Digital Detection of DNA via Impedimetric Tracking of Probe Nanoparticles

Abstract

CMOS-based nanocapacitor arrays are an emerging technology that permits spatially resolved, high-frequency impedance measurements at the nanoscale. Their capability to detect micro- and nanoscale entities has already been established through nonspecific interactions with the targets. Here, we demonstrate their application in specific macromolecular capture and detection using single-stranded DNA (ssDNA) as a model analyte. While individual ssDNA strands fall below the detection threshold, we employ a strand displacement assay that links DNA hybridization to target ssDNA induced displacement of reporter nanoparticles. This displacement reaction results in distinct electrical signatures with complex spatiotemporal patterns, details that remain unresolved in conventional macroscale impedance spectroscopy techniques due to their limited resolution and signal averaging that obscures localized interactions. The proposed system’s massively parallel architecture and the ability to detect complex dynamics of individual nanoparticle–nanoelectrode interactions make it a promising candidate for scalable, portable, and cost-effective biosensing applications in clinical diagnostics and beyond.