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Bioresorbable thin-film silicon diodes for the optoelectronic excitation and inhibition of neural activities

Nature Biomedical Engineering volume 7, pages 486–498 (2023)Cite this article

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Abstract

Neural activities can be modulated by leveraging light-responsive nanomaterials as interfaces for exerting photothermal, photoelectrochemical or photocapacitive effects on neurons or neural tissues. Here we show that bioresorbable thin-film monocrystalline silicon pn diodes can be used to optoelectronically excite or inhibit neural activities by establishing polarity-dependent positive or negative photovoltages at the semiconductor/solution interface. Under laser illumination, the silicon-diode optoelectronic interfaces allowed for the deterministic depolarization or hyperpolarization of cultured neurons as well as the upregulated or downregulated intracellular calcium dynamics. The optoelectronic interfaces can also be mounted on nerve tissue to activate or silence neural activities in peripheral and central nervous tissues, as we show in mice with exposed sciatic nerves and somatosensory cortices. Bioresorbable silicon-based optoelectronic thin films that selectively excite or inhibit neural tissue may find advantageous biomedical applicability.

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Fig. 1: Thin-film Si junctions and their optoelectronic responses in aqueous solutions.
Fig. 2: Optoelectronic excitation and inhibition of cell activities in vitro with thin-film Si junctions.
Fig. 3: Imaging cellular calcium dynamics optically modulated by thin-film p+n and n+p Si junctions in vitro.
Fig. 4: Optoelectronic excitation and inhibition of peripheral neural activities in vivo with p+n and n+p Si films, respectively.
Fig. 5: Optoelectronic excitation and inhibition of brain cortex activities in vivo with p+n and n+p Si films, respectively.
Fig. 6: In vitro and in vivo degradation and biocompatibilities of Si films.

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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 available for research purposes from the corresponding authors on reasonable request. Source data are provided with this paper.

Code availability

Custom codes used in this study are available at https://github.com/shengxingstars/2022-Si-diodes-modulation.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (NSFC) (61874064, to X.S.; 52171239, to L.Y.; and T2122010, to L.Y.), the National Key R&D Program of China (2018YFA0701400, to X.L.; 2017YFA0701102, to S.W.), the Beijing Municipal Natural Science Foundation (4202032, to X.S.), Tsinghua University Initiative Scientific Research Program (to X.S.), and the Center for Flexible Electronics Technology at Tsinghua University (to X.S. and L.Y.).

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Author notes

  1. These authors contributed equally: Yunxiang Huang, Yuting Cui, Hanjie Deng.

Authors and Affiliations

  1. Department of Electronic Engineering, Beijing National Research Center for Information Science and Technology, Institute for Precision Medicine, Center for Flexible Electronics Technology, Tsinghua University, Beijing, China

    Yunxiang Huang, Huachun Wang, Junyu Chen, Lizhu Li, Yang Xie & Xing Sheng

  2. School of Materials Science and Engineering, The Key Laboratory of Advanced Materials of Ministry of Education, State Key Laboratory of New Ceramics and Fine Processing, Center for Flexible Electronics Technology, Tsinghua University, Beijing, China

    Yunxiang Huang, Pengcheng Sun, Xin Fu & Lan Yin

  3. IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, China

    Yunxiang Huang, Shuhan Hu, Hanqing Hou, Wei Xiong, Song-Hai Shi, Minmin Luo & Xing Sheng

  4. Chinese Institute for Brain Research, Beijing, China

    Yuting Cui & Minmin Luo

  5. National Institute of Biological Sciences, Beijing, China

    Yuting Cui & Minmin Luo

  6. CAS Key Laboratory of Brain Connectome and Manipulation, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China

    Hanjie Deng, Jingjing Wang, Rongqi Hong & Xiaojian Li

  7. School of Life Sciences, Tsinghua University, Beijing, China

    Shuhan Hu, Hanqing Hou, Wei Xiong, Song-Hai Shi & Minmin Luo

  8. Beijing Advanced Innovation Center for Intelligent Robots and Systems, Beijing Institute of Technology, Beijing, China

    Yuanrui Dong & Shirong Wang

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  1. Yunxiang Huang
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Contributions

Y.H. and X.S. developed the concepts. Y.H., H.W., Y.X., P.S. and X.F. performed material design, fabrication and characterization. Y.H., H.W., J.C., L.L. and X.S. performed numerical simulations. Y.H., Y.C., H.D., J.W., R.H., S.H., H.H., Y.D., X.F., S.W. and X.L. designed and performed biological experiments. L.Y., W.X., M.L., S.-H.S., S.W., X.L. and X.S. provided tools and supervised the research. Y.H. and X.S. wrote the paper in consultation with the rest of the authors.

Corresponding authors

Correspondence to Shirong Wang, Xiaojian Li or Xing Sheng.

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Nature Biomedical Engineering thanks Ravi Bellamkonda, Bozhi Tian and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.

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Extended data

Extended Data Fig. 1

Schematic illustration of processing flow for the fabrication and transfer printing of doped silicon membranes.

Source data

Extended Data Fig. 2 Measurement of photocurrents induced by p+n and n+p Si diode films.

a, Scheme of the setup for the transient photoresponse measurement. The transient photocurrents are taken by voltage-clamp recording (filter at 10 kHz and sampled at 200 kHz) and the resistance of pipette is ~1 MΩ. Lightly doped surfaces (n-side for p+n Si, and p-side for n+p Si) contact the solution. b, The transient photocurrents generated on the Si surfaces, with pulsed light duration 500 ms and intensity 1.2 W cm−2. Most of the currents are photocapacitive, and negligible Faradic currents are observed.

Source data

Extended Data Fig. 3 Depolarized membrane current with the p+n Si film.

a, Scheme of the setup for the whole-cell recording of the DRG grown on p+n Si. b, Typical recorded membrane currents in response to the photostimulation with varying light intensities within a 10-s-long illumination, showing the slowly increased depolarized currents.

Source data

Extended Data Fig. 4 Hyperpolarized membrane current with the n+p Si film.

a, Scheme of the setup for the whole-cell recording of the DRG grown on n+p Si. b, Typical recorded membrane currents in response to the photostimulation with varying light intensities within a 1-s-long illumination (left), and enlarged details of the hyperpolarized currents (right).

Source data

Extended Data Fig. 5 Circuit model developed to understand the polarity-dependent photostimulation.

a, Scheme of the setup for the whole-cell patch clamp recording of DRG cells cultured on Si films. b, Equivalent circuit of the recorded membrane potential influenced by photovoltaic stimulations. Here we assume the cell has a hemispheric shape with a diameter of 30 µm. Rm1 = 66.9 MΩ, Rm2 = 33.45 MΩ, Cm1 = 27.3 pF, Cm2 = 54.6 pF, CSi = 70.7 pF and Rattach = 1.4 kΩ. The initial holding potential Vhold = −65 mV. c, Parameters used for photovoltages Vph generated by p+n and n+p Si films (taken from Fig. 1b,c), as well as transmembrane inward and outward currents Iin and Iout (taken and normalized from Extended Data Figs. 3 and 4), in response to various light intensities.

Source data

Extended Data Fig. 6 Simulation results based on the circuit model.

a,b, Inward (a) and outward (b) transmembrane currents (Iin and Iout) applied in the model, based on parameters in Extended Data Fig. 5. c, Calculated membrane voltages (Vm) responding to different inward and outward currents generated by p+n Si and n+p Si, respectively. d, Depolarized and hyperpolarized membrane voltages as a function of the light intensity. The simulation results are in good agreement with experiments in Fig. 2c,d.

Source data

Supplementary information

Supplementary Information

Supplementary figures.

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Supplementary Video 1

Increased Ca2+ fluorescence in cultured DRGs evoked by a p+n Si film under optical stimulation.

Supplementary Video 2

Decreased Ca2+ fluorescence in cultured DRGs suppressed by an n+p Si film under optical stimulation. AMPA is initially applied for cell activation.

Supplementary Video 3

Evoked CMAPs and hindlimb lifting by exciting in the sciatic nerve with a p+n Si film under optical stimulation.

Supplementary Video 4

Decreased CMAPs and hindlimb lifting by inhibiting the sciatic nerve with an n+p Si film under optical stimulation.

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Huang, Y., Cui, Y., Deng, H. et al. Bioresorbable thin-film silicon diodes for the optoelectronic excitation and inhibition of neural activities. Nat. Biomed. Eng 7, 486–498 (2023). https://doi.org/10.1038/s41551-022-00931-0

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