Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Nat Nanotechnol. 2011 Dec 11;7(2):119-25. doi: 10.1038/nnano.2011.217.
Nanopores could potentially be used to perform single-molecule DNA sequencing at low cost and with high throughput. Although single base resolution and differentiation have been demonstrated with nanopores using ionic current measurements, direct sequencing has not been achieved because of the difficulties in recording very small (∼pA) ionic currents at a bandwidth consistent with fast translocation speeds. Here, we show that solid-state nanopores can be combined with silicon nanowire field-effect transistors to create sensors in which detection is localized and self-aligned at the nanopore. Well-defined field-effect transistor signals associated with DNA translocation are recorded when an ionic strength gradient is imposed across the nanopores. Measurements and modelling show that field-effect transistor signals are generated by highly localized changes in the electrical potential during DNA translocation, and that nanowire-nanopore sensors could enable large-scale integration with a high intrinsic bandwidth.
纳米孔有可能以低成本和高通量进行单分子 DNA 测序。尽管已经使用离子电流测量证明了纳米孔具有单碱基分辨率和区分能力，但由于在与快速迁移速度一致的带宽下记录非常小（约为 pA）的离子电流存在困难，因此尚未实现直接测序。在这里，我们展示了固态纳米孔可以与硅纳米线场效应晶体管结合使用，以创建传感器，其中检测在纳米孔处局部化并自对准。当在纳米孔上施加离子强度梯度时，记录与 DNA 迁移相关的明确的场效应晶体管信号。测量和建模表明，场效应晶体管信号是由 DNA 迁移过程中局部电势能的高度变化产生的，并且纳米线-纳米孔传感器可以实现大规模集成和高固有带宽。
