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: 10027319
• 负责人: Boone M. Prentice
• 金额: $ 30.48万
• 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/10027319
• 关键词: Address; Affect; Amines; Amino Acids; Antineoplastic Agents; Biochemical; Biochemical Pathway; Biochemical Process; Biological; Biological Process; Biomedical Research; Cell physiology; Cells; Chemical Structure; Chemicals; Chemistry; Choline; Clinical; Communicable Diseases; Complex Mixtures; Detection; Development; Diabetes Mellitus; Failure; Fatty Acids; Functional disorder; Gases; Generations; Goals; Head; Image; In Situ; Individual; Ions; 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; Structure; Surface; Technology; Time; Tissue Sample; Tissue imaging; Tissues; Visualization; base; design; detector; experimental study; flexibility; functional group; imaging approach; imaging modality; improved; instrument; instrumentation; interest; mass spectrometer; 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.

项目总结