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An artificial cilia-based array system for sound frequency decoding and resonance-responsive drug release

Nature Biomedical Engineering (2025)Cite this article

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Abstract

Hair cells in the human ear contain cilia of varying lengths that sense varied acoustic signals. Here, inspired by this, we report an artificial cilia-based sound-decoding device capable of directly recognizing and responding to sound frequencies without relying on electricity and algorithms. We create 3D-printed micrometre-sized (40–200 μm) artificial cilia-based arrays with varying length-to-diameter ratios (30–100) that can sense and decode sound frequency signals (100–6,000 Hz), including piano music and human voices, on the basis of acoustic resonance. The artificial cilia can also vibrate accordingly in water to initiate subsequent tasks such as controlling drug release profiles of two distinct therapeutics (insulin and glucagon) in an acoustic-frequency-responsive manner to treat type 1 diabetic mice. This cochlear cilia-inspired device holds potential for broad applications such as recognizing complicated physiological sounds and performing various tasks in personalized voice interactions.

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Fig. 1: Schematic of cochlear hair cell-inspired artificial cilia array and its applications.
Fig. 2: Fabrication and characterization of artificial cilia array.
Fig. 3: Sound decoding by artificial cilia array.
Fig. 4: Hydrodynamics of artificial cilia array upon acoustic stimulation in the water.
Fig. 5: Acoustic-frequency-responsive drug release for the treatment of type 1 diabetic mice.

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All data supporting the findings of this study are presented in the Article and its Supplementary Information. Source data are provided with this paper.

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Acknowledgements

This work was supported by the grants from “Pioneer” and “Leading Goose” R&D Program of Zhejiang (grant no. 2024C03085) and Zhejiang University’s start-up packages, National Natural Science Foundation of China (grant nos. 82100911 and 32201082), National Natural Science Fund for Excellent Young Scientist Fund Program (Overseas) (grant no. 588020-X42208/061), Zhejiang Provincial Natural Science Foundation (grant no. LQ18H070004). We thank S. Liu from the Core Facilities, Zhejiang University School of Medicine, for her technical support in Confocal Microscopy. We thank G. Zhu and D. Song in the Center of Cryo-Electron Microscopy (CCEM), Zhejiang University, for their assistance with SEM. We appreciate S. Yang from Hangzhou Liuxia Primary School for her guidance on music theory.

Author information

Authors and Affiliations

  1. State Key Laboratory of Advanced Drug Delivery and Release Systems, School of Pharmacy, Zhejiang University, Hangzhou, China

    Xinwei Wei, Yanfang Wang, Wentao Zhang, Kaihui Li, Licheng Han, Jianchang Xu, Yuejun Yao, Yingqi Huang, Jianqing Gao, Jinqiang Wang & Zhen Gu

  2. Jinhua Institute of Zhejiang University, Jinhua, China

    Xinwei Wei, Jianchang Xu, Yuejun Yao, Jianqing Gao, Jinqiang Wang & Zhen Gu

  3. Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, School of Pharmacy, Zhejiang University, Hangzhou, China

    Xinwei Wei, Jianchang Xu, Yuejun Yao, Jianqing Gao, Jinqiang Wang & Zhen Gu

  4. Institute of Cyber-Systems and Control, College of Control Science and Engineering, State Key Laboratory for Industrial Control Technology, Zhejiang University, Hangzhou, China

    Hanlin Wang & Chao Xu

  5. Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou, China

    Changming Chen & Ping Wang

  6. Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, USA

    Joseph Rufo & Tony Jun Huang

  7. The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou, China

    Tianyu Zhang & Xiangsheng Liu

  8. Zhejiang Provincial Engineering Research Center for Intelligent Mobile Unmanned Systems Technology and Huzhou Key Lab for Autonomous Systems, Huzhou Institute of Zhejiang University, Huzhou, China

    Chao Xu

  9. Department of Pharmacy, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Jinqiang Wang

  10. MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, China

    Zhen Gu

  11. Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Zhen Gu

  12. Liangzhu Laboratory, Hangzhou, China

    Zhen Gu

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  1. Xinwei Wei
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  2. Hanlin Wang
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  3. Yanfang Wang
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Contributions

Z.G., J.W. and X.W. conceived and designed the study. X.W., H.W., Y.W., W.Z., C.C., K.L., L.H., J.R., J.X., Y.Y., Y.H. and T.Z. conducted experiments and collected related data. X.W., H.W., X.L., J.G., P.W., C.X., J.W. and Z.G. analysed the data and wrote the paper. T.J.H. edited the paper.

Corresponding authors

Correspondence to Jinqiang Wang or Zhen Gu.

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Competing interests

Z.G. is the co-founder of Zcapsule Inc. and μZen Inc. The other authors declare no competing interests.

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Nature Biomedical Engineering thanks Daniel Ahmed and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information (download PDF )

Supplementary Figs. 1–13 and Videos 1 and 2.

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Supplementary Video 1 (download MP4 )

The vibration of artificial cilia in response to sound stimuli in the air recorded by the high-speed camera.

Supplementary Video 2 (download MP4 )

The vibration of artificial cilia array upon the acoustic stimulation by PZT in the water.

Supplementary Data (download XLSX )

Statistical source data for the Supplementary Information.

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Wei, X., Wang, H., Wang, Y. et al. An artificial cilia-based array system for sound frequency decoding and resonance-responsive drug release. Nat. Biomed. Eng (2025). https://doi.org/10.1038/s41551-025-01505-6

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