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Highly accurate random DNA sequencing using inherent interlayer potential traps of bilayer MoS2 nanopores

Sen, P.; Hoi, H.; Nandi, D.; Gupta, M.

2020-04-23 bioengineering
10.1101/2020.04.21.053595 bioRxiv
Show abstract

Solid-state MoS2 nanopores are emerging as potential real-time DNA sequencers due to their ultra-thinness and pore stability. One of the major challenges in determining random nucleotide sequence (unlike polynucleotide strands) is the non-homogeneity of the charge interaction and velocity during DNA translocation. This results in varying blockade current for the same nucleotide, reducing the sequencing confidence. In this work, we studied the inherent impedance-tunability (due to vertical interlayer potential gradient and ion accumulation) of multilayered MoS2 nanopores along with its effect on improving analyte capture and charge interaction, for more sensitive and confident sensing. Experimentally we demonstrate that 2-3 nm diameter bilayer MoS2 pores are best suited for high accuracy (~90%) sequencing of mixed nucleotides with signal-to-noise-ratio greater than 11 in picomolar concentration solutions. High temporal resolution demonstrated by bilayer MoS2 nanopores can help detect neutral proteins in future. The high accuracy detection in low concentration analyte can hence be applied for control and prevention of hereditary diseases and understanding health effects of rare microbial strains.

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