A High Content Screening Platform for High Throughput, High Content Imaging and Analysis

用于高通量、高内涵成像和分析的高内涵筛选平台

• 批准号: 10431416
• 负责人: Patricia Helen McDonald
• 金额: $ 125.49万
• 依托单位: H. LEE MOFFITT CANCER CTR & RES INST
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2023-09-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10431416
• 关键词: 3-Dimensional; Adoption; Apoptosis; Award; Cancer Biology; Cancer Center; Cell Death; Cell Proliferation; Cells; Cellular Metabolic Process; Cellular Morphology; Complex; Comprehensive Cancer Center; Computer software; Custom; Data; Data Set; Faculty; Florida; Funding; Grant; Image; Image Analysis; Imaging technology; Knowledge; Liquid substance; Machine Learning; Measures; Microscopy; Minor; NCI Center for Cancer Research; Nature; Oncology; Outcome; Output; Phenotype; Principal Investigator; Research; Research Institute; Research Personnel; Resource Sharing; Robotics; Screening procedure; Speed; System; Technology; Therapeutic; Training; United States National Institutes of Health; Whole Organism; anticancer research; cancer genetics; cellular imaging; cost; drug discovery; experience; experimental study; fluorescence imaging; high resolution imaging; imaging system; instrument; large datasets; microscopic imaging; monolayer; screening; tumor metabolism; tumor microenvironment

Project Summary/Abstract The Moffitt Cancer Center & Research Institute, Florida’s only NCI-designated Comprehensive Cancer Center is requesting funds to purchase Perkin Elmer’s ‘Opera Phenix’ Plus High Content Screening (HCS) imaging System. HCS, the application of automated microscopy and image analysis initially found its place in oncology research due to early applications that measured apoptosis. Now, HCS imaging systems are used in numerous applications relevant to cancer research, including, cell morphology, cell proliferation, cell death, cell tracking, subcellular localization, colocalization, cell metabolism, and drug discovery. Furthermore, multiple single endpoints as well as phenotypic outcomes can be measured simultaneously in cell monolayers, microtissues, spheroids and even whole organisms. Research labs at Moffitt Cancer Center (MCC) use many of these applications to investigate the complex, multi-faceted nature of cancer biology; however, current imaging technology at MCC lacks the combination of sensitivity and experimental throughput afforded by HCS systems, leading to datasets that lack scope and/or image quality. To justify the need for a high throughput (HT)-HCS instrument, we present the research of 10 major users and 3 minor users whose primarily NIH-funded research would be substantially positively impacted by access to such an instrument. The Opera Phenix Plus HCS system from Perkin Elmer, Inc. has been identified as the most suitable instrument, because it incorporates the necessary technology and software to meet the diverse HCS needs of MCC faculty. This HCS platform is considered ‘best in class’ due to a number of advanced hardware and software features, that when combined, provide high resolution images with minimized spectrum cross-talk and true point confocality at unmatched acquisition speeds. When paired with onboard environmental controls and robotic liquid/plate handling, the system is a complete HT-HCS tool. The built in ‘Harmony’ software grants access to more powerful image analysis functions including, 3D rendering, customized analysis building blocks, and PhenoLogic machine learning. Our investigators will leverage the power of the Opera Phenix Plus to unlock mysteries in cancer genetics and metabolism, interrogate the tumor micro-environment, and screen for potential therapeutics. They will use high content, live-cell, multiplex fluorescence imaging of cells, microtissues, and spheroids to generate multi-parametric data outputs, acquiring more quantitative data, more efficiently, with the added benefit of reduced costs per experiment. If awarded, the Opera Phenix Plus will be installed in the MCC shared resource Analytic Microscopy Core (AMC) facilitating widespread adoption of this technology. The AMC staff possess the necessary Microscopy knowledge and experience to effectively operate the instrument and manage large datasets. The principal investigator for this proposal, Dr. Patricia McDonald, is formally trained and well experienced in HTS and HCS technology and will oversee the scientific direction of the instrument. The PI, together with the AMC director and staff will train the user group on how to prepare HCS experiments, operate the instrument, analyze images and execute HTS campaigns.

项目总结/摘要 莫菲特癌症中心和研究所，佛罗里达唯一的国家癌症研究所指定的综合癌症中心， 申请资金购买Perkin Elmer的'Opera Phenix' Plus高内容筛选（HCS）成像 系统HCS，自动显微镜和图像分析的应用最初在肿瘤学中找到了自己的位置 研究由于早期应用程序，测量细胞凋亡。现在，HCS成像系统被用于许多 与癌症研究相关的应用，包括细胞形态学、细胞增殖、细胞死亡、细胞跟踪， 亚细胞定位、共定位、细胞代谢和药物发现。此外，多个单一终点 以及表型结果可以同时在细胞单层、微组织、球状体和 甚至整个生物体。莫菲特癌症中心（MCC）的研究实验室使用许多这些应用程序， 研究癌症生物学的复杂性，多方面的性质;然而，MCC目前的成像技术缺乏 HCS系统所提供的灵敏度和实验吞吐量的组合，导致数据集缺乏 范围和/或图像质量。为了证明对高通量（HT）-HCS仪器的需求，我们提出了 10个主要用户和3个次要用户的研究，他们主要由NIH资助的研究将在很大程度上 积极地影响到获得这样的文书。Perkin Elmer，Inc.的Opera Phenix Plus HCS系统。 被认为是最合适的工具，因为它包含了必要的技术和软件， 以满足MCC教师的不同HCS需求。该HCS平台被认为是“同类最佳”， 先进的硬件和软件功能，当结合起来，提供高分辨率的图像， 以无与伦比的采集速度实现光谱串扰和真点共焦。当与板载 通过环境控制和机器人液体/板处理，该系统是一个完整的HT-HCS工具。内置的 “Harmony”软件赠款访问更强大的图像分析功能，包括3D渲染、自定义 分析构建块和PhenoLogic机器学习。我们的调查人员会利用歌剧院的力量 Phenix Plus可解开癌症遗传学和代谢的奥秘，询问肿瘤微环境， 筛选潜在的治疗方法他们将使用高含量，活细胞，细胞的多重荧光成像， 微组织和球体，以生成多参数数据输出，获取更多定量数据， 有效地，具有降低每次实验成本的附加益处。如果获奖，Opera Phenix Plus将成为 安装在MCC共享资源分析显微镜核心（AMC）中，促进了这种技术的广泛采用。 技术. AMC工作人员拥有必要的显微镜知识和经验，以有效运作 仪器和管理大型数据集。该提案的主要研究员帕特里夏·麦克唐纳博士是 在HTS和HCS技术方面接受过正式培训并具有丰富经验，并将监督 仪器PI将与AMC主任和工作人员一起培训用户组如何准备HCS 实验，操作仪器，分析图像和执行HTS活动。