High-throughput Screening

HT-Screening

NEXUS specializes in assay development, high-throughput screening and data analysis and gives you access to high-end lab automation equipment, unique state-of-the-art small-molecule libraries, as well as gene manipulation tools such as shRNA libraries.

NEXUS operates a fully integrated high-throughput screening system combining automated cell culturing, liquid handling and analysis tools within a BioSafety Level 2 environment.

Screening plate moved by robot in the system for cell-based and biochemical assay

NEXUS has extensive experience in a variety of different cell-​based and biochemical assays. Highlight projects illustrating our broad assay portfolio are:

  • Viability advanced cell systems:
    luminescent cell viability assay using patient derived cancer organoids
  • Lead identification:
    high-content screen with immunocytochemical staining
  • Repurposing of known drugs:
    high-content screen in primary cancer cells
  • Chemical probe identification:
    cell viability screen with different cancer cell lines
  • Protein Inhibition / Activation:
    biochemical assay using luminescence readout
  • Target gene identification:
    3D Spheroid high-content screen using an shRNA library

Please contact us with your own idea for a screening campaign. We look forward to working out and integrating your idea on our automation system.  

Screening Workflow

Assay Development and Scaling
The assay will be set-up by the investigator using the final assay format ideally in close collaboration with NEXUS to avoid later pitfalls in the automation process. Positive and negative controls are defined.

Assay Transfer
A meeting takes place between the client and NEXUS to discuss the assay protocol, the manual set-up, and the data quality (Z’-factor) of the assay that has been manually performed by the investigator. If necessary, processes are aligned to the automation capabilities. Further, timelines for the individual project milestones are defined.

Assay Automation
NEXUS sets up the automation methods for the assay based on the protocols provided by the investigator.

Pilot Experiments
The pilot experiments allow to assess and compare the quality of the manual to the quality of the fully automated assay. Once the quality checks are passed, SOPs for all processes are worked out and approved by the client during a dry run.

Pre-screen

A fully automated pre-screen is performed according to the SOPs using cell lines/proteins that were provided by the investigator.

Screen
Once the pre-screen is finished successfully and the quality control of the pre-screen is passed, the screen is performed according to SOPs defined previously.

Quality Control of Screen
The raw data are automatically processed and the Z’-factor is calculated per plate. The raw data are linked to the treatment.

Data Analysis, Hit Selection and Report
(optional)
A detailed data analysis report is worked out according to a separate statement of work. Main components of the report are the identification and correction of geometric patterns, the calculation of Z’-factor, the normalization of data, the selection of the hits and the generation of publication ready figures.

End of Project Meeting
The screening results and if applicable the screening report is discussed and the client is asked for feedback about the entire collaboration.
 

In addition to providing the screening infrastructure, NEXUS offers unique customized chemical libraries ranging from chemical diverse collections to clinical test compounds for cell-based or biochemical screening. As an alternative for chemical probe screening, NEXUS also offers screening with shRNA libraries and collaborates within the virtual platform Screening@ETH with ScopeM for siRNA and GEML for CRISPR-Cas9 screening.

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