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通过结构修饰的固态纳米孔提高 DNA 检测的灵敏度。

Enhancing the sensitivity of DNA detection by structurally modified solid-state nanopore.

机构信息

Department of Materials Science and Engineering, Seoul National University, Seoul 08826, Republic of Korea.

出版信息

Nanoscale. 2017 Nov 23;9(45):18012-18021. doi: 10.1039/c7nr05840c.

Abstract

Solid-state nanopore is an ionic current-based biosensing platform, which would be a top candidate for next-generation DNA sequencing and a high-throughput drug-screening tool at single-molecular-scale resolution. There have been several approaches to enhance the sensitivity and reliability of biomolecule detection using the nanopores particularly in two aspects: signal-to-noise ratio (SNR) and translocation dwell time. In this study, an additional nano-well of 100-150 nm diameter and the aspect ratio of ∼5 called 'guide structure' was inserted in conventional silicon-substrate nanopore device to increase both SNR and dwell time. First, the magnitude of signals (conductance drop (ΔG)) increased 2.5 times under applied voltage of 300 mV through the guide-inserted nanopore compared to the conventional SiN/Si nanopore in the same condition. Finite element simulation was conducted to figure out the origin of ΔG modification, which showed that the guide structure produced high ΔG due to the compartmental limitation of ion transports through the guide to the sensing nanopore. Second, the translocation velocity decreased in the guide-inserted structure to a maximum of 20% of the velocity in the conventional device at 300 mV. Electroosmotic drag formed inside the guide structure, when directly applied to the remaining segment of translocating DNA molecules in cis chamber, affected the DNA translocation velocity. This study is the first experimental report on the effect of the geometrical confinement to a remnant DNA on both SNR and dwell time of nanopore translocations.

摘要

固态纳米孔是一种基于离子电流的生物传感平台,它将成为下一代 DNA 测序和高通量药物筛选工具的首选,具有单分子级分辨率。已经有几种方法可以提高使用纳米孔进行生物分子检测的灵敏度和可靠性,特别是在两个方面:信噪比 (SNR) 和迁移停留时间。在这项研究中,在传统的硅衬底纳米孔器件中插入了一个额外的直径为 100-150nm、纵横比约为 5 的纳米阱,称为“导向结构”,以提高 SNR 和停留时间。首先,与相同条件下的传统 SiN/Si 纳米孔相比,在 300mV 的外加电压下,通过插入导向结构的纳米孔,信号幅度(电导下降 (ΔG)) 增加了 2.5 倍。通过有限元模拟得出了 ΔG 变化的原因,表明导向结构产生了高 ΔG,这是由于离子通过导向结构向传感纳米孔的传输受到了隔室限制。其次,在导向插入结构中,迁移速度下降到传统装置的最大 20%,外加电压为 300mV。当直接施加于 cis 腔中迁移的 DNA 分子的剩余部分时,在导向结构内形成的电动拖拽影响了 DNA 的迁移速度。本研究是关于几何限制对纳米孔迁移的 SNR 和停留时间的影响的第一个实验报告。

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