Real-time monitoring of epithelial barrier function by impedance spectroscopy in a microfluidic platform
Real-time monitoring of epithelial barrier function by impedance spectroscopy in a microfluidic platform
A multichannel microfluidic platform for real-time monitoring of epithelial barrier integrity by electrical impedance has been developed. Growth and polarization of human epithelial cells from the airway or gastrointestinal tract was continuously monitored over 5 days in 8 parallel, individually perfused microfluidic chips. Electrical impedance data were continuously recorded to monitor cell barrier formation using a low-cost bespoke impedance analyser. Data was analysed using an electric circuit model to extract the equivalent transepithelial electrical resistance and epithelial cell layer capacitance. The cell barrier integrity steadily increased overtime, achieving an average resistance of 418 ± 121 Ω cm
2 (airway cells) or 207 ± 59 Ω cm
2 (gastrointestinal cells) by day 5. The utility of the polarized airway epithelial barrier was demonstrated using a 24 hour challenge with double stranded RNA to mimic viral infection. This caused a rapid decrease in barrier integrity in association with disruption of tight junctions, whereas simultaneous treatment with a corticosteroid reduced this effect. The platform is able to measure barrier integrity in real-time and is scalable, thus has the potential to be used for drug development and testing.
Fernandes, Joao, Cabaco
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Karra, Nikita
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Bowring, Joel
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Reale, Riccardo
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James, Jonathan
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Pell, Theresa
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Blume, Cornelia
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Rowan, Wendy
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Davies, Donna
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Swindle, Emily
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Morgan, Hywel
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22 April 2022
Fernandes, Joao, Cabaco
03326cb4-3918-4bde-94d7-ba3b2eea718e
Karra, Nikita
8037beb7-98d3-40b2-9e02-51e4e917b3c0
Bowring, Joel
0fb54787-3cba-46f5-b8e9-45aebc5ebfb8
Reale, Riccardo
c7651c37-e622-45aa-a0e1-595d35ca4b2c
James, Jonathan
82925b58-0a9e-423c-8483-49c4b7c667cb
Pell, Theresa
7e560e90-6a1d-4f5d-8c16-14490bc09920
Blume, Cornelia
aa391c64-8718-4238-906b-d6bb1551a07b
Rowan, Wendy
b3d9ce62-0649-44ba-bd16-966eb5e7884d
Davies, Donna
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Swindle, Emily
fe393c7a-a513-4de4-b02e-27369bd7e84f
Morgan, Hywel
de00d59f-a5a2-48c4-a99a-1d5dd7854174
Fernandes, Joao, Cabaco, Karra, Nikita, Bowring, Joel, Reale, Riccardo, James, Jonathan, Pell, Theresa, Blume, Cornelia, Rowan, Wendy, Davies, Donna, Swindle, Emily and Morgan, Hywel
(2022)
Real-time monitoring of epithelial barrier function by impedance spectroscopy in a microfluidic platform.
Lab on a Chip.
(doi:10.1039/D1LC01046H).
Abstract
A multichannel microfluidic platform for real-time monitoring of epithelial barrier integrity by electrical impedance has been developed. Growth and polarization of human epithelial cells from the airway or gastrointestinal tract was continuously monitored over 5 days in 8 parallel, individually perfused microfluidic chips. Electrical impedance data were continuously recorded to monitor cell barrier formation using a low-cost bespoke impedance analyser. Data was analysed using an electric circuit model to extract the equivalent transepithelial electrical resistance and epithelial cell layer capacitance. The cell barrier integrity steadily increased overtime, achieving an average resistance of 418 ± 121 Ω cm
2 (airway cells) or 207 ± 59 Ω cm
2 (gastrointestinal cells) by day 5. The utility of the polarized airway epithelial barrier was demonstrated using a 24 hour challenge with double stranded RNA to mimic viral infection. This caused a rapid decrease in barrier integrity in association with disruption of tight junctions, whereas simultaneous treatment with a corticosteroid reduced this effect. The platform is able to measure barrier integrity in real-time and is scalable, thus has the potential to be used for drug development and testing.
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d1lc01046h
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In preparation date: 18 November 2021
Accepted/In Press date: 8 April 2022
e-pub ahead of print date: 22 April 2022
Published date: 22 April 2022
Additional Information:
Funding Information:
This work was funded by the EPSRC, GlaxoSmithKline, IUK (102522) and the Asthma Allergy and Inflammation Research charity. We would like to thank Katie Chamberlain for her assistance with fabrication of glass chips, Mark Long, Anthony Gardener and Jamie Stone for their technical assistance with micro milling and 3D printing and David Johnstone for his support with confocal microscopy. 16HBBE14o- cells were gifted from Prof. D.C. Gruenert, San Francisco, USA. Caco-2 cells were gifted by Prof. P. Calder and provided by his PhD student Luke Dirkin, University of Southampton, UK.
Publisher Copyright:
© 2022 The Royal Society of Chemistry
Identifiers
Local EPrints ID: 456810
URI: http://eprints.soton.ac.uk/id/eprint/456810
ISSN: 1473-0197
PURE UUID: d828cb74-a180-4e4c-9c10-5f3dcbf67be9
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Date deposited: 11 May 2022 16:52
Last modified: 06 Jun 2024 01:47
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Contributors
Author:
Joao, Cabaco Fernandes
Author:
Nikita Karra
Author:
Joel Bowring
Author:
Riccardo Reale
Author:
Jonathan James
Author:
Theresa Pell
Author:
Wendy Rowan
Author:
Hywel Morgan
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