Labeling method for high-resolution imaging of hundreds of tissue antigens

数百种组织抗原高分辨率成像的标记方法

• 批准号: 8904759
• 负责人: JAY K TRAUTMAN
• 金额: $ 22.5万
• 依托单位: ARATOME, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8904759
• 关键词: Age; Alzheimer' s Disease; Antibodies; Antigens; Architecture; Base Sequence; Biological Neural Networks; Brain; Cataloging; Catalogs; Chemicals; Collection; Communities; Complex; Computer Simulation; DNA; Data; Data Set; Detection; Development; Dimensions; Disease; Disease Progression; Due Process; Excision; Fluorescence; Funding; Goals; Human; Image; Immunohistochemistry; Individual; Label; Lateral; Methods; Microfluidics; Molecular; Molecular Analysis; Motivation; Nerve Degeneration; Neurodegenerative Disorders; Oligonucleotides; Parkinson Disease; Pathology; Phase; Plant Resins; Population; Process; Proteins; Proteomics; Publications; Quantum Dots; Reading; Reagent; Relative (related person); Research; Research Personnel; Resolution; Running; Sampling; Services; Slice; Staining method; Stains; Synapses; System; Technology; Testing; Time; Tissue Embedding; Tissues; base; cost; crosslink; effective therapy; fluorophore; imaging modality; instrument; instrumentation; meetings; neural circuit; novel; presynaptic; protein expression; prototype; public health relevance; reconstruction; research study; screening; software development; tomography

 DESCRIPTION (provided by applicant): Neurodegenerative diseases are among the most expensive, disruptive, and least well treated of human maladies, arguably because they are not well understood. Array tomography (AT) is a new method for tissue imaging with resolution in all three dimensions sufficient to resolve individual synapses and provide quantitative characterization of multple molecular constituents. AT imaging data enable description of neural networks in the ontext of the three-­-dimensional tissue architecture. We believe such data will enable researchers to begin o comprehend the proper function of neural circuits and, importantly, to begin to undestand how it is that the various neurodegenerative processes present and progress. AT is, however, complex and expensive, and has been used in relatively few studies following the first publication in 2007 by Micheva and Smith. Aratome is currently providing AT services to the research community. The present application proposes proof-­-of-­-concept studies of a novel direct labeling method that could be the basis of a fully automated AT system, analogous to a NextGen Sequencer. The sample would be loaded into a microfluidic chamber, placed on the imaging instrument and imaging data for tens-­-tohundreds of antigens would be acquired, automatically. We would develop such an instrument, as well as the catalog of directly-­-labeled antibody and detection reagents, under Phase 2 funding.

 描述（由适用提供）：神经退行性疾病是对人类疾病的最昂贵，破坏性且最不受欢迎的疾病之一，这可以说是因为它们没有得到充分的了解。阵列断层扫描（AT）是一种在所有三个维度上分辨率的组织成像的新方法，足以解决单个突触并提供多个分子构成的定量表征。在成像数据上启用了神经网络的描述 三维组织结构的on文文。我们认为，这样的数据将使研究人员能够开始 o理解神经电路的适当功能，重要的是要开始意识到如何存在和进步的各种神经退行性过程。但是，AT是复杂且昂贵的，并且在2007年首次出版的米歇尔和史密斯（Micheva and Smith）的第一次出版物之后，已经使用了相对较少的研究。 Aratome目前正在为研究社区提供服务。当前的应用建议证明 - 对新型直接标记方法的概念研究，该方法可能是完全自动化的系统的基础，类似于NextGen Sequencer。样品将被加载到一个微流体室中，放置在成像仪器上，并自动获取数十万种抗原的成像数据。我们将在第2阶段资金下开发这种仪器，以及直接标记的抗体和检测试剂的目录。