Abstract
A solid-state nanopore platform with a low noise level and sufficient sensitivity to discriminate single-strand DNA (ssDNA) homopolymers of poly-A40 and poly-T40 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-A40 and poly-T40. 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.
Highlights
A solid-state nanopore platform with a low noise level and sufficient sensitivity to discriminate single-strand DNA homopolymers of poly-A40 and poly-T40 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 are used to maximize the signal-to-noise ratio and the spatial depth resolution
A series of impressive developments has been made in the area of protein nanopores using either a-hemolysin[7,8,9,10] or MspA11–13 as they possess a low noise level and guarantee the reliable formation of a small pore aperture (1.5 nm) and an extremely thin sensing zone of approximately 1 nm
Summary
A Low-Noise Solid-State Nanopore Platform Based on a Highly Insulating Substrate. Min-Hyun Lee[1], Ashvani Kumar[1], Kyeong-Beom Park[1], Seong-Yong Cho[1], Hyun-Mi Kim[1], Min-Cheol Lim[2], Young-Rok Kim2 & Ki-Bum Kim[1,3]. The reliable formation of small nanopores (, 2 nm in diameter), fabrication of an extremely thin sensing zone with a thickness comparable to the spacing of each nucleotide, decrease of the noise level, and control of the translocation speed that would guarantee sufficient time to sense each nucleotide are the few challenges that limit the performance of solid-state nanopores. Among these issues, the excess noise level in solid-state nanopores (a few tens of pA to 100 pA: ,10 times larger than that of protein counterparts17–20) has been one of the key issues responsible for the degraded signal-to-noise ratio and temporal and spatial resolution. We demonstrate that this device is capable of successfully detecting 40nucleotides (nt) homopolymer single-strand DNA translocation events with a resolution of discriminating between poly-A40 and poly-T40 molecules
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