High-Throughput Screening Lab

The Nemours High-Throughput Screening (HTS) & Drug Discovery Lab is one of only a few such facilities worldwide dedicated exclusively to technology development and drug discovery for rare childhood diseases underserved by current pharmaceutical development efforts. Projects are selected in disease areas where novel chemical probes will be useful to further biological understanding of the disease and to provide lead compounds for pre-clinical and clinical development. Collaborations are sought with researchers with expertise in disease biology to develop assays for HTS and hit characterization and to screen compound libraries. Seed funding is used to generate preliminary data to support multi-PI grant applications.

Facilities and Resources

The HTS & Drug Discovery group work in 2,200 sq. ft. of purpose-built lab and office space designed specifically for assay development, high-throughput screening (HTS), and hit-to-lead drug discovery.

Facilities. A central HTS bench accommodates liquid handling workstations, reagent dispensers, and plate readers equipped with stackers and barcode readers: JANUS MDT for plate-to-plate transfers using a 384-tip head and a 384-pintool, JANUS Varispan for cherry picking compounds for dose-response testing (Perkin Elmer), MicroFlo reagent dispenser (BioTek Instruments, Winooski, VT), and Envision multimode plate reader. The HTS bench is flanked by lab benches, a chemical fume hood, and a balance bench. A fully equipped tissue culture and sterile screening lab adjoins the main HTS lab, as well as a freezer bay for compound and reagent storage, and cryostorage for cell lines.

Offices and computers. Offices adjacent to the lab foster discussion and collaboration. Researchers are equipped with desktop and laptop computers connected to the Nemours network and University of Delaware’s Medsci network. The Nemours network provides access to hospital and medical resources, including the medical library at Thomas Jefferson University. The Medsci network provides servers for file sharing and remote backup, and access to the University of Delaware library resources. Desktop computers are equipped with Microsoft Excel for data analysis, and GraphPad Prism (GraphPad Software, La Jolla, CA) for curve fitting and IC50 calculation. ActivityBase (IDBS, Guildford, UK) provides an Oracle-based relational database to integrate data management for compound registration, plate mapping, and data analysis and retrieval.

Compound Libraries. Currently, the compound repository comprises the Spectrum collection of 2000 biologically active drugs and natural products (Microsource Discovery, Gaylordsville, CT), the NPL and NDL natural product libraries (3600 compounds, Timtec, Newark, DE), the DiverSet library (100,000 compounds, Chembridge, San Diego, CA), the Natural Products Discovery set of 1,920 fungal, plant, and bacterial extracts (NPDI, Bucks County, PA), and the Orthogonally Compressed Library (96,000 compounds, Lankenau Institute for Medical Research, Wynnewood, PA). Compound libraries are stored in dedicated freezers (Thermo) at -30°C in acrylic dessicators maintained at 20% relative humidity.

Leadership