The High-Throughput Bioscinece Center's mission is to provide researchers at Stanford with the ability to run high-throughput chemical, siRNA, cDNA, and high-content screens for the purpose of drug and/or target discovery. The HTBC is a Stanford University School of Medicine core facility and was created in 2003 by the Department of Chemical and Systems Biology (formerly Molecular Pharmacology). The HTBC is a shared resource (Bioscience Screening Facility) for the Stanford Cancer Institute and the NIH Clinical and Translational Science Award (Spectrum).
This high-throughput screening (HTS) laboratory allows Stanford researchers and others to discover novel modulators of targets that otherwise would not be practical in industry. The center incorporates instrumentation (purchased with NCRR NIH Instrumentation grant numbers S10RR019513 and S10RR026338), databases, compound libraries, and personnel whose previous sole domains were in industry. Among our instrumentation are a Molecular Devices ImageXpress Micro High-Content fluorescence microplate imager, with live cell and phase contrast/brightfield options, a Caliper Life Sciences SciClone ALH3000 and an Agilent Bravo microplate liquid handler, and the Molecular Devices Analyst GT and FlexStation II 384 and Tecan Infinite M1000 fluorescence, luminescence and absorbance multimode microplate readers. We have over 130,000 small molecules for compound screens, 15,000 cDNAs for genomic screens, and whole genome siRNA libraries targeting the human genome (the siARRAY whole human genome siRNA library from ThermoFisher Scientific, formerly Dharmacon, targeting 21,000 human genes) and the mouse genome (Qiagen mouse whole genome siRNA set V1 against ~17,000 genes).
Description of Services
The Stanford HTBC offers the following services to ALL Stanford researchers.
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Fully automated high-throughput screening (HTS) of Compound Libraries (130,000+ compounds) for both enzyme/protein-based assays and cell-based assays, using the Caliper Life Sciences Staccato system.
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Genomic siRNA screening with the siARRAY whole human genome siRNA library from ThermoFisher Scientific (formerly Dharmacon) targeting 21,000 genes. (Application), using the Agilent Bravo system.
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High-Content Screening using the ImageXpress Micro automated fluorescent microscope with live cell, bright field, phase contrast and integrated plate handling with the Thermo Catalyst CRS, and image analysis using the MetaXpress software.
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High-Throughput Molecular Biology reagents and services, including access to cDNA libraries (Human ORFeome collection, 15,000 genes) and high-throughput cDNA purifications using the Qiagen BioRobot 3000.
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High-throughput assay development assistance with cell culture, experiment design, robotic programming and Standard Operating Procedure drafting.
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Screening data analysis assistance with protocols, hit determination and structure activity analyses using the MDL chemical database ISIS/HOST, Plate Manager, Assay Explorer and Report Manager.
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Use of microplate reader detection systems, including the Tecan Infinite M1000 and Molecular Devices Analyst GT for fluorescence; fluorescence polarization; time-resolved fluorescence; absorbance and luminescence; and the Flexstation II 384, for kinetic fluorescence reads to measure calcium mobilization and ion channels.
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Use of liquid-handling robots, including the Sciclone ALH3000 (96- and 384-well pipetting), Agilent Bravo (96- and 384-well pipetting), Velocity11 VPrep (96-well pipetting), Bio-Tek plate washers/dispensers, Qiagen BioRobot 3000, Matrix Wellmate and Titertek Multidrop microplate dispensers, and Velocity11 PlateLoc plate heat sealer.
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Training for most of these services and much, much more!
Selected References
Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade. Hyman JM, Firestone AJ, Heine VM, Zhao Y, Ocasio CA, Han K, Sun M, Rack PG, Sinha S, Wu JJ, Solow-Cordero DE, Jiang J, Rowitch DH, Chen JK. Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):14132-7. Epub 2009 Aug 5. PubMedID: 19666565; PMCID: PMC2721821
A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability. Paulsen RD, Soni DV, Wollman R, Hahn AT, Yee MC, Guan A, Hesley JA, Miller SC, Cromwell EF, Solow-Cordero DE, Meyer T, Cimprich KA. Mol Cell. 2009 Jul 31; 35 (2): 228-39. PubMedID: 19647519; PMCID: PMC2772893
The roles of cyclin A2, B1, and B2 in early and late mitotic events. Gong D, Ferrell JE Jr. Mol Biol Cell. 2010 Sep 15;21(18):3149-61. Epub 2010 Jul 21. PubMedID: 20660152; PMCID: PMC2938381
