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单宁酸配位膜包覆固态纳米孔实现寡核苷酸区分。

Oligonucleotide Discrimination Enabled by Tannic Acid-Coordinated Film-Coated Solid-State Nanopores.

机构信息

State Key Lab for Mesoscopic Physics and Frontiers Science Center for Nano-Optoelectronics, School of Physics, Peking University, Beijing 100871, China.

The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Zhejiang, 310022 Hangzhou, China.

出版信息

Langmuir. 2022 May 24;38(20):6443-6453. doi: 10.1021/acs.langmuir.2c00638. Epub 2022 May 11.

Abstract

Discrimination of nucleotides serves as the basis for DNA sequencing using solid-state nanopores. However, the translocation of DNA is usually too fast to be detected, not to mention nucleotide discrimination. Here, we utilized polyphenolic TA and Fe, an attractive metal-organic thin film, and achieved a fast and robust surface coating for silicon nitride nanopores. The hydrophilic coating layer can greatly reduce the low-frequency noise of an original unstable nanopore, and the nanopore size can be finely tuned at the nanoscale by simply adjusting the relative ratio of Fe and TA monomers. Moreover, the hydrogen bonding interaction formed between the hydroxyl groups provided by TA and the phosphate groups of DNAs significantly increases the residence time of a short double-strand (100 bp) DNA. More importantly, we take advantage of the different strengths of hydrogen bonding interactions between the hydroxyl groups provided by TA and the analytes to discriminate between two oligonucleotide samples (oligodeoxycytidine and oligodeoxyadenosine) with similar sizes and lengths, of which the current signal patterns are significantly different using the coated nanopore. The results shed light on expanding the biochemical functionality of surface coatings on solid-state nanopores for future biomedical applications.

摘要

基于固态纳米孔的 DNA 测序中,核苷酸的区分是其基础。然而,DNA 的穿隧通常太快而无法被检测到,更不用说核苷酸的区分了。在此,我们利用多酚 TA 和 Fe(一种具有吸引力的金属有机薄膜),在氮化硅纳米孔上实现了快速且稳健的表面涂层。亲水性的涂层极大地降低了原始不稳定纳米孔的低频噪声,并且通过简单地调整 Fe 和 TA 单体的相对比例,纳米孔的尺寸可以在纳米尺度上进行精细调节。此外,由 TA 提供的羟基与 DNA 的磷酸基团之间形成的氢键相互作用显著增加了短双链(100 bp)DNA 的停留时间。更重要的是,我们利用 TA 提供的羟基与分析物之间氢键相互作用的不同强度,来区分两个大小和长度相似的寡核苷酸样品(寡脱氧胞苷和寡脱氧腺苷),其中使用涂层纳米孔时,电流信号模式有显著差异。这些结果为未来生物医学应用中固态纳米孔表面涂层的生化功能扩展提供了思路。

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