Facilities & Equipment

DDSR-HTS offers high-throughput platforms that integrate cell culture, robotics, and detection systems for scalable plate-based screening of libraries of small molecules and select biologic agents. These resources can be used for target-based or phenotypic screening strategies to generate hits and leads for drug discovery and development. Focused rationally designed compound collections can be used to identify molecular probes appropriate for mechanism of action (MOA) studies. These services are flexible to accommodate the diverse needs of users both across OSU and off-campus. We also offer project management, assay/technology development, and assistance with technical writing of HTS-related sections of grants and manuscripts.

Laboratory

The HTS laboratory is housed in dedicated space in 345 Parks Hall in the College of Pharmacy on the OSU main campus. The HTS lab comprises 1800 sq. ft. of wet lab space, an additional 200 sq. ft. of office space for up to four staff members, and a 120 sq. ft. office for the Director of HTS (Dr. Meng Wu) across the hall (340 Parks Hall). The office of Dr. Blake Peterson, Co-Director of the DDSR, is nearby in 606 Riffe Hall. This facility includes a main screening laboratory with robotics, plate readers, and other instruments, a mammalian cell culture room to facilitate cell-based assays, a biochemistry room for microbial production of plasmid DNA and proteins, and a compound management room with freezers for storage of plated libraries.

Libraries

We are continually building and curating multiple small molecule libraries. Our parental chemical libraries are stored at -80 °C.

Our current compound collections (~160K in-house diversity compounds) include:

  1. The Prestwick chemical library of 1520 FDA approved off-patent drugs for pilot screening and repurposing studies

  2. The Harvard / MIT / Broad Institute Repurposing library of 6,800 FDA-approved, clinical, and advanced preclinical candidates

  3. The full NCI NExT collection of 83,536 small molecules for cancer research and three specific subsets (NCI Diversity set VI, NCI Mechanistic set VI, and NCI Natural products set V) comprising 2785 compounds. This general diversity library is designed for the identification of lead compounds for drug discovery projects. The full NExT library is composed of three non-separable subsets from the molecular library small molecule repository (MLSMR) and includes 15 privileged scaffolds from two diversity subsets.

  4. We offer 10,000 drug-like macrocycles from ChemBridge for screening against protein-protein interactions.

  5. We offer informer (scaffold) diversity libraries from MedChemExpress (5000 compounds) and TargetMol (5,000 compounds).

  6. We offer the full 50,000-compound MedChemExpress diversity library for screening.

  7. We have 500,000 prefractionated natural product extracts from the NCI. Hits from this highly diverse set of compounds will require further collaboration with the NCI to elucidate their structures.

  8. We have an agreement in place to access 250,000 open innovation compounds from AstraZeneca Pharmaceuticals for screening at OSU. This library is offered for blind screening where hit series will be provided by AstraZeneca.

Other small molecule focused libraries can be obtained from commercial sources and managed for specific screening projects. Additionally, we  offer numerous cryobanked cell lines for screening applications.

HTS platforms

We can perform HTS in 96-, 384- and 1536-well formats, using multi-mode microplate readers (Tecan Spark Cyto 600 with a plate stacker and a Molecular Devices SpectraMax i3x with a StakMax Microplate Handling System) that measure absorbance, fluorescence and luminescence, including advanced FRET, BRET, and alpha-screen techniques. Our Roche LightCycler 480 II instrument can be used to screen for effects of compounds on gene expression and can be used for label-free differential scanning fluorometry on 96-well or 384-well plates.

HCS via confocal microscopy

Our Perkin-Elmer Opera Phenix Plus Confocal Imaging System with live cell automation is used for HCS. This system is equipped with high power 405 nm, 488 nm, 561 nm, and 640 nm lasers for detection and quantification of phenotypic changes such as cell differentiation, cell migration, neurite outgrowth, and target trafficking on 96-well and 384-well plates. It can also analyze fluorescence intensity and subcellular localization of expressed target proteins and analyze transcription factors or signaling pathways. Its on-board liquid handling system enables rapid fluorescent imaging of Ca2+, K+, Na+ and Cl– in kinetic time course experiments.

HCS via flow cytometry

We offer a Sartorius iQue3 VBR (405 nm, 488 nm, and 640 nm lasers) high throughput flow cytometer for high throughput / high content screening of suspension cells on 96-well and 384-well plates.

Surface Plasmon Resonance (SPR)

We offer a Bruker Sierra SPR-24 Pro instrument for hit validation and analysis of small molecule-protein or protein-protein interactions by SPR. This relatively high throughput instrument uses an array of eight channels/three spots to enable analysis of up to 8800 interactions in 24 hours.

High Throughput Electrophysiology

We are working with Dr. Isabelle Deschenes (Department of Physiology and Cell Biology, OSU) to provide high throughput electrophysiology for screening against ion channels and related targets using the Nanion SyncroPatch 384 system.

Liquid handlers

Our HTS and HCS systems are integrated with robotics and liquid handlers (Hamilton STARlet and Beckman Coulter Echo 650) for plate handling and assay execution and are supported by an automatic dispenser/washer (MultiFlo FX, from BioTek/Agilent). These instruments are suitable for small- or large-scale compound library screens with multiple levels of automation. We also offer a Mantis liquid dispenser for assay development using small volumes of precious reagents.

Auxiliary systems

We additionally offer a PlateLoc Thermal Microplate Sealer (Agilent) and two automated CO2 cell plate incubators. Full cell/tissue culture facilities are available including seven class IIA2 biosafety cabinets, two standing CO2 incubators, two microbial incubators in a separate biochemistry room, two chromatography refrigerators, a liquid nitrogen cryogenic tank, and a -150 °C cryogenic freezer for cell banking.

Data analysis and management

Electronic laboratory notebooks and high throughput data analysis/visualization software are also available for drug discovery. We employ CDDVault, Microsoft OneNote, ChemBioOffice, ChemInventory, and TIBCO Spotfire for compound management, curation, data visualization, and knowledge mining for drug discovery and development. We utilize cloud-based image storage and backup systems for high throughput and high content data and images in collaboration with the High-Performance Computing (HPC) group at the Ohio State University.