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

 描述（由申请人提供）：神经退行性疾病是人类疾病中最昂贵、最具破坏性和治疗最差的疾病之一，可以说是因为它们还没有得到很好的理解。 阵列断层扫描（AT）是一种新的组织成像方法，其三维分辨率足以分辨单个突触并提供多分子成分的定量表征。 AT成像数据使得能够描述神经网络中的 三维组织结构的背景。 我们相信这些数据将使研究人员能够开始 o理解神经回路的正确功能，重要的是，开始理解各种神经退行性过程是如何存在和发展的。然而，AT是复杂和昂贵的，并且在Micheva和Smith于2007年首次发表后，在相对较少的研究中使用。 Aratome目前正在为研究界提供AT服务。 本申请提出了一种新的直接标记方法的概念验证研究，该方法可以是类似于NextGen测序仪的全自动AT系统的基础. 样品将被装载到一个微流控室中，放置在成像仪器上，几十到几百种抗原的成像数据将被自动采集。我们将在第二阶段的资助下开发这样一种仪器，以及直接标记抗体和检测试剂的目录。

 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.