Why partner with us for HTS?
01
Tailored assay strategy
Assay type, format and technology are selected and customized around each target to maximize relevance and screening performance.
02
Validated assays
Robust, reproducible assays designed to support reliable decision making.
03
High-quality compound collection
Over 400,000 screening-ready compounds, with focused subsets for target-specific strategies.
04
Flexible automation
Modular HighRes BioSolutions robotics enabling efficient and adaptable screening campaigns.
05
Secure data management
End to end tracking through LIMS, with analysis and visualization supported by Dotmatics and Vortex.
06
Integrated hit validation
Counter-screens, orthogonal assays, biophysical methods and cell-based approaches to prioritize high confidence hits.
Screening workflow: from pilot screen to confirmed hits
IRBM supports flexible screening strategies using its proprietary compound collection, focused subsets, virtual screening or external collections, selected according to each project’s goals and target requirements.
Biochemical and cell based assay can be used as primary assay for hit identification.
Pilot screen
Compounds are tested at a single concentration to assess assay performance, robustness and campaign feasibility
Primary HTS campaign
Compounds are screened at single concentration
Hit confirmation
Selected compounds are retested in the primary assay, typically at two concentrations and in duplicate, while potential technical artifacts are evaluated.
Potency determination
Dose-response testing defines compound potency and supports the prioritization of confirmed hits for further validation.
High-throughput mass spectrometry
High-throughput MS technologies enable the discovery of both non-covalent and covalent binders.
Affinity Selection Mass Spectrometry (ASMS) identifies binders directly in solution without target tagging and is well suited for protein complexes and RNA targets, enabling the determination of apparent binding constants.
Covalent binders are detected by intact mass analysis of the target protein after incubation in solution, allowing determination of apparent binding constants. Peptide mapping can then be used to identify the binding site specifically.
Covalent screening can also be performed in cellular systems to assess target engagement in a physiologically relevant context.
+ pool of compounds
Non-covalent · ASMSAffinity selection mass spectrometry, from incubation to compound identification.
Covalent · Intact protein MSCovalent binder discovery by intact mass analysis, from incubation to hit identification.
Quality holds across the whole campaign
With validated assays, predefined quality metrics and rigorous data assessment, IRBM ensures that each screening campaign delivers high confidence results to support informed hit selection and progression.
Data driven hit selection
HTS data are analyzed through a structured workflow to ensure robust, reproducible and biologically relevant hit selection. Plate quality is continuously monitored using predefined assay performance criteria, including Z’ factor and potency of reference molecule, so that only reliable data progress to downstream analysis.
The assay held on every plate
Z’ for every plate across a ten-run campaign, colored by run. The red line marks 0.5.
Inhibition across the screened set. The activity threshold sits at mean + 3σ, here 64% inhibition.
Controls repeated the same answer in every run
Compound 1, re-tested in every run. Curves overlay across the pilot and 9 runs.
Compound 2, re-tested alongside it, holds the same potency range run to run.
Primary screening results are monitored day by day. At the end of the screening, hit selection is set using statistical criteria or project specific cut-off combined with chemical inspection to prioritize the molecules for further characterization.
Hit validation
Primary hits may result from assay artifacts or nonspecific mechanisms, including redox activity, DNA intercalation, aggregation, chemical reactivity, and detection interference. Orthogonal biochemical and cell-based assays are subsequently used to confirm target-specific activity and remove false positives prior to series prioritization. Importantly, the hit-validation strategy and associated orthogonal assays are tailored to the biology and mechanism of the target, ensuring the most relevant assessment of compound quality and target engagement.
The platform is configured to the campaign
Your assay sets the configuration, so the campaign runs on the detection and liquid handling it actually needs.
The screening platform is a modular robot from HighRes Biosolutions. It combines liquid handling, low-volume compound dispensing, incubation, and multimode detection capabilities, allowing workflows to be tailored to the specific needs of each screening campaign. Compounds reach the plate as nanoliter volumes by acoustic transfer, which removes cross-contamination and leachates and supports 384 and 1536 formats. Every operation is tracked in a laboratory information management system, with analysis in Dotmatics and visualization in Vortex.
High-quality small molecule collection at IRBM
To assure high quality of molecules in collection, compounds from HTS are regularly QC’d and molecules with low purity removed, and source screening plates are prepared for HTS to ensure compound integrity.
Hamilton Verso
Hamilton Microlab STAR
Beckman Coulter Biomek
Storage capacity of up to 880K tubes or 4300 plates (384 format)
HTS success in action: from robust screening to published impact
IRBM’s Zika program opened with a high throughput phenotypic screen. Target identification followed through resistance mapping, and the optimized compound reached oral efficacy in mouse infection models.
Looking for a tailored HTS strategy and integrated drug discovery program?
Partner with IRBM to design a screening cascade that matches your target and discovery goals.
Frequently Asked Questions
How many compounds are in IRBM’s screening collection?
IRBM’s screening collection holds more than 400,000 compounds, curated for structural diversity, three-dimensional character and drug-like properties, with samples included at above 90% purity. External libraries and virtual screening sets can be screened alongside it, and additional libraries can be hosted. The collection is described in full on the Compound Libraries page.
What assay formats can be screened at high throughput?
Biochemical and cell-based assays are screened in 384 and 1536 well formats, with readouts spanning luminescence, absorbance, fluorescence intensity, fluorescence polarization, TR-FRET and AlphaScreen. Label-free screening by affinity selection mass spectrometry is available where a target has no assayable activity. Covalent and non-covalent MS-based assays are typically performed in a 384-well plate format.
Can IRBM screen our own compound library?
Yes. Additional libraries can be hosted and made ready to screen. An existing assay protocol can also be imported and validated on IRBM instrumentation before the campaign begins, confirming conditions such as cell density, reagent addition and assay duration.
What is the difference between high throughput screening and high content screening?
High-throughput screening (HTS) typically measures one or a few assay readouts across large compound collections to identify active molecules. High-content screening (HCS) combines automated imaging with quantitative image analysis to extract multiple cellular features from each well. Depending on the screening strategy, HCS can be used either as a primary screening platform or as a follow-up approach to characterize and validate HTS hits.
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