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Functionalized helical fibre bundles of carbon nanotubes as electrochemical sensors for long-term in vivo monitoring of multiple disease biomarkers

Nature Biomedical Engineering volume 4, pages 159–171 (2020)Cite this article

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Abstract

Mechanical mismatches between implanted electronics and biological tissues can lead to inaccurate readings and long-term tissue damage. Here, we show that functionalized multi-walled carbon nanotubes twisted into helical fibre bundles that mimic the hierarchical structure of muscle can monitor multiple disease biomarkers in vivo. The flexible fibre bundles are injectable, have a low bending stiffness and display ultralow stress under compression. As proof-of-concept evidence of the sensing capabilities of these fibre bundles, we show that the fibre bundles enable the spatially resolved and real-time monitoring of H2O2 when implanted in tumours in mice, and that they can be integrated with a wireless transmission system on an adhesive skin patch to monitor calcium ions and glucose in the venous blood of cats for 28 d. The versatility of the helical fibre bundles as chemically functionalized electrochemical sensors makes them suitable for multiple sensing applications in biomedicine and healthcare.

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Fig. 1: Hierarchical helical structure and the implantation of CNT fibre.
Fig. 2: Mechanical match, biocompatibility and biointegration of the implanted CNT fibre.
Fig. 3: The structure and performance of the SSF library and the fabrication of MSFs.
Fig. 4: The structure and stability of the MSF.
Fig. 5: The use of MSFs for spatially resolved analysis.
Fig. 6: The use of MSFs for real-time and long-term multiplex monitoring in vivo.

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Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. The raw and analysed datasets that were generated during this study are available from the corresponding authors on reasonable request.

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Acknowledgements

We thank A. L. Chun of Science Storylab for her suggestions and critique; F. Han from Fudan University for help with the wireless-transmitting system. This work was supported by MOST (grant number 2016YFA0203302), NSFC (grant numbers 21634003, 51573027, 51673043, 21604012, 21805044, 21875042, 11602058 and 11872150), STCSM (grant numbers 16JC1400702, 17QA1400400, 18QA1400700, 18QA1400800 and 19QA1400500), SHMEC (grant number 2017-01-07-00-07-E00062), SEDF (grant number 16CG01) and Yanchang Petroleum Group and China Postdoctoral Science Foundation (grant numbers 2017M610223 and 2018T110334). This work was also supported by Shanghai Municipal Science and Technology Major Project (2018SHZDZX01) and ZJLab (to H.Y.).

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Author notes

  1. These authors contributed equally: Liyuan Wang, Songlin Xie, Zhiyuan Wang.

Authors and Affiliations

  1. State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science and Laboratory of Advanced Materials, Fudan University, Shanghai, China

    Liyuan Wang, Songlin Xie, Chengqiang Tang, Xiaoying Wu, Peng Liu, Yongjing Li, Shuang Zheng, Xuemei Sun & Huisheng Peng

  2. Vision Research Laboratory, School of Life Sciences, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Centre for Brain Science, Fudan University, Shanghai, China

    Zhiyuan Wang, Hexige Saiyin & Hongbo Yu

  3. Department of Aeronautics and Astronautics, Fudan University, Shanghai, China

    Fei Liu, Yifan Yang & Fan Xu

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Contributions

X.S., F.X., H.Y. and H.P. conceived and designed the research project. L.W., Z.W. and S.X. performed the experiments. F.L. and Y.Y. performed numerical simulations. L.W., S.X. and Z.W. analysed the data. All of the authors discussed the data and wrote the paper.

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Correspondence to Xuemei Sun, Fan Xu, Hongbo Yu or Huisheng Peng.

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Supplementary Information

Supplementary methods, figures, tables, references and caption for Supplementary Video 1.

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Supplementary Video 1

Wireless monitoring system integrated with MSFs on a living cat for the real-time transmission of data.

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Wang, L., Xie, S., Wang, Z. et al. Functionalized helical fibre bundles of carbon nanotubes as electrochemical sensors for long-term in vivo monitoring of multiple disease biomarkers. Nat Biomed Eng 4, 159–171 (2020). https://doi.org/10.1038/s41551-019-0462-8

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