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Technology Development Initiative – Paper of the Month – May 2023

A figure from this study. Image copyright - Nature.

Image copyright – Nature

Customizable, wireless and implantable neural probe design and fabrication via 3D printing

Published in Nature Protocols (2022)

Authors

Kyle E Parker, Juhyun Lee, Jenny R Kim, Chinatsu Kawakami, Choong Yeon Kim, Raza Qazi, Kyung-In Jang, Jae-Woong Jeong, Jordan G McCall

Paper presented by Dr. Nicholas Beacher and selected by the NIDA TDI Paper of the Month Committee.

Publication Brief Description

Optogenetics uses genetically encoded proteins to manipulate cellular activities via photostimulation at particular wavelengths of light. The light sources for activating optogenetic proteins can require expensive probes and equipment that prohibit large scale experiments. Furthermore, limitations of using commercial sourced probe shanks can make ‘multi-region’ optogenetics experiments in the brain challenging. Parker*, Lee*, Kim* et. al. provides a protocol including all procedures, designs, and product information for researchers to establish wireless optogenetics in their lab for low cost and high subject output.  The paper details the following: 1) a custom manufacturing technique for 3D-printing large number of optogenetic probes of any length and number of ‘shanks’ in ~2 days, 2) a low-cost, custom, wireless harnesses, and 3) software for a smartphone app to control the timing and frequency of delivered light. The described technology can readily be applied for social interaction experiments where large groups of rats or mice need to be group-housed and implanted with probes in specific brain regions of interest. Wirelessly exciting or inhibiting specific neuronal subtypes in multiple regions and analyzing the associated behavioral changes using deep learning software may provide insight into the neural mechanisms involved in social interaction and clinically relevant social behaviors.


Parker, Kyle E; Lee, Juhyun; Kim, Jenny R; Kawakami, Chinatsu; Kim, Choong Yeon; Qazi, Raza; Jang, Kyung-In; Jeong, Jae-Woong; McCall, Jordan G

Customizable, wireless and implantable neural probe design and fabrication via 3D printing Journal Article

In: Nat Protoc, vol. 18, no. 1, pp. 3–21, 2023, ISSN: 1750-2799.

Abstract | Links

@article{pmid36271159,
title = {Customizable, wireless and implantable neural probe design and fabrication via 3D printing},
author = {Kyle E Parker and Juhyun Lee and Jenny R Kim and Chinatsu Kawakami and Choong Yeon Kim and Raza Qazi and Kyung-In Jang and Jae-Woong Jeong and Jordan G McCall},
url = {https://pubmed.ncbi.nlm.nih.gov/36271159/},
doi = {10.1038/s41596-022-00758-8},
issn = {1750-2799},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {Nat Protoc},
volume = {18},
number = {1},
pages = {3--21},
abstract = {This Protocol Extension describes the low-cost production of rapidly customizable optical neural probes for in vivo optogenetics. We detail the use of a 3D printer to fabricate minimally invasive microscale inorganic light-emitting-diode-based neural probes that can control neural circuit activity in freely behaving animals, thus extending the scope of two previously published protocols describing the fabrication and implementation of optoelectronic devices for studying intact neural systems. The 3D-printing fabrication process does not require extensive training and eliminates the need for expensive materials, specialized cleanroom facilities and time-consuming microfabrication techniques typical of conventional manufacturing processes. As a result, the design of the probes can be quickly optimized, on the basis of experimental need, reducing the cost and turnaround for customization. For example, 3D-printed probes can be customized to target multiple brain regions or scaled up for use in large animal models. This protocol comprises three procedures: (1) probe fabrication, (2) wireless module preparation and (3) implantation for in vivo assays. For experienced researchers, neural probe and wireless module fabrication requires ~2 d, while implantation should take 30-60 min per animal. Time required for behavioral assays will vary depending on the experimental design and should include at least 5 d of animal handling before implantation of the probe, to familiarize each animal to their handler, thus reducing handling stress that may influence the result of the behavioral assays. The implementation of customized probes improves the flexibility in optogenetic experimental design and increases access to wireless probes for in vivo optogenetic research.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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This Protocol Extension describes the low-cost production of rapidly customizable optical neural probes for in vivo optogenetics. We detail the use of a 3D printer to fabricate minimally invasive microscale inorganic light-emitting-diode-based neural probes that can control neural circuit activity in freely behaving animals, thus extending the scope of two previously published protocols describing the fabrication and implementation of optoelectronic devices for studying intact neural systems. The 3D-printing fabrication process does not require extensive training and eliminates the need for expensive materials, specialized cleanroom facilities and time-consuming microfabrication techniques typical of conventional manufacturing processes. As a result, the design of the probes can be quickly optimized, on the basis of experimental need, reducing the cost and turnaround for customization. For example, 3D-printed probes can be customized to target multiple brain regions or scaled up for use in large animal models. This protocol comprises three procedures: (1) probe fabrication, (2) wireless module preparation and (3) implantation for in vivo assays. For experienced researchers, neural probe and wireless module fabrication requires ~2 d, while implantation should take 30-60 min per animal. Time required for behavioral assays will vary depending on the experimental design and should include at least 5 d of animal handling before implantation of the probe, to familiarize each animal to their handler, thus reducing handling stress that may influence the result of the behavioral assays. The implementation of customized probes improves the flexibility in optogenetic experimental design and increases access to wireless probes for in vivo optogenetic research.

Close

  • https://pubmed.ncbi.nlm.nih.gov/36271159/
  • doi:10.1038/s41596-022-00758-8

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