列旨在创建高密度离子的离子压缩策略
人口。最重要的是,在MS分析之前,我们将利用离子的高度压缩性质
通过使这些物种受到高强度的紫外光诱导分子
并产生更多关于目标生物系统的信息。同时使用激光的努力
辐射和一种新型的UV-C发光二极管将与后者进行比较,后者提供了相当大的
节省成本。本项目的第三个综合目标是解决现有超薄的负载循环问题
通过完全多路复用串联式超薄紫外光解离(UVPD)平台。添加了
IMSN的功能和扩展的多通道细长路径,系统的分离能力是
预计将代表最先进的技术。在拟议的研究结束时,我们预计将实现
全功能、高效率的超薄UVPD框架,能够与所有质量分析仪类别和
准备解决从代谢组学到结构生物学的一系列生物学问题。
英文摘要
Project Summary
In addition to concentration, the orientation and conformation of proteins, carbohydrates, metabolites, and
nucleic acids are essential characteristics differentiating healthy and diseased states. In fact, broadly available
advances in mass spectrometry (MS), with unparalleled levels of selectivity, speed, and sensitivity, have armed
researchers with new biological insights and prompt additional questions regarding molecular and biophysical
parameters that differentiate disease states but transcend MS measurements. Ion mobility spectrometry (IMS)
is a gas-phase separation technique that directly complements MS measurements and expands understanding
regarding molecular shape and dynamics in biological systems. However, comparatively low sample utilization
and separation efficiencies have hindered its broad adoption in the bioanalytical and clinical communities. With
recent, broadly available technological advances in the field of printed circuit board (PCB) manufacturing a new
class of ion mobility separation is enabled that largely alleviates the drawbacks of its predecessors. The
Structures for Lossless Ion Manipulations (SLIM) framework achieves this goal by establishing a dynamic electric
field capable of confining ionized molecules for expanded periods of time along with a means to efficiently
fractionate the different classes prior to analysis using MS. Contemporary SLIM experiments achieve impressive
levels of gas-phase ion separation, but focus only on one dimension of separation due to restrictions largely
imposed by the underlying PCB electrode arrangements and control electronics. To cast the SLIM platform into
multiple separation dimensions and achieve new levels of biologically relevant diagnostics, the present effort
aims to develop and disseminate an economical tandem IMS platform that integrates a series of innovative,
simplifying strategies. These include the integration of a low-cost electrode switch that expands the experimental
versatility within the SLIM platform and a series of ion compression strategies aimed at creating high-density ion
populations. Most importantly, and prior to MS analysis, we will exploit the highly compressed nature of the ion
beams within the SLIM by subjecting these species to high intensity ultraviolet photons to induce molecular
disruption and yield more information regarding the target biological system. Concurrent efforts using laser
irradiation and a new class of UV-C light emitting diodes will be compared with the latter offering considerable
cost-savings. The third, composite goal of this project is to address the duty cycle issues of existing SLIM
concepts by fully multiplexing the tandem SLIM-ultraviolet photodissociation (UVPD) platform. With the added
functionality of IMSn and the extended, multi-channel SLIM paths, the separation power of the system is
anticipated to represent the state-of-the-art. At the conclusion of the proposed research we expect to realize a
fully functioning, high-efficiency SLIM-UVPD framework capable of interfacing to all mass analyzers classes and
ready to address a suite of biological problems ranging from metabolomics to structural biology.
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会议论文
Tractable Tandem Ion Mobility Technology using Structures for Lossless Ion Manipulations and Photodissociation
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批准号:10386669
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项目类别:
-
资助金额:$19.99万
-
财政年份:2021
-
负责人:Brian Clowers
-
依托单位:
Tractable Tandem Ion Mobility Technology using Structures for Lossless Ion Manipulations and Photodissociation
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批准号:10322113
-
项目类别:
-
资助金额:$29.5万
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财政年份:2021
-
负责人:Brian Clowers
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依托单位:
Innovative Native Ion Mobility Approaches for Transformational Measurements in Structural Biology
-
批准号:10689746
-
项目类别:
-
资助金额:$28.77万
-
财政年份:2020
-
负责人:Brian Clowers
-
依托单位:
Innovative Native Ion Mobility Approaches for Transformational Measurements in Structural Biology
-
批准号:10042584
-
项目类别:
-
资助金额:$30.31万
-
财政年份:2020
-
负责人:Brian Clowers
-
依托单位:
Innovative Native Ion Mobility Approaches for Transformational Measurements in Structural Biology
-
批准号:10252003
-
项目类别:
-
资助金额:$28.85万
-
财政年份:2020
-
负责人:Brian Clowers
-
依托单位:
Innovative Native Ion Mobility Approaches for Transformational Measurements in Structural Biology
-
批准号:10477459
-
项目类别:
-
资助金额:$28.85万
-
财政年份:2020
-
负责人:Brian Clowers
-
依托单位:
海外基金