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
• 负责人: Boone M. Prentice
• 金额: $ 31.73万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/10669048
• 关键词: Address; Affect; Amines; Amino Acids; Biochemical; Biochemical Pathway; Biochemical Process; Biological; Biological Process; Biomedical Research; Cell physiology; Cells; Chemical Structure; Chemicals; Chemistry; Choline; Chromatography; Clinical; Communicable Diseases; Complex Mixtures; Detection; Development; Diabetes Mellitus; Failure; Fatty Acids; Functional disorder; Gases; Generations; Goals; Head; Image; In Situ; Individual; Ions; Isomerism; Kinetics; Label; Lecithin; Lipids; Malignant Neoplasms; Maps; Mass Spectrum Analysis; Measurement; Methodology; Methods; Modification; Molecular; Peptides; Performance; Pharmaceutical Preparations; Pharmacology; Phase; Phosphatidylethanolamine; Phosphatidylserines; Play; Positioning Attribute; Proteomics; Reaction; Reagent; Reproducibility; Resolution; Resources; Role; Sampling; Scanning; Series; Signal Transduction; Site; Spatial Distribution; Specificity; Specimen; Speed; Sphingomyelins; Surface; Technology; Time; Tissue Sample; Tissue imaging; Tissues; Visualization; design; detection limit; detector; experimental study; flexibility; functional group; imaging approach; imaging modality; improved; instrument; instrumentation; interest; lipidomics; mass spectrometer; mass spectrometric imaging; metabolomics; microscopic imaging; molecular imaging; molecular mass; novel; pi bond; prevent; small molecule; tandem mass spectrometry; tool; treatment strategy

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.

项目概要 分子成像通过实现生物可视化在生物医学研究中发挥着关键作用。 直接在组织中进行处理，可以在空间背景下记录细胞功能的原位评估。 使用质谱作为分子成像方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的成像。 质谱 (IMS) 提供组织中多种生物分子的无标记图谱 准确识别发育和功能障碍期间的生化途径。 为各种应用（例如糖尿病研究）设计新颖治疗策略的关键一步， 然而，在区分方面仍然存在严重缺陷。 以及成像质谱实验中检测到的分子的结构鉴定 组织样本的化学成分极其复杂，无法充分分离和识别这些样本。 化合物产生由具有重叠质量的多种不同化合物组成的离子图像。 分子分布的扭曲图像影响了对成像产生的生化图的解释 质谱法并妨碍对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，使组织成像达到无与伦比的水平 这将通过发现和开发来实现。 针对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、灵活的方法，而无需 操纵组织样本，可以提高检测限和更广泛的化学物质 开发可重复和定量的离子/离子反应方法将能够实现 从组织中进行可靠的测量（具体目标 2）。 以高通量进行气相离子/离子反应将使这些转化能够进行 直接在成像质谱实验期间（具体目标 3）预计会出现这些“反应”图像。 揭示传统成像方式无法获得的空间生化细节 不断发展。 为了越来越多地解决这些问题，新的分析技术（例如本文提出的技术）至关重要 复杂的生物学和临床问题。

项目成果

Separation of Isobaric Lipids in Imaging Mass Spectrometry Using Gas-Phase Charge Inversion Ion/Ion Reactions.

使用气相电荷反转离子/离子反应在成像质谱中分离同量脂质。

• 发表时间: 2023-09-06
• 影响因子: 3.2
• 作者: Specker, Jonathan T;Prentice, Boone M
• 通讯作者: Prentice, Boone M

A multi-modal image fusion workflow incorporating MALDI imaging mass spectrometry and microscopy for the study of small pharmaceutical compounds.

结合 MALDI 成像质谱和显微镜的多模态图像融合工作流程，用于研究小药物化合物。

• 发表时间: 2024-03-13
• 作者: Liang, Zhongling;Guo, Yingchan;Sharma, Abhisheak;McCurdy, Christopher R;Prentice, Boone M
• 通讯作者: Prentice, Boone M

Gas-Phase Ion-Ion Reactions for Lipid Identification in Biological Tissue Sections.

用于生物组织切片中脂质鉴定的气相离子-离子反应。

• 发表时间: 2022
• 作者: Prentice; Boone M
• 通讯作者: Boone M

Quantification of pharmaceutical compounds in tissue and plasma samples using selective ion accumulation with multiple mass isolation windows.

使用具有多个质量隔离窗口的选择性离子积累对组织和血浆样品中的药物化合物进行定量。

• 发表时间: 2023-07
• 作者: Liang, Zhongling;Prentice, Boone M
• 通讯作者: Prentice, Boone M

Structural Elucidation and Relative Quantification of Sodium- and Potassium-Cationized Phosphatidylcholine Regioisomers Directly from Tissue Using Electron Induced Dissociation.

使用电子诱导解离直接从组织中进行钠和钾阳离子化磷脂酰胆碱区域异构体的结构阐明和相对定量。

• DOI: 10.1016/j.ijms.2022.116998
• 发表时间: 2022-12-01
• 期刊: International journal of mass spectrometry
• 影响因子: 1.8
• 作者: Tingting Yan;M. Born;B. Prentice
• 通讯作者: B. Prentice