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Asymmetrical Flow Field-Flow Fractionation for Sizing of Gold Nanoparticles in Suspension
Published on: September 11, 2020
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Going hi-res in bulk: flowless multiangle dynamic light scattering for detection on asymmetric flow field flow
Lavinia Rita Doveri1, Giorgia Dal Pan1, Giovanni Tomaselli1
1inLAB, Department of Chemistry, University of Pavia, Via Taramelli 12, Pavia, 27100, Italy. ydf@unipv.it.
Journal of Materials Chemistry. B
|May 23, 2025
Summary
A new method combining asymmetric flow field flow fractionation (AF4) and multiangle dynamic light scattering (MADLS) accurately measures nanoparticle size without calibration. This technique offers a universal approach for nanomedicine quality control.
Area of Science:
- Nanomedicine
- Analytical Chemistry
- Materials Science
Background:
- Nanomedicine requires precise analytical methods for regulatory compliance and safety.
- Accurate particle size and distribution measurements are crucial for nanomedicine R&D and quality control.
- Existing methods may require calibration materials, limiting their applicability and affordability.
Purpose of the Study:
- To develop and validate a novel analytical approach for nanoparticle size determination.
- To combine multidetector asymmetric flow field flow fractionation (MD-AF4) with multiangle dynamic light scattering (MADLS) for accurate sizing without calibration.
- To evaluate the method's performance on various nanoparticles relevant to nanomedicine, environmental, and drug delivery applications.
Main Methods:
- Utilized a combined MD-AF4 and MADLS system for nanoparticle characterization.
- Employed model liposome formulations, prepared via lipid thin-film extrusion, for benchmarking.
- Validated results against cryogenic transmission electron microscopy (cryoTEM) and standalone MADLS.
- Investigated the influence of sample concentration on analytical bias in AF4-DLS measurements.
- Extended analysis to polystyrene and polymethyl methacrylate particles.
Main Results:
- Achieved accurate particle size determination for bioinspired colloids and polymeric particles without calibration standards.
- Demonstrated that analytical bias in in-flow DLS measurements follows a universal law, independent of nanoparticle material.
- The combined AF4-MADLS approach, with fraction collection, provided high-resolution size distributions and accurate number concentration.
- Liposomes exhibited high monodispersity and long-term stability, confirmed by cryoTEM and MADLS.
Conclusions:
- The proposed MD-AF4-MADLS method offers a robust, calibration-free solution for nanoparticle sizing.
- The findings suggest a universal behavior in DLS-based sizing bias, simplifying analytical method development.
- This approach enhances analytical tools for nanomedicine, potentially leading to wider adoption of AF4-DLS instrumentation.

