Zhang Xiaoxiao, Beebe Tyler, Jen Nelon, Lee Chia-An, Tai Yuchong, Hsiai Tzung K
Department of Medical Engineering, California Institute of Technology, Pasadena, California, USA.
Department of Bioengineering, UCLA School of Engineering & Applied Sciences, Los Angeles, CA 90095.
Biosens Bioelectron. 2015 Sep 15;71:150-157. doi: 10.1016/j.bios.2015.04.027. Epub 2015 Apr 14.
Flexible electronics are the next generation of sensors for mobile health and implantation. Zebrafish (Danio rerio) is an emergent strategy for pre-clinical drug development and toxicity testing. To address the confounding effects from sedation of fish and removal from the aquatic habitat for micro-electrocardiogram (µECG) measurements, we developed waterproof and wearable sensors to uncover the circadian variation in heart rate (HR) and heart rate variability (HRV) (Massin et al., 2000). The parylene-C based ECG sensor consisted of an ultra-soft silicone integrated jacket designed to wrap around the fish during swimming. The Young's modulus of this silicone jacket matched with the fish surface, and an extended parylene cable connected the underwater chest electrodes with the out-of water electronics. In addition, embedded micro-glass spheres in the silicone effectively reduced the effective density of the jacket to ~1 g cm(-3). These innovations enabled physiological ECG telemetry in the fish's natural habitat without the need for sedation. Furthermore, a set of non-linear signal processing techniques filtered out the breathing and electromagnetic artifacts from the recorded signals. We observed a reduction in mean HR and an increase in HRV over 24h at 10 dpa, accompanied by QT prolongation as well as diurnal variations, followed by normalization in mean HR and QT intervals at 26 days post ventricular amputation (dpa). We revealed Amiodarone-mediated QTc prolongation, HR reduction and HRV increase otherwise masked by sedation. The novel features of the flexible silicon jacket for µECG telemetry unraveled the biological clock and normalization of QT intervals at 26 dpa, providing the first evidence of new physiological phenomena during cardiac injury and repair as well as cardiac drug-mediated aberrant rhythms. Thus, the light weight and waterproof design holds promise to advance the next generation of mobile health and drug discovery.
柔性电子器件是用于移动健康和植入的下一代传感器。斑马鱼（Danio rerio）是临床前药物开发和毒性测试的一种新兴策略。为了解决鱼类镇静以及将其从水生栖息地移出以进行微心电图（µECG）测量所带来的混杂效应，我们开发了防水且可穿戴的传感器，以揭示心率（HR）和心率变异性（HRV）的昼夜变化（Massin等人，2000年）。基于聚对二甲苯-C的心电图传感器由一个超柔软的硅胶集成护套组成，该护套设计用于在鱼游泳时包裹住鱼。这种硅胶护套的杨氏模量与鱼的表面相匹配，一条延长的聚对二甲苯电缆将水下胸部电极与水外电子设备相连。此外，硅胶中嵌入的微玻璃球有效地将护套的有效密度降低至约1 g/cm³。这些创新使得在鱼类的自然栖息地中无需镇静即可进行生理心电图遥测。此外，一组非线性信号处理技术从记录的信号中滤除了呼吸和电磁伪影。我们观察到在心室截肢后10天（dpa），平均心率降低，HRV在24小时内增加，同时伴有QT延长以及昼夜变化，随后在心室截肢后26天，平均心率和QT间期恢复正常。我们揭示了胺碘酮介导的QTc延长、心率降低和HRV增加，否则这些变化会被镇静所掩盖。用于µECG遥测的柔性硅胶护套的新颖特性揭示了26 dpa时生物钟和QT间期的正常化，为心脏损伤和修复过程中以及心脏药物介导的异常节律期间新的生理现象提供了首个证据。因此，这种轻质且防水的设计有望推动下一代移动健康和药物发现的发展。
