Accurate Sizing and Resolution of Nominal 200 nm Diameter Polystyrene Nanospheres With Charge Detection Mass Spectrometry

ABSTRACT Charge detection mass spectrometry (CDMS) with electrostatic ion traps has been used to characterize the mass distributions of a variety of nanoparticles that have masses ranging from ∼1 to 400 megadaltons (MDa). Here, samples of polystyrene nanospheres from three different manufacturers with diameters ∼200 nm and masses of several gigadaltons (GDa) were characterized by both CDMS and transmission electron microscopy (TEM). From the centroid masses of ∼2.320, ∼2.602, and ∼2.897 GDa, centroid diameters of 191.4, 199.1, and 204.8 nm were obtained, respectively. These diameters are within 1% of those obtained from TEM measurements. The size distributions of the individual components in a mixture of these three samples were readily resolved with CDMS but not with TEM. The greater measurement time required for a statistically meaningful measurement from TEM led to some particle shrinkage that was not uniform between particles. The width of the most monodisperse nanoparticle sample distribution indicates that CDMS could distinguish two nanoparticle samples that differed by just 2 nm in diameter at this particle size (1%). The high resolution, minimal sample preparation requirements, compatibility with automation, and now extended mass range make CDMS a powerful high‐throughput nanoparticle characterization tool for nanoparticles in biomedicine, advanced electronics, and material science.