A sticky measurement problem: number concentration of agglomerated nanoparticles.

Measuring the number concentration of colloidal nanoparticles is critical for assessing reproducibility, compliance with regulation and performing risk assessments of nanoparticle-enabled products. For nanomedicines, their number concentration directly relates to their dose. However, the lack of relevant reference materials and established traceable measurement approaches make the validation of methods for nanoparticle number concentration difficult. Furthermore, commercial products often exhibit agglomeration, but guidelines for dealing with non-ideal samples are scarce. We have compared the performance of five benchtop measurement methods for the measurement of colloidal number concentration in presence of different levels of agglomeration. The methods are: UV-Visible spectroscopy, differential centrifugal sedimentation (DCS), dynamic light scattering (DLS), particle tracking analysis (PTA) and single particle inductively coupled plasma mass spectrometry (spICP-MS). We find that both ensemble and particle-by-particle methods are in close agreement for monodisperse nanoparticle samples and three methods are within 20% agreement for agglomerated samples. We discuss the sources of measurement uncertainties, including how particle agglomeration affects measurement results. This work validate and expands the toolbox of methods available for the measurement of real-world nanoparticle products.