Whole-brain fluorescence and brightfield imaging at single-cell level

描述(申请人提供)：该项目的目标是开发一个开放和灵活的成像平台，能够快速、0.5-5？m像素分辨率的大面积组织切片(高达125 mm×175 mm)的图像捕获，在Brightfield和通过外荧光光学切片。该项目涉及最先进的仪器开发和应用程序编程接口(API)，为用户提供可靠的、多功能的研究仪器。高速大幅面成像系统的开发将极大地加速研究，如阿尔茨海默病的淀粉样蛋白研究或即刻早期基因(IEG)的表达，以了解认知的细胞基础。随着组织学切片的尺寸超过1个“W3”玻片的尺寸，数字成像系统的选择数量急剧减少。此外，由于目前的供应商正专注于解剖病理的数字化，他们的系统往往是封闭和僵化的，以适应对医疗设备的监管限制。DMetrix发现的市场机会是一个强大可靠的商业成像平台，具有研究小组重视的灵活性和定制选项。该项目分为两个阶段，其间是与仪器和软件性能有关的量化标准的演示。第一阶段的主要目标是论证大面积、快速的亮场和表观荧光成像仪的可行性。第二个目标是一种图像查看器应用程序，它允许与仪器将生成的TB级图像数据集进行实际交互。选择第二阶段的具体目标是为了在项目结束时推出产品。第二阶段的目标包括开发“V6”、六个成像模块的幻灯片扫描仪、图像管理软件和一个先进的图像查看器应用程序。此外，第二阶段的工作利用了DMetrix的核心专业知识，即开发快速、并行的图像捕获仪器。第二阶段工作的一个重要部分将是使拟议的仪器能够以最低的售出货物成本(COGS)制造，并针对适用性进行优化。DMetrix与亚利桑那大学的一个跨学科学术专家小组在这个项目上进行了合作。该大学的团队包括来自麦克奈特脑研究所的卡罗尔·巴恩斯博士、放射学和生物医学工程系的泰德·特劳拉德博士，以及心理学系脑成像、行为和衰老实验室主任吉恩·亚历山大博士。这些亚利桑那大学的科学家代表了拟议的成像平台对神经科学研究的广泛影响的不同样本。

DESCRIPTION (provided by applicant): The goal of this project is to develop an open and flexible imaging platform capable of rapid, 0.5- 5 ¿m pixel resolution image capture of large-area histology sections (up to 125 mm by 175 mm), in brightfield and by epi-fluorescence optical sectioning. The project involves state-of-the- art instrumentation development coupled with application programming interfaces (APIs) to provide users with a reliable, multi-purpose research instrument. The development of a high speed large format imaging system will dramatically accelerate investigations such as amyloid protein studies for Alzheimer's disease or the expression of immediate-early genes (IEG) in understanding of the cellular basis of cognition. The number of digital-imaging system options decreases dramatically as the size of histology sections outgrows 1" W 3" glass slides. Further, because the current vendors are concentrating on digitizing anatomic pathology, their systems tend to be closed and inflexible to accommodate the regulatory constraints on medical devices. The market opportunity that DMetrix has identified is a robust and reliable commercial imaging platform with the flexibility and customization options valued by research groups. The project is divided into two Phases, punctuated by a demonstration of quantitative criteria, related to instrument and software performance. The primary goal of Phase I is the demonstration of feasibility of the large-area, rapid imaging instrument for brightfield and epi-fluorescence. A second goal is an image-viewer application that allows practical interaction with terabyte image data sets as will be generated by the instrument. The Specific Aims of Phase II are selected to lead to a product launch at the conclusion of the project. The Phase II Aims include the development of a "V6," six-imaging-module slide scanner, image- management software, and an advanced image-viewer application. Further, the work in Phase II leverages the core expertise of DMetrix, namely the development of fast, parallel image-capture instruments. A significant part of the Phase II effort will be directed at making the proposed instrument manufacturable at a minimum cost of goods sold (COGS) and optimized for serviceability. DMetrix has teamed on this project with an interdisciplinary group of academic experts from the University of Arizona. The University team includes Dr. Carol Barnes from the McKnight Brain Institute, Dr. Ted Trouard, Department of Radiology and Biomedical Engineering, and Dr. Gene Alexander, Director of the Brain Imaging, Behavior and Aging Lab in the Department of Psychology. These University of Arizona scientists represent a diverse sampling of the broad impact of the proposed imaging platform on neuroscience research.