imec, Kapeldreef 75, 3001, Leuven, Belgium.
Department of Physics and Astronomy, KU Leuven, 3001, Leuven, Belgium.
Nat Commun. 2018 Apr 30;9(1):1733. doi: 10.1038/s41467-018-04118-7.
Solid-state nanopores promise a scalable platform for single-molecule DNA analysis. Direct, real-time identification of nucleobases in DNA strands is still limited by the sensitivity and the spatial resolution of established ionic sensing strategies. Here, we study a different but promising strategy based on optical spectroscopy. We use an optically engineered elongated nanopore structure, a plasmonic nanoslit, to locally enable single-molecule surface enhanced Raman spectroscopy (SERS). Combining SERS with nanopore fluidics facilitates both the electrokinetic capture of DNA analytes and their local identification through direct Raman spectroscopic fingerprinting of four nucleobases. By studying the stochastic fluctuation process of DNA analytes that are temporarily adsorbed inside the pores, we have observed asynchronous spectroscopic behavior of different nucleobases, both individual and incorporated in DNA strands. These results provide evidences for the single-molecule sensitivity and the sub-nanometer spatial resolution of plasmonic nanoslit SERS.
固态纳米孔有望成为单分子 DNA 分析的可扩展平台。直接实时识别 DNA 链中的核碱基仍然受到现有离子传感策略的灵敏度和空间分辨率的限制。在这里，我们研究了一种基于光谱学的不同但有前途的策略。我们使用一种经过光学设计的拉长纳米孔结构，即等离子体纳米狭缝，在局部实现单分子表面增强拉曼光谱 (SERS)。将 SERS 与纳米孔流体相结合，既有利于通过电动力学捕获 DNA 分析物，也有利于通过直接拉曼光谱对四个核碱基进行局部识别。通过研究暂时被吸附在孔内的 DNA 分析物的随机波动过程，我们观察到不同核碱基的异步光谱行为，无论是单独存在还是存在于 DNA 链中。这些结果为等离子体纳米狭缝 SERS 的单分子灵敏度和亚纳米空间分辨率提供了证据。
