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Application Notes

AN-1005: Pre-SPR solubility and aggregation triage of entire hit lists on ORYL F1

Surface Plasmon Resonance (SPR) campaigns depend on clean hit lists.

Pre-SPR solubility and aggregation triage of entire hit lists on ORYL F1

Per-compound operating-concentration profiling for SPR hit lists, using two-timepoint plate-based Linear Light Scattering (LLS) on ORYL F1.

Louis Dumas, Antonia Turberville, Nicolas Houvenaghel, Orly Tarun
ORYL Photonics SA, Route de la Corniche 5B, 1066 Epalinges, Switzerland
Hit Discovery, Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge, UK

Summary

Surface Plasmon Resonance (SPR) campaigns depend on clean hit lists. Aggregators that survive into the SPR queue generate false positives, distort kinetic constants, and damage microfluidics, driving regular sensor-chip rework and full system cleaning cycles. We demonstrate a plate-based pre-SPR triage workflow on ORYL F1 that profiles entire hit lists at SPR-relevant timepoints in ~15 minutes per 384-well plate, using ~2 μL per datapoint. A 142-compound hit list, including SPR-flagged problematic compounds, was measured at two timepoints (1 h and 24 h) with eight concentrations and two replicates.

The workflow returns per-compound diagnostics: a safe operating concentration, an avoid-above threshold, peak aggregation amplitude, a timepoint-shift behavior class, and quality flags — all with bootstrap confidence intervals. F1 risk calls concord with the SPR assay’s internal severity assessments across 10 of 11 scored compounds. The per-compound output drops directly into an SPR queue as an operating-concentration input. A ROI estimator on a 1,000-compound campaign places savings on the order of ~20 kCHF per campaign in chip consumables, rework, and microfluidics maintenance.

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AN-1002: DMSO Compound Library QC

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