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Real-time monitoring of epithelial barrier function by impedance spectroscopy in a microfluidic platform
Lab on a Chip ( IF 6.1 ) Pub Date : 2022-04-22 , DOI: 10.1039/d1lc01046h João Fernandes 1 , Nikita Karra 1 , Joel Bowring 1 , Riccardo Reale 1 , Jonathan James 2 , Cornelia Blume 2, 3, 4 , Theresa J Pell 5 , Wendy C Rowan 5 , Donna E Davies 2, 3, 4 , Emily J Swindle 2, 3, 4 , Hywel Morgan 1, 3
Lab on a Chip ( IF 6.1 ) Pub Date : 2022-04-22 , DOI: 10.1039/d1lc01046h João Fernandes 1 , Nikita Karra 1 , Joel Bowring 1 , Riccardo Reale 1 , Jonathan James 2 , Cornelia Blume 2, 3, 4 , Theresa J Pell 5 , Wendy C Rowan 5 , Donna E Davies 2, 3, 4 , Emily J Swindle 2, 3, 4 , Hywel Morgan 1, 3
Affiliation
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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 cm2 (airway cells) or 207 ± 59 Ω cm2 (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.
中文翻译：
在微流控平台中通过阻抗谱实时监测上皮屏障功能
开发了一种通过电阻抗实时监测上皮屏障完整性的多通道微流体平台。在 8 个平行、单独灌注的微流控芯片中，连续 5 天监测来自气道或胃肠道的人类上皮细胞的生长和极化。使用低成本定制阻抗分析仪连续记录电阻抗数据以监测细胞屏障的形成。使用电路模型分析数据以提取等效跨上皮电阻和上皮细胞层电容。细胞屏障完整性随着时间的推移稳步增加，达到 418 ± 121 Ω cm 2（气道细胞）或 207 ± 59 Ω cm 2的平均电阻（胃肠细胞）到第 5 天。极化气道上皮屏障的效用通过用双链 RNA 进行 24 小时攻击来模拟病毒感染来证明。这导致与紧密连接破坏相关的屏障完整性迅速降低，而同时使用皮质类固醇治疗会降低这种影响。该平台能够实时测量屏障完整性并且具有可扩展性，因此具有用于药物开发和测试的潜力。
更新日期：2022-04-22
中文翻译：
在微流控平台中通过阻抗谱实时监测上皮屏障功能
开发了一种通过电阻抗实时监测上皮屏障完整性的多通道微流体平台。在 8 个平行、单独灌注的微流控芯片中，连续 5 天监测来自气道或胃肠道的人类上皮细胞的生长和极化。使用低成本定制阻抗分析仪连续记录电阻抗数据以监测细胞屏障的形成。使用电路模型分析数据以提取等效跨上皮电阻和上皮细胞层电容。细胞屏障完整性随着时间的推移稳步增加，达到 418 ± 121 Ω cm 2（气道细胞）或 207 ± 59 Ω cm 2的平均电阻（胃肠细胞）到第 5 天。极化气道上皮屏障的效用通过用双链 RNA 进行 24 小时攻击来模拟病毒感染来证明。这导致与紧密连接破坏相关的屏障完整性迅速降低，而同时使用皮质类固醇治疗会降低这种影响。该平台能够实时测量屏障完整性并且具有可扩展性，因此具有用于药物开发和测试的潜力。
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