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High Throughput Screening (HTS) Shared Service: Services

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There are three main components to the successful operation of the HTS SS: instrumentation, compound libraries, and technical staff to consult on optimizing assays. The HTS SS operates two types of instruments, automated liquid handling workstations to enable high throughput processing, and microplate readers equipped with a variety of detection mechanisms. The HTS SS provides the investigators access to the equipment needed to perform HTS, compound libraries for screening, consulting and training, and can perform all aspects of a screening project if necessary.

Equipment Use

The HTS SS allows investigators to operate the equipment themselves, providing training and oversight only, for set hourly rates. The equipment includes the automated laboratory workstations and the microplate readers:

Beckman Coulter Biomek FX Automated Laboratory Workstation is a flexible automated liquid handling system with a large work surface, 23 positions on the deck, capable accommodating most any high throughput job size. The system is currently configured with a 96-well head and capable of rapid liquid transfers in 96, 384, and 1536-well plates and large reservoirs. It has a single arm capable of moving and stacking tip boxes, plates, and lids on deck positions.
Beckman Coulter Biomek NXp Automated Laboratory Workstation is a smaller instrument then the FX equipped with a Span-8 pipetting head allowing it the flexibility to aliquot and dispense in 6, 12, 48, 96, and 384 well plates, test tubes, microfuge tubes, and various other containers, including the ability to "cherry pick" select wells or containers. It is very useful in reformatting, for examples transferring reagents from microfuge tubes to a microplate format, and unlike the larger FX it can easily perform serial dilutions across a single plate a very useful feature for determining binding affinities or IC50s.
BMG FLUOstar Microplate Reader is a lens based microplate reader capable of reading absorbance, and fluorescence intensity in a range of microplates including 96- and 384-well plates.
BMG POLARstar Microplate Reader is a lens based microplate reader capable of reading absorbance, fluorescence intensity and polarization, FRET, TR-FRET, and luminescence in a range of microplates including 96- and 384-well plates.

Compound Libraries

Portions of compound libraries can be purchased for use by the investigator as needed for their screens either performed in the HTS SS or in their own lab. This provides the investigator access to the full diversity of the library without having to incur the cost of buying the entire library. There is a cost to the aliquot and reformatting the library that is done by the HTS SS staff to assure the library stocks are maintained properly. The current libraries available our as follows:

ChemDiv 40,000 - Currently, the HTS SS has a library of 40,000 diverse chemical compounds purchased from Chemical Diversity Labs (ChemDiv). The 40,000 compounds were selected from ChemDiv's ~600,000 compound collection, which consists of ChemDiv's internal synthesis efforts (CombiLab: ~420,000) as well as procurement from laboratories around the world (International Diversity Collection: ~180,000), to represent maximal chemical and structural diversity. The compounds are stored at 10 mM in DMSO in 384-well plate format.
Maybridge HitFinder 14,400 - The complete Maybridge Hitfinder (Maybridge, Trevillet, Tintagel, Cornwall, U.K.), collection consists of 14,400 drug like compounds that have been selected by the company to represent the diversity of the complete Maybridge Screening Collection by using a clustering algorithm based on standard Daylight Fingerprints and Tanimoto similarity and they generally follow the Lipinski's rule of 5. The HTS SS purchased the entire library in 10 aliquots of 0.1 mmole of each compound in 384-well plates as a lyophilized film. This allows each user to purchase a portion of the library that has been stored as a dry film, the most stable way to store compounds.
Microsource Spectrum Collection 2,000 - Collection of 2000 biologically active and structurally diverse compounds gathered from marketed and experimental drugs and natural products. The compounds are 10 mM in DMSO in 96-well format.

Technical Expertise and Customized Services

The HTS SS can be involved in all or just partial aspects of the screen development, transferring it to an automated platform, to performing all aspects of the day to day screening such as maintain cell lines for cellular assays, running sample, and data mining and organization. These services are quoted out on an individual basis due to each assay being very individual using different assay plates, media, reagents, etc., and requiring varying time and equipment, therefore, the final costs cannot be fully determined until this final version of the assay is set. The general scope of the assays can also vary from and investigator using the robotics to perform a simple task that may take only a day, to long term projects that span over several years.

NMR Based Screening

In collaboration with the UMB NMR Center, it is possible to use the Bruker 800 MHz NMR with the B-ACS 60 Automatic Sample Changer for automated NMR spectra collection on proteins and other molecules. This is a very unique instrument in that typically autoloaders are not installed on high field NMRs that will allow spectra of of proteins to be determined rapidly and be used to screen for protein-compound interaction. Change in the NMR spectra of molecules occur when they bind ligands allowing the interaction of molecules to be determined over a wide range of affinities making it an ideal instrument for screening fragment libraries that may only bind with micro to millimolar affinities.

This page was last updated on: March 3, 2010.