Key Laboratory of Biomedical Engineering of Ministry of Education, Biosensor National Special Laboratory, Department of Biomedical Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China; State Key Laboratory of Transducer Technology, Chinese Academy of Sciences, Shanghai 200050, China.
Key Laboratory of Biomedical Engineering of Ministry of Education, Biosensor National Special Laboratory, Department of Biomedical Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China; ACEA Biosciences Inc., San Diego, CA 92121, USA.
Biosens Bioelectron. 2018 Oct 15;117:354-365. doi: 10.1016/j.bios.2018.06.017. Epub 2018 Jun 8.
Cardiac issues are always one of major health problems that attract wide attention by the public. It is urgent to explore a preclinical strategy to efficiently prevent the life-threatening arrhythmias by precisely assessing the cardiac excitation-contraction behavior. Conventional label-free asynchronous strategies are difficult to synchronously record and precisely match the excitation and contraction signals in vitro, while label-based strategies generally present pharmacological adverse effects and phototoxicity that significantly interfere the natural excitation and contraction signals. Both types of strategies preclude to exactly understand how cardiac excitation-contraction coupling changes in quantitative and coherent detail when dysfunctions occur. Here, we show a label-free synchronized electromechanical integration detection strategy that can synchronously monitor electrical and mechanical signals of cardiomyocytes over a long period of time by an integrated microelectrode-interdigitated electrode (ME-IDE). ME-IDE can detect subtle changes in electromechanical integration signals induced by drugs that target excitation-contraction coupling. Moreover, electromechanical integration delay is explored to specifically recognize the sodium channel inhibition. Furthermore, biomimetic electronic pacemaker function provides an alternative way to efficiently assess the drug-induced arrhythmia using refractory period of cardiomyocytes.
心脏问题一直是引起公众广泛关注的主要健康问题之一。迫切需要探索一种临床前策略,通过精确评估心脏兴奋-收缩行为,有效地预防危及生命的心律失常。传统的无标记异步策略很难在体外同步记录和精确匹配兴奋和收缩信号,而基于标记的策略通常会产生药理学副作用和光毒性,这会严重干扰自然的兴奋和收缩信号。这两种策略都无法准确了解当出现功能障碍时,心脏兴奋-收缩偶联如何在定量和连贯的细节上发生变化。在这里,我们展示了一种无标记的同步机电一体化检测策略,该策略可以通过集成的微电极-叉指电极(ME-IDE)长时间同步监测心肌细胞的电和机械信号。ME-IDE 可以检测到针对兴奋-收缩偶联的药物引起的机电一体化信号的细微变化。此外,还探索了机电一体化延迟,以专门识别钠通道抑制。此外,仿生电子起搏器功能提供了一种替代方法,可使用心肌细胞的不应期来有效地评估药物引起的心律失常。