基于电阻抗多模式检测芯片的体外热疗
In vitro hyperthermia based on a multi-mode detection chip with impedance sensing

热疗是继手术、化疗、放疗之后对癌症的一大治疗手段，但是目前其机理尚不明确，体外研究结论与临床应用尚有差距。为更好地研究在热应激/热疗过程中的细胞变化，该文构建了一套集成细胞电阻抗非标记动态检测、细胞形态动态记录、荧光标记检测功能并且能够自动测控温度的微全分析系统，对其控温性能进行了仿真与实测检验，对细胞培养及增殖过程进行了非标记连续监测，并利用此实验系统进行了癌细胞在2种热疗条件下的动态多模式检测。实验结果表明：HeLa细胞在41℃，2 h热疗作用下，阻抗呈现“V”型变化，形态快速收缩后又迅速恢复贴壁，荧光标记检测显示细胞活力无明显改变；而在2次55℃，2 min脉冲式热疗作用下，细胞阻抗呈现“L”型变化，细胞杀伤效果明显。该系统将传统标记技术与非标记检测技术结合，可用于细胞热应激/热疗的相关研究。
Abstract：Hyperthermia is a useful method for cancer treatment after surgery, chemotherapy and radiotherapy for numerous types of cancers. However, the mechanism is not yet fully understood and some in vitro results cannot be repeated in clinical applications; thus, further research is needed. In this study, a lab-on-a-chip device and a corresponding detection system was constructed to study in vitro hyperthermia. The device incorporated electric cell-substrate impedance sensing (ECIS), morphological imaging, and fluorescence observation during and after cells were thermally treated in situ with automatic on-chip temperature control. The temperature control was tested in an incubator. The cell culture and impedance sensing were also validated. Then, cancer cells were treated and monitored by the system for two hyperthermia conditions. The impedance curve with rectangle hyperthermia control of 41℃ for 2 h shows a "V" shape change during the 41℃ treatment with the cells quickly shrinking and re-adhering without any obvious viability changes in the fluorescent labeling images. However, two hyperthermia pulses at 55℃ for 2 min caused cell impedance "L" shape changes and killed most of the cells. These results demonstrate that this device with un-labeled and labeled methods is a useful tool for in vitro research on thermal therapy.