Transnational Call

SMALL MOLECULE SCREENING

 

Cell-based screen using an established cell line

Abstract

The High Throughput Biomedicine (HTB) Unit at FIMM, University of Helsinki, offers access to high-throughput screening platform and expertise in laboratory automation (HighRes Biosolutions Acell robotic system), and liquid handling systems (e.g. Echo-based liquid handling), cell-based assay miniaturisation and validation, and chemical library screening. Our instrumentation allows flexible, fully or partially automated assay protocols, using various assay readouts (e.g., luminescence, fluorescence, absorbance, imaging). In this call, we offer our expertise in cell line-based HTS. Proposed assay set-up can be, e.g. viability measurements of a human cancer cell line or a reporter gene-based assay to study regulation of gene expression. 

Description of technology offered under this call

The High Throughput Biomedicine (HTB) Unit at FIMM, University of Helsinki, provides various services related to high-throughput screening technologies and expertise in laboratory automation and liquid handling systems. We have Labcyte Access station for acoustic, low-volume dispensing (Echo 525 and 550) and integrated HighRes Biosolutions Acell robotic system suitable for cell-based and biochemical assay development and chemical library screening in Biosafety Level 1 environment. 

The HTB unit maintains a collection of about 140 000 compounds, including known drugs, bioactives and diversity sets. Our platform allows flexible, fully or partially automated assay protocols, composed e.g. of dispensing cells, compounds and reagents, incubation and using various assay readouts (e.g., luminescence, fluorescence, absorbance, imaging). In this call, we offer our expertise in cell line-based HTS. Proposed assay set-up can be, for example, viability measurements of a human cancer cell line or a reporter gene-based assay to study regulation of gene expression. 

Number of compounds screened

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

Time frame for screen up to validated hits

3 months

Machine/Methods offered under this call

The High Throughput Biomedicine Unit is fully equipped and experienced in running large high throughput screens utilizing automation. Facilities include:

1) Labcyte Access station: This automated setup is used for accurate and reproducible nanoliter scale dispensing of various liquids. It is mostly used for creating assay-ready compound plates, but dispensing of miniaturized assays or arrays on slides or wells is also possible. It integrates a Labcyte Echo 550 -acoustic dispenser (2.5 nL droplet), Labcyte Echo 525 acoustic dispenser (25 nL droplet), Nexus XPeel -plate peeler, Agilent Plateloc -plate sealer, Agilent V-spin –centrifuge, Multidrop nL, Precise Automation robotic arm and Thermo Scientific Cytomat 10 -plate hotel.

2) HighRes Biosolutions Acell system: This automated setup is used for running fully automated screens with cell-based or biochemical assays including siRNA and/or chemicals. It contains a Precise Automation robotic arm, two Thermo Scientific Multidrop Combis, BioTek EL406 plate washer-dispenser, BioTek MultiFlo FX RAD, BMG Pherastar FS multimode reader, Nexus XPeel -plate peeler, Agilent Plateloc -plate sealer, Agilent V-spin –centrifuge, Fritz Gyger Certus Flex – digital bulk filling dispenser, HighRes Lid Valets for delidding and HighRes PicoServe plate hotel. Four devices are placed on carts for modularity: Thermo Scientific Cytomat 10C plate incubator, Thermo Scientific Cytomat 24 plate hotel, Labcyte Echo 550 -acoustic dispenser (2.5 nl droplet), Labcyte Echo 525 acoustic dispenser (25 nl droplet). Two of these can be docked to the system at once allowing flexible change of configuration.

3) Microscopes and plate readers: Stand-alone BMG Pherastar FS -plate reader with stackers, BioTek Cytation 5 -plate reader and microscope.

4) Other equipment: Beckman Coulter Biomek FX pipetting robot with 96- and 384-head, Aushon Biosystems 2470 –Arrayer, Roylan Developments StoragePod chemical storage system, Agilent bar code labeller, Roche Lightcycler 480 II, Intellicyte iQue Screener PLUS, Intellicyte IQue Screener HD.

Services provided under this call

  • Validation of the assay provided by the user to ensure robustness.
  • Miniaturization of the assay into 384-well or 1536-well plates.
  • Pilot screen using 5,000 compounds from the EU-OS compound library.
  • Analysis of pilot screen data (e.g. Dotmatics software).
  • Full screen with the remaining 95,000 compounds of the EU-OS compound library.
  • Data analysis and subsequent selection of primary hits e.g. by using the Dotmatics software.
  • Hit picking of primary hits for hit validation by dose-response experiments (IC50 determination).

Note

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).

Prerequisites for applicants

The prerequisite starting point to qualify for access is the availability of an established bioassay and associated established cell line and key bespoke reagents, developed at lab-scale by the successful applicant.

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.

 

Partner site


UH-FIMM

High Throughput Biomedine Unit, Institute for Molecular Medicine Finland

University of Helsinki 

P.O. Box 20, Tukholmankatu 8 

FI-00014, Helsinki, Finland

https://www.fimm.fi/en/services/technology-centre/high-throughput-biomedicine