The duplex formation mediated by Hg(2+) in a properly designed ssDNA generates a stable hairpin structure, which greatly alters the translocation profile of the ssDNA through a-hemolysin nanopore. From the 2D-events contour plot, the presence of Hg(2+) can be confirmed in as little as 30 min at similar to 7 nM or higher. The sensor is highly selective to Hg(2+), without interference from other metal ions. It can be fabricated from readily available materials, without the processes of synthesis, purification, probe-making, and so forth. This sensing strategy opens new possibilities for detecting many types of analytes which have specific interactions with DNA molecules.