Nanopore biosensor for sensitive and label-free nucleic acid detection based on hybridization chain reaction amplification

A label-free nanopore biosensor for detection of DNA target is proposed utilizing hybridization chain reaction (HCR) strategy for signal amplification. The DNA target triggered HCR to form large DNA nanostructure inside the nanopore and out the nanopore membrane, which inducing the ionic current decrease effectively due to the blockage of the nanopore. The developed method achieves a desirable sensitivity of 30 fM with a wide linear dynamic range from 0.1 to 10 pM and demonstrated good application for real sample analysis. This work has great potential to be applied in the early diagnosis of gene-related diseases and provide a new paradigm for label-free nucleic acid amplification strategy in ultrasensitive nanopore biosensor.