Determination of size- and number-based concentration of silica nanoparticles in a complex biological matrix by online techniques.

We propose for the first time methodology for the determination of a number-based concentration of silica (SiO2) nanoparticles (NP) in biological serum using nanoparticle tracking analysis (NTA) as the online detector for asymmetric flow field-flow fractionation (AF4). The degree of selectivity offered by AF4 was found necessary to determine reliably number-based concentration of the measured NP in the complex matrix with a relative measurement error of 5.1% (as relative standard deviation, n = 3) and without chemical sample pretreatment. The simultaneous online coupling to other size and concentration detectors, such as multiangle light scattering (MALS) and ICPMS, for the measurement of the same NP suspension, was used to confirm the particle size determined with NTA and the equivalent particle number determined by AF4/NTA, respectively. The size- and number-based concentration data obtained by independent techniques were in a good agreement. The developed methodology can easily be extended to other types of particles or particle suspensions and other complex matrices provided that the particle size is above the limit of detection for NTA.