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Nongenetic optical neuromodulation with silicon-based materials

Abstract

Optically controlled nongenetic neuromodulation represents a promising approach for the fundamental study of neural circuits and the clinical treatment of neurological disorders. Among the existing material candidates that can transduce light energy into biologically relevant cues, silicon (Si) is particularly advantageous due to its highly tunable electrical and optical properties, ease of fabrication into multiple forms, ability to absorb a broad spectrum of light, and biocompatibility. This protocol describes a rational design principle for Si-based structures, general procedures for material synthesis and device fabrication, a universal method for evaluating material photoresponses, detailed illustrations of all instrumentation used, and demonstrations of optically controlled nongenetic modulation of cellular calcium dynamics, neuronal excitability, neurotransmitter release from mouse brain slices, and brain activity in the mouse brain in vivo using the aforementioned Si materials. The entire procedure takes ~4–8 d in the hands of an experienced graduate student, depending on the specific biological targets. We anticipate that our approach can also be adapted in the future to study other systems, such as cardiovascular tissues and microbial communities.

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Fig. 1: A rational design principle for Si structures for optically controlled neuromodulation.
Fig. 2: Schematic overview of the entire protocol.
Fig. 3: Experimental setup for the CVD growth of Si materials.
Fig. 4: Structural characterizations of Si material building blocks.
Fig. 5: The fabrication process for the PDMS-supported Si mesh (Steps 25–43).
Fig. 6: Experimental setup of the photoresponse measurement (Steps 44–50).
Fig. 7: Experimental setups for the in vitro photostimulation of cultured neurons (Steps 51–90).
Fig. 8: Experimental setup for the photostimulation of acute brain slices (Steps 91–105).
Fig. 9: Experimental setup for the in vivo photostimulation experiment (Steps 106–122).
Fig. 10: Expected results of Si-based optically controlled neuromodulation.

Data availability

The authors declare that all data supporting the findings of this study are available within the original papers. Other supporting data are available upon reasonable request to the corresponding authors.

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Acknowledgements

This work was supported by the Air Force Office of Scientific Research (AFOSR FA9550-18-1-0503), the US Army Research Office (W911NF-18-1-0042), the US Office of Naval Research (N000141612530, N000141612958), the National Science Foundation (NSF MRSEC, DMR 1420709), the Searle Scholars Foundation, the National Institutes of Health (NIH NS101488, NS061963, GM030376, R21-EY023430, R21-EY027101), an MSTP Training Grant (T32GM007281), and the Paul and Daisy Soros Foundation. Atom-probe tomography was performed at the Northwestern University Center for Atom-Probe Tomography (NUCAPT), whose atom-probe tomography equipment was purchased and upgraded with funding from NSF-MRI (DMR-0420532) and ONR-DURIP (N00014-0400798, N00014-0610539, N00014-0910781) grants. NUCAPT is a Research Facility at the Materials Research Center of Northwestern University, supported by the National Science Foundation’s MRSEC program (grant DMR-1121262). Instrumentation at NUCAPT was further upgraded by the Initiative for Sustainability and Energy at Northwestern (ISEN). This work made use of the Japan Electron Optics Laboratory (JEOL) JEM-ARM200CF and JEOL JEM-3010 TEM in the Electron Microscopy Service of the Research Resources Center at the University of Illinois at Chicago (UIC). The acquisition of the UIC JEOL JEM-ARM200CF was supported by an MRI-R2 grant from the National Science Foundation (DMR-0959470).

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Y.J., R.P., X.L., J.L.C.-d.-S., F.B., G.M.G.S., and B.T. developed the protocol. Y.J., R.P., X.L., and J.L.C.-d.-S. performed the experiments. Y.J., R.P., X.L., and B.T. wrote the manuscript with input from J.L.C.-d.-S., X.G., L.M., F.B., and G.M.G.S.

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Correspondence to Yuanwen Jiang or Bozhi Tian.

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Key references using this protocol

Jiang, Y. et al. Nat. Mater. 15, 1023–1030 (2016): https://doi.org/10.1038/nmat4673

Parameswaran, R. et al. Nat. Nanotechnol. 13, 260–266 (2018): https://doi.org/10.1038/s41565-017-0041-7

Jiang, Y. et al. Nat. Biomed. Eng. 2, 508–521 (2018): https://doi.org/10.1038/s41551-018-0230-1

Supplementary information

Reporting Summary

Supplementary Data 1

Mask design for the Si mesh structure

Supplementary Data 2

Mask design for the SU-8 pillar structure

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Jiang, Y., Parameswaran, R., Li, X. et al. Nongenetic optical neuromodulation with silicon-based materials. Nat Protoc 14, 1339–1376 (2019). https://doi.org/10.1038/s41596-019-0135-9

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