A Low-Noise Solid-State Nanopore Platform Based on a Highly Insulating Substrate

A solid-state nanopore platform with a low noise level and sufficient sensitivity to discriminate single-strand DNA (ssDNA) homopolymers of poly-A(40) and poly-T(40) using ionic current blockade sensing is proposed and demonstrated. The key features of this platform are (a) highly insulating dielectric substrates that are used to mitigate the effect of parasitic capacitance elements, which decrease the ionic current RMS noise level to sub-10 pA and (b) ultra-thin silicon nitride membranes with a physical thickness of 5 nm (an effective thickness of 2.4 nm estimated from the ionic current) are used to maximize the signal-to-noise ratio and the spatial depth resolution. The utilization of an ultra-thin membrane and a nanopore diameter as small as 1.5 nm allow the successful discrimination of 40 nucleotide ssDNA poly-A(40) and poly-T(40). Overall, we demonstrate that this platform overcomes several critical limitations of solid-state nanopores and opens the door to a wide range of applications in single-molecule-based detection and analysis.