Development of a cardiac-and-piezoelectric hybrid system for application in drug screening.

Abstract

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.