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A Closed-Loop-Capable Neural Interface Platform for Deep Brain Modulation via Integrated Non-Viral Gene Delivery, NIR

Chao-Yi Chu1, Zih-Huei Chen2, Chun-Wei Liang1

  • 1Department of Materials Science and Engineering, National Yang Ming Chiao Tung University, No. 1001, Daxue Rd., Hsinchu, 300093, Taiwan, ROC.

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Summary

This study introduces a novel, fiber-free neural interface for precise, cell-specific neuromodulation. The device enables non-viral gene delivery and remote optogenetic stimulation, enhancing deep-brain circuit control.

Keywords:
electroporation‐mediated gene deliverygold inverse opal (AuIO)neural interfaceoptogeneticsupconversion nanoparticles (UCNPs)

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Area of Science:

  • Neuroscience
  • Biomedical Engineering
  • Materials Science

Background:

  • Conventional optogenetics faces challenges with invasiveness, viral gene delivery, and hardware complexity.
  • Precise, stable, and cell-specific neural circuit control is crucial for closed-loop neuromodulation.

Purpose of the Study:

  • To develop a multifunctional, implantable neural interface for fiberless, non-viral optogenetic control.
  • To integrate gene delivery, optogenetic stimulation, and electrophysiological recording into a single device.
  • To demonstrate in vivo efficacy for deep-brain neuromodulation.

Main Methods:

  • Fabrication of a 3D gold inverse opal (AuIO) microelectrode for gene transfection and signal recording.
  • Non-viral gene delivery using Channelrhodopsin-2 (ChR2) plasmid complexed with NT-PEI.
  • Integration of upconversion nanoparticles (UCNPs) for near-infrared (NIR) to blue light conversion via aerosol jet printing.
  • In vivo implantation into the hippocampal dentate gyrus (DG) for functional assessment.

Main Results:

  • Successful non-viral delivery and expression of ChR2 in neurons.
  • Fiberless, remote optogenetic stimulation using NIR light achieved via LSPR enhancement.
  • Real-time, light-evoked neural activity recorded in vivo.
  • Demonstrated stable in vivo operation and biocompatibility.

Conclusions:

  • The developed all-in-one platform offers a fiber-free, biocompatible solution for deep-brain optogenetic engineering.
  • This technology advances precision closed-loop neuromodulation by simplifying surgical requirements and enhancing control.
  • The multifunctional interface holds promise for future therapeutic applications targeting neural circuits.