Mechanochemical Sensing of Single and Few Hg(II) Ions Using Polyvalent Principles

Sensitivity of biosensors is set by the dissociation constant (K_d) between analytes and probes. Although potent amplification steps can be accommodated between analyte recognition and signal transduction in a sensor to improve the sensitivity 4-6 orders of magnitude below K_d, they compromise temporal resolution. Here, we demonstrated mechanochemical sensing that broke the K_d limit by 9 orders of magnitude for Hg detection without amplifications. Analogous to trawl fishing, we introduced multiple Hg binding units (thymine (T)-T pairs) in a molecular trawl made of two poly-T strands. Inspired by dipsticks to gauge content levels, mechanical information (force/extension) of a DNA hairpin dipstick was used to measure the single or few Hg²⁺ ions bound to the molecular trawl, which was levitated by two optically trapped particles. The multivalent binding and single-molecule sensitivity allowed us to detect unprecedented 1 fM Hg ions in 20 min in field samples treated by simple filtrations.