Controlled Ion Transport and Transverse DNA Sensing Using 2D Heterostructure Nanopores

Fast and inexpensive DNA sequencing represents a great challenge in personalized medicine and disease diagnosis. Compared to fluorescence-based sequencing, biological nanopores realize real-time and direct sequencing for long DNA chains without the time-consuming amplification/reconstruction process. Yet the fragile lipid bilayer membrane yields short pore lifetime. In this case, solid-state nanopores offer additional advantages including superior mechanical/chemical/thermal robustness, controllable pore sizes and the potential integration with electronics^[1]. Despite the promise, solid-state nanopores fail to perform sequencing due to the poor spatial resolution and fast translocation^[1]. 2D materials turn out to be promising membranes due to the atomic thickness, making them the optimal choice for achieving single-nucleobase resolution^[1]. However, freestanding 2D materials are prone to leakage and mechanically unstable in salt solution, while adding dielectric support/isolation layers adds to the total membrane thickness, offsetting the advantage rising from the atomic thickness^[2,3]. To realize solid-state nanopores competitive with biological ones requires translocation speed control and sensing mechanisms with spatial resolution unlimited by the total membrane thickness.<br/>We propose a novel solid-state nanopore design based on 2D heterostructure with sub-nm spatial resolution, correlated electrical sensing and translocation speed control. We fabricated out-of-plane diode by stacking p-type WSe₂ and n-type MoS₂ and drilled a nanopore in the overlapping region. The diode architecture allows the application and sensing of voltage and current between the two layers separated by only 6.5 angstroms, comparable to the size of one nucleotide unit (3.3 angstroms). The key questions include how interlayer potential tunes the translocation of ions and molecules through the pore, and how the presence of molecules in the pore affects interlayer conductance.<br/>We first characterized the electronic performance of 2D diode nanopore devices in 10 mM KCl solution under ionic bias across the membrane and interlayer bias. The heterostructure displays diode rectification current as a function of interlayer bias. The ionic voltage tunes the magnitude of diode rectification by electrostatically tuning the relative doping of each layer. Meanwhile, we observed tuning of the ion transport through the pore with interlayer bias as the interlayer potential across the vertical p-n diode exerts a local electric field in the nanopore. Finally, we demonstrated simultaneous ionic and electrical sensing of DNA translocation through the 2D heterostructure-based nanopore, a first demonstration of sensing in this architecture. We achieved sensing of pUC19 circular dsDNA with SNR of 2.<br/>Overall, the heterostructure architecture represents a new paradigm for nanopore mass transport control with simultaneous in-situ sensing. This could be applied to applications including gated molecular sieving and slowing translocation for molecular identification with solid-state nanopores.<br/><b>References:</b><br/>[1] Y. He, M. Tsutsui, Y. Zhou, X. S. Miao, <i>NPG Asia Mater.</i> <b>2021</b>, DOI 10.1038/s41427-021-00313-z.<br/>[2] B. M. Venkatesan, D. Estrada, S. Banerjee, X. Jin, V. E. Dorgan, M. H. Bae, N. R. Aluru, E. Pop, R. Bashir, <i>ACS Nano</i> <b>2012</b>, DOI 10.1021/nn203769e.<br/>[3] S. Banerjee, J. Shim, J. Rivera, X. Jin, D. Estrada, V. Solovyeva, X. You, J. Pak, E. Pop, N. Aluru, R. Bashir, <i>ACS Nano</i> <b>2013</b>, DOI 10.1021/nn305400n.