The three main components of the chemical screening facility are: chemical libraries, liquid handling equipment, and detection equipment.

1. Libraries

Historical libraries – collections of pre-existing organic compounds from different chemical labs selected based on their “drug-likeness”, and collections of pharmacological, bioactive or natural compounds. These libraries can be used for drug discovery as well as for “proof of principle” and assay validation experiments.

Combinatorial libraries – collections of drug-like molecules synthesized by combinatorial chemistry. These libraries are used exclusively for drug discovery.

The Small Molecule Screening Core owns three historical libraries created based on two different principles:

• DIVERSet™ by ChemBridge Corporation (San Diego, CA) – a diverse library of 55,230 compounds. This library consists of organic molecules with molecular weight in a range of 250 – 550, dissolved in DMSO at concentration 5mg/ml or 10-20 mM.
• LOPAC1280 by Sigma (1280 compounds) and Spectrum by MDS, Inc (2000 compounds). are the libraries of pharmacological compounds dissolved in DMSO, in 10 mM concentration (MW is < 500). These libraries include FDA and internationally approved drugs, bioactive and natural compounds with described biological activity.

Library Format

All libraries are available in both the 96- and 384-well format. Screening in the 384-well format is faster and less expensive, but some of the assays are incompatible with this high density format. Figures below depict the location of compounds and empty wells used for controls on 96- and 384-well plates.

2. Liquid handling equipment

Equipment used for automated the delivery of liquid reagents and the transfer of compounds from the library to the assay plates in multi-well format.

Automated Liquid Handling Workstation JANUS by PerkinElmer

JANUS is capable of multichannel pipetting and reagent transfer in 96- and 384-well formats. Two heads (96- and 8- channel) provide great flexibility in choosing different pipetting modes: simple reagent delivery to multiwell plates, automatic preparation of dilutions and different reaction templates (View a video clip of JANUS in action, reformatting the library plates from 96- to 384-well format). Using two pin-tools, library compounds can be delivered to 96- and 384-well plates in nl volumes (see figure below).

96- and 384-pin tools designed for accurate transfer of compounds from the library to assay plate
96 – 90 - 230 nl
384 – 20 – 50 nl

Compact automated reagent dispensers

Compact automated reagent dispensers, such as MicroFill and MicroFlo by BioTek, are designed for accurate and fast distribution of solutions to 96- and 384-well plates. The complete fluid pass of MicroFlo is autoclavable, so it can be used for automated plating of cells for cell-based assays.

3. Detection equipment

Multiwell readers determine the spectrum of readout systems and assays that can be utilized at the screening facility.

Envision Excite multi label reader by PerkinElmer

This reader is the main work horse in our facility. It can be used for a wide range of fluorescence, luminescence and photometry based detection technologies (see the list below).

Fluorescence Intensity
Fluorescence Polarization
TRF – time-resolved fluorescence
FRET – fluorescence resonance energy transfer
Luminescence and enhanced luminescence
Absorbance

EnVision requires a specific filter set for each detection technology. Currently it is equipped with a set of filters for several routinely used assays. If a new assay is required for screening, and the PI demonstrates the commitment and readiness to complete the screening, this reader can be easily upgraded with a new filter set. EnVision is capable of reading in both 96- and 384-well formats and is equipped with a plate stacker.

S5 UV Analyzer by CTL Technology Ltd.

 

This reader is capable of acquiring and analyzing a UV-Fluorescent multicolor image at the microscopic/submicroscopic level in high throughput format.

It can utilize readout systems based on single-cell analysis in 96-well format.

4. TC complex

Dedicated tissue culture equipment simplifies the procedure of cell preparation for cell based readout systems and the plating of the cells in multi well format. Our tissue culture room is equipped with a laminar flow hood, CO2 incubators, water baths, and automatic multichannel pipettes.

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