Southern Research Drug Discovery maintains a state-of-the-art High-Throughput Screening (HTS) Center featuring advanced robotic equipment and a well-trained staff to ensure the highest quality of screening for collaborative and contracted research projects. The HTS Center maintains a collection of approximately 750,000 compounds and has the capacity to run a wide variety of assay types, including cell-based and biochemical assays. Our professional staff has in-depth experience and a demonstrated proficiency in transferring bench-top assays to the robotics platform and executing cell-based and biochemical screens. In addition to executing standard high-throughput screening assays, our research team is experienced in running yeast-based assays as well as assays that require BSL-2 or BSL-3 containment. The HTS Center also incorporates a team of scientists who perform secondary assays to support and drive lead generation efforts arising from HTS hits.

High-Throughput Screening Center

Our HTS facility consists of a suite of three rooms operating at the BSL-2 level. There are two automation platforms housed in this area. The primary automation platforms are located in a central 1150 square-foot automation laboratory. The second automation system is a Vertical Array Loader (VAL ) based system located inside of a containment enclosure with HEPA-in, HEPA-out air handling. Adjacent to the automation lab is a 302 square-foot biochemistry lab for support functions and preparation of reagents for biochemical assays and media for bacterial assays. An equipment monitoring system is in place in the main HTS lab suite and in the Compound Prep Lab to monitor freezers, refrigerators, incubators and room temperatures. It notifies HTS staff of equipment alarms via text message to cell phones. The BSL-3 facility is a modern, state-of-the-art facility capable of select agent handling for BSL-3 level containment assays. The BSL-3 laboratory space is located in proximity to the BSL-2 laboratories and is readily accessible from the HTS Center. This facility is currently registered with CDC as well as USDA for agents that require BSL-3 containment. The facility was completed in 1995, renovated in 2006, and modified with installation of a new Building Automation System (BAS) in 2016.

Compound Management

Southern Research maintains a collection of approximately 750,000 compounds dissolved in DMSO, stored in frozen aliquots dispensed in 384-well plates and ready for assay plate production in HTS. The vast majority of these compounds are non-proprietary and commercially obtained but also includes the Southern Research proprietary collection of 25,000 compounds. All compound plates are labeled with unique barcodes and plate maps are uploaded into the Registration component of ActivityBase . Unique IDs and batch-specific numbers are assigned for each sample received. The chemical structure and associated information (Supplier ID numbers, purity, salt form, etc.) as provided in the vendor-supplied files are uploaded and can be viewed. In addition to general information on each sample, the plate IDs and well locations for each sample is also registered. A record of each compound and plate’s genealogy is created as aliquots are transferred from compound plates into assay plates for testing. Compound information and associated data stored in the database can be restricted to a specific contract thus enabling the confidentiality and exclusivity of information within the Institute. Assay-ready plates in 1536 format are produced on demand for screening by acoustic dispensing of nanoliter volumes from source plates.

 

Assay Capabilities

Informatics Capabilities and Infrastructure

The primary tools for the HTS Informatics group’s data management practices are IDBS’ ActivityBase, DotMatics Registration Database and E-Notebook, Pipeline Pilot, and UNIFlow Laboratory Information Management System (LIMS) by UNIConnect.

ActivityBase (IDBS)

  • Management of HTS Assay Data and Compound Details
    • Stores chemical structures and biological data generated by HTS and Lead Generation Labs

DotMatics (Dotmatics)

  • Registration Database for Internal Compounds
    • Stores chemical structures of proprietary and individually purchased compound
  • Interfaces with ActivityBase for Biological Assay Data
    • Biological data and large compound libraries in ActivityBase are also visible through this tool.

E-Notebook (Dotmatics)

  • Lab Notebook system for compound synthesis and other daily lab work
    • Daily lab notebook, stores details of lab work, results and associated documents

PipelinePilot (BioVia)

  • Workflow tool combining database queries, file selection, chemistry, statistical and formatting capabilities
    • Component-based workflow management tools
    • Data formatting, querying and reporting

UniFlowLIMS (UniConnect)

  • Independent system, hosted off-site, used for real time process tracking of HTS Assays and related details
    • Process Tracking in real time, correlates components/factors of each experiment (example: reagents, cells, media, user, assay protocol, equipment, etc.)

Robotics

Two robotic systems are used to automate a variety of assay processes, the Thermo/CRS Benchtrak and the Biocontainment Vertical Array Loader (VAL). Redundancy has been built into the systems for the majority of assay requirements. Each system has individual specialty equipment to increase flexibility and range of assays that can be automated on the platforms.

Thermo/CRS Benchtrak

  • An integrated robotic platform capable of using 96, 384 and 1536 plate formats to execute automated cell-based and biochemical assays
  • Enhanced capabilities for liquid handling (due to the dual bridge Biomek FX liquid handler), plate sealing and qPCR

VAL

  • An integrated robotic platform designed for BSL-2 containment of assays that use infectious agents
  • Has additional capabilities for cell-based and infectious disease assays, such as the robotically accessed CO2 incubator, a plate washer designed for washing cell monolayers and the Velos low resolution imager

Liquid Handling Equipment

  • Biomek FX Single Bridge Liquid Handler, Biomek FX Dual Bridge Liquid Handler, Biomek NX Span-8, Labcyte Echo550 and 555, Beckman BioRAPTR, Thermo Wellmate, Thermo Combi Non-Contact dispensers

Plate Readers

  • Multi-modal readers: BMG Pherastar and Clariostar, PE Envision, Biotex Synergy 4
  • An integrated robotic platform designed for BSL-2 containment of assays that use infectious agents
  • Has additional capabilities for cell-based and infectious disease assays, such as the robotically accessed CO2 incubator, a plate washer designed for washing cell monolayers and the Velos low resolution imager

Liquid Handling Equipment

  • Biomek FX Single Bridge Liquid Handler, Biomek FX Dual Bridge Liquid Handler, Biomek NX Span-8, Labcyte Echo550 and 555, Beckman BioRAPTR, Thermo Wellmate, Thermo Combi Non-Contact dispensers

Plate Readers

  • Multi-modal readers: BMG Pherastar and Clariostar, PE Envision, Biotex Synergy 4
  • Laser Scanning Cytometry : TTP Labtech Mirroball, Molecular Devices Velos,
  • Other: Roche Lightcycler 1536, BMG Nephelostar Galaxy Reader, Molecular Devices Spectramax Plus 384 Spectrophotometer

Plate Washers and Incubators

  • BioTek ELx405 and ELx405cw Plate Washers, Forma CO2 Incubator, Thermo/Forma CO2 incubator