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Title: A flexible 3-dimensional microelectrode array for in vitro brain models

Abstract

Three-dimensional (3D) in vitro models have become increasingly popular as systems to study cell–cell and cell–ECM interactions dependent on the spatial, mechanical, and chemical cues within the environment of the tissue, which is limited in traditional two-dimensional (2D) models. Although electrophysiological recordings of neuronal action potentials through 2D microelectrode arrays (MEAs) are a common and trusted method of evaluating neuronal function, network communication, and response to chemicals and biologicals, there are currently limited options for measuring electrophysiological activity from many locations simultaneously throughout a 3D network of neurons in vitro. Here, we have developed a thin-film, 3D flexible microelectrode array (3DMEA) that non-invasively interrogates a 3D culture of neurons and can accommodate 256 channels of recording or stimulation. Importantly, the 3DMEA is straightforward to fabricate and integrates with standard commercially available electrophysiology hardware. Polyimide probe arrays were microfabricated on glass substrates and mechanically actuated to collectively lift the arrays into a vertical position, relying solely on plastic deformation of their base hinge regions to maintain vertical alignment. Human induced pluripotent stem cell (hiPSC)-derived neurons and astrocytes were entrapped in a collagen-based hydrogel and seeded onto the 3DMEA, enabling growth of suspended cells in the matrix and the formation and maturationmore » of a neural network around the 3DMEA probes. The 3DMEA supported the growth of functional neurons in 3D with action potential spike and burst activity recorded over 45 days in vitro. This platform is an important step in facilitating noninvasive electrophysiological characterization of 3D networks of electroactive cells in vitro.« less

Authors:
ORCiD logo [1]; ORCiD logo [2];  [1]; ORCiD logo [2]; ORCiD logo [1]; ORCiD logo [1];  [2];  [1];  [1]; ORCiD logo [2]
  1. Engineering Directorate, Lawrence Livermore National Laboratory, Livermore, USA
  2. Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, USA
Publication Date:
Research Org.:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA)
OSTI Identifier:
1594196
Alternate Identifier(s):
OSTI ID: 1615580
Report Number(s):
LLNL-JRNL-795358
Journal ID: ISSN 1473-0197; LCAHAM
Grant/Contract Number:  
17-SI-002; AC52-07NA27344
Resource Type:
Published Article
Journal Name:
Lab on a chip (Print)
Additional Journal Information:
Journal Name: Lab on a chip (Print) Journal Volume: 20 Journal Issue: 5; Journal ID: ISSN 1473-0197
Publisher:
Royal Society of Chemistry
Country of Publication:
France
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; Engineering; Health and safety

Citation Formats

Soscia, David A., Lam, Doris, Tooker, Angela C., Enright, Heather A., Triplett, Michael, Karande, Piyush, Peters, Sandra K. G., Sales, Ana Paula, Wheeler, Elizabeth K., and Fischer, Nicholas O. A flexible 3-dimensional microelectrode array for in vitro brain models. France: N. p., 2020. Web. doi:10.1039/C9LC01148J.
Soscia, David A., Lam, Doris, Tooker, Angela C., Enright, Heather A., Triplett, Michael, Karande, Piyush, Peters, Sandra K. G., Sales, Ana Paula, Wheeler, Elizabeth K., & Fischer, Nicholas O. A flexible 3-dimensional microelectrode array for in vitro brain models. France. doi:10.1039/C9LC01148J.
Soscia, David A., Lam, Doris, Tooker, Angela C., Enright, Heather A., Triplett, Michael, Karande, Piyush, Peters, Sandra K. G., Sales, Ana Paula, Wheeler, Elizabeth K., and Fischer, Nicholas O. Tue . "A flexible 3-dimensional microelectrode array for in vitro brain models". France. doi:10.1039/C9LC01148J.
@article{osti_1594196,
title = {A flexible 3-dimensional microelectrode array for in vitro brain models},
author = {Soscia, David A. and Lam, Doris and Tooker, Angela C. and Enright, Heather A. and Triplett, Michael and Karande, Piyush and Peters, Sandra K. G. and Sales, Ana Paula and Wheeler, Elizabeth K. and Fischer, Nicholas O.},
abstractNote = {Three-dimensional (3D) in vitro models have become increasingly popular as systems to study cell–cell and cell–ECM interactions dependent on the spatial, mechanical, and chemical cues within the environment of the tissue, which is limited in traditional two-dimensional (2D) models. Although electrophysiological recordings of neuronal action potentials through 2D microelectrode arrays (MEAs) are a common and trusted method of evaluating neuronal function, network communication, and response to chemicals and biologicals, there are currently limited options for measuring electrophysiological activity from many locations simultaneously throughout a 3D network of neurons in vitro. Here, we have developed a thin-film, 3D flexible microelectrode array (3DMEA) that non-invasively interrogates a 3D culture of neurons and can accommodate 256 channels of recording or stimulation. Importantly, the 3DMEA is straightforward to fabricate and integrates with standard commercially available electrophysiology hardware. Polyimide probe arrays were microfabricated on glass substrates and mechanically actuated to collectively lift the arrays into a vertical position, relying solely on plastic deformation of their base hinge regions to maintain vertical alignment. Human induced pluripotent stem cell (hiPSC)-derived neurons and astrocytes were entrapped in a collagen-based hydrogel and seeded onto the 3DMEA, enabling growth of suspended cells in the matrix and the formation and maturation of a neural network around the 3DMEA probes. The 3DMEA supported the growth of functional neurons in 3D with action potential spike and burst activity recorded over 45 days in vitro. This platform is an important step in facilitating noninvasive electrophysiological characterization of 3D networks of electroactive cells in vitro.},
doi = {10.1039/C9LC01148J},
journal = {Lab on a chip (Print)},
number = 5,
volume = 20,
place = {France},
year = {2020},
month = {3}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1039/C9LC01148J

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Cited by: 2 works
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