This post explains why we are positioning ORYL F1 around a category we call Ultrafast Light Scattering (ULS) – beside the obvious that it is super fast. What is ULS?
The legacy categories, briefly
From the point of view of light scattering, two categories exist. 1) Static Light Scattering (SLS) measures time-averaged scattered intensity. It is useful for molecular weight and oligomeric state, but indirect for aggregation behaviour, and built around cuvette workflows that do not scale to plate throughput. 2) Dynamic Light Scattering (DLS) measures intensity fluctuations to extract diffusion coefficients and hydrodynamic size. It is also indirect for aggregation, also throughput-limited at the scale modern hit lists demand, and it saturates at high concentrations, which is exactly where biologic formulations actually live.
None of these were built for screening hit lists across small molecules all the way to biologics (PROTACs, peptides, mABs, oligonucleotides, high-concentration biologics). This is where ULS is different.
The ULS, briefly explained
Most light-scattering workflows give you one readout. ULS gives you two — in the same measurement. The ULS Explainer video — walks through why that distinction matters and how Ultrafast Light Scattering makes it possible at plate-based throughput.
Here’s the context behind the technology.
One signal isn’t always enough
Linear Light Scattering (LLS) responds to particle formation, refractive-index contrast, and the amount of aggregated material in solution — the workhorse readout for kinetic solubility, aggregation screening, and concentration-threshold detection. Fast, throughput-friendly, well-understood. But it’s a single signal. On complex or optically challenging samples, it can be ambiguous.
Second Harmonic Scattering (SHS) is different in kind, not just in degree. ORYL F1’s ultrafast pulsed laser fires at 1030 nm; SHS appears as a converted signal at 515 nm in a separate optical channel — a nonlinear process that only occurs when dipolar molecules are arranged in non-centrosymmetric molecular arrangements. For example, in interfaces and ordered assemblies. The specific structural signatures of aggregating molecules. It tells you about the nature and organisation of what’s forming in solution, not just its quantity. Where LLS saturate at high concentration formulation (>10 mg/mL), SHS do not. Where LLS is problematic in cloudy formulation, SHS do not.
With SHS and LLS – the dual readout in ULS, the dynamic range spans from small molecules (nanomolar concentration) to high concentration liquid formulations (oligonucleotides, siRNA) that go as high as 400 mg/mL.
Why the same mass can look completely different
Spherical aggregates are centrosymmetric — they give low SHS signal. Fibrils are non-centrosymmetric — they give high SHS signal. The same sample mass, the same LLS readout, completely different SHS. Without the second channel, that distinction is invisible. In surfactant-containing media, high-concentration formulations, or complex biological matrices, LLS alone routinely can’t distinguish aggregate morphology. SHS can, because it is background insensitive – it picks the aggregation or surface sensitive structural changes in the mixture.
That distinction is exactly why the dual-readout matters for samples where a single-channel workflow has always been the practical limit.
What ultrafast pulsed illumination enables
SHS is a nonlinear optical effect. Generating it reliably in a plate-well requires very high instantaneous peak power — not average power. ORYL F1 uses ~200 fs pulses at ~50 MW peak power, versus approximately 50 mW for a conventional continuous-wave laser. That peak intensity drives SHS while keeping sample exposure benign. Each well takes 50 ms. A full 384-well plate runs in ~15 minutes. LLS and SHS are captured simultaneously — same well, same measurement window, one pass.
Who benefits from the richer readout
Discovery teams get more confident aggregation classification ahead of biophysics. Formulation scientists get richer characterisation across pH and excipient conditions. New small molecule modalities — PROTACs, macrocyclic peptides, and high-concentration biologics, media containing surfactants or bile salts — are handled more reliably by two complementary signals than by either alone.