InCell 6000 High Content Instrument for Cellular Systems Biology Program

描述：通用电气医疗保健，Incell 6000高含量分析(HCA)仪器被要求允许来自匹兹堡大学、匹兹堡大学医学中心和卡内基梅隆大学的研究人员分析固定细胞和活细胞、多细胞模型系统和研究生物(斑马鱼和线虫)中的复杂细胞过程。这款高性能仪器结合了高扫描速率共聚焦成像设备、环境室、4通道荧光、透射光和基于微孔板的系统中的机载液体添加。Incell 6000实现了作为所有细胞和组织功能基础的亚细胞结构和生化反应的自动化、高通量和高时间和空间分辨率。长期目标是将我们目前获取高时间、空间和光谱图像的能力从小样本扩展到从逐个细胞的细胞群体、组织模型和实验动物获取大数据集。这一新能力将使计算和系统生物学工具的应用能够基于统计意义理解生命过程的复杂性，这在以前是不可能的。最好的生物实验系统、基于荧光的试剂和高通量自动化成像的集成将使样本的大规模组合处理成为可能，从而能够探索各种治疗领域中统计上相关的作用机制。美国国立卫生研究院资助的将使用这一仪器的项目包括在 这些研究包括：癌症；干细胞来源的心肌细胞的生理学；头颈部癌症模型中药物反应的异质性；免疫反应在癌症治疗中的作用；活体三维乳腺癌模型及其通路分析；肿瘤模型中的细胞迁移；模型系统中亨廷顿病进展的调控；阿尔法1抗胰蛋白酶缺乏症(ATD)的蛋白质错误折叠疾病模型；以及黑线虫的坏死性小肠结肠炎(NEC)模型。此外，在斑马鱼肾脏再生模型中识别刺激干细胞增殖的小分子，以及应用新一代的 基因编码生物传感器、成像标准和流式细胞术，以及进一步应用主动机器学习优化实验策略。将这一平台应用于基础生物医学研究和转化研究项目，最终将在药物发现和开发方面取得更好的成功，同时有助于定义正常和疾病过程的机制。

DESCRIPTION: The General Electric Healthcare, InCell 6000 High Content Analysis (HCA) instrument is being requested to allow investigators from the University of Pittsburgh, the University of Pittsburgh Medical Center and Carnegie Mellon University to analyze complex cellular processes in both fixed and living cells, multicellular model systems and research organisms (Zebra Fish and C. elegans). This high instrument combines a high scan-rate confocal imaging device, an environmental chamber, 4-channel fluorescence, transmitted light and on-board fluid addition in a microplate-based system. The InCell 6000 permits automated, high throughput and high temporal and spatial resolution of subcelluar structures and biochemical reactions that are the basis of all cellular and tissue functions. The long-term objective is to extend our present capabilities in acquiring high temporal, spatial and spectral images from a small sample size to the acquisition of large data sets from populations of cells on a cell-by-cell basis, tissue models and experimental animals. This new capability will permit the application of computational and systems biology tools to understand the complexities of life processes based on statistical significance not possible before. The integration of the best biological experimental systems, fluorescence-based reagents and high throughput, automated imaging will enable large, combinatorial treatments of samples to allow the exploration of statistically relevant mechanisms of action in a variety of therapeutic areas. The NIH funded projects that will use this instrument include investigations on human adipocyte differentiation in cancer, the physiology of stem cell derived cardiomyocytes, the heterogeneity of drug responses in head and neck cancer models, the role of the immune response in cancer therapies, live, 3D breast cancer models with the analysis of pathways, cell migration in tumor models, modulation of Huntington's Disease progression in model systems, protein misfolding disease model of alpha 1- antitrypsin deficiency (ATD), and necrotizing enterocolitis (NEC) models in C. elgans. In addition, a kidney regeneration model in Zebra fish to identify small molecules that stimulate stem cell proliferation, as well as the application of a new generation of genetically encoded biosensors, standards for imaging and flow cytometry and the further application of active machine learning optimization of experimental strategies. The application of this platform to fundamental biomedical research and translational research programs will ultimately lead to better success in drug discovery and development, while helping to define the mechanisms of normal and disease processes.