Research Services Core (RSC)

研究服务核心 (RSC)

• 批准号: 10908198
• 负责人: Samuel Michael
• 金额: $ 473.89万
• 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/10908198
• 关键词: Acoustics; Aptitude; Astrocytes; Augmented Reality; Automation; Biological; Biological Assay; Biology; Biomanufacturing; Boston; Cancer Biology; Cells; Chemical Structure; Chemicals; Clinical; Collaborations; Collection; Communities; Complex; Computer software; Country; Custom; Dana-Farber Cancer Institute; Data; Data Analyses; Databases; Development; Device Designs; Devices; Dose; Drug Combinations; Emerging Technologies; Engineering; Ensure; Equipment; Evaluation; Feedback; Friends; Hospitals; Hybrids; Hypothalamic structure; Image; Incubators; Internet; Intramural Research Program; Laboratories; Libraries; Liquid substance; Maintenance; Measures; Methods; Mission; National Center for Advancing Translational Sciences; Nature; Neurobiology; Neurons; Neurosciences; Nociceptors; Patients; Peripheral; Phase; Process; Protocols documentation; Rare Diseases; Recording of previous events; Reporting; Research; Research Personnel; Research Support; Reservations; Retrieval; Robot; Robotics; Running; Sampling; Schedule; Scientist; Services; Site; Small Business Innovation Research Grant; Spottings; System; Technology; Testing; Time; Training; Tube; Universities; Validation; Vial device; Work; arm; assay development; cell bank; design; detector; flasks; follow-up; high throughput screening; imager; improved; induced pluripotent stem cell; instrument; instrumentation; medical schools; member; new technology; next generation; operation; preservation; response; scale up; screening; small molecule; stem cells; tissue culture; trophoblast; vigilance

1. Automation a. Two accepted phase 1 proposals for an Automated Flask Cleaning device design. 2 accepted phase 2 SBIR proposals for Augmented Reality for rare diseases. b. Instrumentation and Automation scheduling site stats Automation Scheduling had a total of 142 reservations, 185 protocols were run, 80+ total users registered. Instrumentation site had a total of 112 reservations for stand-alone devices (limited to overflow equipment from Outlook but expanding), there were also 133 maintenance requests to report issues on equipment (increasing) with 200+ registered users. c. 10 complex robotic platforms (ranging from the Primary screening robot to the fully automated BSL-3 system) and at least 250 pieces of regularly used equipment comprised of pintool transfer devices, solenoid valve small volume liquid dispensers, bulk dispensers and washers, acoustic transfer devices, robotic arms, incubators, centrifuges, plate sealers and peelers are maintained by RSC saving hundreds of thousands of dollars. d. Collaboration with DPI ETB members and Arimation Robotics to help design, build and implement an automation-friendly instrument to measure and collect data for Real Time Cellular Thermal Shift Assay (RT-CETSA). Design and testing phases complete with factory acceptance testing planned for September 2023. 2. Compound Management a. Automated tube reformatting and acoustic dispensing system designed, built custom for, and guided by NCATS compound management cutting edge needs. A straight from storage tube acoustic dispenser and a complex liquid handling platform was integrated with our compound store along with necessary peripherals for plate prep/preservation and decapping/capping capabilities to fully automated tube picking through assay ready plate creation while eliminating extra intermediate pipetting steps therefore reducing plastic consumables by 1/3 to 1/2 depending on the process. Installation, site acceptance testing, and training complete. Validation in process. b. Busiest year in history. 2,236 FOTS orders were filled for DPI biology groups and collaborators. Compounds requested 79% internally and 21% externally delivered around the country. c. 4,612 plates produced (acoustic 40% and non-acoustic 60%) for 771 orders. 65% were for Drug Combination, 27% for follow up plates, and 8% were qHTS style plates. 51% of the acoustic spotted plates were produced on our multiple automated acoustic platforms. 3. Automated Cell Technologies a. CellTrio System: RoboCell designed, custom built, and guided by NCATS cell technologies cutting edge needs to increase capability as well as scale up from existing Sartorius CompacT SelecT units. Includes flask handling, decappng/capping, detector, confluency inspection/imaging, complex liquid handling and dispensing as well as storage. Factory acceptance testing is ongoing to ensure necessary functionality. b. Five robotic high throughput biomanufacturing and functional differentiation processes of hiPSCs for Nocicenptors, Astrocytes, Trophoblasts, Hypothalamic neurons as well as adaptation of patient iPSCs in system and clean up. Supports internal (Stem Cell, 3DTBPL, etc) and numerous external collaborators. Involves direct involvement and feedback from scientists on process and evaluation. c. Nociceptors cell bank generated from 12 iPSC lines into 792 cryovials containing 5M cells/vial = 3.96B Nociceptor cells. Collaborators include Boston Childrens Hospital, Harvard Medical School, Department of Neurobiology, Dana Farber Cancer Institute, Department of Cancer Biology, and Nuffield Department of Clinical Neurosciences, The University of Oxford. Astrocytes cell bank generated from 14 iPSC lines into 392 cryovials containing 0.4M 10M cells/vial = 2.5B Astrocyte cells. Hypothalamic neurons generated from 3 iPSC lines into 91 cryovials containing 5M cells/vial = 455M Hypothalamic neurons.

1. 自动化 a. 两个已接受的自动培养瓶清洁装置设计的第1阶段提案。2家接受了针对罕见疾病的增强现实的第2阶段SBIR提案。 B. 仪器仪表和自动化调度站点统计自动化调度共有142个预订，185个协议运行，80+总用户注册。仪器站点共有112个独立设备的保留（仅限于Outlook中的溢出设备，但正在扩展），还有133个维护请求报告200多个注册用户的设备问题（不断增加）。 C. 10个复杂的机器人平台（从初级筛选机器人到全自动BSL-3系统）和至少250件经常使用的设备，包括pintool转移装置，电磁阀小体积液体分配器，散装分配器和清洗机，声学转移装置，机械臂，培养箱，离心机，平板密封机和剥离机，由RSC维护，节省了数十万美元。 D. 与DPI ETB成员和Arimation Robotics合作，帮助设计、构建和实施自动化友好型仪器，以测量和收集真实的时间细胞热位移分析（RT-CETSA）的数据。设计和测试阶段完成，计划于2023年9月进行工厂验收测试。 2. 复合经营 a. 自动化管重新格式化和声学点胶系统设计，定制，并由NCATS化合物管理尖端需求指导。直接从存储管声学分配器和复杂的液体处理平台与我们的复合存储沿着与必要的外围设备集成，用于板准备/保存和开盖/加盖功能，以通过检测准备板创建完全自动化的管拾取，同时消除额外的中间移液步骤，因此根据工艺将塑料耗材减少1/3至1/2。完成安装、现场验收测试和培训。正在进行验证。 B. 史上最忙的一年。2，236 FOTS订单已为DPI生物组和合作者填写。化合物要求79%的内部和21%的外部交付全国各地。 C. 为771个订单生产了4，612个板材（声学40%和非声学60%）。65%用于药物组合，27%用于随访钢板，8%为qHTS型钢板。51%的声学斑点板是在我们的多个自动化声学平台上生产的。 3. 自动化细胞技术 a. CellTrio系统：RoboCell由NCATS细胞技术设计、定制和指导，满足尖端需求，以提高能力，并从现有的Sartorius CompacT SelecT装置扩大规模。包括烧瓶处理、开盖/封盖、检测器、汇合检查/成像、复杂液体处理和分配以及储存。正在进行工厂验收测试，以确保必要的功能。 B. 五个机器人高通量生物制造和hiPSC的功能分化过程，用于伤害感受器，星形胶质细胞，滋养细胞，下丘脑神经元以及患者iPSC在系统和清理中的适应。支持内部（干细胞，3DTBPL等）和众多外部合作者。涉及科学家对过程和评价的直接参与和反馈。 C. 从12个iPSC系产生的伤害感受器细胞库放入含有5 M细胞/小瓶的792个冷冻管中= 3.96 B伤害感受器细胞。合作者包括波士顿儿童医院、哈佛医学院、神经生物学系、达纳法伯癌症研究所、癌症生物学系和牛津大学纳菲尔德临床神经科学系。从14个iPSC系生成的星形胶质细胞细胞库，置于392个冷冻管中，含有0.4 M 10 M细胞/小瓶= 2.5 B星形胶质细胞。下丘脑神经元从3个iPSC系产生到含有5 M细胞/小瓶的91个冷冻管中= 455 M下丘脑神经元。

项目成果

Keeping It Clean: The Cell Culture Quality Control Experience at the National Center for Advancing Translational Sciences.

• DOI: 10.1177/2472555220911451
• 发表时间: 2020-06
• 期刊: SLAS discovery : advancing life sciences R & D
• 作者: Roth JS;Lee TD;Cheff DM;Gosztyla ML;Asawa RR;Danchik C;Michael S;Simeonov A;Klumpp-Thomas C;Wilson KM;Hall MD
• 通讯作者: Hall MD

Development of an assay pipeline for the discovery of novel small molecule inhibitors of human glutathione peroxidases GPX1 and GPX4.

开发用于发现人谷胱甘肽过氧化物酶GPX1和GPX4的新型小分子抑制剂的测定管道。

• DOI: 10.1016/j.redox.2023.102719
• 发表时间: 2023-07
• 期刊: REDOX BIOLOGY
• 影响因子: 11.4
• 作者: Cheff, Dorian M.;Cheng, Qing;Guo, Hui;Travers, Jameson;Klumpp-Thomas, Carleen;Shen, Min;Arner, Elias S. J.;Hall, Matthew D.
• 通讯作者: Hall, Matthew D.

Application of temperature-responsive HIS-tag fluorophores to differential scanning fluorimetry screening of small molecule libraries.

• DOI: 10.3389/fphar.2022.1040039
• 发表时间: 2022
• 期刊: Frontiers in pharmacology
• 影响因子: 5.6

Novel Phenotypic Outcomes Identified for a Public Collection of Approved Drugs from a Publicly Accessible Panel of Assays.

• DOI: 10.1371/journal.pone.0130796
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Lee JA;Shinn P;Jaken S;Oliver S;Willard FS;Heidler S;Peery RB;Oler J;Chu S;Southall N;Dexheimer TS;Smallwood J;Huang R;Guha R;Jadhav A;Cox K;Austin CP;Simeonov A;Sittampalam GS;Husain S;Franklin N;Wild DJ;Yang JJ;Sutherland JJ;Thomas CJ
• 通讯作者: Thomas CJ

Serologic Cross-Reactivity of SARS-CoV-2 with Endemic and Seasonal Betacoronaviruses.

• DOI: 10.1007/s10875-021-00997-6
• 发表时间: 2021-07
• 期刊: Journal of clinical immunology
• 影响因子: 9.1
• 作者: Hicks J;Klumpp-Thomas C;Kalish H;Shunmugavel A;Mehalko J;Denson JP;Snead KR;Drew M;Corbett KS;Graham BS;Hall MD;Memoli MJ;Esposito D;Sadtler K
• 通讯作者: Sadtler K