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

基本信息

批准号：
10026443
负责人：
Julia Laskin
金额：
$ 63万
依托单位：
PURDUE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-15 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10026443
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 mass spectrometer member metabolomics molecular imaging nano nanoprobe new technology novel operation preservation quantitative imaging reconstruction scale up tool

项目摘要

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分析质谱成像 (MSI) 是一种强大的技术，可实现无标记空间绘制生物系统中不同类别的生物分子的图谱。因为它不需要对于任何特殊的样品预处理，环境 MSI 对于高通量都特别有吸引力自动成像应用。环境 MSI 实验的吞吐量通常是有限的通过本质上缓慢的微探针式表面采样，这是一个特征许多化学成像方式的缺点。该项目将结合多个高度解决与高通量高通量相关的挑战的创新方法使用纳喷雾解吸电喷雾解析脂质和代谢物的环境 MSI 电离（纳米 DESI）。 Nano-DESI 是一种环境电离技术，它依赖于温和的将组织切片中的分子局部液体萃取到流动溶剂中两个玻璃毛细管之间。提取的分子被有效地传递到质量光谱仪入口并通过软电喷雾电离进行电离。 Nano-DESI MSI 使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，且无需特殊的样品预处理。此外，在飞行中纳米 DESI 成像实验期间组织切片中脂质和代谢物的定量通过用已知浓度的适当标准品掺杂工作溶剂来实现。该项目将扩展 nano-DESI MSI 的这些强大功能，以实现高通量 HubMAP 联盟感兴趣的大组织切片成像。这将实现使用概念上不同的纳米 DESI 探针设计的组合，优化了鲁棒性、易于制造、空间分辨率和一套先进的机器学习和压缩感知计算方法。这些发展将适用于不同类型的人体组织，并将改变多种的定量分子成像组织切片中的生物分子类别。尽管新成像平台的功能将使用非患病组织进行论证，这些进展将广泛适用与了解健康和疾病相关的科学问题