Fluid Menisci and In Vitro Particle Dosimetry of Submerged Cells

Understanding the mechanisms of interaction between cells and particulate nanomaterials lies in the heart of assessing the hazard associated with nanoparticles. The paradigm of toxicology requires quantifying and interpreting dose-response relationships, and cells cultured in vitro and exposed to particle dispersions rely on mathematical models that estimate the received nanoparticle dose. Yet, none of these models acknowledges the fact that aqueous cell-culture media wet the inner surface of hydrophilic open wells, which results in curved fluid-air interface called meniscus. We show that omitting this phenomenon leads to a nontrivial but systematic error and twists the fundamental concept of nanotoxicology. Given that reproducibility and harmonization between meta analyses, in vitro, in silico, and in vivo studies must be improved, we present an adequate mathematical model that greatly advances such efforts.