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.

项目摘要/摘要 莫菲特癌症中心与研究所，佛罗里达州唯一指定的综合癌症中心是 要求资金购买Perkin Elmer的“ Opera Phenix”以及高内容筛选（HCS）成像 系统。 HCS，自动显微镜和图像分析的应用最初发现了其在肿瘤学中的位置 由于早期应用测量了凋亡的研究。现在，HCS成像系统已在众多 与癌症研究有关的应用，包括细胞形态，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，多个单端点 以及表型结果，可以简单地在细胞单层，微动物，小节和 甚至整个组织。 Moffitt癌症中心（MCC）的研究实验室使用了许多这些应用 研究癌症生物学的复杂，多方面的性质；但是，MCC当前的成像技术缺乏 HCS系统提供的灵敏度和实验吞吐量的结合，导致数据集缺乏 范围和/或图像质量。为了证明需要高通量（HT）-HCS仪器的需要 对10个主要用户和3个未成年人资助的研究的研究将基本上是基本的 通过使用这种工具的积极影响。 Perkin Elmer，Inc。的Opera Phenix Plus HCS系统 已被确定为最合适的工具，因为它包含了必要的技术和软件 满足MCC教师的HCS需求不同。由于一个数字，该HCS平台被认为是“最好的” 高级硬件和软件功能（合并后）提供最小的高分辨率图像 在无与伦比的采集速度下，频谱串扰和真实点共同点。与船上配对时 环境控制和机器人液体/板处理，系统是完整的HT-HCS工具。内置 “ Harmony”软件授予访问更强大的图像分析功能，包括3D渲染，自定义 分析构建块和酚类机器学习。我们的调查人员将利用歌剧的力量 Phenix Plus解锁癌症遗传学和代谢中的神秘感，询问肿瘤微环境和 筛选潜在治疗。他们将使用细胞的高含量，活细胞，多重荧光成像， 微动物和球状素以生成多参数数据输出，从而获得更多的定量数据，更多 有效地，每次实验的成本降低带来了额外的好处。如果被授予，Opera Phenix Plus将是 安装在MCC共享资源分析显微镜核心（AMC）中，支持宽度的采用 技术。 AMC工作人员拥有必要的显微镜知识和经验，可以有效运行 仪器并管理大型数据集。该提案的主要调查员Patricia McDonald博士是 在HTS和HCS技术方面经过正式培训且经验丰富，将监督该科学方向 乐器。 PI与AMC主管和员工一起将培训用户组如何准备HCS 实验，操作仪器，分析图像并执行HTS广告系列。