Spatial Molecular Imager for Translational Research

项目摘要/摘要 该提案详细说明了商业上可用的纳米线空间分子成像(SMI)的资金申请 仪器，这是一个单细胞成像平台，可以通过电源研究完整的组织 空间多重组学。该仪器将安装在翻译和相关研究实验室 (TCSL)，这是一个核心服务中心，由位于 宾夕法尼亚大学佩雷尔曼医学院。该工具将支持美国国立卫生研究院资助的 宾夕法尼亚大学研究人员与美国国立卫生研究院资助的研究人员合作进行的研究。 (例如，国家老龄研究所)，在没有类似技术和专门知识的情况下，以及培训 研究生和博士后研究员。SMI仪器提供检测和量化的能力 数千个RNA和蛋白质分子在亚细胞高复合三维分辨率下使用分子 来自福尔马林固定石蜡包埋(FFPE)生物样本整个切片的数字“条形码”。这 极高的敏感度、分辨率和信息的多路传输特性允许同时分析 大量感兴趣的单个细胞的蛋白质和转录水平 在现成的固定活检和组织切片中的空间背景。SMI的分析能力 因此，用于组织样本的仪器超过了流式细胞仪和单细胞RNA测序的能力 这需要分离细胞和传统的免疫组织化学/原位杂交(IHC/ISH)方法 一次可以被询问的分析物的数量有限。CosMx SMI的能力 弥合高复数、高吞吐量和高分辨率之间差距的平台将转变对 几名宾夕法尼亚大学的调查人员；它将被用来阐明和绘制细胞类型，生成细胞图谱，分析细胞- 细胞相互作用，并发现单细胞生物标记物。将被推进的研究项目范围广泛 范围和所有高影响，包括间皮瘤、前列腺癌、胰腺癌、 淋巴瘤、胶质母细胞瘤、结直肠癌、紫外线皮肤癌、急性髓系白血病、骨髓增生异常 综合症和阿尔茨海默氏症。所寻求的技术相对较新，几乎没有这样的仪器 在全国学术环境中提供(自2019/2020年初以来)，预计将影响一大批 校内和校外用户。该仪器将由在TCSL内非常有经验的团队管理 一个已经很大和强大的研究环境。

Project Summary/Abstract This proposal details a funding request for a commercially available NanoString Spatial Molecular Imaging (SMI) instrument, which is a single-cell imaging platform that enables investigation of intact tissues through the power of spatial multiomics. The instrument will be installed in the Translational and Correlative Studies Laboratory (TCSL), a Core Service Center that is overseen by the Center for Cellular Immunotherapies (CCI) at the Perelman School of Medicine of the University of Pennsylvania (PENN). The instrument will support NIH-funded research by investigators at PENN, collaborative research with NIH-funded researchers from across the U.S. (e.g., National Institute on Aging) where similar technology and expertise is not available, and the training of graduate students and postdoctoral fellows. The SMI instrument offers the ability to detect and quantify thousands of RNA and protein molecules at subcellular high-plex three-dimensional resolution using molecular digital “barcodes” from whole sections of formalin-fixed paraffin embedded (FFPE) biological samples. This extremely high sensitivity, resolution, and the multiplex nature of the information allows simultaneous profiling at both the protein and transcript level of large numbers of individual cells of interest while observing them in their spatial context in readily available fixed biopsies and histological sections. The analytical power of the SMI instrument for tissue samples thus exceeds the capabilities of flow cytometry and single-cell RNA sequencing that require dissociated cells, and traditional immunohistochemistry/in situ hybridization (IHC/ISH) approaches that are limited in the number of analytes that can be interrogated at one time. The ability of the CosMx SMI platform to bridge the gap between high plex, high throughput, and high resolution will transform the research of several PENN investigators; it will be utilized to elucidate and map cell types, generate cell atlases, analyze cell- cell interactions, and discover single-cell biomarkers. The research projects that will be advanced are broad in scope and all high-impact, including investigations of mesothelioma, prostate cancer, pancreatic cancer, lymphoma, glioblastoma, colorectal cancer, UV-induced skin cancer, acute myeloid leukemia, myelodysplastic syndromes, and Alzheimer’s disease. The technology sought is relatively new, with few such instruments available in the academic setting nationwide (since early 2019/2020) and is expected to impact a large group of intra- and extramural users. The instrument will be managed by the very experienced team in the TCSL within an already large and robust research environment.