Since Millikan’ famous oil drop experiment about hundred years ago, measurements of the electrical charge of single particles with accuracy higher than the elementary charge have been successfully applied in air and in vacuum. More recently, the same concept has been demonstrated by the applicants on single particles in nonpolar liquids. The technique relies on measuring discrete charge levels of a single particle, which allows to determine particle sizes and dynamic changes of size and charge with unprecedented accuracy. The aim of this proposal is to further develop the concept of discrete-charge measurements in liquids that are of high interest for the colloid and life sciences, such as water-based dispersions. A strategy of high-field electrophoresis, dedicated microfluidics and fast optical detection of single nanoparticles is proposed based on insights from protein charge ladders, which demonstrate that stable discrete charges can exist on nano-scale objects. With this work we intend to pioneer and advance the field of single-particle discrete-charge analysis, and ultimately open up a wide variety of possibilities such as single-molecule biosensors, analysis of quantized interactions at the solid-liquid interface, and high-accuracy characterization and identification of viruses and other nanoparticles.