High-Throughput Screening - Sanford Burnham Prebys

High-Throughput Screening

close-up photo of lab equipment

Overview

The Screening & Chemical Libraries (S&CL) facility — home of the Center’s High-Throughput Screening (HTS) capabilities — provides the instrumentation, compound libraries, and expertise needed to screen chemical libraries against biological targets. The facility offers diverse screening instrumentation, curated compound collections, and deep expertise in high-throughput screening and laboratory automation, supporting collaborative, user-driven, and facility-driven screening projects. S&CL works closely with assay-development and high-content/imaging colleagues to select and implement the most suitable biochemical or cellular assay for each project, spanning a wide range of plate-reader and imaging formats.

S&CL is part of the Therapeutics Discovery Shared Resource (TDSR), an integrated, end-to-end drug-discovery resource that spans target validation through preclinical lead optimization. As the hit-identification engine of TDSR, S&CL connects seamlessly with structural biology (cryo-EM), medicinal and computational chemistry, and predictive pharmacology (ADME/PK) teams — giving investigators a continuous path from a biological hypothesis to an optimized, preclinically validated lead compound.

The Center maintains collaborations with a select group of pharma and biotech organizations, as well as several clinical hospitals, to develop small-molecule therapeutics, and continues to seek additional partnerships of mutual benefit. These partnerships typically involve a portfolio of projects that the Center drives — in collaboration with the partner — through the early stages of drug discovery (assay development through lead optimization to in vivo proof-of-concept). Engagements often begin as a pilot project that evolves into a broader collaboration or “shared pipeline.”

The Screening & Chemical Libraries facility within the Therapeutics Discovery Shared Resource, which integrates screening, structural biology, medicinal/computational chemistry, and predictive pharmacology into a single end-to-end drug-discovery pipeline.

Services

  • Screening of small-molecule compound libraries in 384- or 1536-well formats using a range of detection technologies (absorbance, fluorescence, luminescence, fluorescence polarization [FP], TR-FRET, and AlphaScreen).
  • Consultation on high-throughput screening strategy, assay design, and detection-technology selection.
  • Conversion of cell-based and biochemical assays into high-throughput / automation-compatible formats.
  • Preparation and handling of compound libraries for high-throughput screening, including pre-spotted plates for rapid pilot screens (members pay only a nominal distribution cost).
  • Rapid hit validation and expansion, including access to on-demand virtual libraries for analog follow-up.
  • Screening data analysis and support for HTS hit follow-up studies (e.g., dose–response confirmation and cherry-picking).
  • Assistance with, and hands-on training on, automated instrumentation — including the three Access Workstations, the EnVision and PHERAstar plate readers, and the Phenix imaging platform.

Opportunity

Therapeutics Discovery Shared Resource (TDSR) facility is open to multiple engagement models tailored to partner needs.

Organization Types

  • Academic investigators needing US-based drug discovery support for NIH grants with foreign component restrictions
  • Biotech companies seeking integrated medicinal chemistry and pharmacology without building in-house capabilities
  • Investigators seeking hit identification through ultra-high-throughput screening of large diverse compound libraries
  • Non-profit disease foundations looking to de-risk early-stage therapeutic programs
  • Government agencies and research consortia needing contract research with scientific depth

Beyond Fee-for-Service
Scientifically guided project support where TDSR scientists contribute expertise throughout the drug discovery process, providing strategic value beyond data generation. Ideal for investigators who need a collaborative partner, not just a service provider.

Strategic Partnership
Longer-term, multidisciplinary collaborations to advance translational research programs. TDSR supports grant applications (including multi-PI and U01/U19 mechanisms), co-develops project strategy, and commits resources to shared milestones. This model is well-suited for organizations seeking a sustained drug discovery partner.

Contract Research
Defined-scope projects with specific deliverables — assay development, compound synthesis, PK studies, or hit-to-lead campaigns with clear milestones and timelines.

Sponsored Research
Industry-funded research programs conducted within the SBP academic environment, leveraging the Institute’s biological expertise alongside CTD chemistry and pharmacology.

TDSR also welcomes pilot projects as a way for new partners to evaluate capabilities before committing to larger programs.

Certain resources, including compound collections and software licenses, were acquired under third-party agreements that specify non-profit or collaborative use. We can advise on options to accommodate fee-for-service projects with for-profit entities, please contact us for details.

Compound Libraries & Collections

The facility maintains a diverse, continually curated compound collection for exploratory and translational cancer research. Specialty collections are assembled in consultation with Center faculty and combine vendor libraries with non-commercial, literature-described compounds synthesized by our medicinal chemists.

  • More than 310,000 diverse, drug-like compounds procured from ChemBridge and Enamine.
  • Over 20,000 bioactive compounds organized into specialty sub-libraries, including kinase inhibitor, epigenetics, protease inhibitor, structure–activity relationship (SAR), fragment, re-purposing, and FDA-approved collections.
  • Focused collections — Epigenetics, Kinase Inhibitors, Protease Inhibitors, and Mechanism-of-Action — curated from faculty recommendations.
  • On-demand access to virtual libraries of ~4.4 trillion make-on-demand compounds (including the Enamine REAL / xREAL database) for rapid hit validation and analog expansion.
compound libraries and screen modalities

Left: composition of the facility’s physical compound libraries and specialty collections. Right: distribution of assay/detection modalities across screens performed over the last five years.

Detection & Assay Modalities

The facility supports a broad range of biochemical and cell-based readouts in 384- and 1536-well formats:

  • Absorbance
  • Fluorescence intensity
  • Fluorescence polarization (FP)
  • Luminescence (including glow luminescence)
  • FRET / TR-FRET
  • AlphaScreen
  • Phenotypic / high-content (imaging) readouts in collaboration with HCS core
  • NMR-based screening in collaboration with Med. Chem. core

Equipment & Resources

  • Automated Liquid Handling & Compound Dispensing
    • Three Access™ Laboratory Workstations (Labcyte/Beckman), built around two Echo 655s and an Echo 555 acoustic liquid handler with a precision robotic arm, random-access plate racks, a de-lid station, a low-volume bulk dispenser, a microplate centrifuge, a plate peeler, and an Agilent PlateLoc sealer with Argon gas purge, controlled by Labcyte TEMPO automation software. The three systems are configured for distinct workflows — Biochemical Screening, Cellular Screening, and SAR Support; the Cellular Screening workstation additionally integrates a Thermo Scientific Cytomat automated incubator for fully automated cell-based HTS. These systems enable fully automated, multi-plate, small-volume dispensing — particularly useful for dose–response testing of large compound sets and cherry-pick confirmation of primary hits.
    • Plate-processing workstation (Agilent) — a Bravo automated liquid handler with a BenchCel 4x plate handler (four stacker towers), an Agilent PlateLoc thermal sealer, and a Vcode barcode label print-and-apply system.
    • Two Beckman Coulter Biomek FX liquid-handling systems (one fully enclosed) with 96- and 384-well multichannel heads and Span-8 arms.
    • Two TTP Labtech (SPT Labtech) Mosquito nanoliter liquid handlers for low-volume, positive-displacement transfer (assay miniaturization, qPCR setup, and dose–response preparation).
    • Two Certus FLEX digital dispensers (Fritz Gyger micro-valve technology) for contactless, nanoliter-to-microliter dispensing of up to eight fluids.
    • Three INTEGRA WELLJET reagent dispensers for fast, precise bulk plate filling (0.5 µl–10 ml, 6- to 1536-well formats).
    • Multiple Thermo Scientific Multidrop Combi / Multidrop DW bulk reagent dispensers.
  • Detection & Kinetics Instruments
    • Revvity EnVision Nexus multimode reader with stackers and Alpha capability for walk-away, high-throughput detection housed in a dedicated, environmentally controlled ‘green-room’ suite
    • Hamamatsu FDSS/µCELL kinetic plate imager — a high-speed, whole-plate fluorescence and luminescence imager with simultaneous dispensing to all wells (e.g., for GPCR, calcium-flux, ion-channel, glow-luminescence, and enzyme-kinetics assays).
  • Stand-alone Instruments
    • Two Labcyte Echo 555 acoustic liquid handlers
    • BMG LABTECH PHERAstar FSX multimode plate reader (stand-alone, with plate stacker) –An additional BMG LABTECH PHERAstar FSX equipped with injectors and lasers
    • BioTek plate washers — two EL406 washer dispensers and an ELx405 Select CW washer
    • BlueCatBio BlueWasher centrifugal plate washer for gentle, near-zero-residual-volume washing of cellular and bead-based assays (96- to 1536-well).
    • Agilent PlateLoc thermal plate sealers and plate label print-and-apply systems.
    • Six Applied Biosystems ViiA 7 real-time PCR systems and four Eppendorf Mastercycler X50 thermal cyclers (shared with Assay Development).
  • Compound Management & Sample Handling
    • Sensitive Mettler Toledo analytical and micro balances in draft enclosures for precise compound weighing.
    • 2D-barcoded tube scanning and tracking: LVL technologies whole-rack 2D-barcode scanners and a BioMicroLab SampleScan Mini, using LVL SAFE -barcoded storage tubes.
    • Automated LVL tube decapping/recapping: single-row and full-plate (96-format) decappers for 2D-barcoded compound tubes.
    • Tube and plate labeling for compound tubes and plates: Brady thermal label printers and an LVL plate sealer.

Price List

For a Price List, please call (858) 795-5164  or email us.

Leadership

Raghuveer Ramachandra, PhD
Director, Automation and Drug Discovery Services

Contact

Please call (858) 795-5164 or use the button below to send us an email.

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