Capillary Electrophoresis Methods for the Characterization of Synthetic Nanoparticles

ABSTRACT

Nanoparticles (NPs) exhibit properties distinct from bulk materials of identical chemical composition, with their behavior and functionality intrinsically linked to parameters such as size, composition, surface functionality, and (surface) charge. Accurate characterization of these parameters is therefore essential for understanding and optimizing NP performance in a variety of applications, including coatings, cosmetics, sunscreens, drug delivery systems, and vaccines. Conventional analytical techniques for NP characterization include microscopy‐, scattering‐, field‐flow fractionation‐, and chromatography‐based methods, which are mainly employed for size determination. Infrared and nuclear magnetic resonance spectroscopy provide ensemble information on chemical composition, while mass spectrometry of NPs larger than 10 nm remains challenging. Among more established techniques, capillary electrophoresis (CE) represents an interesting alternative for NP characterization, due to its inherent selectivity toward size, charge, and surface properties. In this review, literature from the past seven years is surveyed to outline and discuss CE‐based approaches for NP analysis. It is demonstrated that, through appropriate calibration or use of theoretical models, CE can provide size information, (surface) charge, and zeta (ζ) potential. In addition, CE can be applied to assess NP stability, composition, and interactions with, for example, ligands. Importantly, owing to its separation capability, CE can reveal physicochemical heterogeneity within NP populations, rather than only ensemble‐averaged values. Furthermore, the coupling of CE with complementary separation or detection techniques, particularly asymmetric‐flow field‐flow fractionation (AF4) and single‐particle inductively coupled plasma mass spectrometry (SP‐ICP‐MS), offers comprehensive analytical platforms providing orthogonal information on NP size, composition, and charge simultaneously.