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An integrated wearable microneedle array for the continuous monitoring of multiple biomarkers in interstitial fluid

Nature Biomedical Engineering volume 6, pages 1214–1224 (2022)Cite this article

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Abstract

Implementations of wearable microneedle-based arrays of sensors for the monitoring of multiple biomarkers in interstitial fluid have lacked system integration and evidence of robust analytical performance. Here we report the development and testing of a fully integrated wearable array of microneedles for the wireless and continuous real-time sensing of two metabolites (lactate and glucose, or alcohol and glucose) in the interstitial fluid of volunteers performing common daily activities. The device works with a custom smartphone app for data capture and visualization, comprises reusable electronics and a disposable microneedle array, and is optimized for system integration, cost-effective fabrication via advanced micromachining, easier assembly, biocompatibility, pain-free skin penetration and enhanced sensitivity. Single-analyte and dual-analyte measurements correlated well with the corresponding gold-standard measurements in blood or breath. Further validation of the technology in large populations with concurrent validation of sensor readouts through centralized laboratory tests should determine the robustness and utility of real-time simultaneous monitoring of several biomarkers in interstitial fluid.

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Fig. 1: Illustrations of the multiplexed microneedle-based wearable sensor system and its subcomponents.
Fig. 2: Electronics and sensor architecture.
Fig. 3: In vivo performance of the single-analyte sensors.
Fig. 4: In vivo performance of the multiplexed sensors.

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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 generated during the study are too large to be publicly shared, yet they are available for research purposes from the corresponding authors on reasonable request. Source data are provided with this paper.

Code availability

The firmware for the electronic hardware, custom-developed and written in C, and the source code for the app, custom-developed in Swift, are available from the authors for research purposes on reasonable request.

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Acknowledgements

This work is supported by the Center for Wearable Sensors (CWS) at the University of California San Diego and the NIH National Institute of Neurological Disorders and Stroke (Grant Number R21 NS114764 - 01A1). We thank W. Shipley for his support in mechanical characterization of this study.

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  1. These authors contributed equally: Farshad Tehrani, Hazhir Teymourian, Brian Wuerstle, Jonathan Kavner.

Authors and Affiliations

  1. Department of Nanoengineering, University of California San Diego, La Jolla, CA, USA

    Farshad Tehrani, Hazhir Teymourian, Hamed Hosseini-Toudeshki, Fangyu Zhang, Kuldeep Mahato, Zhengxing Li, Abbas Barfidokht, Lu Yin, Paul Warren & Joseph Wang

  2. Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, CA, USA

    Brian Wuerstle, Ravi Patel, Christopher Brown & Patrick P. Mercier

  3. Department of Bioengineering, University of California San Diego, La Jolla, CA, USA

    Jonathan Kavner, Allison Furmidge, Reza Aghavali, Nickey Huang & Zina Patel

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Contributions

F.T., H.T., B.W. and J.K. contributed equally to this work. F.T., H.T., B.W. and J.K. conceived the original project, designed and performed experiments, analysed data, and participated in the figure design and writing of the manuscript. R.P. contributed to the app design and development; A.F., R.A., P.W., N.H. and Z.P. performed the integrated device and sensor fabrications; H.H.-T. contributed to the mechanical stability experiments; C.B. contributed to the electronics design and development; F.Z. and Z.L. performed the cytotoxicity and biocompatibility studies; K.M., A.B. and L.Y. performed the sensor preparations and characterizations. J.W. and P.P.M. conceived the original project, designed the experiments, analysed data, participated in the figure design and manuscript writing, and provided guidance to the project.

Corresponding authors

Correspondence to Patrick P. Mercier or Joseph Wang.

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Nature Biomedical Engineering thanks Pawan Jolly, Nicolas Voelcker and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary figures, tables and video captions.

Reporting Summary

Supplementary Video 1

Wearable device assembly and its placement on the arm of a participant.

Supplementary Video 2

Demonstration of the sensor app.

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SD for Figs. 3,4

Source data for Figs. 3 and 4.

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Tehrani, F., Teymourian, H., Wuerstle, B. et al. An integrated wearable microneedle array for the continuous monitoring of multiple biomarkers in interstitial fluid. Nat. Biomed. Eng 6, 1214–1224 (2022). https://doi.org/10.1038/s41551-022-00887-1

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