Your small-molecule workflow wasn’t built for PROTACs. Your PROTAC workaround wasn’t built for peptides. And every new modality your chemistry team brings in is another round of method development for someone in the lab.
That’s been the pattern. We tested whether it has to be.
Three compound classes, one method.
Our latest application note runs nine compounds — three small molecules, three peptides, three PROTACs — through a single 384-well plate on ORYL F1. One Linear Light Scattering (LLS) method, part of the ULS dual-readout. No changes to the core measurement workflow between compound classes.
315 wells measured in 12 minutes. Median within-well %CV below 5% across the full nine-compound panel — consistent reproducibility regardless of compound class.
For the three small molecules with published reference values, the LLS-derived solubility limits were cross-validated against HPLC-MS/UV measurements. Albendazole (5.14 µM), Dipyridamole (20.68 µM), and Caffeine (>100 µM) matched the rank order of the reference data and agreed closely under the defined assay conditions. 8 of 9 compounds returned a called solubility limit within the tested concentration range; Caffeine remained soluble across the full range and was correctly reported as such. The peptide and PROTAC data carry no orthogonal reference — they are included to show that the same workflow delivers interpretable LLS-derived profiles and limit calls for compound classes that would otherwise require separate assay development.
That’s three compound classes, one workflow, screening-timeline throughput, and the data is both internally consistent and externally cross-validated.
Why it works without class-specific tuning
Light scattering is an intrinsic physical measurement of what a compound is doing in solution — aggregating, precipitating, or staying dissolved — regardless of chromophore, ionisation state, or chromatographic behaviour. That’s why it generalises across modalities: you’re measuring the physics of the system, not the chemistry of the column.
Ultrafast pulse illumination plus precision optical engineering is what makes this possible at plate scale. Pulsed light compresses each well measurement to ~50 ms — turning an hours-long specialist experiment into a 15-minute plate run. Precision optical engineering preserves signal fidelity across the plate, so measurements stay clean. A full plate of physical-property data in minutes, not hours or days.
What this means for diverse hit lists
Teams building custom assays around each new modality get that time back. Discovery scientists screening diverse hit lists — PROTACs, peptides, and classical small molecules in the same campaign — no longer need to route compounds to separate measurement paradigms. Pre-formulation inherits a consistent data layer across programmes, not a patchwork of class-specific methods.
The value here isn’t only the throughput number. It’s that the output — concentration-dependent LLS profiles, called solubility limits with confidence intervals, and flags for compounds that remain soluble or show gradual onset — is directly interpretable for triage decisions, across the whole hit list, in the same run.
Small molecules, peptides, PROTACs — same plate, same day, no workarounds.
The full data — compound-by-compound profiles and HPLC cross-validation — is in Application Note AN-1004.