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Stretchable ionic–electronic bilayer hydrogel electronics enable in situ detection of solid-state epidermal biomarkers

Nature Materials volume 23, pages 1115–1122 (2024)Cite this article

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Abstract

Continuous and in situ detection of biomarkers in biofluids (for example, sweat) can provide critical health data but is limited by biofluid accessibility. Here we report a sensor design that enables in situ detection of solid-state biomarkers ubiquitously present on human skin. We deploy an ionic–electronic bilayer hydrogel to facilitate the sequential dissolution, diffusion and electrochemical reaction of solid-state analytes. We demonstrate continuous monitoring of water-soluble analytes (for example, solid lactate) and water-insoluble analytes (for example, solid cholesterol) with ultralow detection limits of 0.51 and 0.26 nmol cm−2, respectively. Additionally, the bilayer hydrogel electrochemical interface reduces motion artefacts by a factor of three compared with conventional liquid-sensing electrochemical interfaces. In a clinical study, solid-state epidermal biomarkers measured by our stretchable wearable sensors showed a high correlation with biomarkers in human blood and dynamically correlated with physiological activities. These results present routes to universal platforms for biomarker monitoring without the need for biofluid acquisition.

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Fig. 1: Design and mechanism of a stretchable sensor for SEBs.
Fig. 2: In vitro characterization of solid-state analyte sensors.
Fig. 3: Mechanoelectrochemical characterization and modelling of solid-state analyte sensors.
Fig. 4: On-body evaluation of the SEB sensor.

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Data availability

All data needed to evaluate the conclusions in the paper are available in the main text or the Supplementary Information. Source data for each figure are provided. Additional data related to this paper may be requested from the authors. Source data are provided with this paper.

Code availability

The customized code used to model the electrochemical kinetics of the sensor patch is available from the corresponding author upon request.

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Acknowledgements

This work is financially supported by the AME Programmatic Cyber-Physiochemical Interfaces (A18A1b0045 to L.Y.), the MTC Programmatic ‘BLISS’ (M24M9b0013 to X.T.Z., L.Y. and Yuxin Liu), the Singapore National Research Foundation Fellowship (NRF-NRFF15-2023-0011 to L.Y.), the A*STAR Central Research Fund (to L.Y.), a National University of Singapore Presidential Young Professorship Award (22-4974-A0003 to Yuxin Liu), an Advanced Research and Technology Innovation Centre (ARTIC) grant (HFM-RP6 to Yuxin Liu), iHealthtech Other Operating Expenses (OOE) funding (to Yuxin Liu), Wellcome Leap’s Dynamic Resilience Program jointly funded by Temasek Trust (to H.L., Z.L. and Yuxin Liu), and an MOE AcRF Tier 1 grant (22-5402-A0001-0 to Yuxin Liu).

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering (BME), National University of Singapore, Singapore, Singapore

    Ruth Theresia Arwani, Archana Sundarapandi, Weifeng Yang, Yuan Ching Ang & Yuxin Liu

  2. Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore

    Ruth Theresia Arwani, Sherwin Chong Li Tan, Wei Peng Goh, Xin Ting Zheng, Yong Yu, Changyun Jiang, Siew Lang Teo, Xiaodong Chen, Le Yang & Yuxin Liu

  3. The N.1 Institute for Health, National University of Singapore, Singapore, Singapore

    Ruth Theresia Arwani, Archana Sundarapandi & Yuxin Liu

  4. Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, Singapore

    Ruth Theresia Arwani, Archana Sundarapandi & Yuxin Liu

  5. Institute of High-Performance Computing (IHPC), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore

    Yin Liu, Fong Yew Leong, Hongying Li & Zhuangjian Liu

  6. State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai, P. R. China

    Weifeng Yang

  7. School of Chemistry, Chemical Engineering and Biotechnology (CCEB), Nanyang Technological University, Singapore, Singapore

    Lingxuan Kong & Peng Chen

  8. Institute for Digital Molecular Analytics and Science (IDMxS), Nanyang Technological University, Singapore, Singapore

    Peng Chen

  9. Department of Ophthalmology, Yong Loo Lin School of Medicine, Singapore, Singapore

    Xinyi Su

  10. Institute of Molecular Cell and Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore

    Xinyi Su

  11. Innovative Center for Flexible Devices (iFLEX), Max Planck-NTU Joint Laboratory for Artificial Senses, School of Materials Science and Engineering (MSE), Nanyang Technological University, Singapore, Singapore

    Xiaodong Chen

  12. Department of Materials Science and Engineering (MSE), National University of Singapore, Singapore, Singapore

    Le Yang

Authors
  1. Ruth Theresia Arwani
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Contributions

R.T.A. and Yuxin Liu conceived and designed the project. R.T.A., S.C.L.T., A.S., W.P.G., S.L.T. and Yuxin Liu carried out the experiments. L.K. carried out experiments with supervision from P.C. R.T.A., S.C.L.T., A.S., X.T.Z., Y.Y., L.Y. and Yuxin Liu discussed and analysed data. R.T.A., W.P.G., C.J. and Yuxin Liu fabricated the sensor patches. R.T.A., A.S., S.C.L.T., X.C., L.Y. and Yuxin Liu designed and conducted the human study. Yin Liu, F.Y.L., Y.C.A., H.L. and Z.L. conducted the computer modelling of the sensor electrochemical kinetics. R.T.A. and W.Y. prepared the figures. R.T.A. and Yuxin Liu wrote the paper. All authors commented on the paper. L.Y. and Yuxin Liu revised the paper and supervised the work.

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Correspondence to Le Yang or Yuxin Liu.

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Nature Materials thanks Sheng Xu and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary Figs. 1–45, Notes, Table 1, Video Caption 1 and References.

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Supplementary Video 1

In situ real-time detection of solid-state lactate using SEB sensor.

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Processed data for all graphs shown in main text Fig. 2.

Source Data Fig. 3

Processed data for all graphs shown in main text Fig. 3.

Source Data Fig. 4

Processed data for all graphs shown in main text Fig. 4.

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Arwani, R.T., Tan, S.C.L., Sundarapandi, A. et al. Stretchable ionic–electronic bilayer hydrogel electronics enable in situ detection of solid-state epidermal biomarkers. Nat. Mater. 23, 1115–1122 (2024). https://doi.org/10.1038/s41563-024-01918-9

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