Bubble-Mediated Ultrasensitive Multiplex Detection of Metal Ions in Three-Dimensional DNA Nanostructure-Encoded Microchannels

The development of rapid and sensitive point-of-test devices for on-site monitoring of heavy-metal contamination has great scientific and technological importance. However, developing fast, inexpensive, and sensitive microarray sensors to achieve such a goal remains challenging. In this work, we present a DNA-nanostructured microarray (DNM) with a tubular three-dimensional sensing surface and an ordered nanotopography. This microarray enables enhanced molecular interaction toward the rapid and sensitive multiplex detection of heavy-metal ions. In our design, the use of DNA tetrahedral-structured probes engineers the sensing interface with spatially resolved and density-tunable sensing spots that improve the microconfined molecular recognition. A bubble-mediated shuttle reaction was used inside the DNM-functionalized microchannel to improve the target-capturing efficiency. Using this novel DNM biosensor, the sensitive and selective detection of multiple heavy-metal ions (i.e., Hg2+, Ag+, and Pb2+) was achieved within 5 min, the detection limit was down to 10, 10, and 20 nM for Hg2+, Ag+, and Pb2+, respectively. The feasibility of our DNM sensor was further demonstrated by probing heavy-metal ions in real water samples with a direct optical readout. Beyond metal ions, this unique DNM sensor can easily be extended to in vitro bioassays and clinical diagnostics.