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Functionalized graphene oxide in situ initiated ring-opening polymerization for highly sensitive sensing of cytokeratin-19 fragment

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Abstract

Improving the sensitivity of detection is crucial to monitor biomarker, assess toxicity, and track therapeutic agent. Herein, a sensitivity-improved immunosensor is reported for the first time via functionalized graphene oxide (GO) and a “grafting-to” ring-opening polymerization (ROP) dual signal amplification strategy. Through the ROP reaction using 2-[(4-ferrocenylbutoxy)methyl] oxirane (FcEpo) as the monomer, lots of electroactive tags are linked in situ from multiple initiation sites on the GO surface modified with ethanol amine (GO-ETA), thereby achieving high sensitivity even in the case of trace amounts of tumor markers. The utmost important factor for achieving this high sensitivity is to select functionalized GO as the initiator that contains a large number of repeated hydroxyl functional groups so as to trigger additional ROP reaction. Under the optimal conditions, the high sensitivity and applicability is demonstrated by the use of GO-ETA-mediated ROP-based immunosensor to detect non-small cell lung cancer (NSCLC)–specific biomarker down to 72.58 ag/mL (equivalent to ~6 molecules in a 5 μL sample). Furthermore, the satisfactory results for the determination of biomarkers in clinical serum samples highlighted that this immunosensor holds a huge potential in practical clinical application.

Graphical abstract

This work described an electrochemical immunosensor for ultrasensitive detection of CYFRA 21-1 via the functionalized graphene oxide (GO) and a “grafting-to” ring-opening polymerization (ROP) dual signal amplification strategy, which hold the merits of high sensitivity, applicability, selectivity, efficiency, easy operation and environmental friendliness.

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Funding

This work was supported by the project of tackling of key scientific and technical problems in Henan Province (192102310033), National Natural Science Foundation of China (21974068), and the project of tackling of key scientific and technical problems in Henan Province (202102310149).

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Authors and Affiliations

  1. Pharmacy College, Henan University of Chinese Medicine, Zhengzhou, 450046, People’s Republic of China

    Yanju Liu, Lulu Hao & Huaixia Yang

  2. Henan Key Laboratory of TCM Syndrome and Prescription in Signaling, Henan International Joint Laboratory of TCM Syndrome and Prescription in Signaling, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, People’s Republic of China

    Wenbin Wang & Fuchun Si

  3. School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, 210094, People’s Republic of China

    Jinming Kong

Authors
  1. Yanju Liu
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  2. Lulu Hao
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  3. Wenbin Wang
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  4. Huaixia Yang
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  5. Fuchun Si
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  6. Jinming Kong
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Corresponding authors

Correspondence to Huaixia Yang, Fuchun Si or Jinming Kong.

Ethics declarations

The clinical serum samples were obtained from The Third Affiliated Hospital of Henan University of Chinese Medicine. The Ethics Committee of Henan Province Hospital of Traditional Chinese Medicine approved the exploitation of serum samples for research purpose, and ten volunteers provided written informed consent before collecting serum samples.

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The authors declare no competing of interests.

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Liu, Y., Hao, L., Wang, W. et al. Functionalized graphene oxide in situ initiated ring-opening polymerization for highly sensitive sensing of cytokeratin-19 fragment. Microchim Acta 188, 123 (2021). https://doi.org/10.1007/s00604-021-04780-7

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