Research Services Core (RSC)

研究服务核心 (RSC)

• 批准号: 10011454
• 负责人: Samuel Michael
• 金额: $ 836.4万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10011454
• 关键词: Acoustics; Aptitude; Archives; Automation; Biological; Biological Assay; Biology; Calcium Channel; Caustics; Cells; Chemical Structure; Chemicals; Collection; Communities; Complement; Complex; Computer software; Core Facility; Custom; Data; Data Analyses; Data Quality; Databases; Detection; Development; Dimethyl Sulfoxide; Dose; Emerging Technologies; Engineering; Equipment; Hybrids; Incubators; Institutes; Internet; Intramural Research Program; Laboratories; Libraries; Liquid substance; Maintenance; Methods; Mission; Monitor; Nature; Plasma; Preparation; Process; Productivity; Protocols documentation; RNA Interference; RNA interference screen; Reader; Reagent; Recording of previous events; Research; Research Personnel; Research Support; Resolution; Resources; Retrieval; Robotics; Run-On Assays; Running; Sampling; Scientist; Services; Solvents; Stem cells; Support System; System; Technology; Time; Toxicology; Training; Translations; Transportation; Vial device; Work; arm; assay development; cohesion; design; follow-up; high throughput screening; imager; instrument; instrumentation; member; new technology; next generation; operation; programs; response; screening; small molecule; tissue culture; tool; vigilance

Research Services Core (RSC) staff provide support to the NCATS activities in high-throughput screening, assay development, and optimization as well as follow-up and dose-response library-plating services for NCATS screening activities. The Compound Management team works in conjunction with the Automation team to provide follow-up and dose-response library-plating services for NCATS screening activities. Systems supported by the Automation team include primary screening system, Tox21 screening system, RNAi screening system, the RNAi hit picking system for assay follow ups, and the High Resolution Biosystems (HRB) acoustic plating system. In the past year, we have also installed and begun to operate a Thermo Scientific Spinnaker plate preparation workstation used to pin compounds and dispense reagents into plates in a batch format. Together, all of these systems combined provide a wide variety of automation and compound plating tasks used to enable all facets of the NCATS intramural scientific program. The primary screening system utilizes three robotic arms for plate transportation, a storage capacity of more than 3 million compound wells (approximately 2,000 1,536-well compound plates), and more than 1.5 million assay wells (approximately 1,100 1,536-well assay plates) to achieve a world-class screening productivity while maintaining the high level of data quality required by researchers. It also has the ability to run multiple assays in parallel. Center experts have developed custom software to monitor and control the system, in addition to archiving the complete process history for every screen in real time. The Tox21 screening system uses a single robotic arm for plate transportation and a storage capacity of nearly 1 million compound or assay wells (about 600 1,536-well compound or assay plates) to screen smaller scale compound libraries not present on the primary screening system and the Tox21 compound library. This platform is designed to complement the primary system, and it is easily customizable, allowing for the rapid integration of additional screening technologies. The RSC team additionally provides screening system services to intramural programs within NCATS. The Tox21 screening system contains a single robotic arm for plate transportation and a storage capacity of about 1.5 million compound wells (about 1,000 1,536-well compound plates) and more than 1.5 million assay wells (approximately 1,100 1,536-well assay plates). With a pin tool and two acoustic dispensers for compound addition, four low-volume dispensers for reagent addition, and three plate readers enabling a variety of assay detection methods, this system can rapidly screen, in triplicate, the Toxicology in the 21st Century (Tox21) library of 10,000 compounds. This year, the RSC team was also able to complete the installation of the Hamamatsu FDSS plate reader allowing the Tox21 program to expand the kinds of assays run on the platform, in particular calcium channel. The FDSS itself was modified to include a custom 1536 pintool cleaner developed by IonField; which is a first of its kind using cold plasma technology instead of DMSO and other solvents to clean, providing both better data due to minimizing carry-over effects between plates and reducing the need for caustic solvents which in the past have damaged the instrument. NCATS experts monitor and control this system with the same custom software used for the primary screening system. The RNAi screening system has two robotic arms for plate transportation with incubators for assay plate storage and plate stackers to facilitate continuous system operation. A multichannel pipettor, low volume dispensers, an aspirator for plate washing, and two different plate readers support a wide variety of detection methods for this RNAi-focused system. RSC staff also continue to support the newly formed Stem Cell Translation Laboratory (SCTL). Various team members have provided a large amount of support with a vast array of equipment including automated tissue culture systems, flow cytometers, cell sorters, and high content imagers. Special mention should be given to the automated tissue culture platform which has established itself as a core capability for all NCATS researchers now with the demand becoming so great that another system is most likely on order. These resources require a tremendous amount of expertise to operate and maintain. In the past year, RSC has begun to act as a core facility for these technologies, enabling different biology groups to increase their capabilities. Related to the high content imagers, more high content assays were run in the past year due to the increased capabilities as compared to the previous four years combined.

研究服务核心（RSC）工作人员为NCATS的高通量筛选、检测开发和优化活动提供支持，并为NCATS筛选活动提供随访和剂量反应文库平板接种服务。化合物管理团队与自动化团队合作，为NCATS筛选活动提供随访和剂量反应文库平板接种服务。自动化团队支持的系统包括初级筛选系统、Tox 21筛选系统、RNAi筛选系统、用于检测跟踪的RNAi命中挑选系统以及高分辨率生物系统（HRB）声学平板系统。在过去的一年中，我们还安装并开始运行Thermo Scientific Spinnaker平板制备工作站，用于将化合物固定并以批次形式将试剂分配到平板中。 总之，所有这些系统相结合，提供了各种各样的自动化和复合电镀任务，用于实现NCATS校内科学计划的各个方面。 初筛系统利用三个机械臂进行平板运输，存储容量超过300万个化合物威尔斯孔（约2，000个1，536孔化合物平板），以及超过150万个测定威尔斯孔（约1，100个1，536孔测定平板），以实现世界一流的筛选生产率，同时保持研究人员所需的高水平数据质量。它还具有并行运行多个测定的能力。中心专家开发了定制软件来监测和控制系统，此外还可以真实的实时存档每个屏幕的完整工艺历史。Tox 21筛选系统使用单个机械臂进行板运输，并具有近100万个化合物或测定威尔斯孔（约600个1，536孔化合物或测定板）的存储容量，以筛选初级筛选系统和Tox 21化合物文库上不存在的较小规模化合物文库。该平台旨在补充主系统，并且易于定制，允许快速集成其他筛选技术。 RSC团队还为NCATS内部的校内项目提供筛选系统服务。Tox 21筛选系统包含用于板运输的单个机械臂和约150万个化合物威尔斯孔（约1，000个1，536孔化合物板）和超过150万个测定威尔斯孔（约1，100个1，536孔测定板）的储存容量。通过一个针工具和两个用于化合物添加的声学分配器、四个用于试剂添加的低容量分配器以及三个支持各种分析检测方法的酶标仪，该系统可以一式三份快速筛选21世纪毒理学（Tox 21）10，000种化合物库。 今年，RSC团队还完成了Hamamatsu FDSS酶标仪的安装，使Tox 21项目能够扩展平台上运行的检测种类，特别是钙通道。 对FDSS本身进行了修改，以包括IonField开发的定制1536 pintool清洁剂;这是同类产品中首次使用冷等离子体技术代替DMSO和其他溶剂进行清洁，由于最大限度地减少了板之间的残留效应，并减少了对过去损坏仪器的腐蚀性溶剂的需求，因此提供了更好的数据。NCATS专家使用与初级筛查系统相同的定制软件监测和控制该系统。RNAi筛选系统具有用于平板运输的两个机械臂，具有用于测定平板储存的孵育器和用于促进连续系统操作的平板堆叠器。多通道移液器、低容量分液器、用于平板洗涤的抽吸器和两种不同的平板读取器支持用于该RNAi聚焦系统的各种检测方法。 RSC的工作人员还继续支持新成立的干细胞翻译实验室（SCTL）。不同的团队成员提供了大量的支持，包括自动化组织培养系统，流式细胞仪，细胞分选仪和高容量成像仪。 特别值得一提的是自动化组织培养平台，它已经成为所有NCATS研究人员的核心能力，现在需求变得如此之大，以至于另一个系统很可能正在订购。 这些资源需要大量的专业知识来操作和维护。在过去的一年里，RSC已经开始作为这些技术的核心设施，使不同的生物群体能够提高他们的能力。 与高含量成像仪相关，由于与前四年的总和相比，能力有所增加，因此在过去一年中运行了更多的高含量测定。