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Microphysiological system with continuous analysis of albumin for hepatotoxicity modeling and drug screening
Journal of Industrial and Engineering Chemistry ( IF 5.9 ) Pub Date : 2021-03-27 , DOI: 10.1016/j.jiec.2021.03.035
Arun Asif , Sung Hyuk Park , Afaque Manzoor , Muhammad Asad Ullah Khalid , Abdul Rahim Chattikatikatuveli Salih , Bohye Kang , Faheem Ahmed , Kyung Hwan Kim , Kyung Hyun Choi

In microfluidics, the emerging field of microphysiological systems (MPS) is overcoming the challenge of physiological irrelevancy by animal models for drug discovery and development. Liver function is critically influenced by drugs owing to its role in drug metabolism and detoxification. Human serum albumin (HSA) is one of the most important secreted biomarkers which indicate normal liver function. A microfluidic albumin immunosensor was developed to be integrated with liver-on-a-chip MPS for continuous feedback over disease modeling and treatment. A gold-electrode based electrochemical immunosensor was established by anti-HSA antibody immobilization. The liver MPS was found to be efficient for live monitoring of disease modelling and drug treatment over the period of 6 days. The system emulated and analyzed real-time toxicity modeling with HSA sensing. The detection limit of integrated sensor was 1 μg/ml with successive reproducibility. The proposed sensor was also validated with metabolic biomarkers’ assays. Molecular assays supported the sensor monitoring and depicted liver injury and recovery. The liver MPS with combined albumin sensor chip may be a promising platform to mimic real-time drug assessment.



中文翻译:

连续分析白蛋白的微生理系统用于肝毒性建模和药物筛选

在微流控技术中,微生理系统(MPS)的新兴领域正在克服用于药物发现和开发的动物模型对生理无关性的挑战。肝功能由于其在药物代谢和排毒中的作用而受到药物的严重影响。人血清白蛋白(HSA)是最重要的分泌生物标志物之一,可指示肝功能正常。开发了一种微流白蛋白免疫传感器,可与单片肝MPS集成在一起,从而在疾病建模和治疗方面提供连续反馈。通过抗HSA抗体固定化建立了基于金电极的电化学免疫传感器。发现肝脏MPS在6天的时间内可有效监测疾病模型和药物治疗。该系统使用HSA传感对实时毒性建模进行仿真和分析。集成传感器的检出限为1 μg/ ml,具有连续的重现性。拟议的传感器也已通过代谢生物标志物的测定得到验证。分子测定支持传感器监测并描述了肝损伤和恢复。结合白蛋白传感器芯片的肝脏MPS可能是模仿实时药物评估的有前途的平台。

更新日期:2021-04-26
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