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用于药物毒性测试的芯片上双光子代谢成像

On chip two-photon metabolic imaging for drug toxicity testing.

作者信息

Yu Fang, Zhuo Shuangmu, Qu Yinghua, Choudhury Deepak, Wang Zhiping, Iliescu Ciprian, Yu Hanry

机构信息

Singapore Institute of Manufacturing Technology, ASTAR, 71 Nanyang Dr, Singapore, Singapore, 638075.

出版信息

Biomicrofluidics. 2017 May 11;11(3):034108. doi: 10.1063/1.4983615. eCollection 2017 May.

DOI:10.1063/1.4983615
PMID:28529673
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5426952/
Abstract

We have developed a microfluidic system suitable to be incorporated with a metabolic imaging method to monitor the drug response of cells cultured on a chip. The cells were perfusion-cultured to mimic the blood flow . Label-free optical measurements and imaging of nicotinamide adenine dinucleotide and flavin adenine dinucleotide fluorescence intensity and morphological changes were evaluated non-invasively. Drug responses calculated using redox ratio imaging were compared with the drug toxicity testing results obtained with a traditional well-plate system. We found that our method can accurately monitor the cell viability and drug response and that the IC50 value obtained from imaging analysis was sensitive and comparable with a commonly used cell viability assay: MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium) assay. Our method could serve as a fast, non-invasive, and reliable way for drug screening and toxicity testing as well as enabling real-time monitoring of cultured cells.

摘要

我们开发了一种微流控系统,该系统适合与代谢成像方法相结合,以监测芯片上培养细胞的药物反应。对细胞进行灌注培养以模拟血流。通过无标记光学测量,对烟酰胺腺嘌呤二核苷酸和黄素腺嘌呤二核苷酸的荧光强度以及形态变化进行非侵入性成像评估。将使用氧化还原比率成像计算得到的药物反应与传统微孔板系统获得的药物毒性测试结果进行比较。我们发现,我们的方法能够准确监测细胞活力和药物反应,并且通过成像分析获得的半数抑制浓度(IC50)值灵敏,且与常用的细胞活力检测方法:MTS(3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲氧基苯基)-2-(4-磺基苯基)-2H-四唑)检测相当。我们的方法可作为一种快速、非侵入性且可靠的药物筛选和毒性测试方法,还能够对培养细胞进行实时监测。

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