Gene

microRNA

Colloid

Cell biology

Extracellular vesicles

Nanoparticle

Biology

Materials science

Refractive index

Microvesicles

Biochemistry

Particle size

Physical chemistry

Physics

Nanotechnology

Optics

Nanoparticle tracking analysis

Characterization (materials science)

Interferometry

Colloidal particle

Particle-size distribution

Chemistry

Biological system

Optoelectronics

Nature Methods

Characterization of the size and material properties of particles in liquid suspensions is in very high demand, for example, in the analysis of colloidal samples or of bodily fluids such as urine or blood plasma. However, existing methods are limited in their ability to decipher the constituents of realistic samples. Here we introduce iNTA as a new method that combines interferometric detection of scattering with nanoparticle tracking analysis to reach unprecedented sensitivity and precision in determining the size and refractive index distributions of nanoparticles in suspensions. After benchmarking iNTA with samples of colloidal gold, we present its remarkable ability to resolve the constituents of various multicomponent and polydisperse samples of known origin. Furthermore, we showcase the method by elucidating the refractive index and size distributions of extracellular vesicles from Leishmania parasites and human urine. The current performance of iNTA already enables advances in several important applications, but we also discuss possible improvements.

Precision size and refractive index analysis of weakly scattering nanoparticles in polydispersions