Centre for Nano Science and Engineering, Indian Institute of Science, Bangalore 560012, India.
Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, United States.
ACS Appl Bio Mater. 2021 Jan 18;4(1):451-461. doi: 10.1021/acsabm.0c00929. Epub 2020 Dec 31.
Cost-effective, fast, and reliable DNA sequencing can be enabled by advances in nanopore-based methods, such as the use of atomically thin graphene membranes. However, strong interaction of DNA bases with graphene leads to undesirable effects such as sticking of DNA strands to the membrane surface. While surface functionalization is one way to counter this problem, here, we present another solution based on a heterostructure nanopore system, consisting of a monolayer of graphene and hexagonal boron nitride (hBN) each. Molecular dynamics studies of DNA translocation through this heterostructure nanopore revealed a surprising and crucial influence of the heterostructure layer order in controlling the base specific signal variability. Specifically, the heterostructure with graphene on top of hBN had nearly 3-10× lower signal variability than the one with hBN on top of graphene. Simulations point to the role of differential underside sticking of DNA bases as a possible reason for the observed influence of the layer order. Our studies can guide the development of experimental systems to study and exploit DNA translocation through two-dimensional heterostructure nanopores for single molecule sequencing and sensing applications.
基于纳米孔的方法（如原子级薄的石墨烯膜的使用）的进步可以实现具有成本效益、快速且可靠的 DNA 测序。然而，DNA 碱基与石墨烯的强烈相互作用会导致不理想的效果，例如 DNA 链粘在膜表面上。虽然表面功能化是解决此问题的一种方法，但在这里，我们基于异质结构纳米孔系统提出了另一种解决方案，该系统由单层石墨烯和六方氮化硼 (hBN) 组成。通过这种异质结构纳米孔的 DNA 转位的分子动力学研究揭示了异质结构层序在控制碱基特异性信号变异性方面的惊人而关键的影响。具体而言，具有石墨烯在 hBN 顶部的异质结构的信号变异性比具有 hBN 在石墨烯顶部的异质结构低近 3-10 倍。模拟指出了 DNA 碱基底面粘差异的作用，这可能是观察到的层序影响的原因。我们的研究可以为实验系统的开发提供指导，以研究和利用二维异质结构纳米孔中的 DNA 转位，用于单分子测序和传感应用。
