Assessing particle count in electron microscopy measurements of nanomaterials to support regulatory guidance

In the European Union, nanomaterials are regulated through different pieces of sectoral legislation. This legislation often requires risk assessments and thus reliable characterization data, for which regulatory guidance generally recommend electron microscopy. The guidance provides best practices for measurements but lacks requirements on how many particles to measure. Using transmission electron microscopy data of nanomaterials, a strategy based on repeated subsampling is proposed to establish, for different particle size and shape measurands, mathematical relationships between particle count and precision, and subsequently to determine the minimum particle count. Our results confirm that the minimum particle count generally depends on the width of the size and shape distributions and that the median of the distribution can be determined with the highest precision. When the precision uncertainty is combined with uncertainties from sample preparation, imaging, analysis, calibration and trueness, a limit to the attainable uncertainty is reached that can only be marginally reduced by measuring more particles. This fixes a maximum particle count above which measuring more particles becomes ineffective. Our findings offer an experimental approach for determining the minimum particle count to measure particle size and shape by electron microscopy. It enables efficient analyses and facilitates compliance with legislation addressing nanomaterials across various application domains

WOUTERS Charlotte;  KESTENS Vikram;  VERLEYSEN Evelin;  MAST Jan; 

2025-12-02

NATURE PORTFOLIO

JRC139189

2045-2322 (online),   

https://doi.org/10.1038/s41598-025-92266-4,    https://publications.jrc.ec.europa.eu/repository/handle/JRC139189,   

10.1038/s41598-025-92266-4 (online),