Novel Platform for Quantitative Subcellular Resolution Imaging of Human Tissues Using Mass Spectrometry

使用质谱对人体组织进行定量亚细胞分辨率成像的新平台

• 批准号: 10219212
• 负责人: Julia Laskin
• 金额: $ 62万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10219212
• 关键词: Address; Automation; Biological; Blood capillaries; Characteristics; Chemicals; Collaborations; Complex; Computer software; Data; Data Analyses; Detection; Development; Disease; Electrospray Ionization; Ensure; Glass; Health; Histology; Human BioMolecular Atlas Program; Image; Imaging Techniques; Ions; Label; Lipids; Liquid substance; Machine Learning; Maps; Mass Spectrum Analysis; Measurement; Microfluidics; Microscope; Molecular; Mus; Oligosaccharides; Optics; Peptides; Performance; Pharmaceutical Preparations; Phase; Play; Process; Proteins; Proteomics; RNA; Research; Resolution; Role; Sampling; Sensitivity and Specificity; Slide; Solvents; Spatial Distribution; Spectrometry, Mass, Electrospray Ionization; Structure; Surface; Techniques; Technology; Time; Tissue Sample; Tissues; United States National Institutes of Health; Validation; automated analysis; biological systems; data acquisition; design; experimental study; human imaging; human tissue; imaging capabilities; imaging modality; imaging platform; innovation; interest; ionization technique; lipidomics; mass spectrometer; member; metabolomics; molecular imaging; nano; nanoprobe; new technology; novel; operation; preservation; quantitative imaging; reconstruction; scale up; tool

Novel Platform for Quantitative Subcellular Resolution Imaging of Human Tissues Using Mass Spectrometry Mass spectrometry imaging (MSI) is a powerful technique that enables label-free spatial mapping of different classes of biomolecules in biological systems. Because it does not require any special sample pretreatment, ambient MSI is particularly attractive for high throughput automated imaging applications. The throughput of ambient MSI experiments is typically limited by the inherently slow microprobe-type sampling from surfaces, which is a characteristic shortcoming of many chemical imaging modalities. This project will combine several highly innovative approaches to address challenges associated with the high-throughput high- resolution ambient MSI of lipids and metabolites using nanospray desorption electrospray ionization (nano-DESI). Nano-DESI is an ambient ionization technique, which relies on gentle localized liquid extraction of molecules from tissue sections into a flowing solvent confined between two glass capillaries. The extracted molecules are efficiently delivered to a mass spectrometer inlet and ionized by soft electrospray ionization. Nano-DESI MSI enables detection of hundreds of metabolites, lipids, and peptides in tissue sections with high sensitivity, high spatial resolution, and without special sample pretreatment. Furthermore, on-the-fly quantification of lipids and metabolites in tissue sections during nano-DESI imaging experiments is achieved by doping the working solvent with appropriate standards of known concentration. This project will extend these powerful capabilities of nano-DESI MSI to enable high-throughput imaging of large tissue sections of interest to the HubMAP Consortium. This will be achieved using a combination of a conceptually different nano-DESI probe design optimized for robustness, ease of fabrication, and spatial resolution and a suite of advanced machine learning and compressed sensing computational approaches. These developments will be applicable to different types of human tissues and will transform quantitative molecular imaging of multiple classes of biomolecules in tissue sections. Although the capabilities of the new imaging platform will be demonstrated using non-diseased tissue, these developments will be broadly applicable to scientific problems associated with understanding health and disease

用于人体组织定量亚细胞分辨率成像的新平台 质谱 质谱成像（MSI）是一种强大的技术，其能够实现无标记的空间分析。 生物系统中不同类别生物分子的映射。因为它不需要 任何特殊的样品预处理，环境MSI对于高通量特别有吸引力 自动成像应用。环境MSI实验的通量通常是有限的 通过从表面进行固有的缓慢的微探针类型采样，这是一个特征， 许多化学成像模式的缺点。本项目将联合收割机与几个高度 创新的方法，以解决与高通量高， 使用纳米喷雾解吸电喷雾的脂质和代谢物的分辨率环境MSI 离子化（纳米DESI）。Nano-DESI是一种环境电离技术，其依赖于温和的 将分子从组织切片局部液体提取到受限的流动溶剂中 在两个玻璃毛细管之间。提取的分子被有效地输送到质量 质谱仪入口，并通过软电喷雾离子化进行离子化。Nano-DESI MSI使 以高灵敏度检测组织切片中的数百种代谢物、脂质和肽， 空间分辨率高，无需特殊的样品预处理。此外，在飞行中， 在纳米DESI成像实验期间定量组织切片中的脂质和代谢物 通过用已知浓度的适当标准物掺杂工作溶剂来实现。 该项目将扩展纳米DESI MSI的这些强大功能， HubMAP联盟感兴趣的大组织切片的成像。完成这项工作的方法是 使用优化的概念上不同的纳米DESI探针设计的组合， 鲁棒性，易于制造，空间分辨率和一套先进的机器学习 和压缩传感计算方法。这些发展将适用于 不同类型的人体组织，并将改变定量分子成像的多个 组织切片中的生物分子种类。虽然新成像平台的功能 将证明使用非病变组织，这些发展将是广泛适用的 与理解健康和疾病相关的科学问题