ACS Publications. Most Trusted. Most Cited. Most Read
Peptide Nucleic Acid-Functionalized Nanochannel Biosensor for the Highly Sensitive Detection of Tumor Exosomal MicroRNA
My Activity
    Article

    Peptide Nucleic Acid-Functionalized Nanochannel Biosensor for the Highly Sensitive Detection of Tumor Exosomal MicroRNA
    Click to copy article linkArticle link copied!

    • Ping-Ping Xiao
      Ping-Ping Xiao
      School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan 430065, China
    • Qiang-Qiang Wan
      Qiang-Qiang Wan
      School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan 430065, China
      Wuhan First Hospital, Wuhan 430022, China
    • Tangbin Liao
      Tangbin Liao
      School of Pharmacy, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan 430065, China
      More by Tangbin Liao
    • Ji-Yuan Tu
      Ji-Yuan Tu
      School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan 430065, China
      More by Ji-Yuan Tu
    • Guo-Jun Zhang*
      Guo-Jun Zhang
      School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan 430065, China
      *Email: [email protected]
    • Zhong-Yue Sun*
      Zhong-Yue Sun
      School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan 430065, China
      *Email: [email protected]
    Other Access OptionsSupporting Information (1)

    Analytical Chemistry

    Cite this: Anal. Chem. 2021, 93, 31, 10966–10973
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.analchem.1c01898
    Published July 30, 2021
    Copyright © 2021 American Chemical Society

    Abstract

    Click to copy section linkSection link copied!
    Abstract Image

    Compared with free miRNAs in blood, miRNAs in exosomes have higher abundance and stability. Therefore, miRNAs in exosomes can be regarded as an ideal tumor marker for early cancer diagnosis. Here, a peptide nucleic acid (PNA)-functionalized nanochannel biosensor for the ultrasensitive and specific detection of tumor exosomal miRNAs is proposed. After PNA was covalently bound to the inner surface of the nanochannels, the detection of tumor exosomal miRNAs was achieved by the charge changes on the surface of nanochannels before and after hybridization (PNA–miRNA). Due to the neutral characteristics of PNA, the efficiency of PNA–miRNA hybridization was improved by significantly reducing the background signal. This biosensor could not only specifically distinguish target miRNA-10b from single-base mismatched miRNA but also achieve a detection limit as low as 75 aM. Moreover, the biosensor was further used to detect exosomal miRNA-10b derived from pancreatic cancer cells and normal pancreatic cells. The results indicate that this biosensor could effectively distinguish pancreatic cancer tumor-derived exosomes from the normal control group, and the detection results show good consistency with those of the quantitative reverse-transcription polymerase chain reaction method. In addition, the biosensor was used to detect exosomal miRNA-10b in clinical plasma samples, and it was found that the content of exosomal miRNA-10b in cancer patients was generally higher than that of healthy individuals, proving that the method is expected to be applied for the early diagnosis of cancer.

    Copyright © 2021 American Chemical Society

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    Supporting Information

    Click to copy section linkSection link copied!

    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.analchem.1c01898.

    • Characterization of exosomes, qRT-PCR protocol, PNA probe sequence and miRNA sequences, comparison of different methods for exosomal miRNA detection, FE-SEM images of conical PET nanochannels, wettability of nanochannel before and after PNA modification, optimizations of experimental conditions, stability of the PNA-functionalized nanochannel biosensor, and TEM characterizations and NTA results of H6C7 exosomes (PDF)

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    Click to copy section linkSection link copied!

    This article is cited by 43 publications.

    1. Xiaojin Zhang, Haowen Cai, Tiantian Hu, Meihua Lin, Yu Dai, Fan Xia. DNA-Functionalized Solid-State Nanochannels with Enhanced Sensing. Accounts of Materials Research 2024, Article ASAP.
    2. Weiwei Zhang, Miaoyu Chen, Qun Ma, Zhixiao Si, Sanmei Jin, Qiujiao Du, Limin Zhang, Yu Huang, Fan Xia. Role of Outer Surface Probes on Bullet-Shaped Asymmetric Solid-State Nanochannels for Lysozyme Protein Sensing. Analytical Chemistry 2024, 96 (6) , 2445-2454. https://doi.org/10.1021/acs.analchem.3c04413
    3. Bochen Ma, Li Li, Yuting Bao, Liang Yuan, Songlin Liu, Liqing Qi, Sihui Tong, Yating Xiao, Lubin Qi, Xiaohong Fang, Yifei Jiang. Optical Imaging of Single Extracellular Vesicles: Recent Progress and Prospects. Chemical & Biomedical Imaging 2024, 2 (1) , 27-46. https://doi.org/10.1021/cbmi.3c00095
    4. Lin Shi, Haiying Cai, Han Wang, Qiwei Wang, Lili Shi, Tao Li. Proximity-Enhanced Electrochemiluminescence Sensing Platform for Effective Capturing of Exosomes and Probing Internal MicroRNAs Involved in Cancer Cell Apoptosis. Analytical Chemistry 2023, 95 (48) , 17662-17669. https://doi.org/10.1021/acs.analchem.3c03412
    5. Xiujuan Qiao, Zeng-Hui Qian, Wenpeng Sun, Chuan-Yong Zhu, Yanxin Li, Xiliang Luo. Phosphorylation of Oligopeptides: Design of Ultra-Hydrophilic Zwitterionic Peptides for Anti-Fouling Detection of Nucleic Acids in Saliva. Analytical Chemistry 2023, 95 (29) , 11091-11098. https://doi.org/10.1021/acs.analchem.3c01843
    6. Yanhu Wang, Mengchun Yang, Shenguang Ge, Xiao Wang, Jinghua Yu. Piezotronic Effect-Assisted Photoelectrochemical Exosomal MicroRNA Monitoring Based on an Electron Donor Self-Supplying Strategy. Analytical Chemistry 2022, 94 (39) , 13522-13532. https://doi.org/10.1021/acs.analchem.2c02821
    7. Yufan Zhang, Fan Yang, Wei Wei, Yeyu Wang, Shuangshuang Yang, Jinze Li, Yi Xing, Liping Zhou, Wenhao Dai, Haifeng Dong. Self-Propelled Janus Mesoporous Micromotor for Enhanced MicroRNA Capture and Amplified Detection in Complex Biological Samples. ACS Nano 2022, 16 (4) , 5587-5596. https://doi.org/10.1021/acsnano.1c10437
    8. Siqi Zhang, Wei Shi, Kai-Bin Li, De-Man Han, Jing-Juan Xu. Ultrasensitive and Label-Free Detection of Multiple DNA Methyltransferases by Asymmetric Nanopore Biosensor. Analytical Chemistry 2022, 94 (10) , 4407-4416. https://doi.org/10.1021/acs.analchem.1c05332
    9. Yanhu Wang, Mengchun Yang, Huihui Shi, Shenguang Ge, Xiao Wang, Jinghua Yu. Photoelectrochemical Detection of Exosomal miRNAs by Combining Target-Programmed Controllable Signal Quenching Engineering. Analytical Chemistry 2022, 94 (7) , 3082-3090. https://doi.org/10.1021/acs.analchem.1c04086
    10. Shijun Lin, Yiheng Liu, Jingjing Hu, Fan Xia, Xiaoding Lou. Towards effective functionalization of nanopores/nanochannels: the role of amidation reactions. Chemical Communications 2025, 40 https://doi.org/10.1039/D4CC06316C
    11. Tang-Bin Liao, Ke-Xin Luo, Ji-Yuan Tu, Yu-Lin Zhang, Guo-Jun Zhang, Zhong-Yue Sun. DSN signal amplification strategy based nanochannels biosensor for the detection of miRNAs. Bioelectrochemistry 2024, 160 , 108771. https://doi.org/10.1016/j.bioelechem.2024.108771
    12. Zhiwei Shang, Defang Ding, Zixuan Deng, Jing Zhao, Mengyu Yang, Yuling Xiao, Wenjing Chu, Shijun Xu, Zhicheng Zhang, Xiaoqing Yi, Meihua Lin, Fan Xia. Programming the Dynamic Range of Nanochannel Biosensors for MicroRNA Detection Through Allosteric DNA Probes. Angewandte Chemie 2024, 141 https://doi.org/10.1002/ange.202417280
    13. Zhiwei Shang, Defang Ding, Zixuan Deng, Jing Zhao, Mengyu Yang, Yuling Xiao, Wenjing Chu, Shijun Xu, Zhicheng Zhang, Xiaoqing Yi, Meihua Lin, Fan Xia. Programming the Dynamic Range of Nanochannel Biosensors for MicroRNA Detection Through Allosteric DNA Probes. Angewandte Chemie International Edition 2024, 33 https://doi.org/10.1002/anie.202417280
    14. Pearl Arora, Haiyan Zheng, Sathishkumar Munusamy, Rana Jahani, Xiyun Guan. Nanopore‐based detection of periodontitis biomarker miR31 in saliva samples. ELECTROPHORESIS 2024, 45 (21-22) , 2034-2044. https://doi.org/10.1002/elps.202400134
    15. Jing Ye, Qi Liang, Qianglong Tan, Mengyao Chai, Wendai Cheng, Minzhi Fan, Yunshan Zhang, Jie Zhan, Yaxin Wang, Jiahong Wen, Yongjun Zhang, Xiaoyu Zhao, Diming Zhang. A bulged-type enzyme-free recognition strategy designed for single nucleotide polymorphisms integrating with label-free electrochemical biosensor. Biosensors and Bioelectronics 2024, 263 , 116601. https://doi.org/10.1016/j.bios.2024.116601
    16. Shuanglin Deng, Wenyan Li, Zhenrun Li, Peilin Wang, Qiang Ma. Bright luminescent Zn2GeO4:Mn NP/MXene hydrogel-based ECL biosensor for glioblastoma diagnosis. Talanta 2024, 276 , 126214. https://doi.org/10.1016/j.talanta.2024.126214
    17. Xiaoyan Sun, Yafei Chen, Haiyan Li, Wei Xing, Mingli Chen, Jianhua Wang, Lei Ye. A cubic DNA nanocage probe for in situ analysis of miRNA-10b in tumor-derived extracellular vesicles. Chemical Communications 2024, 60 (36) , 4777-4780. https://doi.org/10.1039/D4CC01049C
    18. Xiaofan Pu, Chaolei Zhang, Guoping Ding, Hongpeng Gu, Yang Lv, Tao Shen, Tianshu Pang, Liping Cao, Shengnan Jia. Diagnostic plasma small extracellular vesicles miRNA signatures for pancreatic cancer using machine learning methods. Translational Oncology 2024, 40 , 101847. https://doi.org/10.1016/j.tranon.2023.101847
    19. Jixuan Han, Chen Wang, Ling Zhu, Yanlian Yang. Emerging Sensing and In Situ Detection Technologies for the Analysis of Extracellular Vesicle miRNAs. Advanced NanoBiomed Research 2024, 4 (1) https://doi.org/10.1002/anbr.202300067
    20. Yi Yu, Chunzi Liang, Qiang-Qiang Wan, Dan Jin, Xi Liu, Zhiyong Zhang, Zhong-Yue Sun, Guo-Jun Zhang. Integrated FET sensing microsystem for specific detection of pancreatic cancer exosomal miRNA10b. Analytica Chimica Acta 2023, 1284 , 341995. https://doi.org/10.1016/j.aca.2023.341995
    21. Siqi Zhang, Huahao Shao, Kai-Bin Li, Wei Shi, De-Man Han. Nanofluidic sensing platform for PNK assay using nonlinear hybridization chain reaction and its application in DNA logic circuit. Biosensors and Bioelectronics 2023, 240 , 115632. https://doi.org/10.1016/j.bios.2023.115632
    22. Yu Huang, Lingxiao Liu, Cihui Luo, Wei Liu, Xiaoding Lou, Lei Jiang, Fan Xia. Solid-state nanochannels for bio-marker analysis. Chemical Society Reviews 2023, 52 (18) , 6270-6293. https://doi.org/10.1039/D2CS00865C
    23. Xiande Yang, Ying Chen, Yijin Qin, Lizhen Wen. CdS Nanoparticles Self-Assembled in Porous Anodic Aluminum Oxide Nanochannels and Used for Carcinoembryonic Antigen Detection. Journal of Electronic Materials 2023, 52 (8) , 5662-5669. https://doi.org/10.1007/s11664-023-10510-x
    24. Fereshteh Rahdan, Fateme Bina, Elham Norouz Dolatabadi, Donya Shaterabadi, Seyyed Hossein Khatami, Yousof Karami, Nafiseh Dorosti, Mortaza Taheri-Anganeh, Peyman Asadi, Rahmatollah Soltani, Mohammad Reza Pashaei, Ahmad Movahedpour. MicroRNA electrochemical biosensors for pancreatic cancer. Clinica Chimica Acta 2023, 548 , 117472. https://doi.org/10.1016/j.cca.2023.117472
    25. Wei Yi, Chuanping Zhang, Qianchun Zhang, Changbo Zhang, Yebo Lu, Lanhua Yi, Xingzhu Wang. Solid-State Nanopore/Nanochannel Sensing of Single Entities. Topics in Current Chemistry 2023, 381 (4) https://doi.org/10.1007/s41061-023-00425-w
    26. Yanxin Li, Shuju Zhao, Zhenying Xu, Xiujuan Qiao, Mingxuan Li, Youke Li, Xiliang Luo. Peptide nucleic acid and antifouling peptide based biosensor for the non-fouling detection of COVID-19 nucleic acid in saliva. Biosensors and Bioelectronics 2023, 225 , 115101. https://doi.org/10.1016/j.bios.2023.115101
    27. Zhe Lu, Wei Ni, Nian Liu, Dan Jin, Tingxian Li, Kun Li, Yuling Zhang, Qunfeng Yao, Guo-Jun Zhang. CRISPR/Cas12a-based fluorescence biosensor for detection of exosomal miR-21 derived from lung cancer. Microchemical Journal 2023, 187 , 108370. https://doi.org/10.1016/j.microc.2022.108370
    28. Rui Lv, Xing Wang, Zhiqiang Mao, Yurong Bai, Junxing Hao, Fan Zhang. Engineering Sandwiched Nanochannel Aptasensor for Efficiently Screening Cancer Cells. Chemistry – A European Journal 2023, 29 (14) https://doi.org/10.1002/chem.202203380
    29. Qun Ma, Liang Chen, Pengcheng Gao, Fan Xia. Solid-state nanopore/channels meet DNA nanotechnology. Matter 2023, 6 (2) , 373-396. https://doi.org/10.1016/j.matt.2022.11.026
    30. Shuo Yin, Aipeng Chen, Yue Ding, Jia Song, Rui Chen, Peng Zhang, Chaoyong Yang. Recent advances in exosomal RNAs analysis towards diagnostic and therapeutic applications. TrAC Trends in Analytical Chemistry 2023, 158 , 116840. https://doi.org/10.1016/j.trac.2022.116840
    31. Erna Jia, Na Ren, Xianquan Shi, Rongkui Zhang, Haixin Yu, Fan Yu, Shaoyou Qin, Jinru Xue. Extracellular vesicle biomarkers for pancreatic cancer diagnosis: a systematic review and meta-analysis. BMC Cancer 2022, 22 (1) https://doi.org/10.1186/s12885-022-09463-x
    32. Jinyue Shi, Yu Lin, Weiling Qin, Mingxiang Li, Yuyi Zhou, Yeyu Wu, Hu Luo, Ke-Jing Huang, Xuecai Tan. Superior performance of a graphdiyne self-powered biosensor with exonuclease III-assisted signal amplification for sensitive detection of microRNAs. The Analyst 2022, 147 (22) , 4991-4999. https://doi.org/10.1039/D2AN01384C
    33. Bingqian Lin, Jinting Jiang, Jingxuan Jia, Xiang Zhou. Recent Advances in Exosomal miRNA Biosensing for Liquid Biopsy. Molecules 2022, 27 (21) , 7145. https://doi.org/10.3390/molecules27217145
    34. Eric Z. Zeng, Isabelle Chen, Xingchi Chen, Xuegang Yuan. Exosomal MicroRNAs as Novel Cell-Free Therapeutics in Tissue Engineering and Regenerative Medicine. Biomedicines 2022, 10 (10) , 2485. https://doi.org/10.3390/biomedicines10102485
    35. Zhichu Xiang, Lele Li, Yuliang Zhao. Recent progress in PNA-based biosensing technology. SCIENTIA SINICA Chimica 2022, 52 (9) , 1592-1600. https://doi.org/10.1360/SSC-2022-0070
    36. Xin-Xin Peng, Xiaoling Qin, You Qin, Yuanhang Xiang, Guo-Jun Zhang, Fan Yang. Bioprobes-regulated precision biosensing of exosomes: From the nanovesicle surface to the inside. Coordination Chemistry Reviews 2022, 463 , 214538. https://doi.org/10.1016/j.ccr.2022.214538
    37. Kun Li, Jiyuan Tu, Yulin Zhang, Dan Jin, Tingxian Li, Jiahao Li, Wei Ni, Meng-Meng Xiao, Zhi-Yong Zhang, Guo-Jun Zhang. Ultrasensitive detection of exosomal miRNA with PMO-graphene quantum dots-functionalized field-effect transistor biosensor. iScience 2022, 25 (7) , 104522. https://doi.org/10.1016/j.isci.2022.104522
    38. Yu-Lin Liu, Yu-Xiang Zhao, Ya-Bei Li, Zhao-Yang Ye, Jun-Jie Zhang, Yan Zhou, Tian-Yang Gao, Fei Li. Recent Advances of Nanoelectrodes for Single-Cell Electroanalysis: From Extracellular, Intercellular to Intracellular. Journal of Analysis and Testing 2022, 6 (2) , 178-192. https://doi.org/10.1007/s41664-022-00223-1
    39. Huisi Yang, Jiaying Zhao, Jiangbo Dong, Li Wen, Zhikun Hu, Congjuan He, Faliang Xu, Danqun Huo, Changjun Hou. Simultaneous detection of exosomal microRNAs by nucleic acid functionalized disposable paper-based sensors. Chemical Engineering Journal 2022, 438 , 135594. https://doi.org/10.1016/j.cej.2022.135594
    40. Weiwei Wang, Jing Zhao, Changlong Hao, Shudong Hu, Chen Chen, Yi Cao, Zhengyu Xu, Jun Guo, Liguang Xu, Maozhong Sun, Chuanlai Xu, Hua Kuang. The Development of Chiral Nanoparticles to Target NK Cells and CD8 + T Cells for Cancer Immunotherapy. Advanced Materials 2022, 34 (16) https://doi.org/10.1002/adma.202109354
    41. Ting-Ting Liang, Xiaoling Qin, Yuanhang Xiang, Yujin Tang, Fan Yang. Advances in nucleic acids-scaffolded electrical sensing of extracellular vesicle biomarkers. TrAC Trends in Analytical Chemistry 2022, 148 , 116532. https://doi.org/10.1016/j.trac.2022.116532
    42. Zhe Lu, wei Ni, Nian Liu, Dan Jin, Tingxian Li, Kun Li, Yulin Zhang, Qunfeng Yao, Guo-Jun Zhang. Crispr/Cas12a-Based Fluorescence Biosensor for Detection of Exosomal Mir-21 Derived from Lung Cancer. SSRN Electronic Journal 2022, 72 https://doi.org/10.2139/ssrn.4088276
    43. Yulin Zhang, Zhe Lu, wei Ni, Nian Liu, Dan Jin, Tingxian Li, Kun Li, Yuling Zhang, Qunfeng Yao, Guo-Jun Zhang. Crispr/Cas12a-Based Fluorescence Biosensor for Detection of Exosomal Mir-21 Derived from Lung Cancer. SSRN Electronic Journal 2022, 72 https://doi.org/10.2139/ssrn.4112020

    Analytical Chemistry

    Cite this: Anal. Chem. 2021, 93, 31, 10966–10973
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.analchem.1c01898
    Published July 30, 2021
    Copyright © 2021 American Chemical Society

    Article Views

    3170

    Altmetric

    -

    Citations

    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.