Stunner LNP Characterization

Importance of the Topic

Lipid nanoparticles (LNPs) serve as essential vehicles for delivery of mRNA and other biologics. Comprehensive characterization of particle size, concentration, aggregation and payload content ensures reproducible performance in research, development and manufacturing settings.

Objectives and Study Overview

This document presents the Stunner system, which integrates UV/Vis spectroscopy, rotating angle dynamic light scattering (RADLS) and multi-angle light scattering on a 2 µL sample. The aim is to deliver rapid, high-throughput LNP quality assessment covering concentration, size, mass distribution, aggregate detection and total RNA quantification in a single experiment.

Used Instrumentation

• UV/Vis spectrophotometer with xenon flash lamp, wavelength range 230–750 nm, dual fixed pathlengths of 0.1 mm and 0.7 mm.
• Dynamic light scattering (DLS) and rotating angle DLS using 660 nm laser diodes and avalanche photodiode detectors across multiple angles.
• 96-well microplate format requiring only 2 µL samples, compatible with automation and robotic systems.

Main Results and Discussion

Combining DLS and multi-angle light scattering data enables accurate measurement of hydrodynamic diameter and particle concentration across a wide range (0.3–1000 nm, 1×10^9–5×10^13 particles/mL). Aggregates are detected via intensity and mass distributions, revealing minor aggregate peaks otherwise masked by bulk population. UV/Vis measurements with Unmix technology deconvolve turbidity and payload absorbance, permitting reliable total RNA quantification. Throughput reaches 96 concentration readings in 10 minutes and full profiling in approximately two hours.

Benefits and Practical Applications

• High-throughput screening of LNP formulations during formulation development and process scale-up.
• Minimal sample consumption (2 µL) reduces material cost and simplifies workflow.
• Integration of concentration, size, aggregation and payload quantification in a single platform accelerates decision-making in research and quality control.

Future Trends and Opportunities

Advances are expected in integration with automated liquid handling and AI-driven data analysis to further streamline nanoparticle characterization. Expanding spectral unmixing approaches and light scattering modalities may extend applicability to other nanoparticle systems and complex formulations.

Conclusion

The Stunner system provides a unified, high-throughput solution for LNP characterization, delivering critical quality attributes with minimal sample volume and rapid turnaround. This platform supports accelerated development and robust quality control of nanomedicine candidates.