Introduction to HTS Facility
The TDI employs a number of liquid handling robotics to facilitate both large and small volume liquid handling.
In late September of 2014 the TDI expanded our automation portfolio with the installation of a multimillion pound flagship open-access, state-of-the-art, high content phenotypic screening platform as part of the UK - National Phenotypic Screening Centre.
The MircoStar Hub facilitates our research into new drug-like agents; providing a fully integrated system is part of a new intiative to maximise interactions between national and international initiatives in translational medicine; with the TDI acting as a progenitor for a multiple additional sattelite sites; taking primary research from our screens and providing specialist screening. The MicroStar hub is a six point enclosure, within is housed a GE InCell 6000, a PE Envision, a Labcyte Echo, a Formulatrix Tempest, a Biotek Elx405, a Brooks Xpeel, an Agilent PlateLoc, HighRes Steristore and HighRes Microspin.
The mainstay instruments for cell based screening work are our two fully integrated Perkin Elmer Janus liquid handling workstations; each is housed in a Cat 2 enclosure.
Each workstation is equipped with 96 and 384 compatible MDT; a highly sensitive 8 channel Varispan arm and a gripper tool for moving deckware across deck locations.
Each workstation is also equipped with a Biotek plate washer, Perkin Elmer FlexDrop reagent dispenser and a plate stacker - providing off deck plate storage locations.
The integrated workstations provide maximum flexibility to screen large scale 96; 384 and 1536 fully automated assays.
As part of our liquid handling capabilites we also employ an Echo Acoustic Dispenser allowing scale down to ultra low volume (in nanolitre to microlitre range) we utilise our Echo for small compound and siRNA 'assay-ready' plate creation; minimising wastage and maximising library usage. The Echo is equipped with a fully articulated robotic arm, integrated centrifuge and Combi bulk-fill reagent dispenser. The machine is able to process a range of liquid classes from DMSO to Serum dispensing.
In addition to the liquid handling workstations, the TDI makes use of several instruments for HTS readouts.
The TDI employs a Perkin Elmer Envision plate reader which has luminescence, fluorescence, fluorescence polarization, time-resolved fluorescence, and absorbance detection capabilities.
High content screening is automated image based screening of cells to measure phenotypic changes through external treatment with siRNA or small compounds. These screens are performed in 96 or 384 well plates over the course of several days. Proteins or structures being investigated are detected using fluorescent tags, for example GFP, or by fluorescently labeled antibodies. We utilize a SCARA robot integrated with an InCell 1000 for our high throughput high content screens.
Flow cytometry in HTS uses fluorescent probes which bind to specific cell associated molecules and allows measurements of various phenotypic, biochemical and molecular characteristics of individual cells. The TDI currently utilizes a BD twin laser FACSCalibur with an integrated BD High Throughput Sampler (HTS) for FACS based high throughput screens.
In addition to the HTS equipment, the TDI has several siRNA and small compound libraries available to investigators for high throughput screening. These include ThermoFisher onTarget plus whole genome and custom designed "druggable" siRNA libraries available in both human and mouse species. Our small compound libraries include biologically active, diverse small compound and FDA Approved