About Us

The University of Connecticut High-Throughput Screening Facility (HTS Facility) was established in 2011 with funding awarded through the University’s Major Equipment Competition. Over the last 20 years, high-throughput screening has become an integral tool utilized by both pharmaceutical industry and academic institutions to identify new lead compounds for drug development. The HTS Facility is comprised of integrated instrumentation dedicated to aiding researchers in the small molecule screening and drug discovery process. The Facility is housed in the Pharmacy and Biology Building, Room 616 and is available to all members of the University of Connecticut research community as well as external academic and industrial users for a variety of screening purposes. The Facility is managed by Drs. Kyle Hadden and Dennis Wright, Department of Pharmaceutical Sciences, who are available to provide user support and services.

Instrumentation

The Facility houses an array of instruments, including:

• Integrated multi-mode microplate reader and microplate stacker
• Benchtop liquid handler
• Water-jacketed CO₂ incubator
• Commercial small molecule library (150K compounds)
• Small molecules and natural product extracts collected from the University community

Services

The services offered to users of the Facility can be classified into two categories: (1) primary screening and (2) ancillary services.

Primary Screening:

• Daughter plates for screening (80 compounds/plate, 5 uL of 5 mM stock solution in DMSO)
• Use of the liquid handler for assay automation
• Use of the reader and stacker for plate reading and analysis
• Facility Co-Head support during the assay optimization and screening process

Ancillary Services are considered on a case-by-case basis and potentially include:

• DNA/RNA quantification on small volumes (2 uL)
• Use of the multi-mode reader for assay readout (absorbance, luminescence, fluorescence, fluorescence polarization, and FRET)
• Use of the reader and liquid handler for assay development and optimization
• Duplication of natural product libraries

Research Potential

The modulation of cellular processes by small molecules has powerful ramifications, providing opportunities to dissect biological pathways with chemical probes and to develop new therapeutic agents. The discovery of a novel small molecule with a desired profile of activity is a challenging task. Even when a high-resolution structure of the intended target macromolecule is available, it is extremely difficult to formulate a novel ligand de novo. Given this difficulty, it is not surprising that high-throughput screening has emerged as the method of choice to locate chemical leads for important biological pathways.
The availability of a High-Throughput Screening Facility will enable researchers to (1) develop robust, reproducible assays for screening; and (2) screen large libraries of diverse small molecules to identify a suitable lead compound for further development.

Training and Education

Training and expertise is available in several areas related to the screening process, including, but not limited to:

• Optimizing and automating assays for screening
• Selecting libraries for screening
• Performing medium- and high-throughput screens
• Data mining and analysis of "hits" generated from the screening process

Use of the Facility

Because of the nature of high-throughput screening and the necessary planning involved, there will be an extended preliminary stage (typically 4-6 weeks) before a screen can be undertaken. This is particularly true with respect to automating an assay with the liquid handler. Users should plan accordingly and contact a Facility Co-Head during their planning stage to provide sufficient preparation time. After a screen has been performed, the Facility Co-Heads will be available for data analysis to identify hits and to provide assistance for hit validation and subsequent optimization procedures.

Cost for Services:

Researchers who use the HTS Facility for primary screening purposes will be charged a set fee per plate screened. Separate, hourly fees for training and usage of the instrumentation will be assessed. The Facility will provide pipet tips for use with the liquid handler; however, investigators will be individually responsible for providing all other reagents and consumables required for their screen. University members who use the equipment for ancillary purposes not specifically related to primary screening will be charged the same fee for training and usage and allowed access to the Facility.

All rates are subject to periodic review and change.