Base-by-base ratcheting of single-stranded DNA through a solid-state nanopore: toward low-cost and high-throughput sequencing of the human Genome

The benefits of low-cost and high-throughput sequencing of the human genome to medical science has inspired recent experimental work focused on DNA translocation through solid-state nanopores. Given that microelectronic fabrication methods permit the integration of nano-electronics devices to sense each DNA base, the genetic code (DNA sequence) could be read out during the translocation by measurement of transverse electrical current, voltage signal, ionic current or hydrogen-bond mediated tunneling signal generated by each base in DNA. However, DNA translocation inside a solid-state nanopore remains poorly controlled and DNA moves too rapidly to be detected at the desired single-base resolution. In this talk, I show using realistic atomistic modeling that the recently proposed DNA transistor can achieve the single-base control. These simulation results and a simple theoretical model inspired by the numerical studies demonstrate that when pulled by an optical tweezer as in a single molecule experiment or driven by a biasing electric field as in a high-throughput sequencing mode, the DNA transistor allows single-stranded DNA to transit a nanopore in a stick-slip or ratchet-like fashion, i.e. DNA alternatively stops and advances quickly one nucleotide spacing. In a trapped state, a DNA base could be positioned in front of a sensor for an accurate read-out. Ideally, the DNA transistor could be utilized in conjunction with a nanopore-based DNA sensing technology to achieve the goal of fast and cheap DNA sequencing.