Determining what really counts: modeling and measuring nanoparticle number concentrations

Particle number concentration (PNC) measurements are critical for research and regulatory decision making related to the potential applications and implications of nanotechnology. However, the degree to which different analytical methods yield similar PNCs has not yet been studied. In this study, monodisperse gold nanoparticles (AuNPs) with varying sizes (30 nm or 60 nm) and surface coatings (citrate, polyvinylpyrrolidone, or branched polyethyleneimine) were evaluated using five techniques: scanning electron microscopy (SEM), dynamic light scattering (DLS), differential mobility analysis (DMA), nanoparticle tracking analysis (NTA), and single particle inductively coupled plasma-mass spectrometry (spICP-MS). The two techniques that only measured the NP core size (spICP-MS and SEM), as opposed to the larger hydrodynamic diameter, yielded PNCs with the closest agreement (within 20% of each other), while PNCs among all techniques sometimes varied by a factor of 3. Positively charged AuNPs coated with branched polyethyleneimine yielded the most variable results. Deriving the PNC using the particle size distribution has several advantages over using only the mean size based on these results and statistical modeling given the substantial impact of the tails of the distribution toward smaller particles. The size distributions measured by the different techniques were also used to model the AuNP concentration that would reach the cells in an in vitro toxicity experiment. Surprisingly, there was a strong impact of the analytical technique on the modeled cellular AuNP concentration for some of the AuNPs.