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Development of a cardiac-and-piezoelectric hybrid system for application in drug screening.
Lab on a Chip ( IF 6.1 ) Pub Date : 2020-08-03 , DOI: 10.1039/d0lc00433b
Yun-Han Huang,Chiou-Fong Yang,Yu-Hsiang Hsu

In this paper, a cardiac-and-piezoelectric hybrid system is developed for drug screening. The core structure is a polyvinylidene-fluoride piezoelectric membrane that serves as a flexible structure to interact with hiPSC cardiomyocytes and that measures the contraction profile of cardiomyocytes. This design enables the capability of electrically monitoring cardiomyocytes without the aid of an optical system. To guide cardiomyocytes aligning on this circular piezoelectric membrane, concentric rings of polydimethylsiloxane microgrooves are bonded to its surface. Experimental results demonstrate that seeded cardiomyocytes can align and elongate along the circular microgrooves to form a concentric pattern. To promote cardiomyocyte maturation, bipolar stimulation is conducted using a pin and a ring electrode made of a 304 stainless steel sheet. Furthermore, to maintain body temperature and minimize environmental noise, a 304 stainless steel box is constructed to enclose the cardiac-and-piezoelectric hybrid platform. It serves as an incubator and is electrically grounded for electromagnetic interference shielding. Using this system, continuous and repeated contractions of cardiomyocytes can be developed and monitored electrically. The system performance is verified using two commercial drugs: isoproterenol and metoprolol. It is experimentally demonstrated that this system can monitor the dosage effect of both drugs. Our results also show that the measured EC50 and IC50 values of contraction frequency and amplitude are in the same range. These findings suggest that both drugs can influence the beat frequency and contraction force simultaneously. In summary, taking advantage of the electro-mechanical coupling effect of the piezoelectric membrane, this system could be scaled up to perform automatic and parallel screenings for drug discoveries.

中文翻译:

开发了心脏和压电混合系统,用于药物筛选。

在本文中,开发了一种心脏与压电混合系统用于药物筛选。核心结构是聚偏二氟乙烯压电膜,该膜用作与hiPSC心肌细胞相互作用的柔性结构,并测量心肌细胞的收缩情况。这种设计无需借助光学系统即可实现电监控心肌细胞的功能。为了引导心肌细胞在该圆形压电膜上对齐,将聚二甲基硅氧烷微槽的同心环结合到其表面。实验结果表明,植入的心肌细胞可以沿着圆形微槽对齐并延伸,形成同心圆图案。为了促进心肌细胞的成熟,使用由304不锈钢薄板制成的销和环形电极进行双极刺激。此外,为了保持体温并最大程度地减少环境噪音,构造了一个304不锈钢盒以封闭心脏和压电混合平台。它用作孵化器,并已电气接地以屏蔽电磁干扰。使用该系统,可以开发和监测心肌细胞的连续和重复收缩。使用两种商业药物验证了系统性能:异丙肾上腺素和美托洛尔。实验证明该系统可以监测两种药物的剂量效应。我们的结果还表明,测得的EC 它用作孵化器,并已电气接地以屏蔽电磁干扰。使用该系统,可以开发和监测心肌细胞的连续和重复收缩。使用两种商业药物验证了系统性能:异丙肾上腺素和美托洛尔。实验证明该系统可以监测两种药物的剂量效应。我们的结果还表明,测得的EC 它用作孵化器,并已电气接地以屏蔽电磁干扰。使用该系统,可以开发和监测心肌细胞的连续和重复收缩。使用两种商业药物验证了系统性能:异丙肾上腺素和美托洛尔。实验证明该系统可以监测两种药物的剂量效应。我们的结果还表明,测得的EC收缩频率和幅度的50和IC 50值在相同范围内。这些发现表明,两种药物均可同时影响搏动频率和收缩力。总之,利用压电膜片的机电耦合效应,该系统可以按比例放大以对药物发现进行自动和并行筛选。
更新日期:2020-09-15
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