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

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. Access

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BIORESORBABLE THIN-FILM SILICON DIODES FOR THE OPTOELECTRONIC EXCITATION AND INHIBITION OF NEURAL ACTIVITIES Article 05 September 2022 NEURAL MODULATION WITH PHOTOTHERMALLY ACTIVE

NANOMATERIALS Article 31 January 2023 IMPLANTABLE NANOPHOTONIC NEURAL PROBES FOR INTEGRATED PATTERNED PHOTOSTIMULATION AND ELECTROPHYSIOLOGICAL RECORDING Article Open access 05 April 2025

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

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(2009). Article  CAS  Google Scholar  Download references 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). AUTHOR INFORMATION Author notes *

These authors contributed equally: Yuanwen Jiang, Ramya Parameswaran, Xiaojian Li, João L. Carvalho-de-Souza. AUTHORS AND AFFILIATIONS * Department of Chemistry, The University of Chicago,

Chicago, IL, USA Yuanwen Jiang & Bozhi Tian * The James Franck Institute, The University of Chicago, Chicago, IL, USA Yuanwen Jiang, Xiang Gao & Bozhi Tian * The Graduate Program in

Biophysical Sciences, The University of Chicago, Chicago, IL, USA Ramya Parameswaran * Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

Xiaojian Li & Gordon M. G. Shepherd * Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA João L. Carvalho-de-Souza & Francisco Bezanilla *

Insitute for Molecular Engineering, The University of Chicago, Chicago, IL, USA Lingyuan Meng * Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA Francisco

Bezanilla & Bozhi Tian * Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile Francisco Bezanilla Authors * Yuanwen

Jiang View author publications You can also search for this author inPubMed Google Scholar * Ramya Parameswaran View author publications You can also search for this author inPubMed Google

Scholar * Xiaojian Li View author publications You can also search for this author inPubMed Google Scholar * João L. Carvalho-de-Souza View author publications You can also search for this

author inPubMed Google Scholar * Xiang Gao View author publications You can also search for this author inPubMed Google Scholar * Lingyuan Meng View author publications You can also search

for this author inPubMed Google Scholar * Francisco Bezanilla View author publications You can also search for this author inPubMed Google Scholar * Gordon M. G. Shepherd View author

publications You can also search for this author inPubMed Google Scholar * Bozhi Tian View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS 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. CORRESPONDING AUTHORS Correspondence to Yuanwen Jiang or Bozhi Tian. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no

competing interests. ADDITIONAL INFORMATION JOURNAL PEER REVIEW INFORMATION: _Nature Protocols_ thanks Tal Dvir and other anonymous reviewer(s) for their contribution to the peer review of

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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 RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE

CITE THIS ARTICLE Jiang, Y., Parameswaran, R., Li, X. _et al._ Nongenetic optical neuromodulation with silicon-based materials. _Nat Protoc_ 14, 1339–1376 (2019).

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