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基于纳米孔的 DNA 测序传感器:综述。

Nanopore-based sensors for DNA sequencing: a review.

机构信息

School of Integrated Circuits, Tsinghua University, Beijing 100084, China.

Department of Microelectronics, Delft University of Technology, 2628 CD Delft, The Netherlands.

出版信息

Nanoscale. 2024 Oct 17;16(40):18732-18766. doi: 10.1039/d4nr01325e.

DOI:10.1039/d4nr01325e
PMID:39295590
Abstract

Nanopore sensors, owing to their distinctive structural properties, can be used to detect biomolecular translocation events. These sensors operate by monitoring variations in electric current amplitude and duration, thereby enabling the calibration and distinction of various biomolecules. As a result, nanopores emerge as a potentially powerful tool in the field of deoxyribonucleic acid (DNA) sequencing. However, the interplay between testing bandwidth and noise often leads to the loss of part of the critical translocation signals, presenting a substantial challenge for the precise measurement of biomolecules. In this context, innovative detection mechanisms have been developed, including optical detection, tunneling current detection, and nanopore field-effect transistor (FET) detection. These novel detection methods are based on but beyond traditional nanopore techniques and each of them has unique advantages. Notably, nanopore FET sensors stand out for their high signal-to-noise ratio (SNR) and high bandwidth measurement capabilities, overcoming the limitations typically associated with traditional solid-state nanopore (SSN) technologies and thus paving the way for new avenues to biomolecule detection. This review begins by elucidating the fundamental detection principles, development history, applications, and fabrication methods for traditional SSNs. It then introduces three novel detection mechanisms, with a particular emphasis on nanopore FET detection. Finally, a comprehensive analysis of the advantages and challenges associated with both SSNs and nanopore FET sensors is performed, and then insights into the future development trajectories for nanopore FET sensors in DNA sequencing are provided. This review has two main purposes: firstly, to provide researchers with a preliminary understanding of advancements in the nanopore field, and secondly, to offer a comprehensive analysis of the fabrication techniques, transverse current detection principles, challenges, and future development trends in the field of nanopore FET sensors. This comprehensive analysis aims to help give researchers in-depth insights into cutting-edge advancements in the field of nanopore FET sensors.

摘要

纳米孔传感器具有独特的结构特性,可用于检测生物分子的转位事件。这些传感器通过监测电流幅度和持续时间的变化来工作,从而能够校准和区分各种生物分子。因此,纳米孔在脱氧核糖核酸 (DNA) 测序领域成为一种潜在的强大工具。然而,测试带宽和噪声之间的相互作用常常导致关键转位信号的部分丢失,这对生物分子的精确测量构成了重大挑战。在这种情况下,已经开发出了创新的检测机制,包括光学检测、隧道电流检测和纳米孔场效应晶体管 (FET) 检测。这些新的检测方法基于但超越了传统的纳米孔技术,它们各自具有独特的优势。值得注意的是,纳米孔 FET 传感器因其高信噪比 (SNR) 和高带宽测量能力而脱颖而出,克服了传统固态纳米孔 (SSN) 技术通常存在的限制,为生物分子检测开辟了新途径。本综述首先阐明了传统 SSN 的基本检测原理、发展历史、应用和制造方法。然后介绍了三种新型检测机制,特别强调了纳米孔 FET 检测。最后,对 SSN 和纳米孔 FET 传感器相关的优缺点进行了全面分析,并对纳米孔 FET 传感器在 DNA 测序中的未来发展轨迹进行了展望。本综述有两个主要目的:首先,为研究人员提供对纳米孔领域进展的初步了解;其次,对纳米孔 FET 传感器的制造技术、横向电流检测原理、挑战和未来发展趋势进行全面分析。这种全面的分析旨在帮助研究人员深入了解纳米孔 FET 传感器领域的前沿进展。

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