Automated dynamic and static light scattering in microwell plates for fast, productive development of biologics

Importance of the Topic

Protein and nanoparticle characterization across nanoscale size ranges is critical for biologics development. Dynamic and static light scattering methods offer insights into size, molecular weight, aggregation and colloidal stability. Automation and high-throughput screening reduce labor, sample volume and accelerate decision-making in formulation, stability and process optimization.

Objectives and Study Overview

This white paper introduces the DynaPro Plate Reader III (PRIII) as an advanced microscale instrument. It aims to demonstrate its capabilities for simultaneous in-plate dynamic (DLS) and static light scattering (SLS) measurements, diagnostic imaging, high-content screening, and integration with automated workflows for biologics characterization.

Methodology and Instrumentation

• The PRIII uses standard 96, 384 and 1536 well plates for in situ DLS and SLS.
• An integrated camera captures images of each well to detect bubbles, debris or precipitation.
• A new linear and fast avalanche photodiode module enables reliable molar mass determination by SLS without compromising DLS speed.
• DYNAMICS software and SpectralView visualization support experiment setup, automated plate scans, temperature ramps and heat-map generation.
• Optional integration with robotic handlers and plate samplers via the DYNAMICS API allows end-to-end automation.

Main Results and Discussion

• True weight-averaged molar mass (Mw) and second virial coefficient (A2) are measured directly in plate format, eliminating assumptions on molecular conformation.
• DLS yields diffusion coefficients, hydrodynamic radii, polydispersity and aggregation fraction rapidly across hundreds of samples.
• Thermal stability parameters—aggregation onset (Tagg), unfolding onset (Tonset) and melting temperature (Tm)—are obtained simultaneously by DLS and SLS.
• Viscosity screening using tracer nanoparticles correlates closely with conventional techniques, requiring only microliter volumes.
• Phase diagrams combining formulation variables (pH, salts, excipients) with multiple biophysical readouts are generated in a single high-content run.
• On-board camera diagnostics eliminate guesswork by flagging wells with bubbles or precipitation in situ.

Practical Benefits and Applications

• High-throughput profiling supports formulation screening, crystallization buffer optimization, accelerated stability testing and developability assessment.
• Microliter-scale volumes and plate format dramatically reduce sample consumption and operator time compared to cuvette-based systems.
• Integration with liquid-handling automation enables screening campaigns with thousands of conditions.
• Comprehensive data enables robust statistical analysis and Quality by Design in biotherapeutic development.

Future Trends and Potential Applications

• Deeper integration of light scattering data with other analytical modalities in automated pipelines for multi-attribute characterization.
• Expansion of plate-based multi-angle and static detectors to extend direct size and mass measurement toward larger particles.
• Advanced software tools for real-time decision-making, machine-learning-assisted data interpretation and predictive stability modeling.
• Applications in nanomedicine, vaccine platforms, exosome and virus-like particle studies leveraging microscale screening.

Conclusion

The DynaPro Plate Reader III provides a quantum leap in automated light scattering for biologics research. By delivering simultaneous DLS and SLS measurements, inline imaging diagnostics and seamless high-throughput workflows, it enables comprehensive biophysical profiling with minimal sample and maximal efficiency. This platform accelerates formulation development, stability screening and process optimization while ensuring data quality and statistical robustness.

Instrumentation

• DynaPro Plate Reader III (Wyatt Technology)
• DYNAMICS® software with SpectralView heat-map module
• Integrated on-board imaging camera and temperature control
• DYNAMICS API for robotic integration