Controlled Ionic Transport and Electrical Sensing of DNA using Van der Waals Heterojunction Nanopores

Sequencing the human genome has helped to improve our understanding of disease, inheritance and individuality. Solid-state nanopores could potentially meet the demand for even cheaper and faster genome sequencing, owing to their superior mechanical, chemical and thermal robustness and durability, and potential for integration into high-density electronic arrays.¹ Despite the promise, solid state nanopores have yet to demonstrate DNA sequencing. Two key challenges remain, i.e., achieving few-base spatial resolution and slowing the translocation of the DNA molecule. 2D materials such as graphene² and MoS₂³ have emerged as attractive possibilities, since the thickness of these films is in the range of a few nucleotides. However, atomic membranes alone are not robust in fluid under an electric field.⁴ 2D materials sandwiched within dielectrics could provide a stable platform,⁵ but the resulting stack thickness limits the spatial resolution. Resolving these challenges requires new sensing mechanisms beyond ionic currents and translocation control.<br/><br/>This work reports a novel solid state nanopore sensor that has the desired sub-nanometer spatial resolution, integrated electrical sensing, and can potentially control the translocation of the DNA molecule. In this architecture, the nanopore is drilled through a vertical 2D heterostructure consisting of n-type MoS₂ and p-type WSe₂ using focused electron beams. The heterostructure forms an atomically thin out-of-plane p-n diode. The diode is passivated by atomic layer deposition (ALD) of HfO₂ for electrical insulation. We demonstrated modulation of ionic current by the interlayer potential of the van der Waals heterostructure diode. Ionic current modulation is more effective with smaller pores and lower salt concentrations, and thus is not caused by leakage or edge electrochemistry. Modulation of ionic transport is also more effective under forward bias than under reverse bias, as a larger fraction of in-plane bias drops across the vertical p-n junction under forward bias.⁶ Finally, we obtained signatures of DNA translocation in ionic and diode channels simultaneously. DNA translocation in 10 mM KCl resulted in current increase in ionic channel, as well as current increase in diode channel. Overall, this heterojunction architecture represents a new paradigm for nanopore mass transport control with simultaneous electrical sensing, which could be applied to applications such as gated molecular sieving and slowing translocation for molecular identification with solid-state nanopores.<br/><b>References:</b><br/>(1) Lindsay, S. The Promises and Challenges of Solid-State Sequencing. <i>Nat. Nanotechnol.</i> <b>2016</b>, <i>11</i> (2), 109–111.<br/>(2) Garaj, S.; Hubbard, W.; Reina, A.; Kong, J.; Branton, D.; Golovchenko, J. A. Graphene as a Subnanometre Trans-Electrode Membrane. <i>Nature</i> <b>2010</b>, <i>467</i> (7312), 190–193.<br/>(3) Feng, J.; Liu, K.; Bulushev, R. D.; Khlybov, S.; Dumcenco, D.; Kis, A.; Radenovic, A. Identification of Single Nucleotides in MoS₂ Nanopores. <i>Nat. Nanotechnol.</i> <b>2015</b>, <i>10</i> (12), 1070–1076.<br/>(4) Graf, M.; Lihter, M.; Thakur, M.; Georgiou, V.; Topolancik, J.; Ilic, B. R.; Liu, K.; Feng, J.; Astier, Y.; Radenovic, A. Fabrication and Practical Applications of Molybdenum Disulfide Nanopores. <i>Nat. Protoc.</i> <b>2019</b>, <i>14</i> (4), 1130–1168.<br/>(5) Venkatesan, B. M.; Estrada, D.; Banerjee, S.; Jin, X.; Dorgan, V. E.; Bae, M. H.; Aluru, N. R.; Pop, E.; Bashir, R. Stacked Graphene-Al₂O₃ Nanopore Sensors for Sensitive Detection of DNA and DNA-Protein Complexes. <i>ACS Nano</i> <b>2012</b>, <i>6</i> (1), 441–450.<br/>(6) Lee, C. H.; Lee, G. H.; Van Der Zande, A. M.; Chen, W.; Li, Y.; Han, M.; Cui, X.; Arefe, G.; Nuckolls, C.; Heinz, T. F.; et al. Atomically Thin P-n Junctions with van Der Waals Heterointerfaces. <i>Nat. Nanotechnol.</i> <b>2014</b>, <i>9</i> (9), 676–681.