Administrative Supplements for Equipment Purchase

设备采购行政补充

• 批准号: 10580922
• 负责人: Boone M. Prentice
• 金额: $ 22.5万
• 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/10580922
• 关键词: Address; Administrative Supplement; Antineoplastic Agents; Biochemical; Biochemical Pathway; Biochemical Process; Biological; Biological Process; Biomedical Research; Cell physiology; Chemical Structure; Chemicals; Clinical; Communicable Diseases; Development; Diabetes Mellitus; Failure; Functional disorder; Gases; Image; In Situ; Ions; Label; Lipids; Malignant Neoplasms; Maps; Mass Spectrum Analysis; Measurement; Methodology; Methods; Molecular; Pharmaceutical Preparations; Pharmacology; Phase; Play; Reaction; Reproducibility; Role; Specificity; Specimen; Technology; Tissue Sample; Tissue imaging; Tissues; Visualization; design; detection limit; equipment acquisition; experimental study; flexibility; functional group; imaging approach; imaging modality; improved; instrumentation; mass spectrometer; mass spectrometric imaging; microscopic imaging; molecular imaging; novel; prevent; 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.

项目摘要 分子成像在生物医学研究中起关键作用。通过启用生物学的可视化 直接在组织中的过程，可以在空间环境中记录细胞功能的原位评估。这 使用质谱法作为分子成像方式，结合了高水平的分子特异性 由质谱仪提供的具有微观成像方法的空间保真度。这样，成像 质谱法（IMS）提供了组织中广泛的生物分子的无标记映射 标本。在开发过程中对生化途径的准确鉴定和功能障碍是 设计针对各种应用的新型治疗策略（例如糖尿病研究）的关键步骤， 传染病，药理和癌症。但是，严重的缺陷仍然存在 以及在成像质谱实验中检测到的分子的结构鉴定， 组织样品的巨大化学复杂性。无法充分分开并确定这些 化合物导致由多种不同化合物和重叠质量组成的离子图像。这 分子分布的扭曲图片蒙蒙了成像产生的生化图的解释 质谱法并防止对细胞组成和功能的完整，准确的了解。 该建议旨在开发方法和仪器，以使组织成像以无与伦比的水平进行 灵敏度，分离和识别。这将通过发现和发展来实现 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 （特定目标1）。这些反应为分子转化提供了快速而灵活的手段 操纵组织样品，并可能提高检测极限和更广泛的化学物质 结构信息。开发可再现和定量离子/离子反应方法将实现 可靠的测量值是由组织进行的（特定的目标2）。可以开发仪器 用高吞吐量执行气相离子/离子反应将使这些转换能够进行 在成像质谱实验中直接直接（特定目标3）。预计这些“反应性”图像 传统成像方式无法揭示空间生化细节。持续发展 在本文提出的新分析技术中，对于越来越多的解决方案至关重要 复杂的生物学和临床问题。