Some prior experiments that studied the toxicity of nanoparticles may be invalidated due to an overlooked detail of experimental design, according to Younan Xia, a scientist at Washington University in St. Louis, United States. Standard laboratory tests of the biological activity of nanoparticles and their toxicity rely on the ability of scientists to quantify the interaction between the nanoparticles and the cells, particularly the uptake of nanoparticles by the cells. In these tests, cells are plated on the bottom of a dish and a culture containing nanoparticles is poured on top of them. Xia began to wonder if it would make a difference, in his experiments with gold nanoparticles, if the cells were upside down – would it change their uptake rate? “People assumed that if they prepared a suspension, the suspension was going to have the same concentration everywhere, including at the surface of the cells,” says Xia. Xia’s team found that nanoparticles above certain sizes and weights, in both standard and upside-down set-ups, will settle out, thus the concentrations of nanoparticles near the cell surfaces are different from those in the bulk solution, and cellular uptake rates are higher. “Studies on the cellular uptake of nanoparticles that have been conducted with cells in the upright configuration may have given rise to erroneous and misleading data, “ the team wrote in the journal Nature Nanotechnology. “All earlier work may need to be re-evaluated to account for the effects of sedimentation on nanoparticle dosimetry,” the authors conclude. According to Xia, “It’s no different from medicines that have to be shaken to suspend a powder in a water. If you don’t shake the bottle, you end up under- or overdosing yourself.”