Chemical Biology Core Facility

Small molecules play essential roles in many areas of basic research and are often used to address important biological questions.


High Throughput Screening (HTS) allows a researcher to quickly conduct thousands of tests against a biological target through the use of automation (robotics, liquid handling devices, sensitive detectors), data processing and control software.

Through this process one can rapidly identify active compounds (hits) which undergo further medical chemistry optimization to make them more suitable for development as drugs. A large number of projects at the core facility employ HTS as a part of project workflow.

Our expertise

  • Assay development
    • Selection of an appropriate assay readout
    • Assessing the compatibility of the target assay with automation and  high-throughput screening
    • Developing and optimising assays for high-throughput screening
    • Assisting in the design of secondary selectivity assays
  • Execution of HTS campaigns for biochemical, cell-based and protein-protein assays
  • Follow up of hits with reporting of EC50/IC50 and solubility data
  • Assay consultancy services (selection of assay technology, design, optimisation)
  • Cell culture for cell-based assay targets
  • Affinity studies for large protein and small molecules through Biacore surface plasmon resonance
Typical project workflow

Facilities, services and equipment

Automated platform

The facility has a fully integrated automated platform for running biochemical and cell-based screening campaigns. At the core of the platform is a Janus integrator fitted with a gripper tool which can access the Cytomat, de-lid cell plates, transfer to the Multidrop for reagent addition and return the cell plates to the cell incubator or the EnVision microplate reader. Furthermore, the devices on the platform can be used independently or as standalone units:

Janus (PerkinElmer)

(equipped with a 384 channel head) used for the transfer of fluids in plate replication, reformatting of e.g. 96 to 384 well, IC50/EC50 and assay plate preparation.

MultiDrop Combi (ThermoFisher)

Fast bulk dispenser for reagents and cells. Can dispense reagents in the range of 0.5 µl to 2500 µl into 96, 384 and 1536 well plates.

Cytomat 10C Incubator (ThermoFisher)

Features rotatable plate carousels. Capacity for 210 multi-well cell assay plates. Automation access from the rear or front in stand-alone mode.

EnVisionTM Xcite (PerkinElmer)

Single detector multilabel reader with 2 channel injection module.

Biacore T200

Our Biacore T200 supports the use of 96- and 384-well microplates. The use of all four flow cells allows four interactions to be simultaneously monitored.

Surface Plasmon Resonance (SPR) for ligand-binding assays

  • Kinetics/affinity characterisation
  • Kinetics/affinity screening
  • Single-cycle kinetics (fast runs without regeneration)
  • LMW interaction analysis
  • Fragment screening
  • Concentration analysis
  • Calibration-free concentration analysis
  • Thermodynamics
Loading of 96 well microplate on the Biacore.

Cell culture suite

With access to a dedicated safety level S1 cell culture suite, the facility has experience in handling transient and stable mammalian cells as well as patient-derived cells to supply cell-based HTS campaigns run at the CBCF.

We require two vials of your cell lines which are Mycoplasma free, for which we determine the growth rates, bulk up and bank several vials to support your project.

Cell culture hood

Liquid handling

In addition to the devices on the automation platform, the facility has two stand-alone liquid handling devices:

PerkinElmer FlexDropTM IV EXi

(Fast bulk dispenser for reagents and cells)
Can dispense up to 4 reagents in the range of 200nl to 2ml into 96, 384 and 1536 well plates.
Can handle up to 50 microplates in the various densities.

PerkinElmer MultiProbe® II Plus Ex 4-Channel Pipettor

Fitted with 4 varispan tips and used primarily for dissolving compounds, preparation of master plates, cherry picking and assay development.

Multilabel readers

The facility has 4 stand-alone readers capable covering a large spectrum of detection technologies:

EnVisionTM HTS (PerkinElmer)

  • Fast dual detector reader fitted with plate stackers (50 plate maximum capacity)
  • Absorbance
  • Fluorescence intensity
  • AlphaScreenTM (Amplified Luminescent Proximity Homogeneous Assay)
  • Enhanced luminescence

Safire 2 (Tecan)

Monochromator plate reader allowing the use of any combination of excitation and emission wavelengths and supporting following technologies:

  • Absorbance
  • Fluorescence intensity

MicroBeta2 LumiJet (PerkinElmer)

Liquid scintillation and luminescence counter.

  • Beta or gamma counter
  • Scintillation proximity assays (SPA)
  • Flash or glow luminescence
  • Compatible with  24, 96 or 384 microplates

NEPHELOstar (BMG Labtech)

Laser-based microplate nephelometer reader for detection of particles in solution. Applications include:

  • Compound solubility testing in 96- and 384-well plates
  • Monitoring microbial growth and protein binding


Chemical Biology Core Facility
EMBL Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany

Phone: +49 6221 387-8303
Fax: +49 6221 387-8306
Email: General enquiries

Screening library

Our diversity oriented screening library is composed of 110,000 compounds. This library was selected from more than 5 million structures that were collected “virtually” and put through a rigorous filtering process. In addition, they were analysed on the basis of their ‘scaffold’ content to ensure the optimum coverage of chemical space – each compound structure was virtually fragmented into its core (the scaffold) and side chains.

The scaffold-based approach provides high information content for screening:

  • The structural space around each scaffold is covered appropriately;
  • Any hit compounds from a high-throughput screen can be rapidly followed up by selecting similar compounds to enable initial structure-activity relationships to be discerned;
  • This will help in the prioritisation of the hit compounds for further medicinal chemistry optimisation.

Selected compounds were finally checked for drug-likeness, structural and shape diversity, novelty, and compliance with medicinal chemistry requirements. Individual compound selection was done by picking representative compounds around selected scaffolds.

We offer access to our compound collection for screening at the facility or externally in your laboratory.

The compounds are prepared at 10mM in 100% DMSO and stored at -20oC. Batches of assay ready plates are typically produced in advance of the screening campaigns. This reduces the cost of processing the assay plates and means initiation of HTS is not dependent on availability of resources.

An array of frozen compound stocks in a storage rack

Diversity oriented screening library

  • 110,000 compounds.

Covalent Binder libraries

  • 15.000 covalent binders from Enamine
  • 800 covalent binders (fragment size) from ChemDiv

Annotated drug libraries

  • NIH
  • Microsource
  • Selleck Bioactive compounds II
  • Sigma (Pfizer library)
  • Fragment library (100mM in 100% DMSO)