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A wearable aptamer nanobiosensor for non-invasive female hormone monitoring

Nature Nanotechnology (2023)Cite this article

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Abstract

Personalized monitoring of female hormones (for example, oestradiol) is of great interest in fertility and women’s health. However, existing approaches usually require invasive blood draws and/or bulky analytical laboratory equipment, making them hard to implement at home. Here we report a skin-interfaced wearable aptamer nanobiosensor based on target-induced strand displacement for automatic and non-invasive monitoring of oestradiol via in situ sweat analysis. The reagentless, amplification-free and ‘signal-on’ detection approach coupled with a gold nanoparticle-MXene-based detection electrode offers extraordinary sensitivity with an ultra-low limit of detection of 0.14 pM. This fully integrated system is capable of autonomous sweat induction at rest via iontophoresis, precise microfluidic sweat sampling controlled via capillary bursting valves, real-time oestradiol analysis and calibration with simultaneously collected multivariate information (that is, temperature, pH and ionic strength), as well as signal processing and wireless communication with a user interface (for example, smartphone). We validated the technology in human participants. Our data indicate a cyclical fluctuation in sweat oestradiol during menstrual cycles, and a high correlation between sweat and blood oestradiol was identified. Our study opens up the potential for wearable sensors for non-invasive, personalized reproductive hormone monitoring.

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Fig. 1: A wearable nanobiosensor based on strand-displacement aptamer switch for non-invasive reagentless female reproductive hormone analysis.
Fig. 2: Design and characterization of the reagentless amplification-free aptamer oestradiol sensor.
Fig. 3: Microfluidic wearable system integration for automatic in situ hormone analysis.
Fig. 4: Evaluation of the wearable sensor for non-invasive female hormone monitoring in human participants.

Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. Source data for Figs. 2–4 are provided with this paper.

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Acknowledgements

This project was supported by the National Institutes of Health grant nos. R01HL155815 and R21DK13266, National Science Foundation grant no. 2145802, Office of Naval Research grant nos. N00014-21-1-2483 and N00014-21-1-2845, American Cancer Society Research Scholar grant no. RSG-21-181-01-CTPS and a Sloan Research Fellowship. We gratefully acknowledge critical support and infrastructure provided for this work by the Kavli Nanoscience Institute at Caltech.

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Author notes

  1. These authors contributed equally: Cui Ye, Minqiang Wang.

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

    Cui Ye, Minqiang Wang, Jihong Min, Roland Yingjie Tay, Heather Lukas, Juliane R. Sempionatto, Jiahong Li, Changhao Xu & Wei Gao

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Contributions

W.G. and C.Y. initiated the concept and designed the overall studies. W.G. supervised the work. C.Y. and M.W. led the experiments and collected the overall data. J.M., R.Y.T., H.L., J.R.S. and C.X. contributed to sensor characterization and validation. J.L. contributed to the numerical simulation. All authors contributed the data analysis and provided feedback on the manuscript.

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Correspondence to Wei Gao.

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Nature Nanotechnology thanks Fabiana Arduini, Eden Morales-Narvaez 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 methods, discussion, figures, tables, references and video captions.

Reporting Summary

Supplementary Video 1

Numerical simulation of the electric field enhanced oestradiol sensing.

Supplementary Video 2

Microfluidic sweat sampling using a finger-worn wearable sensor patch.

Supplementary Video 3

Real-time wireless oestradiol monitoring.

Source data

Source Data Fig. 2

Source data for Fig. 2.

Source Data Fig. 3

Source data for Fig. 3.

Source Data Fig. 4

Source data for Fig. 4.

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Ye, C., Wang, M., Min, J. et al. A wearable aptamer nanobiosensor for non-invasive female hormone monitoring. Nat. Nanotechnol. (2023). https://doi.org/10.1038/s41565-023-01513-0

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