silicon and Cardiotoxicity

The development of efficient tools for predicting drug-induced cardiotoxicity in the preclinical phase would greatly benefit the drug development process. This study presents an SU-8 cantilever integrated with a single-crystal silicon strain sensor to enhance force sensitivity in toxicity screening methods based on changes in the contraction force of cardiomyocytes. The proposed cantilever device enables real-time measurements of cardiomyocytes contraction force with high sensitivity, thereby facilitating the assessment of drug cardiotoxicity. The experimental results obtained herein demonstrate the responsiveness of the proposed platform in detecting forces smaller than 0.02 μN with a force sensitivity that is nearly 17 times higher than those of conventional metal-based strain sensors. Moreover, the integration of strain sensors demonstrates the potential for manufacturing cantilever arrays that can be used in high-throughput screening applications. The developed methodology successfully facilitates in vitro culturing of cardiomyocytes and allows for continuous monitoring of their contraction force. The practical applicability of the proposed platform is further validated through cardiotoxicity analysis. The cultured cardiomyocytes are treated with two cardiovascular drugs, namely verapamil (an L-type calcium channel blocker) and isoproterenol (a sympathomimetic drug targeting β1 and β2 adrenergic receptors), to analyze the drug induced effects in the cardiomyocytes.

Topics: Biosensing Techniques; Cardiotoxicity; Humans; Myocardial Contraction; Myocytes, Cardiac; Silicon

This paper proposes the use of sensor-integrated silicon cantilever arrays to measure drug-induced cardiac toxicity in real time. The proposed cantilever sensors, unlike the conventional electrophysiological methods, aim to evaluate cardiac toxicity by measuring the contraction force of the cardiomyocytes corresponding to the target drugs. The surface of the silicon cantilever consists of microgrooves to maximize the alignment and the contraction force of the cardiomyocytes. This type of surface pattern also helps in the maturation of the cardiomyocytes by increasing the sarcomere length. The preliminary characterization of the cantilever sensors was performed on the cantilever surface, with the cardiomyocytes seeded with a density of 1000 cells/mm

Topics: Cardiotoxicity; Humans; Mechanical Phenomena; Myocytes, Cardiac; Reproducibility of Results; Silicon