School of Mechanical Engineering, Chonnam National University, Gwangju, 61186, Republic of Korea.
Green Energy & Nano Technology R&D Group, Korea Institute of Industrial Technology (KITECH), Gwangju, 61012, Republic of Korea.
Biosens Bioelectron. 2024 Jan 1;243:115756. doi: 10.1016/j.bios.2023.115756. Epub 2023 Oct 11.
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.
开发有效的工具来预测临床前阶段的药物诱导性心脏毒性,将极大地有益于药物开发过程。本研究提出了一种 SU-8 悬臂梁与单晶硅应变传感器集成的方法,以增强基于心肌细胞收缩力变化的毒性筛选方法的力灵敏度。所提出的悬臂梁装置能够以高灵敏度实时测量心肌细胞的收缩力,从而有助于评估药物的心脏毒性。本文获得的实验结果表明,该平台在检测小于 0.02μN 的力时具有响应性,其力灵敏度比传统金属基应变传感器高近 17 倍。此外,应变传感器的集成展示了制造可用于高通量筛选应用的悬臂梁阵列的潜力。所开发的方法成功地促进了心肌细胞的体外培养,并允许连续监测它们的收缩力。通过心脏毒性分析进一步验证了所提出平台的实际适用性。培养的心肌细胞用两种心血管药物处理,即维拉帕米(一种 L 型钙通道阻滞剂)和异丙肾上腺素(一种针对β1 和β2 肾上腺素能受体的拟交感神经药物),以分析药物对心肌细胞的诱导作用。