Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Skin-like drift-free biosensors with stretchable diode-connected organic field-effect transistors

Abstract

Biosensors based on organic field-effect transistors can offer mechanical flexibility, stretchability and operational stability for conformal on-skin monitoring. However, bending, stretching, moisture and temperature changes can lead to signal artefacts and drifts. Here we report skin-like drift-free biosensors based on stretchable diode-connected organic field-effect transistors. Our approach relies on capacitive coupling and the subtraction of interference signals using two extended gates functionalized separately with target and reference bioreceptors. It reduces signal distortion by up to two orders of magnitude compared with an unconnected organic field-effect transistor, despite changes in the sampling environment, including bias stress instability, uniaxial strain (up to 100%), compression (up to 50 mN) and temperature variations (25–40 °C). We apply the approach to aptamer-based sensing for cortisol, enzyme-based sensing for glucose and ion-selective membrane-based potentiometric sensing for sodium ions. We also develop a hybrid wearable system, including soft sensors and a flexible printed circuit board, which wirelessly communicates with a smartphone app. We show that the system can perform cortisol sensing from human sweat under acute stress events.

This is a preview of subscription content, access via your institution

Access options

Buy this article

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Skin-like diode-connected OFETs for drift-free multimodal biosensing.
Fig. 2: Fabrication and characterizations of diode-connected OFET.
Fig. 3: Drift-free, temperature-insensitive and mechanical-strain-insensitive output diode-connected OFET pairs.
Fig. 4: Sensing examples with self-referenced OFET biosensors.
Fig. 5: Hybrid system-level integration of soft and wireless systems.

Similar content being viewed by others

Data availability

The datasets generated during and/or analysed in this study are available from the corresponding author upon reasonable request. Source data are provided with this paper.

References

  1. Zhao, C., Park, J., Root, S. E. & Bao, Z. Skin-inspired soft bioelectronic materials, devices and systems. Nat. Rev. Bioeng. 2, 671–690 (2024).

    Google Scholar 

  2. Wang, Y. et al. Skin bioelectronics towards long-term, continuous health monitoring. Chem. Soc. Rev. 51, 3759–3793 (2022).

    Google Scholar 

  3. Cho, K. W. et al. Soft bioelectronics based on nanomaterials. Chem. Rev. 122, 5068–5143 (2022).

    Google Scholar 

  4. Lin, M., Hu, H., Zhou, S. & Xu, S. Soft wearable devices for deep-tissue sensing. Nat. Rev. Mater. 7, 850–869 (2022).

    Google Scholar 

  5. Khodagholy, D. et al. In vivo recordings of brain activity using organic transistors. Nat. Commun. 4, 1575 (2013).

    Google Scholar 

  6. Jiang, Y. et al. Topological supramolecular network enabled high-conductivity, stretchable organic bioelectronics. Science 375, 1411–1417 (2022).

    Google Scholar 

  7. Wu, J. et al. Adhesive anti-fibrotic interfaces on diverse organs. Nature 630, 360–367 (2024).

    Google Scholar 

  8. Li, Y., Li, N., De Oliveira, N. & Wang, S. Implantable bioelectronics toward long-term stability and sustainability. Matter 4, 1125–1141 (2021).

    Google Scholar 

  9. Le Floch, P. et al. 3D spatiotemporally scalable in vivo neural probes based on fluorinated elastomers. Nat. Nanotechnol. 19, 319–329 (2024).

    Google Scholar 

  10. Zhu, C. et al. Stretchable temperature-sensing circuits with strain suppression based on carbon nanotube transistors. Nat. Electron. 1, 183–190 (2018).

    MathSciNet  Google Scholar 

  11. Li, J. et al. Thin, soft, wearable system for continuous wireless monitoring of artery blood pressure. Nat. Commun. 14, 5009 (2023).

    Google Scholar 

  12. Schwartz, G. et al. Flexible polymer transistors with high pressure sensitivity for application in electronic skin and health monitoring. Nat. Commun. 4, 1859 (2013).

    Google Scholar 

  13. Sim, K. et al. An epicardial bioelectronic patch made from soft rubbery materials and capable of spatiotemporal mapping of electrophysiological activity. Nat. Electron. 3, 775–784 (2020).

    Google Scholar 

  14. Li, N. et al. Bioadhesive polymer semiconductors and transistors for intimate biointerfaces. Science 381, 686–693 (2023).

    Google Scholar 

  15. Wang, S. et al. Skin electronics from scalable fabrication of an intrinsically stretchable transistor array. Nature 555, 83–88 (2018).

    Google Scholar 

  16. Wang, W. et al. Neuromorphic sensorimotor loop embodied by monolithically integrated, low-voltage, soft e-skin. Science 380, 735–742 (2023).

    Google Scholar 

  17. Yuvaraja, S. et al. Organic field-effect transistor-based flexible sensors. Chem. Soc. Rev. 49, 3423–3460 (2020).

    Google Scholar 

  18. Dai, Y., Hu, H., Wang, M., Xu, J. & Wang, S. Stretchable transistors and functional circuits for human-integrated electronics. Nat. Electron. 4, 17–29 (2021).

    Google Scholar 

  19. Sugiyama, M. et al. An ultraflexible organic differential amplifier for recording electrocardiograms. Nat. Electron. 2, 351–360 (2019).

    Google Scholar 

  20. Kondo, M. et al. Imperceptible magnetic sensor matrix system integrated with organic driver and amplifier circuits. Sci. Adv. 6, eaay6094 (2020).

    Google Scholar 

  21. Mirshojaeian Hosseini, M. J. et al. 270 nm ultra-thin self-adhesive conformable and long-term air-stable complimentary organic transistors and amplifiers. npj Flex. Electron. 7, 38 (2023).

    Google Scholar 

  22. Kim, J., Campbell, A. S., de Ávila, B. E.-F. & Wang, J. Wearable biosensors for healthcare monitoring. Nat. Biotechnol. 37, 389–406 (2019).

    Google Scholar 

  23. Li, J. et al. A tissue-like neurotransmitter sensor for the brain and gut. Nature 606, 94–101 (2022).

    Google Scholar 

  24. Zhao, C. et al. Implantable aptamer–field-effect transistor neuroprobes for in vivo neurotransmitter monitoring. Sci. Adv. 7, eabj7422 (2021).

    Google Scholar 

  25. Ye, C. et al. A wearable aptamer nanobiosensor for non-invasive female hormone monitoring. Nat. Nanotechnol. 19, 330–337 (2024).

    Google Scholar 

  26. Wang, B. et al. Wearable aptamer-field-effect transistor sensing system for noninvasive cortisol monitoring. Sci. Adv. 8, eabk0967 (2022).

    Google Scholar 

  27. Wang, M. et al. A wearable electrochemical biosensor for the monitoring of metabolites and nutrients. Nat. Biomed. Eng. 6, 1225–1235 (2022).

    Google Scholar 

  28. Sempionatto, J. R. et al. An epidermal patch for the simultaneous monitoring of haemodynamic and metabolic biomarkers. Nat. Biomed. Eng. 5, 737–748 (2021).

    Google Scholar 

  29. Macchia, E. et al. Single-molecule detection with a millimetre-sized transistor. Nat. Commun. 9, 3223 (2018).

    Google Scholar 

  30. Park, S., Kim, S. H., Choi, H. H., Kang, B. & Cho, K. Recent advances in the bias stress stability of organic transistors. Adv. Funct. Mater. 30, 1904590 (2019).

    Google Scholar 

  31. Iqbal, H. F. et al. Suppressing bias stress degradation in high performance solution processed organic transistors operating in air. Nat. Commun. 12, 2352 (2021).

    Google Scholar 

  32. Kaisti, M. Detection principles of biological and chemical FET sensors. Biosens. Bioelectron. 98, 437–448 (2017).

    Google Scholar 

  33. Torsi, L., Magliulo, M., Manoli, K. & Palazzo, G. Organic field-effect transistor sensors: a tutorial review. Chem. Soc. Rev. 42, 8612–8628 (2013).

    Google Scholar 

  34. Picca, R. A. et al. Ultimately sensitive organic bioelectronic transistor sensors by materials and device structure design. Adv. Funct. Mater. 30, 1904513 (2020).

    Google Scholar 

  35. White, S. P., Dorfman, K. D. & Frisbie, C. D. Operating and sensing mechanism of electrolyte-gated transistors with floating gates: building a platform for amplified biodetection. J. Phys. Chem. C 120, 108–117 (2016).

    Google Scholar 

  36. Torricelli, F. et al. Electrolyte-gated transistors for enhanced performance bioelectronics. Nat. Rev. Methods Prim. 1, 66 (2021).

    Google Scholar 

  37. Kwon, J. et al. Nanoscale FET-based transduction toward sensitive extended-gate biosensors. ACS Sens. 4, 1724–1729 (2019).

    Google Scholar 

  38. Wang, W. et al. Strain-insensitive intrinsically stretchable transistors and circuits. Nat. Electron. 4, 143–150 (2021).

    Google Scholar 

  39. Thomas, M. S., Adrahtas, D. Z., Frisbie, C. D. & Dorfman, K. D. Modeling of quasi-static floating-gate transistor biosensors. ACS Sens. 6, 1910–1917 (2021).

    Google Scholar 

  40. Arcus, V. L., van der Kamp, M. W., Pudney, C. R. & Mulholland, A. J. Enzyme evolution and the temperature dependence of enzyme catalysis. Curr. Opin. Struct. Biol. 65, 96–101 (2020).

    Google Scholar 

  41. Zheng, Y. et al. A molecular design approach towards elastic and multifunctional polymer electronics. Nat. Commun. 12, 5701 (2021).

    Google Scholar 

  42. Li, S. G. et al. Implantable hydrogel-protective DNA aptamer-based sensor supports accurate, continuous electrochemical analysis of drugs at multiple sites in living rats. ACS Nano 17, 18525–18538 (2023).

    Google Scholar 

  43. Chan, D. et al. Combinatorial polyacrylamide hydrogels for preventing biofouling on implantable biosensors. Adv. Mater. 34, e2109764 (2022).

    Google Scholar 

  44. Zhong, D. et al. High-speed and large-scale intrinsically stretchable integrated circuits. Nature 627, 313–320 (2024).

    Google Scholar 

  45. Wu, C. et al. Strain-induced performance variation in stretchable carbon-nanotube thin-film transistors and the solution through a circular channel design. IEEE Trans. Electron Dev. 71, 3411–3416 (2024).

    Google Scholar 

  46. Yoo, H., Jo, H. & Oh, S. S. Detection and beyond: challenges and advances in aptamer-based biosensors. Mater. Adv. 1, 2663–2687 (2020).

    Google Scholar 

  47. Nakatsuka, N. et al. Aptamer–field-effect transistors overcome debye length limitations for small-molecule sensing. Science 362, 319–324 (2018).

    Google Scholar 

  48. Poudineh, M. et al. A fluorescence sandwich immunoassay for the real-time continuous detection of glucose and insulin in live animals. Nat. Biomed. Eng. 5, 53–63 (2021).

    Google Scholar 

  49. Gerson, J. et al. High-precision monitoring of and feedback control over drug concentrations in the brains of freely moving rats. Sci. Adv. 9, eadg3254 (2023).

    Google Scholar 

  50. Gao, W. et al. Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis. Nature 529, 509–514 (2016).

    Google Scholar 

  51. Xu, C. et al. A physicochemical-sensing electronic skin for stress response monitoring. Nat. Electron. 7, 168–179 (2024).

    Google Scholar 

  52. Zdrachek, E. & Bakker, E. Potentiometric sensing. Anal. Chem. 91, 2–26 (2019).

    Google Scholar 

  53. Chung, H. U. et al. Binodal, wireless epidermal electronic systems with in-sensor analytics for neonatal intensive care. Science 363, eaau0780 (2019).

    Google Scholar 

  54. Matsuhisa, N., Chen, X., Bao, Z. & Someya, T. Materials and structural designs of stretchable conductors. Chem. Soc. Rev. 48, 2946–2966 (2019).

    Google Scholar 

  55. Widlund, T., Yang, S., Hsu, Y.-Y. & Lu, N. Stretchability and compliance of freestanding serpentine-shaped ribbons. Int. J. Solids Struct. 51, 4026–4037 (2014).

    Google Scholar 

  56. Jiang, Y. et al. A universal interface for plug-and-play assembly of stretchable devices. Nature 614, 456–462 (2023).

    Google Scholar 

  57. Schwabe, L., Haddad, L. & Schachinger, H. HPA axis activation by a socially evaluated cold-pressor test. Psychoneuroendocrinology 33, 890–895 (2008).

    Google Scholar 

  58. Torrente-Rodríguez, R. M. et al. Investigation of cortisol dynamics in human sweat using a graphene-based wireless mhealth system. Matter 2, 921–937 (2020).

    Google Scholar 

  59. Tang, W. et al. Touch-based stressless cortisol sensing. Adv. Mater. 33, 2008465 (2021).

    Google Scholar 

  60. Wang, G.-J. N. et al. Nonhalogenated solvent processable and printable high-performance polymer semiconductor enabled by isomeric nonconjugated flexible linkers. Macromolecules 51, 4976–4985 (2018).

    Google Scholar 

Download references

Acknowledgements

We acknowledge financial support from the National Science Foundation (SENSE-2037304). C. Zhao acknowledges funding from an F32 fellowship from the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (F32EB034156, C. Zhao). R.K.M. was supported by the Department of Defense (DoD) through the National Defense Science and Engineering Graduate (NDSEG) Fellowship Program. A.B. acknowledges the National Science Foundation Graduate Research Fellowship (grant number DGE-1656518, A.B.) and the Stanford Graduate Fellowship. Z.B. is a Chan Zuckerberg Biohub San Francisco investigator and an Arc Institute innovation investigator. Z.B. acknowledges support from the Tianqiao and Chrissy Chen Ideation and Prototyping Lab and Stanford Wearable Electronics Initiative (eWEAR) seed funding. We thank the Bin Lin and Daisy Liu Family Fund for the generous support of the Bao Group’s research at Stanford University. Part of this work was performed at the Stanford Nano Shared Facilities (SNSF), supported by the NSF award ECCS-2026822. We thank the Asahi Kasei Corporation for providing SEBS. We thank E. Luis for feedback on the paper and J.-Y. Chang for technical assistance on data collection.

Author information

Authors and Affiliations

Authors

Contributions

C. Zhao, J.P. and Z.B. designed the project and experiments. C. Zhao, J.P. and D.M. carried out the experiments and collected the related data. C. Zhao, D.M., Y.Y., W.W. and Q.L. fabricated the OFET biosensors. C. Zhao, J.P., D.M., D.Z., C.W. and C. Zhu carried out the circuit model design and analysis of diode-connected OFETs for biosensing. C. Zhao, J.P., D.M. and Changhao Xu carried out the biosensing tests. Y.Z., X.J. and Z.Y. designed and synthesized the azide compounds (azide, BA and BH). R.K.M. and X.J. designed and synthesized the conjugated polymer (DPPTT). H.L. carried out the scanning electron microscopy imaging. Ying Jiang fabricated the BIND interconnects for the soft-flexible interface. C. Zhao and J.P. conducted and analysed the on-body data. Chengyi Xu and B.S. carried out the laser cutting for the microfluidics. A.B. printed out the 3D resins for encapsulation. L.M., Yuanwen Jiang, S.W., J.S., A.A., E.K. and M.K. helped with the experimental design and device fabrication. C. Zhao, J.P. and Z.B. wrote the paper. All authors reviewed and commented on the paper.

Corresponding author

Correspondence to Zhenan Bao.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Electronics thanks Magnus Berggren and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Notes 1–4, Figs. 1–31 and Table 1.

Reporting Summary

Supplementary Data 1

Statistical source data.

Source data

Source Data Fig. 2

Statistical source data.

Source Data Fig. 3

Statistical source data.

Source Data Fig. 4

Statistical source data.

Source Data Fig. 5

Statistical source data.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, C., Park, J., Maulà, D. et al. Skin-like drift-free biosensors with stretchable diode-connected organic field-effect transistors. Nat Electron 8, 981–993 (2025). https://doi.org/10.1038/s41928-025-01465-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41928-025-01465-4

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing