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Identification of single nucleotides in MoS2 nanopores

Abstract

The size of the sensing region in solid-state nanopores is determined by the size of the pore and the thickness of the pore membrane, so ultrathin membranes such as graphene and single-layer molybdenum disulphide could potentially offer the necessary spatial resolution for nanopore DNA sequencing. However, the fast translocation speeds (3,000–50,000 nt ms–1) of DNA molecules moving across such membranes limit their usability. Here, we show that a viscosity gradient system based on room-temperature ionic liquids can be used to control the dynamics of DNA translocation through MoS2 nanopores. The approach can be used to statistically detect all four types of nucleotide, which are identified according to current signatures recorded during their transient residence in the narrow orifice of the atomically thin MoS2 nanopore. Our technique, which exploits the high viscosity of room-temperature ionic liquids, provides optimal single nucleotide translocation speeds for DNA sequencing, while maintaining a signal-to-noise ratio higher than 10.

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Figure 1: Schematic and characterization of the RTILs/KCl viscosity gradient system in MoS2 nanopores.
Figure 2: Slowing of DNA translocation.
Figure 3: Differentiation of 30-mer oligonucleotides in the MoS2 nanopore.
Figure 4: Identification of single nucleotides in a MoS2 nanopore.

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Acknowledgements

The authors thank J. Wu and H. Zhang for discussions about the physicochemical characteristics of ionic liquids and P. De los Rios for discussion about the force drag mechanism. The authors acknowledge the Centre Interdisciplinaire de Microscopie Electronique (CIME) at EPFL for access to electron microscopes, and special thanks go to D.T.L. Alexander for providing training and technical assistance with the TEM. Device fabrication was partially carried out at the EPFL Center for Micro/Nanotechnology (CMi). The authors thank all members from LBEN and LANES for assistance and discussions. The work was supported financially by the European Research Council (grant no. 259398, PorABEL: Nanopore integrated nanoelectrodes for biomolecular manipulation and sensing, and SNF Sinergia grant no. 147607). The authors thank C. Dekker for reading the manuscript.

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Contributions

J.F. and A.R. conceived the idea. J.F., K.L. and A.R designed the experiments. J.F. and K.L. fabricated and characterized the devices, performed experiments and analysed the data. R.D.B. performed single-molecule fluorescence measurements. S.K and R.D.B. performed COMSOL modelling. D.D. performed chemical vapour deposition MoS2 growth with A.K.'s supervision. J.F., K.L., A.K. and A.R. wrote the paper. All authors provided important suggestions for the experiments, discussed the results and contributed to the manuscript.

Corresponding author

Correspondence to Aleksandra Radenovic.

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The authors declare an intellectual property interest in a provisional patent WO/121394 A1.

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Feng, J., Liu, K., Bulushev, R. et al. Identification of single nucleotides in MoS2 nanopores. Nature Nanotech 10, 1070–1076 (2015). https://doi.org/10.1038/nnano.2015.219

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