Many toxicology studies on insoluble and poorly soluble nanoparticles point out surface area as an indicator of inhalation exposure. Measuring this criterion thus constitutes an important challenge. Instruments exist which can measure particle surface area concentration in real-time, but it is not known how well they perform when faced with polydisperse nanostructured aerosols. In this study, the response functions of three commercially available instruments based on diffusion charging (LQ1-DC, Matter Engineering; NSAM, TSI model 3550; AeroTrak™ 9000, TSI) were measured for monodisperse aerosols of four different chemical natures with particles ranging in size from 15 to 520 nm. Our results show good agreement between the experimental and theoretical response functions for the three instruments studied. In addition, no significant effect of the chemical nature, density or particle morphology was revealed. Instrument response was also tested with polydisperse aerosols. For these aerosols, discrepancies were observed between measurements and calculated concentrations based on response function and particle number size distribution. Relative differences varied between −60 and +55 % with an average value of −20 %. These differences may be explained by different factors; among them, the existence of a distribution of electrical charges on particles can lead to identical signals measured, and differential diffusion charging performance might lead to concentration-dependent response.