A Universal Strategy for Aptamer‐Based Nanopore Sensing through Host–Guest Interactions inside α‐Hemolysin

Nanopore emerged as a powerful single-molecule technique over the past two decades, and has shown applications in the stochastic sensing and biophysical studies of individual molecules. Here, we report a versatile strategy for nanopore sensing by employing the combination of aptamers and host-guest interactions. An aptamer is first hybridized with a DNA probe which is modified with a ferrocene⊂cucurbit[7]uril complex. The presence of analytes causes the aptamer-probe duplex to unwind and release the DNA probe which can quantitatively produce signature current events when translocated through an α-hemolysin nanopore. The integrated use of magnetic beads can further lower the detection limit by approximately two to three orders of magnitude. Because aptamers have shown robust binding affinities with a wide variety of target molecules, our proposed strategy should be universally applicable for sensing different types of analytes with nanopore sensors.