Physical characterization of nanomaterials in dispersion by transmission electron microscopy in a regulatory framework

Abstract

TEM is one of the few techniques that can identify nanoparticles according to the current definitions. This chapter focuses on the different steps required to analyze dispersed nanomaterials by TEM. Methodologies to obtain homogeneous and stable dispersions of colloidal nanomaterials and powders are presented. The preparation of TEM specimens to obtain a representative distribution of particles on the grid is discussed. The application of TEM imaging methods, electron diffraction, and analytical TEM to obtain complementary information on the size, morphology, crystallographic structure, electronic structure, and composition of nanomaterials is reviewed. In a qualitative TEM analysis, the key properties of the physical form of the nanomaterial under which it is exposed to in vitro and in vivo test systems are described based on TEM micrographs. Subsequently, a quantitative analysis which includes detection, classification, and measurement of primary particle properties and validation of the measurement results can be performed. The possibility to extract 3D information by fractal analysis of electron micrographs of aggregated nanomaterials with a fractal-like structure is explored.