Real-time kinetic cell-based assays using the FLIPR Tetra HTS system

The FLIPR Tetra System offers the possibility to validate and run a broad diversity of fluorescence real-time kinetic cell-based assays measuring the ligand activity on ion channels, receptors, GPCRs, transporters, membrane potential, enzymes and gene reporters. In addition, MEDINA’s compound management platform involves liquid handling robotic systems and data management software, and the required expertise to guarantee the correct analysis, traceability, standardization and QC of the screening data.

MEDINA has longstanding expertise in drug discovery and compound safety assessment and can help to customize cell-based enzymatic assays from the initial experimental approach to screening data analysis. Cell-based enzymatic assays support research applications in the study of a broad diversity of cell functions including specific signaling pathways, as well as cell toxicity.

MEDINA offers a fluorescence reporting technology based on the FLIPR Tetra System which is a robust screening platform to address real-time kinetic cell-based assays. The system features a multiwavelength kinetic reading based on fluorescence detection, using 96- and 384-well plates with simultaneous liquid transfer, agile internal plate handling, and elevated instrument intelligence that reduce costs and increase assay efficiency. The platform is a valuable screening system for assays with different types of complexity and involving among others, ligand binding kinetics to ion channels, receptors, GPCRs, transporters, membrane potential, enzymes and gene reporter expression.

Assays can be miniaturized and standardized, and the required low screening volumes is ensured by the liquid handling robotic equipment available at MEDINA (384-well pipetors (Evo, Tecan; Biomek FX, Beckman Coulter) and a nanodispenser Acoustic Droplet Ejection System (ECHO 550, Labcyte).

In addition, MEDINA has an extended expertise in screening data management (from compound plate information and traceability, to data acquisition and analysis), using an proprietary compound/plate database software coupled to Screener software (Genedata AG). This setting guarantees the correct analysis, traceability, standardization and QC of the screening data, including IC50 curves and Z factors calculations.

Number of compounds screened

100,000 (full commercial set) of the EU-OPENSCREEN ERIC compound library

Time frame for screen up to validated hits

8 months (the time may vary depending on the development stage of the screen and the complexity in the execution)

• FLIPR Tetra High-Throughput Cellular Screening System (Molecular Devices).
• An integrated compound management system involving the Acoustic Droplet Ejection System ECHO (ECHO 550, Labcyte), an Evo (Tecan) and a Biomek FX (Beckman Coulter)
• Genedata Screener software (Genedata AG).
• In-house data management databases and application.
• Validation and development of fluorescencereal-time kinetic cell-based assays.

• Validation of the assay provided by the user to ensure robustness (Genedata Screener software)
• Miniaturization of the assay into 96 and 384-well formats (Acoustic Droplet Ejection System ECHO (ECHO 550)
• Pilot screen using 5,000 compounds from the EU-OS compound library (FLIPR Tetra System)
• Analysis of pilot screen data (Genedata Screener software)
• Full screen with the remaining 95,000 compounds of the EU-OS compound library (ECHO 550& Biomek FX / FLIPR Tetra System)
• Data analysis and subsequent selection of primary hits (In-house data management app and Genedata Screener software)
• Hit picking of primary hits for hit validation (ECHO 550 & Biomek FX)
• Method of hit validation: Dose response and IC₅₀

Please note that this project includes the possibility of re-screening during potential chemical optimization under the medicinal chemistry call starting in 2021 (tentative date).

The prerequisite for accessing the technology offered is the availability of an established fluorescent bioassay and associated key bespoke reagents. The assay can be used in cell cultures and the availability of associated reagents, fluorochromes, antibodies, dyes, etc., needed to set-up and develop the assay. The target of the assay can be related to any therapeutic area.

As specifics of the assay transfer procedure may vary between partner sites, the applicant and the individual sites will agree on the appropriate steps and logistics together.

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Topics / Keywords:

drug discovery, small molecules, high-throughput screening, cell-based assays

Open Time:

Start date:
June-01-2019 (20:00 CET)

Closing date:
September-30-2019 (20:00 CET)

Contacts:

Scientific contact: olga.genilloud@medinaandalucia.es

Technical contact: francisca.vicente@medinaandalucia.es

Machine/Methods contact: carmen.ramos@medinaandalucia.es