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A laser-engraved wearable sensor for sensitive detection of uric acid and tyrosine in sweat

Abstract

Wearable sweat sensors have the potential to provide continuous measurements of useful biomarkers. However, current sensors cannot accurately detect low analyte concentrations, lack multimodal sensing or are difficult to fabricate at large scale. We report an entirely laser-engraved sensor for simultaneous sweat sampling, chemical sensing and vital-sign monitoring. We demonstrate continuous detection of temperature, respiration rate and low concentrations of uric acid and tyrosine, analytes associated with diseases such as gout and metabolic disorders. We test the performance of the device in both physically trained and untrained subjects under exercise and after a protein-rich diet. We also evaluate its utility for gout monitoring in patients and healthy controls through a purine-rich meal challenge. Levels of uric acid in sweat were higher in patients with gout than in healthy individuals, and a similar trend was observed in serum.

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Fig. 1: Schematics of the sweat sensor for metabolic and nutritional management.
Fig. 2: Schematics and characterization of the LEG-based UA and Tyr sensor.
Fig. 3: Design and characterization of the LEG-based vital-sign sensors.
Fig. 4: Design and characterization of the microfluidic system.
Fig. 5: In vivo system validation of the lab on the skin.
Fig. 6: Non-invasive gout management using the sweat sensor.

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Data availability

The data that support the plots within this paper and other findings of this study are available from the corresponding author upon request.

Code availability

The custom code used to program microcontroller is available from the corresponding author upon request.

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Acknowledgements

This work was supported by a California Institute of Technology Startup grant, the Rothenberg Innovation Initiative (RI2) program, the Carver Mead New Adventures Fund and an American Heart Association grant 19TPA34850157 (all to W.G.). Y.S., X.B. and M.W. acknowledge the China Scholarship Council (CSC) for financial support. J.T. was supported by the National Science Scholarship (NSS) from the Agency of Science Technology and Research (A*STAR) Singapore. We gratefully acknowledge critical support and infrastructure provided for this work by the Kavli Nanoscience Institute and Jim Hall Design and Prototyping Lab at Caltech, and we gratefully thank M. Hunt and B. Dominguez for their help. This project benefited from the use of instrumentation made available by the Caltech Environmental Analysis Center and we gratefully acknowledge guidance from N. Dalleska. We also thank Z. Wang for valuable inputs in patch pattern design.

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Contributions

W.G. and Y.Y. initiated the concept. W.G., Y.Y., Y.S., X.B., T.K.H. and Z.L. designed the experiments; Y.Y., Y.S., X.B. and J.M. led the experiments and collected the overall data; O.S.P., L.Z. and Y.Y. performed the flow simulation and modeling; J.M. performed the circuit design and test; M.W., J.T. and A.K. contributed to sensor characterization and validation; W.G., Y.Y., Y.S., X.B., J.M., O.S.P., L.Z. and H.Z. contributed the data analysis and co-wrote the paper. All authors provided the feedback on the manuscript.

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Correspondence to Wei Gao.

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Supplementary Figs. 1–41, Supplementary Tables 1–4 and Supplementary Note 1.

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Yang, Y., Song, Y., Bo, X. et al. A laser-engraved wearable sensor for sensitive detection of uric acid and tyrosine in sweat. Nat Biotechnol 38, 217–224 (2020). https://doi.org/10.1038/s41587-019-0321-x

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