High-throughput QC of 10 mM DMSO compound stocks, powered by Ultrafast Light Scattering (ULS)
A plate-based workflow on ORYL F1, using complementary Second Harmonic Scattering (SHS) and Linear Light Scattering (LLS)
Orly Tarun1, Louis Dumas1, Antoine Gibelin2
1ORYL Photonics SA, Route de la Corniche 5B, 1066 Epalinges, Switzerland.
2Biomolecular Screening Facility, EPFL, 1015 Lausanne, Switzerland
Summary
Compound management teams store large libraries as nominal 10 mM DMSO stocks, but not every stock remains fully dissolved during storage and handling. When aggregates are already present in the stored stock, the dissolved fraction can fall below the intended concentration and introduce avoidable uncertainty into downstream screening workflows. This application note describes a high-throughput, low-compound, plate-based workflow on ORYL F1 for Go/No-Go QC of stored compound stocks using complementary second harmonic scattering (SHS) and linear light scattering (LLS) readouts.
Compounds were loaded directly into an ECHO low-dead-volume plate and scanned non-destructively on the ORYL F1. The two readouts were interpreted together to provide a robust and reliable QC call. When SHS and LLS both support the same conclusion, confidence in the result is increased. When one readout, e.g. SHS, is affected by sample optical properties such as a green-colored stock, the complementary readout, e.g. LLS can be used to support the classification. Visual inspection of the stock wells was used as an orthogonal validation layer.
Once plates are ready, 384 wells can be measured in approximately 15 minutes. The workflow is designed as a practical first-pass QC step for compound management teams that need decision-ready results before assay deployment or compound redistribution, helping de-risk downstream screening and reduce avoidable rework.
Common questions about AN-1002
Published studies report 15–26% of compounds can precipitate at 10 mM in DMSO over time, and that 80–95% of initial HTS hits are screening artifacts — a meaningful fraction tracing back to source-stock issues. When dissolved compound in the stored stock falls below the intended concentration, downstream assays under-dose and generate false negatives. AN-1002 demonstrates a plate-scale Go/No-Go workflow on ORYL F1 — non-destructive, ECHO-plate compatible, 384 wells in approximately 15 minutes — that flags precipitating stocks before they reach primary screening.
Published industry practice ranges from quarterly to every 4 weeks — Cheng et al. (2003) and follow-up repository studies sample every 4 weeks across 6-month monitoring windows. The right frequency depends on library age, DMSO hydration, and how sensitive your downstream assays are to source-side error. The historical constraint has been throughput: LC-MS-based QC at a monthly cadence is rarely practical for cost or turnaround. AN-1002 demonstrates a plate-scale workflow on ORYL F1 that scans 384 wells in approximately 15 minutes — bringing a monthly QC schedule into reach for primary screening libraries.