High-throughput assessment of compound solubility, powered by Ultrafast Light Scattering (ULS)
A plate-based workflow on ORYL F1, using Linear Light Scattering (LLS)
Louis Dumas, Aristea Massaras, Orly Tarun
ORYL Photonics SA, Route de la Corniche 5B, 1066 Epalinges, Switzerland
Summary
Solubility remains a discovery bottleneck as hit lists expand, molecules become more complex, and early screening increasingly includes new modalities. This application note describes a high-throughput, low-compound, plate-based workflow on ORYL F1 for compound solubility assessment using Linear Light Scattering (LLS), within the broader ORYL Ultrafast Light Scattering (ULS) platform. Starting from 10 mM DMSO stock solutions, compounds were prepared in a 384-well format, diluted into PBS pH 7.4, incubated for 24 h with shaking, measured on ORYL F1 using ORYL Screener software, and analyzed in ORYL Analyzer to generate LLS-derived solubility profiles, LLS-derived solubility limits, and confidence intervals. Once plates are ready, the 384 wells can be measured in 15 minutes.
Data is shown for a discovery-triage panel comprising three standard small molecules, three peptides, and three PROTACs, each tested in 11- or 12-point concentration series with three replicate wells. The results illustrate the type of decision-ready output obtained from the F1 workflow across diverse compound classes, including new modalities. For Albendazole, Dipyridamole, and Caffeine, HPLC-MS derived reference values are available and match our LLS-derived solubility limits, providing a focused external credibility anchor for the workflow.
Common questions about AN-1004
Yes. The AN-1004 dataset includes three PROTACs tested in 11–12 point concentration series with three replicates. The Linear Light Scattering (LLS) readout on ORYL F1 measures their solubility limits in a 384-well plate workflow alongside small molecules and peptides — full plate in approximately 15 minutes.
Yes. AN-1004 reports LLS-derived solubility limits for three peptides alongside PROTACs and small molecules on the same plate, demonstrating the workflow handles new modalities that fall outside the small-molecule chemical space HPLC was built for.
In terms of actual workflow, unlike HPLC, F1 directly measures solubility and aggregation in plate-based approach, no columns, no separation and using ~100x less compound with ~100x more throughput.
Nephelometry and DLS are limited by detection sensitivity. LLS on ORYL F1 delivers quantitative concentration-response data with sub-micromolar sensitivity at 5-10x more throughput (compared to DLS or nephelometry) in a 384-well plate format — making it practical for modalities where compound is scarce.