Short-chain oligonucleotide detection by glass nanopore using targeting-induced DNA tetrahedron deformation as signal amplifier.

Glass capillary nanopore has been developed as a promising sensing platform for bioassay with single-molecule resolution. Although the diameter of glass capillary nanopore can be easily tuned, direct event-readouts of small biomacromolecules, like short-chain oligonucleotide fragments (within ∼20 nucleotides) remain great challenge, which limited by the configuration of the conical-shaped nanopore and the instrumental temporal resolution. Here, we exploit a smart strategy for glass nanopore detection of short-chain oligonucleotides by using relatively big-sized tetrahedral DNA nanostructures as a signal amplifier, which can amplify the signals and retard the translocation speed meanwhile. The tetrahedral DNA nanostructure with a hairpin loop sequence in one edge, undergoes a shape transformation upon the complementary combination of the target oligonucleotides, in which the presence of short-chain target oligonucleotide can be readout due to obvious variation in amplitude of ion current pulse that caused by volume change of the DNA tetrahedral. Therefore, this strategy is promising for extending glass nanopore sensing platform for sensitive detection of short-chain oligonucleotides.