Imaging mass spectrometry at isomeric chemical resolution using gas phase ion/ion reactions

使用气相离子/离子反应进行异构化学分辨率成像质谱分析

基本信息

  • 批准号:
    10027319
  • 负责人:
  • 金额:
    $ 30.48万
  • 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
  • 起止时间:
    2020-09-01 至 2025-06-30
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Molecular imaging plays a pivotal role in biomedical research. By enabling the visualization of biological processes directly in tissue, in situ assessments of cellular function can be recorded with spatial context. The use of mass spectrometry as a molecular imaging modality combines the high level of molecular specificity provided by the mass spectrometer with the spatial fidelity of a microscopic imaging approach. By this, imaging mass spectrometry (IMS) provides for the label-free mapping of a wide array of biomolecules in tissue specimens. Accurate identification of the biochemical pathways altered during development and dysfunction is a key step in designing novel treatment strategies for a variety of applications, such as in studies of diabetes, infectious disease, drug pharmacology, and cancer. However, severe deficiencies remain in the differentiation and structural identification of molecules detected during imaging mass spectrometry experiments due to the enormous chemical complexity of tissue samples. The failure to adequately separate and identify these compounds results in ion images consisting of multiple different compounds with overlapping masses. This distorted picture of molecular distributions clouds the interpretation of the biochemical maps produced by imaging mass spectrometry and prevents a complete and accurate understanding of cellular compositions and functions. This proposal aims to develop methods and instrumentation that will enable tissue imaging at unparalleled levels of sensitivity, separation, and identification. This will be achieved through the discovery and development of novel gas-phase ion/ion reactions that target specific chemical functional groups in lipids and metabolites (Specific Aim 1). These reactions offer rapid and flexible means for molecular transformations without manipulating the tissue sample and can result in improved detection limits and more extensive chemical structural information. Developing reproducible and quantitative ion/ion reaction methodologies will enable reliable measurements to be made from tissue (Specific Aim 2). The development of instrumentation that can perform gas-phase ion/ion reactions with high throughput will enable these transformations to be performed directly during imaging mass spectrometry experiments (Specific Aim 3). These ‘reactive’ images are anticipated to reveal spatial biochemical detail unobtainable by conventional imaging modalities. The continual development of new analytical technologies such as those proposed herein is crucial in order to address increasingly complicated biological and clinical questions.
项目摘要 分子影像学在生物医学研究中起着举足轻重的作用。通过实现生物学的可视化, 直接在组织中进行,可以用空间背景记录细胞功能的原位评估。的 使用质谱作为分子成像模式结合了高水平的分子特异性 由质谱仪提供,具有显微成像方法的空间保真度。通过这个,成像 质谱(IMS)提供了组织中大量生物分子的无标记映射 标本准确识别发育和功能障碍过程中改变的生化途径, 这是为各种应用设计新型治疗策略的关键一步,例如糖尿病研究, 传染病、药物药理学和癌症。然而,在差异化方面仍然存在严重缺陷, 以及在成像质谱实验期间检测到的分子的结构鉴定, 组织样本的巨大化学复杂性未能充分区分和识别这些 化合物导致由具有重叠质量的多种不同化合物组成的离子图像。这 分子分布的扭曲图像模糊了成像产生的生化图的解释 质谱分析,并阻止细胞组成和功能的完整和准确的理解。 该提案旨在开发方法和仪器,使组织成像达到前所未有的水平 敏感性、分离性和识别性。这将通过发现和发展 靶向脂质和代谢物中特定化学官能团的新型气相离子/离子反应 (具体目标1)。这些反应为分子转化提供了快速和灵活的手段, 操作组织样品,并且可以导致改进的检测限和更广泛的化学分析。 结构信息。开发可重复和定量的离子/离子反应方法将使 对组织进行可靠的测量(具体目标2)。仪器的发展, 以高通量进行气相离子/离子反应将使得能够进行这些转化 直接在成像质谱实验期间进行(具体目标3)。这些“反应性”图像是预期的 以揭示常规成像方式无法获得的空间生化细节。不断发展 新的分析技术,如本文提出的是至关重要的,以解决日益增加的 复杂的生物学和临床问题。

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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Boone M. Prentice其他文献

Spatial mapping of phosphatidylcholine <em>sn</em>-positional isomers using CID of divalent metal complexes in imaging mass spectrometry
  • DOI:
    10.1016/j.ijms.2024.117370
  • 发表时间:
    2025-02-01
  • 期刊:
  • 影响因子:
  • 作者:
    Tingting Yan;Zunaira Naeem;Zhongling Liang;Hassan Azari;Brent A. Reynolds;Boone M. Prentice
  • 通讯作者:
    Boone M. Prentice
Formation of multiple ion types during MALDI imaging mass spectrometry analysis of emMitragyna speciosa/em alkaloids in dosed rat brain tissue
在对给药大鼠脑组织中的帽蕊木生物碱进行基质辅助激光解吸电离成像质谱分析过程中多种离子类型的形成
  • DOI:
    10.1016/j.talanta.2024.125923
  • 发表时间:
    2024-07-01
  • 期刊:
  • 影响因子:
    6.100
  • 作者:
    Zhongling Liang;Yingchan Guo;Nicholas Ellin;Tamara I. King;Erin C. Berthold;Sushobhan Mukhopadhyay;Abhisheak Sharma;Christopher R. McCurdy;Boone M. Prentice
  • 通讯作者:
    Boone M. Prentice
Spatial mapping of the brain metabolome lipidome and glycome
大脑代谢组、脂质组和糖组的空间映射
  • DOI:
    10.1038/s41467-025-59487-7
  • 发表时间:
    2025-05-12
  • 期刊:
  • 影响因子:
    15.700
  • 作者:
    Harrison A. Clarke;Xin Ma;Cameron J. Shedlock;Terrymar Medina;Tara R. Hawkinson;Lei Wu;Roberto A. Ribas;Shannon Keohane;Sakthivel Ravi;Jennifer L. Bizon;Sara N. Burke;Jose Francisco Abisambra;Matthew E. Merritt;Boone M. Prentice;Craig W. Vander Kooi;Matthew S. Gentry;Li Chen;Ramon C. Sun
  • 通讯作者:
    Ramon C. Sun
Liberation of host heme by emClostridioides difficile-/emmediated damage enhances emEnterococcus faecalis/em fitness during infection
艰难梭菌介导的宿主血红素释放损伤增强了粪肠球菌在感染期间的适应性
  • DOI:
    10.1128/mbio.01656-23
  • 发表时间:
    2023-12-11
  • 期刊:
  • 影响因子:
    4.700
  • 作者:
    Alexander B. Smith;Jonathan T. Specker;Katharine K. Hewlett;Troy R. Scoggins;Montana Knight;Abigail M. Lustig;Yanhong Li;Kirsten M. Evans;Yingchan Guo;Qianxuan She;Michael W. Christopher;Timothy J. Garrett;Ahmed M. Moustafa;Daria Van Tyne;Boone M. Prentice;Joseph P. Zackular;Kimberly A. Kline
  • 通讯作者:
    Kimberly A. Kline
A mass spectrometry–based assay for mouse IgG N-glycan screening in biofluids
  • DOI:
    10.1007/s00216-025-05994-x
  • 发表时间:
    2025-07-07
  • 期刊:
  • 影响因子:
    3.800
  • 作者:
    Ariana E. Stratton;Hassan Moussa;Yingchan Guo;Justin M. Ellenburg;Carl Atkinson;Boone M. Prentice
  • 通讯作者:
    Boone M. Prentice

Boone M. Prentice的其他文献

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{{ truncateString('Boone M. Prentice', 18)}}的其他基金

Administrative Supplements to Support Undergraduate Summer Research Experiences
支持本科生暑期研究经历的行政补充
  • 批准号:
    10393320
  • 财政年份:
    2020
  • 资助金额:
    $ 30.48万
  • 项目类别:
Administrative Supplements for Equipment Purchase
设备采购行政补充
  • 批准号:
    10580922
  • 财政年份:
    2020
  • 资助金额:
    $ 30.48万
  • 项目类别:
Imaging mass spectrometry at isomeric chemical resolution using gas phase ion/ion reactions
使用气相离子/离子反应进行异构化学分辨率成像质谱分析
  • 批准号:
    10246507
  • 财政年份:
    2020
  • 资助金额:
    $ 30.48万
  • 项目类别:
Imaging mass spectrometry at isomeric chemical resolution using gas phase ion/ion reactions
使用气相离子/离子反应进行异构化学分辨率成像质谱分析
  • 批准号:
    10418780
  • 财政年份:
    2020
  • 资助金额:
    $ 30.48万
  • 项目类别:
Imaging mass spectrometry at isomeric chemical resolution using gas phase ion/ion reactions
使用气相离子/离子反应进行异构化学分辨率成像质谱分析
  • 批准号:
    10669048
  • 财政年份:
    2020
  • 资助金额:
    $ 30.48万
  • 项目类别:
Molecular Profiling of Pancreatic Pathophysiology by Imaging Mass Spectrometry
通过成像质谱法对胰腺病理生理学进行分子分析
  • 批准号:
    8908974
  • 财政年份:
    2015
  • 资助金额:
    $ 30.48万
  • 项目类别:

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