Self-calibrated concentration measurements of polydisperse nanoparticles

Quantitative characterization of nanoparticles, e.g. accurate estimation of concentration distributions, is critical to many pharmaceutical and biological applications. We present a method that enables for the first time highly accurate size and absolute concentration measurements of polydisperse nanoparticles in solution, based on fluorescence single particle tracking, that are self-calibrated in the sense that the detection region volume is estimated based on the tracking data. The method is evaluated using simulations and experimental data of polystyrene nanospheres in water/sucrose solution. In addition, the method is used to quantify aggregation and clearance of different types of liposomes after intravenous injection in rats, where additional and more accurate information can be obtained that was previously unavailable, which can help elucidate their usefulness as drug carriers.