Real-time measurement of toxicity: Application to nanotechnology and synthetic pathogens

Cellular based biosensing can serve as an effective method for detection of unknown toxins by monitoring cellular response. Electric cell-substrate impedance sensing (ECIS) does this by measuring the impedance of a cell monolayer grown on interdigitated gold electrodes. This is done in situ and in real time without disrupting the monolayer. As the monolayer settles and grows to confluence an increase in resistance is seen. The formation of tight junctions between the cells increases the resistance further until the resistance stabilizes with minor fluctuations due to micromotility. When the cells are exposed to a toxin a change in the barrier function, a measure of the resistance cause by tight junctions, is seen. This real time quantified data allows for continuous measurement of toxic exposure. Toxicity of copper nanoparticles (~100 nm) could be seen as low as 1 μg per 105 cells. Fluorescent stainingwas performed on parallel cultures to confirm the activity of the cells and the disruption of tight junctions over time.