Tracking Fast Oligomerization Kinetics in Poly(ADP-ribose) (PAR) Mediated Condensates Using Low-Volume, Multi-Angle DLS

Tracking rapid oligomerization and aggregation processes in low-volume biomolecular samples remains a key challenge for conventional Dynamic Light Scattering (DLS) measurements. This work evaluates a simultaneous multi-angle, time-resolved DLS approach with low-volume samples (~75 µL) for kinetic studies of Poly(ADP-ribose), an RNA-like polymer mediated condensate relevant to DNA repair and protein phase separation. Stable and reproducible autocorrelation functions and particle size measurements were acquired from three simultaneous scattering angles, confirming consistent detection even in narrow cuvettes where optical access is constrained. The system’s software-defined, per-photon time-tagging and correlation architecture allowed short acquisition windows (Δt ≈ seconds) and overlapping time traces, making it suitable for tracking size evolution on seconds-to-minutes timescales. Compared to conventional single-angle DLS instruments or those with a goniometer providing sequential scanning, the simultaneous multi-angle capability improves sensitivity to changes in particle hydrodynamic size and allows for real-time consistency checks, providing richer insights into early-stage oligomer formation and transient intermediates.

These results demonstrate a simultaneous multi-angle DLS system for low-volume, time-resolved kinetics studies, helping to bridge the measurement gap between single-angle DLS and large-scale SAXS platforms in fast biophysical processes.