Nucleotide discrimination upon DNA immobilization in graphene nanopore sequencing

Abstract

Solid-state nanopore sequencing requires sufficient dwell time for base-resolution. This motivates strategies to extend the residence time of DNA within the sensing region. Here, using all-atom molecular dynamics, we compare ionic current signatures of mobile versus immobilized ssDNA in a graphene nanopore. We find that immobilization –despite maximizing dwell time- reduces nucleotide current contrast by up to 90% and degrades the signal-to-noise ratio. This originates from the loss of the dynamic ionic screening cloud dragged by the translocating DNA. Our results highlight that mobility is critical to signal generation, implying that optimal slowdown strategies must preserve local ion–DNA co-dynamics.