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The proof of concept of a nanoparticle displacement assay that enables the use of large diameter nanopores for the detection of targets of smaller molecular dimensions is presented. We hypothesized that an inherent signal amplification should arise from the selective displacement of nanoparticles preloaded in a nanopore by a much smaller molecular target. The method is demonstrated using peptide nucleic acid (PNA)-functionalized gold nanopore arrays in which short DNA-modified gold nanoparticles are anchored by weak interaction. Complementary microRNAs are detected via the resistance change caused by competitive displacement of nanoparticles from the PNA-functionalized nanopores.
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•A novel nanopore-based sensing concept suitable for nucleic acid detection is introduced.•Nanoparticles are immobilized reversibly in nanopores.•A nanoparticle displacement assay with nanopores is demonstrated.