The scientific foundation behind ORYL F1 — combining second harmonic scattering and linear light scattering for deep molecular insight.
Technology
Ultrafast Light Scattering
What is Ultrafast Light Scattering?
Ultrafast Light Scattering (ULS) is the category name for the measurement technology at the core of the ORYL F1. It combines two complementary optical techniques — second harmonic scattering (SHS) and linear light scattering (LLS) — into a single, high-throughput platform.
This dual-readout approach provides molecular-level insight into solubility and aggregation behavior that cannot be obtained from either technique alone. ULS enables scientists to detect subtle changes — including early-onset aggregation at the nanometer scale — well before they become visible through conventional turbidity measurements.
Complementary Readouts
Two techniques, one platform
Second Harmonic Scattering (SHS)
SHS is a nonlinear optical technique that is sensitive to molecular-level organization and symmetry breaking at interfaces. In the context of solubility and aggregation measurement, SHS probes early-onset aggregation events — changes that occur at the nanometer scale before particles grow large enough to scatter light in the conventional sense.
This makes SHS a powerful complement to LLS: it reveals the earliest stages of aggregation, providing insight that precedes turbidity-based detection by a significant margin.
Linear Light Scattering (LLS)
LLS is a well-established technique for characterizing particle size and scattering behavior. In the ORYL F1, LLS provides a complementary readout to SHS — tracking how particles evolve in size as aggregation progresses.
Together, SHS and LLS offer a complete picture of solubility and aggregation: from molecular-level onset (SHS) through particle growth (LLS). This dual measurement approach delivers robust and reliable results that support confident decision-making.
Advantages
Why Ultrafast Light Scattering matters
Earlier detection
Detect early onset of aggregation prior to turbidity. SHS reveals nanometer-scale changes that conventional light scattering methods miss entirely.
Higher throughput
Profile a full 384-well plate in approximately 15 minutes. Roughly 100× higher throughput compared to traditional HPLC-based solubility workflows.
Lower compound consumption
Use approximately 100× less compound than HPLC-based methods. Practical for early-stage work where compound is scarce.
Complementary readouts
Dual SHS + LLS measurement provides a more complete picture of solubility and aggregation than either technique alone.
FAQ
Common questions about Ultrafast Light Scattering
Ultrafast Light Scattering (ULS) is the category name for ORYL Photonics’ measurement technology. It combines Second Harmonic Scattering (SHS) and Linear Light Scattering (LLS) on the same sample, profiling solubility and aggregation at high throughput with low compound consumption.
No. ORYL F1 is not a replacement for HPLC. It is a high-throughput, low-compound triage layer that runs before HPLC, removing aggregators and poorly-soluble compounds before they consume downstream resources such as SPR and HTS.
Dynamic Light Scattering (DLS) saturates above approximately 5 mg/mL and has approximately 5 to 20 micromolar sensitivity. ULS pairs two readouts that each break a different DLS limit: ORYL’s LLS, with its unique optical geometry, delivers below 1 micromolar sensitivity for small molecules, PROTACs, and macrocycles; SHS, because it responds to molecular interfaces rather than bulk scattering, continues to deliver signal above 50 mg/mL where DLS, SLS and LLS saturate. Together on the same plate they cover both ends of the concentration range that no single conventional method spans.
ORYL F1 is the only plate-based instrument that reliably profiles high-concentration biologics above 50 mg/mL and new modalities — PROTACs, macrocycles, constrained peptides — where DLS, SLS and HPLC saturate or fail.
Yes. ULS requires no chromophore, fluorophore, or chemical modification. The measurement is performed directly on the compound in its formulation buffer of choice, in standard 96-well or 384-well microplate format, with minimal sample preparation.
Scientific Publications & Posters
Explore peer-reviewed publications and conference posters on ULS and its applications.
Want to see ULS data from your own compounds?
Request a demo or send samples for a measurement service.