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Application Notes

AN-1002: DMSO Compound Library QC

Compound management teams store large libraries as nominal 10 mM DMSO stocks, but not every stock remains fully dissolved during storage and handling.

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.

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FAQ

Common questions about AN-1002

The ORYL F1 detects precipitation and aggregation in stored 10 mM DMSO compound stocks — including suspended particulates that have not yet become visible as turbidity. The complementary SHS + LLS readouts on each well deliver a Go/No-Go QC call per compound in a single 384-well plate scan of approximately 15 minutes.

Published industry studies report 5–26% of compounds can precipitate in DMSO stocks depending on library type and concentration — at 10 mM, the most common HTS storage concentration, up to 26% of compounds in a typical diversity library may have precipitated particulates (Popa-Burke & Russell, GSK, *J Biomol Screen* 2014, doi:10.1177/1087057114541146). Separately, aggregation-based artifacts account for up to 80–95% of initial HTS hits in assays that do not include detergent or other aggregation controls (Feng et al., Shoichet Lab, *J Med Chem* 2007, doi:10.1021/jm061317y). 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. A widely-cited industry study by Ilouga et al. (Bayer, J Biomol Screen 2007, PMID:17099243) assessed 778 compounds in DMSO every 4 weeks across a 6-month window under three storage conditions, finding 12–58% compound loss depending on temperature and atmosphere. Foundational compound-stability work at Abbott (Cheng et al., J Biomol Screen 2003, doi:10.1177/1087057103008003007) established water as the dominant degradation driver. The right QC frequency for your library depends on its age, DMSO hydration, and how sensitive your downstream assays are to source-side error. The historical constraint has been throughput: LC-MS is not 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.

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

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