打破玻璃纳米孔中的尺寸障碍至2 nm：高分辨率生物分子指纹的途径
Breaking the Size Barrier in Glass Nanopores to 2 nm: A Path to High-Resolution Biomolecular Fingerprinting.
摘要(中文译文)
玻璃纳米孔因其低本征噪声、易于制备和优异的可集成性，已成为一种有前景的单分子传感平台。制备直径小至1-3 nm的玻璃纳米孔——这一尺度可与核酸和肽相媲美——是实现这些分子高分辨率指纹识别或事件测序的关键步骤，然而这仍然是一项重大挑战。在此，我们通过直接制备约2 nm的玻璃纳米孔克服了这一障碍，并以双链DNA（dsDNA）的检测为例，展现出卓越的信噪比（SNR），其离子电流阻塞率超过80%。此外，我们展示了对短至40个碱基对（bp）的dsDNA的区分，以及对单链DNA（ssDNA）同聚物（40个核苷酸）的鉴别。最后，进一步强调，卓越的优越分辨率成功检测到了一种包含40个核苷酸（nt）缺口的dsDNA拓扑结构，而使用较大直径的玻璃纳米孔极难分辨这一特征。这项工作标志着玻璃纳米孔领域的里程碑，并为高分辨率生物分子传感、指纹识别乃至测序铺平了道路。
Abstract
Glass nanopores have emerged as a promising single-molecule sensing platform due to their low intrinsic noise, facile fabrication, and excellent integrability. The fabrication of glass nanopores with diameters down to 1-3 nm, a scale comparable to nucleic acids and peptides, is a critical step toward high-resolution fingerprinting or event sequencing of these molecules, yet it remains a significant challenge. Here, it has overcome this obstacle by direct fabrication of ~2 nm glass nanopores, exemplified by the detection of double-stranded DNA (dsDNA) with an exceptional signal-to-noise ratio (SNR), exhibiting over 80% ionic current blockade. Furthermore, we demonstrate the discrimination of dsDNA as short as 40 base pairs (bp), the differentiation of single-stranded DNA (ssDNA) homopolymers (40 nucleotides). Finally, it is further highlighted that remarkably superior resolution successfully detects a DNA topological structure containing a 40-nucleotide (nt) gap within dsDNA, a feature that is extremely challenging to resolve using larger-diameter glass nanopores. This work marks a milestone in glass nanopores and paves the way for high-resolution biomolecular sensing, fingerprinting, and even sequencing.
如何引用
AMA
Xiaoyu Chen, Yaxian Liu, Fan Zhang, Aiyuan Li, Yufei Li, Ran Ji, et al. Breaking the Size Barrier in Glass Nanopores to 2 nm: A Path to High-Resolution Biomolecular Fingerprinting.. Small (Weinheim an der Bergstrasse, Germany). 2026; doi:10.1002/smll.73779.
APA
Xiaoyu Chen, Yaxian Liu, Fan Zhang, Aiyuan Li, Yufei Li, Ran Ji, et al (2026). Breaking the Size Barrier in Glass Nanopores to 2 nm: A Path to High-Resolution Biomolecular Fingerprinting.. Small (Weinheim an der Bergstrasse, Germany). https://doi.org/10.1002/smll.73779
GB/T 7714
Xiaoyu Chen, Yaxian Liu, Fan Zhang, Aiyuan Li, Yufei Li, Ran Ji, et al. Breaking the Size Barrier in Glass Nanopores to 2 nm: A Path to High-Resolution Biomolecular Fingerprinting.[J]. Small (Weinheim an der Bergstrasse, Germany), 2026 doi:10.1002/smll.73779.
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