Integrating Accelerated Droplet Chemistry with LC-MS for High Throughput Quantitative Analysis
将加速液滴化学与 LC-MS 相结合进行高通量定量分析
基本信息
- 批准号:10607125
- 负责人:
- 金额:$ 30.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-01-01 至 2026-12-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAcidsAddressBiological ProcessBiomedical ResearchBlood capillariesCell physiologyCellsChargeChemicalsChemistryClinical ResearchComplex MixturesCouplingDedicationsDerivation procedureDevelopmentDevicesDimensionsElectrospray IonizationEnvironmentExposure toGasesGenerationsGoalsHigh Pressure Liquid ChromatographyHumanIn SituInjectionsIonsIsomerismLipidsLiquid ChromatographyMass Spectrum AnalysisMetabolismMethodsModificationMole the mammalMolecular ConformationMonosaccharidesNatureNoiseNucleic AcidsPatternPerformancePhasePlasmaPlayPositioning AttributeProcessProteinsReactionReactive Oxygen SpeciesReagentResearchRoleSamplingSignal TransductionSilicon DioxideSolventsSourceSpectrometrySpectrometry, Mass, Electrospray IonizationStereoisomerStructureTechniquesTechnologyTimeTriglyceridesadductanalytical methodanomercombinatorialcombinatorial chemistrydesigndisease diagnosisexperimental studyhigh throughput analysisimprovedinstrumentinstrumentationinterestion mobilityion sourceionizationliquid chromatography mass spectrometrymass spectrometermethod developmentmilligrammillisecondmonomernovelprogramsprotein structuresugartandem mass spectrometryvoltage
项目摘要
Project Summary/Abstract
There is an increasing need to improve the characterization of lipids and saccharides for clinical and
biomedical research purposes. NMR is the method of choice for obtaining detailed structural information about
saccharides. However, NMR typically requires milligram (micromole) quantities of analyte; this often exceeds
biologically relevant levels. For lipids, mass spectrometry (MS) provides an efficient avenue for rapid profiling,
but quantitative analysis is challenged by difficulty in isolating species of interest due to wide structural diversity.
A new MS approach is proposed that fundamentally addresses challenges in quantitative and qualitative MS
by utilizing online accelerated droplet chemistry. Since ion suppression effects in electrospray ionization (ESI)
MS occur during droplet formation, our method is designed to tackle this intellectual challenge exactly at the
point of droplet formation – not before by adding reagents in solution, and not after by performing gas-phase
reactions. This strategy simplifies instrumentation requirements and allows effective coupling to liquid
chromatography (LC). Selected droplet-based reactions improve signal-to-noise ratios to enable femtomole
sensitivity using <1 µL sample volume. Gas-phase ion intensities generated by our platform reflect the
corresponding analyte concentration in solution. Importantly, selected droplet-based reactions allow isomers of
lipids and saccharides to be differentiated. We propose to couple online droplet reactions with LC to enable high
throughput quantification of lipids and saccharides in complex mixtures. The specific research aims are:
Aim 1: To develop a functional contained-electrospray platform for coupling accelerated droplet
chemistry on LC-MS for saccharide analysis. A novel contained-ESI source is proposed to couple droplet
chemistry with LC-MS. Our method will enable LC mobile phase and ESI spray solvent to be independently
optimized. This orthogonal feature is expected to allow effective separation of isomeric saccharides (linkage,
anomeric, and position isomers). Selected droplet reactions will improve detectability of saccharides and provide
a second layer of identification for isomers that co-elute. The LC-contained-ESI-MS/MS platform will be validated
via high throughput combinatorial studies.
Aim 2: To develop a plasma-droplet fusing contained-electrospray source for coupling LC-MS for
lipid analysis. We propose to include etched silica capillaries on our LC-contained-ESI-MS/MS platform for
accurate quantification of all types of lipids, including triglycerides. The device is expected to enable
instantaneous determination of degree of unsaturation, C=C bond position, and bond orientation (cis/trans).
The tandem development of quantitative analytical methods for lipids and saccharides will result in
concomitant creation of versatile platforms for applications in diseases diagnosis and high throughput analysis
of rare sugars to effectively guide synthetic method development. The proposed strategy will also be valuable in
biomedical research using existing instruments without modification.
项目摘要/摘要
越来越需要改进脂类和糖类的特性,以用于临床和
生物医学研究目的。核磁共振是获取有关的详细结构信息的首选方法
糖类。然而,核磁共振通常需要毫克(微摩尔)的分析物;这通常超过
与生物相关的水平。对于脂质,质谱仪(MS)提供了一种快速分析的有效途径,
但是,由于广泛的结构多样性,定量分析在分离感兴趣的物种方面遇到了困难。
提出了一种新的MS方法,从根本上解决了定量和定性MS方面的挑战
通过利用在线加速液滴化学。由于电喷雾电离中的离子抑制效应
MS发生在液滴形成期间,我们的方法旨在准确地解决这一智力挑战
液滴形成点-不是在溶液中加入试剂之前,也不是在执行气相操作之后
反应。这种策略简化了仪器要求,并允许有效地耦合到液体
层析(LC)。选定的基于液滴的反应提高了信噪比,使Femtomole成为可能
灵敏度采用<;1微米L样品体积。我们的平台产生的气相离子强度反映了
溶液中相应的分析物浓度。重要的是,选定的基于液滴的反应允许
脂类和糖类有待区分。我们建议将在线液滴反应与LC相结合,以实现高
复杂混合物中脂类和糖类的吞吐量定量。具体研究目标是:
目的1:研制一种用于耦合加速液滴的功能性内容式电喷雾平台
液质联用在糖类分析中的应用提出了一种用于耦合液滴的新型包含-ESI源
LC-MS的化学分析我们的方法将使LC流动相和ESI喷雾溶剂独立
最优化。该正交特征有望允许有效地分离异构体糖(连接,
异构体和位置异构体)。选定的液滴反应将提高糖类的可检测性,并提供
对共洗脱的异构体进行第二层鉴定。将验证LC-Contained-ESI-MS/MS平台
通过高通量的组合研究。
目的2:研制液质联用等离子体-液滴熔融型电喷雾源
脂肪分析。我们建议在我们的LC-Contained-ESI-MS/MS平台上包括蚀刻的二氧化硅毛细管
准确定量所有类型的脂类,包括甘油三酯。预计该设备将启用
瞬时测定不饱和度、C=C键位置和键取向(顺式/反式)。
脂类和糖类定量分析方法的相继发展将导致
伴随而来的是为疾病诊断和高通量分析应用创建通用平台
以有效地指导合成方法的发展。拟议的战略也将在
使用现有仪器进行生物医学研究,无需修改。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Abraham Badu-Tawiah其他文献
Abraham Badu-Tawiah的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Abraham Badu-Tawiah', 18)}}的其他基金
Multiplexed Paper-Based Blood Test for Early-Stage Colorectal Cancer Screening
用于早期结直肠癌筛查的多重纸质血液检测
- 批准号:
10578142 - 财政年份:2022
- 资助金额:
$ 30.57万 - 项目类别:
Malaria Management through an On-demand Diagnostic Approach using Novel Ionic Probes
使用新型离子探针通过按需诊断方法进行疟疾管理
- 批准号:
10159195 - 财政年份:2019
- 资助金额:
$ 30.57万 - 项目类别:
Malaria Management through an On-demand Diagnostic Approach using Novel Ionic Probes
使用新型离子探针通过按需诊断方法进行疟疾管理
- 批准号:
10399621 - 财政年份:2019
- 资助金额:
$ 30.57万 - 项目类别:
Malaria Management through an On-demand Diagnostic Approach using Novel Ionic Probes
使用新型离子探针通过按需诊断方法进行疟疾管理
- 批准号:
9926216 - 财政年份:2019
- 资助金额:
$ 30.57万 - 项目类别:
Malaria Management through an On-demand Diagnostic Approach using Novel Ionic Probes
使用新型离子探针通过按需诊断方法进行疟疾管理
- 批准号:
10615736 - 财政年份:2019
- 资助金额:
$ 30.57万 - 项目类别:
相似国自然基金
具有抗癌活性的天然产物金霉酸(Aureolic acids)全合成与选择性构建2-脱氧糖苷键
- 批准号:22007039
- 批准年份:2020
- 资助金额:24.0 万元
- 项目类别:青年科学基金项目
海洋放线菌来源聚酮类化合物Pteridic acids生物合成机制研究
- 批准号:
- 批准年份:2019
- 资助金额:10.0 万元
- 项目类别:省市级项目
手性Lewis Acids催化的分子内串联1,5-氢迁移/环合反应及其在构建结构多样性手性含氮杂环化合物中的应用
- 批准号:21372217
- 批准年份:2013
- 资助金额:80.0 万元
- 项目类别:面上项目
对空气稳定的新型的有机金属Lewis Acids催化剂制备、表征与应用研究
- 批准号:21172061
- 批准年份:2011
- 资助金额:30.0 万元
- 项目类别:面上项目
钛及含钛Lewis acids促臭氧/过氧化氢体系氧化性能的广普性、高效性及其机制
- 批准号:21176225
- 批准年份:2011
- 资助金额:60.0 万元
- 项目类别:面上项目
基于Zip Nucleic Acids引物对高度降解和低拷贝DNA检材的STR分型研究
- 批准号:81072511
- 批准年份:2010
- 资助金额:31.0 万元
- 项目类别:面上项目
海洋天然产物Makaluvic acids 的全合成及其对南海鱼虱存活的影响
- 批准号:30660215
- 批准年份:2006
- 资助金额:21.0 万元
- 项目类别:地区科学基金项目
相似海外基金
Lipid nanoparticle-mediated Inhalation delivery of anti-viral nucleic acids
脂质纳米颗粒介导的抗病毒核酸的吸入递送
- 批准号:
502577 - 财政年份:2024
- 资助金额:
$ 30.57万 - 项目类别:
CAREER: Highly Rapid and Sensitive Nanomechanoelectrical Detection of Nucleic Acids
职业:高度快速、灵敏的核酸纳米机电检测
- 批准号:
2338857 - 财政年份:2024
- 资助金额:
$ 30.57万 - 项目类别:
Continuing Grant
Double Incorporation of Non-Canonical Amino Acids in an Animal and its Application for Precise and Independent Optical Control of Two Target Genes
动物体内非规范氨基酸的双重掺入及其在两个靶基因精确独立光学控制中的应用
- 批准号:
BB/Y006380/1 - 财政年份:2024
- 资助金额:
$ 30.57万 - 项目类别:
Research Grant
Quantifying L-amino acids in Ryugu to constrain the source of L-amino acids in life on Earth
量化 Ryugu 中的 L-氨基酸以限制地球生命中 L-氨基酸的来源
- 批准号:
24K17112 - 财政年份:2024
- 资助金额:
$ 30.57万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Synthetic analogues based on metabolites of omega-3 fatty acids protect mitochondria in aging hearts
基于 omega-3 脂肪酸代谢物的合成类似物可保护衰老心脏中的线粒体
- 批准号:
477891 - 财政年份:2023
- 资助金额:
$ 30.57万 - 项目类别:
Operating Grants
Metabolomic profiles of responders and non-responders to an omega-3 fatty acids supplementation.
对 omega-3 脂肪酸补充剂有反应和无反应者的代谢组学特征。
- 批准号:
495594 - 财政年份:2023
- 资助金额:
$ 30.57万 - 项目类别:
Molecular recognition and enantioselective reaction of amino acids
氨基酸的分子识别和对映选择性反应
- 批准号:
23K04668 - 财政年份:2023
- 资助金额:
$ 30.57万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Integrated understanding and manipulation of hypoxic cellular functions by artificial nucleic acids with hypoxia-accumulating properties
具有缺氧累积特性的人工核酸对缺氧细胞功能的综合理解和操纵
- 批准号:
23H02086 - 财政年份:2023
- 资助金额:
$ 30.57万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Basic research toward therapeutic strategies for stress-induced chronic pain with non-natural amino acids
非天然氨基酸治疗应激性慢性疼痛策略的基础研究
- 批准号:
23K06918 - 财政年份:2023
- 资助金额:
$ 30.57万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Molecular mechanisms how arrestins that modulate localization of glucose transporters are phosphorylated in response to amino acids
调节葡萄糖转运蛋白定位的抑制蛋白如何响应氨基酸而被磷酸化的分子机制
- 批准号:
23K05758 - 财政年份:2023
- 资助金额:
$ 30.57万 - 项目类别:
Grant-in-Aid for Scientific Research (C)














{{item.name}}会员




