On the Operational Aspects of Measuring Nanoparticle Sizes

Area of Science:

• Nanotechnology
• Materials Science
• Analytical Chemistry

Background:

• Nanoparticles (NPs) are critical in various applications but pose toxicological concerns.
• Accurate size determination of NPs is essential for safety and efficacy.
• Existing measurement techniques can yield significant variations, especially for complex NP samples.

Purpose of the Study:

• To conduct an intercomparison of common laboratory techniques for measuring nanoparticle sizes.
• To evaluate the accuracy and variability of different methods across monodisperse and multimodal NP samples.
• To identify challenges and provide recommendations for robust NP size characterization.

Main Methods:

• Evaluated techniques include transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), wet/dry scanning transmission electron microscopy (STEM), and atomic force microscopy (AFM).
• Tested on calibrated beads, monodisperse SiO₂ Ludox®, and toxicologically relevant NPs (Ag, TiO₂).
• Compared size measurements for monomodal and multimodal NP distributions.

Main Results:

• For monomodal NPs, techniques agreed within 25% variation.
• For multimodal NPs (Ag, TiO₂), inter-technique variation reached up to 300%.
• Operational aspects and protocol choices significantly impact NP size measurement outcomes.

Conclusions:

• Averaging NP size across multiple biophysical techniques is more reliable than relying on a single method.
• Size distribution is more informative than average values for heterogeneous NPs.
• Nanotoxicologists and regulatory agencies should test multiple techniques for comprehensive NP characterization.