The Influence of Fluid Menisci on Nanoparticle Dosimetry in Submerged Cells

Understanding the interaction between cells and nanoparticles (NPs) is important to understand the hazard associated with nanoparticles. This requires quantifying and interpreting dose-response relationships, and cells cultured in vitro and exposed to particle dispersions mainly rely on mathematical models that estimate the received nanoparticle dose. Yet, none of these models consider that aqueous cell-culture media wet the inner surface of hydrophilic open wells, which results in a curved fluid-air interface called meniscus. Here we address in detail the impact of the meniscus on nanoparticle dosimetry. We present experiments, build an advanced mathematical model, and find that the presence of meniscus may bring about systematic errors that must be considered to advance reproducibility and harmonization. Finally, we also propose simple practical solutions to this problem, such as covering the air-liquid interface with a permeable lid or soft rocking of the cell culture well plate.