Tumor-treating fields (TTFields) are alternating electrical fields of intermediate frequency and low intensity that can slow or inhibit tumor growth by disrupting mitosis division of cancerous cells through cell cycle proteins. In this work, for the first time, an in-house fabricated cyclo-olefin polymer made microfluidic bioreactors are integrated with Cr/Au interdigitated electrodes to test TTFields on yeast cells with fluorescent protein:Nop56 gene. A small gap between electrodes (50 μm) allows small voltages (<150 mV) to be applied on the cells; hence, uninsulated gold electrodes are used in the non-faradaic region without causing any electrochemical reaction at the electrode-medium interface. Electrochemical modeling as well as impedance characterization and analysis of the electrodes are done using four different cell nutrient media. The experiments with yeast cells are done with 150 mV, 150 kHz and 30 mV, 200 kHz sinusoidal signals to generate electrical field magnitudes of 6.58 V/cm and 1.33 V/cm, respectively. In the high electrical field experiment, the cells go through electroporation. In the experiment with the low electrical field magnitude for TTFields, the cells have prolonged mitosis from typical 80–90 min to 200–300 min. Our results confirm the validity of the electrochemical model and the importance of applying a correct magnitude of the electrical field. Compared to the so far reported alternatives with insulated electrodes, the here developed thermoplastic microfluidic bioreactors with uninsulated electrodes provide a new, versatile, and durable platform for in vitro cell studies toward the improvement of anti-cancer therapies including personalized treatment.

中文翻译：

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具有集成电极的热塑性微流体生物反应器，用于研究酵母细胞上的肿瘤治疗领域。

肿瘤治疗场（TTFields）是中频和低强度的交替电场，可通过破坏癌细胞通过细胞周期蛋白的有丝分裂而减慢或抑制肿瘤的生长。在这项工作中，首次将内部制造的由环烯烃聚合物制成的微流体生物反应器与Cr / Au叉指电极整合在一起，以测试带有荧光蛋白：Nop56基因的酵母细胞上的TTField。电极之间的小间隙（50  μm）允许在电池上施加小的电压（<150 mV）；因此，在非法拉第区域中使用未绝缘的金电极，而不会在电极-介质界面处引起任何电化学反应。使用四种不同的细胞营养培养基进行电极的电化学建模以及阻抗表征和分析。使用150 mV，150 kHz和30 mV，200 kHz正弦信号进行酵母细胞实验，分别产生6.58 V / cm和1.33 V / cm的电场强度。在高电场实验中，细胞经过电穿孔。在TTFields的电场强度较低的实验中，细胞的有丝分裂时间从典型的80–90分钟延长至200–300分钟。我们的结果证实了电化学模型的有效性以及施加正确幅度的电场的重要性。与迄今报道的带绝缘电极的替代品相比，此处开发的具有非绝缘电极的热塑性微流体生物反应器提供了一种新型，通用且耐用的平台体外细胞研究，旨在改善抗癌疗法，包括个性化治疗。