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纳米孔技术在用于生物标志物检测的肽和蛋白质传感中的潜力。

The Potential of Nanopore Technologies in Peptide and Protein Sensing for Biomarker Detection.

作者信息

Șoldănescu Iuliana, Lobiuc Andrei, Caliman-Sturdza Olga Adriana, Covasa Mihai, Mangul Serghei, Dimian Mihai

机构信息

Integrated Center for Research, Development, and Innovation for Advanced Materials, Nanotechnologies, Manufacturing and Control Distributed Systems (MANSiD), Stefan cel Mare University of Suceava, 720229 Suceava, Romania.

Department of Computer, Electronics and Automation, Stefan cel Mare University of Suceava, 720229 Suceava, Romania.

出版信息

Biosensors (Basel). 2025 Aug 16;15(8):540. doi: 10.3390/bios15080540.

DOI:10.3390/bios15080540
PMID:40863000
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12384913/
Abstract

The increasing demand for high-throughput, real-time, and single-molecule protein analysis in precision medicine has propelled the development of novel sensing technologies. Among these, nanopore-based methods have garnered significant attention for their unique capabilities, including label-free detection, ultra-sensitivity, and the potential for miniaturization and portability. Originally designed for nucleic acid sequencing, nanopore technology is now being adapted for peptide and protein analysis, offering promising applications in biomarker discovery and disease diagnostics. This review examines the latest advances in biological, solid-state, and hybrid nanopores for protein sensing, focusing on their ability to detect amino acid sequences, structural variants, post-translational modifications, and dynamic protein-protein or protein-drug interactions. We critically compare these systems to conventional proteomic techniques, such as mass spectrometry and immunoassays, discussing advantages and persistent technical challenges, including translocation control and signal deconvolution. Particular emphasis is placed on recent advances in protein sequencing using biological and solid-state nanopores and the integration of machine learning and signal-processing algorithms that enhance the resolution and accuracy of protein identification. Nanopore protein sensing represents a disruptive innovation in biosensing, with the potential to revolutionize clinical diagnostics, therapeutic monitoring, and personalized healthcare.

摘要

精准医学中对高通量、实时和单分子蛋白质分析的需求不断增加,推动了新型传感技术的发展。其中,基于纳米孔的方法因其独特的能力而备受关注,包括无标记检测、超灵敏度以及小型化和便携性的潜力。纳米孔技术最初设计用于核酸测序,现在正被应用于肽和蛋白质分析,在生物标志物发现和疾病诊断方面具有广阔的应用前景。本文综述了用于蛋白质传感的生物、固态和混合纳米孔的最新进展,重点关注它们检测氨基酸序列、结构变体、翻译后修饰以及动态蛋白质-蛋白质或蛋白质-药物相互作用的能力。我们将这些系统与传统蛋白质组学技术(如质谱和免疫分析)进行了严格比较,讨论了其优势和持续存在的技术挑战,包括转运控制和信号反卷积。特别强调了使用生物和固态纳米孔进行蛋白质测序的最新进展,以及机器学习和信号处理算法的整合,这些算法提高了蛋白质鉴定的分辨率和准确性。纳米孔蛋白质传感代表了生物传感领域的一项颠覆性创新,有可能彻底改变临床诊断、治疗监测和个性化医疗。

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本文引用的文献

1
Nanopore-based enzyme-linked immunosorbent assay for cancer biomarker detection.基于纳米孔的酶联免疫吸附测定法用于癌症生物标志物检测。
Nat Nanotechnol. 2025 May 14. doi: 10.1038/s41565-025-01918-z.
2
Nanopores with an Engineered Selective Entropic Gate Detect Proteins at Nanomolar Concentration in Complex Biological Sample.具有工程化选择性熵门的纳米孔可在复杂生物样品中检测纳摩尔浓度的蛋白质。
J Am Chem Soc. 2025 May 7;147(18):15050-15065. doi: 10.1021/jacs.4c17147. Epub 2025 Apr 22.
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Exploring a solid-state nanopore approach for single-molecule protein detection from single cells.
探索一种用于从单细胞中进行单分子蛋白质检测的固态纳米孔方法。
Chem Sci. 2025 Apr 7;16(19):8501-8508. doi: 10.1039/d5sc01764e. eCollection 2025 May 14.
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Nanopore sensing of protein and peptide conformation for point-of-care applications.用于即时检测应用的蛋白质和肽构象的纳米孔传感
Nat Commun. 2025 Apr 4;16(1):3211. doi: 10.1038/s41467-025-58509-8.
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Probing nanopores: molecular dynamics insights into the mechanisms of DNA and protein translocation through solid-state and biological nanopores.探测纳米孔:通过固态和生物纳米孔进行DNA和蛋白质转位机制的分子动力学见解
Soft Matter. 2025 Mar 26;21(13):2385-2399. doi: 10.1039/d4sm01534g.
6
The role of functionalization in the translocation of peptides through multilayer graphene nanopores.功能化在肽通过多层石墨烯纳米孔转运中的作用。
J Chem Phys. 2025 Feb 14;162(6). doi: 10.1063/5.0249099.
7
Aerolysin Nanopore Electrochemistry.气单胞菌溶素纳米孔电化学
Acc Chem Res. 2025 Feb 18;58(4):517-528. doi: 10.1021/acs.accounts.4c00630. Epub 2025 Jan 28.
8
Successful adaptation of a MinION nanopore for protein sequencing.MinION纳米孔成功应用于蛋白质测序。
Synth Biol (Oxf). 2024 Nov 8;9(1):ysae017. doi: 10.1093/synbio/ysae017. eCollection 2024.
9
Nanopore approaches for single-molecule temporal omics: promises and challenges.用于单分子时间组学的纳米孔方法:前景与挑战。
Nat Methods. 2025 Feb;22(2):241-253. doi: 10.1038/s41592-024-02492-3. Epub 2024 Nov 18.
10
Controlled Translocation of Proteins through a Biological Nanopore for Single-Protein Fingerprint Identification.通过生物纳米孔对蛋白质进行可控转运,实现单蛋白质指纹识别。
Nano Lett. 2024 Nov 6;24(44):14118-14124. doi: 10.1021/acs.nanolett.4c04510. Epub 2024 Oct 24.