Influence of microchannel geometry on device performance and electrophysiological recording fidelity during long-term studies of connected neural populations

Compartmentalized microfluidic neural cell culture platforms, which physically separate axons from the neural soma using a series of microchannels, have been used for studying a wide range of pathological conditions and basic neuroscience questions. While each study has different experimental needs,...

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Bibliographic Details
Published inLab on a chip Vol. 22; no. 2; pp. 3961 - 3975
Main Authors Goshi, Noah, Girardi, Gregory, da Costa Souza, Felipe, Gardner, Alexander, Lein, Pamela J, Seker, Erkin
Format Journal Article
LanguageEnglish
Published England Royal Society of Chemistry 11.10.2022
Subjects
Animals
Axons
Axons - physiology
Design parameters
Electrophysiological Phenomena
Microchannels
Microelectrodes
Microfluidics
Neuroglia
Neurons
Populations
Rats
Signal to noise ratio
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Summary:Compartmentalized microfluidic neural cell culture platforms, which physically separate axons from the neural soma using a series of microchannels, have been used for studying a wide range of pathological conditions and basic neuroscience questions. While each study has different experimental needs, the fundamental design of these devices has largely remained unchanged and a systematic study to establish long-term neural cultures in this format is lacking. Here, we investigate the influence of microchannel geometry and cell seeding density on device performance particularly in the context of long-term studies of synaptically-connected, yet fluidically-isolated neural populations of neurons and glia. Of the different experimental parameters, the microchannel height was the principal determinant of device performance, where the other parameters offer additional degrees of freedom in customizing such devices for specific applications. We condense the effects of these parameters into design rules and demonstrate their utility in engineering a microfluidic neural culture platform with integrated microelectrode arrays. The engineered device successfully recorded from primary rat cortical cells for 59 days in vitro with more than on order of magnitude enhancement in signal-to-noise ratio in the microchannels. This study examines the role of microchannel geometry on the long-term performance of compartmentalized microfluidic neural cell culture platforms and provides general design rules for different experimental objectives.
Bibliography:https://doi.org/ 10.1039/d2lc00683a
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NG and ES designed the experiments. NG performed device fabrication, cell culture, electrophysiological recordings, imaging, and data analysis and wrote the main manuscript text. GG contributed to the development and fabrication of microfluidic devices and microelectrode arrays, and data analysis. FDCS contributed to the development of the cell culture. AG contributed to electrophysiological data analysis. ES and PJL contributed to the interpretation of experimental results and edited the manuscript. All authors read and approved the final manuscript.
Author Contributions
ISSN:1473-0197
1473-0189
DOI:10.1039/d2lc00683a