Institute of Quantitative Biology, Shanghai Institute for Advanced Study, College of Life Sciences, and Department of Physics, Zhejiang University, Hangzhou 310027, China.
Department of Chemistry, Colombia University, New York, NY 10027, USA.
Nanoscale. 2022 May 16;14(18):6922-6929. doi: 10.1039/d1nr07116e.
High-fidelity DNA sequencing using solid-state nanopores remains a big challenge, partly due to difficulties related to efficient molecular capture and subsequent control of the dwell time. To help address these issues, here we propose a sequencing platform consisting of stacked two-dimensional materials with tailored structures containing a funnel-shaped step defect and a nanopore drilled inside the nanochannel. Our all-atom molecular dynamics (MD) simulations showed that, assisted by the step defect, single-stranded DNA (ssDNA) can be transported to the nanopore in a deterministic way by pulsed transversal electric fields. Furthermore, different types of DNA bases can reside in the pore for a sufficiently long time which can be successfully differentiated by longitudinal ionic currents. By using the decoupled driving forces for ssDNA transport and ionic current measurements, this approach holds potential for high-fidelity DNA sequencing.
使用固态纳米孔进行高保真度 DNA 测序仍然是一个巨大的挑战，部分原因是与有效分子捕获和随后的停留时间控制相关的困难。为了帮助解决这些问题，我们在这里提出了一个由堆叠的二维材料组成的测序平台，该平台具有定制的结构，包含一个漏斗形阶跃缺陷和纳米通道内部钻取的纳米孔。我们的全原子分子动力学 (MD) 模拟表明，在阶跃缺陷的辅助下，单链 DNA（ssDNA）可以通过脉冲横向电场以确定的方式被输送到纳米孔中。此外，不同类型的 DNA 碱基可以在孔中停留足够长的时间，这可以通过纵向离子电流成功区分。通过使用 ssDNA 传输和离子电流测量的解耦驱动力，这种方法有可能实现高保真度 DNA 测序。
