Interaction dynamics and site-specific electronic recognition of DNA-nicks with 2D solid-state nanopores

Single-stranded breaks in the DNA backbone caused by many endogenous and exogenous agents often lead to double-stranded breaks that are known causes of chromosomal instabilities leading to copious diseases. We describe a label-free detection technique using two-dimensional (2D) solid-state nanopore field-effect transistors (FETs) to sense and map site-specific nicks in the DNA backbone. We use all-atom molecular dynamics simulations coupled with electronic transport modeling to illustrate the 2D membrane device capability to sense minute structural changes of any translocating biomolecules via their in-plane electronic sheet current signatures, whereas Van der Waals analyses explain the distinct hydrophobic interactions between various DNA-nick types with graphene and MoS₂ nanopore membranes. Specifically, we describe the atypical unzipping behavior of DNA strands caused by the biomolecule sticking at nicked site in the graphene nanopore, under the influence of voltage-specific translocations.