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Interfacing 3D Engineered Neuronal Cultures to Micro-Electrode Arrays: An Innovative In Vitro Experimental Model
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Bioelectrical interfaces with cortical spheroids in three-dimensions.

Anna Kalmykov1, Jay W Reddy2, Esther Bedoyan2

  • 1Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, United States of America.

Journal of Neural Engineering
|March 26, 2021
PubMed
Summary
This summary is machine-generated.

A novel 3D self-rolled biosensor array (3D-SR-BA) enables simultaneous electrophysiology recording and calcium imaging in neuronal spheroids. This technology advances neurological disorder research and drug discovery by providing high-resolution functional readouts of 3D brain cultures.

Keywords:
bioelectronicsbiosensorcortical spheroidmultielectrode array

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Area of Science:

  • Neuroscience
  • Bioengineering
  • Biomedical Devices

Background:

  • Three-dimensional (3D) neuronal spheroid cultures are vital for studying neurological disorders and drug discovery.
  • Existing electrophysiology (ephys) monitoring methods lack the resolution to capture activity across the entire 3D geometry of these cultures.
  • High-resolution functional readout techniques are needed for comprehensive analysis of 3D neuronal constructs.

Purpose of the Study:

  • To develop and demonstrate a 3D self-rolled biosensor array (3D-SR-BA) for integrated ephys recording and Ca2+ imaging in 3D neuronal spheroids.
  • To establish a platform for simultaneous functional readout and drug effect monitoring in complex neuronal cultures.
  • To enable high spatiotemporal resolution neural activity monitoring in native 3D spheroid geometries.

Main Methods:

  • Integration of a 3D self-rolled biosensor array (3D-SR-BA) with 3D cortical spheroid cultures.
  • Simultaneous in vitro electrophysiology (ephys) recording and functional Ca2+ imaging.
  • Development of a signal processing pipeline for high-resolution neural firing detection using spike sorting methods.
  • Assessment of drug effects, specifically the response to glutamate.

Main Results:

  • The 3D-SR-BA achieved stable, high-sensitivity recording of neural action potentials with amplitudes <50 µV.
  • The system demonstrated drug screening capabilities by observing increased neural firing rates upon glutamate addition.
  • Observed neural firing rate changes correlated well with simultaneous functional Ca2+ imaging data.

Conclusions:

  • The developed system, integrating 3D-SR-BAs with neuronal spheroids, enables simultaneous ephys recording and Ca2+ imaging with high spatiotemporal resolution.
  • This toolset facilitates chemical stimulation studies and provides a powerful platform for research into tissue development and disease progression.
  • The technology holds significant promise for drug testing and screening, particularly with human-derived spheroid cultures.