Fig. 1

Integrated nanodosimetry approach overview. Methodologies required for accurate nano-dosimetry include: 1) standardized dispersion preparation protocols, 2) detailed colloidal suspension characterization including size and effective density of formed agglomerates, and 3) computational modeling of transport based on agglomerate, media and system properties. Standardized dispersion protocol to maximize stability of agglomeration state includes sonication of nanomaterial in deionized water to particle-specific critical dispersion sonication energy (DSE _cr), followed by dilution into final application media. Dispersions are analyzed by DLS to determine agglomerate hydrodynamic diameters, and by VCM to determine agglomerate effective density. Transport modeling to determine dose metrics requires d _H from DLS and ρ _EV from VCM, as well as media properties (viscosity, η _m and density, ρ _m) and system parameters (temperature, Τ and media column height, h). Available computational transport models include VCM-ISDD, computational fluid dynamics (CFD) and Distorted Grid (DG, introduced in this report) models. Possible output dose metrics include exposure concentrations in the cell microenvironment at the bottom of the well (including mass, surface area and particle number), fractional or absolute deposition (in terms of mass, surface area and particle number), as well as concentration as a function of vertical position within the well (concentration profile)