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A wireless patch for the monitoring of C-reactive protein in sweat

Nature Biomedical Engineering volume 7, pages 1293–1306 (2023)Cite this article

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Abstract

The quantification of protein biomarkers in blood at picomolar-level sensitivity requires labour-intensive incubation and washing steps. Sensing proteins in sweat, which would allow for point-of-care monitoring, is hindered by the typically large interpersonal and intrapersonal variations in its composition. Here we report the design and performance of a wearable and wireless patch for the real-time electrochemical detection of the inflammatory biomarker C-reactive (CRP) protein in sweat. The device integrates iontophoretic sweat extraction, microfluidic channels for sweat sampling and for reagent routing and replacement, and a graphene-based sensor array for quantifying CRP (via an electrode functionalized with anti-CRP capture antibodies-conjugated gold nanoparticles), ionic strength, pH and temperature for the real-time calibration of the CRP sensor. In patients with chronic obstructive pulmonary disease, with active or past infections or who had heart failure, the elevated concentrations of CRP measured via the patch correlated well with the protein’s levels in serum. Wearable biosensors for the real-time sensitive analysis of inflammatory proteins in sweat may facilitate the management of chronic diseases.

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Fig. 1: Wearable electrochemical biosensor for the automatic, non-invasive and wireless monitoring of inflammation.
Fig. 2: Materials and electrochemical characterizations of the LEG–AuNPs CRP sensor.
Fig. 3: Evaluation of sweat CRP for the non-invasive monitoring of systemic inflammation in healthy and patient populations.
Fig. 4: Multiplexed microfluidic patch for automatic immunosensing.
Fig. 5: On-body evaluation of the multiplexed wearable patch towards non-invasive automatic inflammation monitoring.

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Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. Source data for Figs. 3 and 5 are provided with this paper. All raw and analysed datasets generated during the study are available from the corresponding author on request.

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Acknowledgements

This project was supported by the American Heart Association grant 19TPA34850157, National Institutes of Health (NIH) grants R01HL155815 and R21DK13266, National Science Foundation grant 2145802, Office of Naval Research grants N00014-21-1-2483 and N00014-21-1-2845, High Impact Pilot Research Award T31IP1666 from the Tobacco-Related Disease Research Program, Sloan Research Fellowship and the Technology Ventures Internal Project Fund at Cedars-Sinai. J.T. was supported by the National Science Scholarship from the Agency of Science Technology and Research (A*STAR) Singapore. E.D. was supported by NIH grant T32EB027629. We gratefully acknowledge critical support and infrastructure provided for this work by the Kavli Nanoscience Institute at Caltech. We acknowledge support from the Beckman Institute of Caltech to the Molecular Materials Research Center and Jake Evans for help with XPS. The Proteome Exploration Laboratory is supported by the Beckman Institute and NIH grant 1S10OD02001301. We thank G. R. Rossman for assistance in Raman spectroscopy. We also thank E. Bayoumi, E. Pascual and P.-E. Chen at Cedars-Sinai Medical Center for their assistance in participant recruitment. We thank R. M. Torrente-Rodríguez for constructive feedback on manuscript preparation.

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Authors and Affiliations

  1. Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA

    Jiaobing Tu, Jihong Min, Yu Song, Changhao Xu, Jiahong Li, Elham Davoodi & Wei Gao

  2. Division of Respiratory and Critical Care Physiology and Medicine, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA

    Jeff Moore & Harry B. Rossiter

  3. Division of Cardiology, University of California Los Angeles, Los Angeles, CA, USA

    Justin Hanson, Erin Hu & Jeffrey J. Hsu

  4. Department of Medicine, Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Tanyalak Parimon & Peter Chen

  5. Proteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, CA, USA

    Ting-Yu Wang & Tsui-Fen Chou

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Contributions

W.G. and J.T. initiated the concept and designed the overall studies. W.G. supervised the work. J.T., J. Min and Y.S. led the experiments and collected the overall data. C.X., J.L., T.-Y.W., E.D. and T.-F.C. contributed to sensor characterization and validation. J. Moore, J.H., E.H., T.P., P.C., J.J.H. and H.B.R. contributed to the design of the human trials and to the system’s evaluation in the participants. All authors contributed to data analysis and provided feedback on the paper.

Corresponding author

Correspondence to Wei Gao.

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Supplementary Video 1

Wearable nanobiosensor for automatic, non-invasive and wireless inflammation monitoring.

Supplementary Video 2

Laboratory flow test illustrating the automatic microfluidic immunosensing.

Supplementary Video 3

On-body flow test showing the delivery and refreshment of black dye in the detection reservoir after 5 min of iontophoretic sweat induction.

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Tu, J., Min, J., Song, Y. et al. A wireless patch for the monitoring of C-reactive protein in sweat. Nat. Biomed. Eng 7, 1293–1306 (2023). https://doi.org/10.1038/s41551-023-01059-5

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