A device for long-term perfusion, imaging, and electrical interfacing of brain tissue in vitro

Distributed microelectrode array (MEA) recordings from consistent, viable, ≥ 500 µm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacin...

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Main Authors: Nathaniel J Killian, Varadraj N Vernekar, Steve M Potter, Jelena eVukasinovic
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-03-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00135/full
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author Nathaniel J Killian
Nathaniel J Killian
Varadraj N Vernekar
Steve M Potter
Jelena eVukasinovic
Jelena eVukasinovic
author_facet Nathaniel J Killian
Nathaniel J Killian
Varadraj N Vernekar
Steve M Potter
Jelena eVukasinovic
Jelena eVukasinovic
author_sort Nathaniel J Killian
collection DOAJ
description Distributed microelectrode array (MEA) recordings from consistent, viable, ≥ 500 µm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3 D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step towards the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long) brain slice preparations.
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spelling doaj.art-9bb985666ad14f148581dbecabbcf2eb2022-12-21T23:57:11ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2016-03-011010.3389/fnins.2016.00135188530A device for long-term perfusion, imaging, and electrical interfacing of brain tissue in vitroNathaniel J Killian0Nathaniel J Killian1Varadraj N Vernekar2Steve M Potter3Jelena eVukasinovic4Jelena eVukasinovic5Georgia Institute of TechnologyMassachusetts General HospitalGeorgia Institute of TechnologyGeorgia Institute of TechnologyLena Biosciences, Inc.Georgia Institute of TechnologyDistributed microelectrode array (MEA) recordings from consistent, viable, ≥ 500 µm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3 D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step towards the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long) brain slice preparations.http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00135/fullNeuronMEAbrain slicethree-dimensional cultureperforated microelectrode array
spellingShingle Nathaniel J Killian
Nathaniel J Killian
Varadraj N Vernekar
Steve M Potter
Jelena eVukasinovic
Jelena eVukasinovic
A device for long-term perfusion, imaging, and electrical interfacing of brain tissue in vitro
Frontiers in Neuroscience
Neuron
MEA
brain slice
three-dimensional culture
perforated microelectrode array
title A device for long-term perfusion, imaging, and electrical interfacing of brain tissue in vitro
title_full A device for long-term perfusion, imaging, and electrical interfacing of brain tissue in vitro
title_fullStr A device for long-term perfusion, imaging, and electrical interfacing of brain tissue in vitro
title_full_unstemmed A device for long-term perfusion, imaging, and electrical interfacing of brain tissue in vitro
title_short A device for long-term perfusion, imaging, and electrical interfacing of brain tissue in vitro
title_sort device for long term perfusion imaging and electrical interfacing of brain tissue in vitro
topic Neuron
MEA
brain slice
three-dimensional culture
perforated microelectrode array
url http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00135/full
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