Gencturk Elif, Ulgen Kutlu O, Mutlu Senol
Biosystems Engineering Laboratory, Department of Chemical Engineering, Bogazici University, 34342 Istanbul, Turkey.
BUMEMS Laboratory, Department of Electrical and Electronics Engineering, Bogazici University, 34342 Istanbul, Turkey.
Biomicrofluidics. 2020 May 18;14(3):034104. doi: 10.1063/5.0008462. eCollection 2020 May.
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 m) 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 cell studies toward the improvement of anti-cancer therapies including personalized treatment.
肿瘤治疗电场（TTFields）是一种中频低强度的交变电场，它可以通过细胞周期蛋白破坏癌细胞的有丝分裂，从而减缓或抑制肿瘤生长。在这项工作中，首次将内部制造的环烯烃聚合物微流控生物反应器与Cr/Au叉指电极集成，以测试具有荧光蛋白:Nop56基因的酵母细胞上的肿瘤治疗电场。电极之间的小间隙（50μm）允许在细胞上施加小电压（<150mV）；因此，在非法拉第区域使用未绝缘的金电极，不会在电极-介质界面引起任何电化学反应。使用四种不同的细胞营养培养基对电极进行电化学建模以及阻抗表征和分析。用150mV、150kHz和30mV、200kHz的正弦信号对酵母细胞进行实验，分别产生6.58V/cm和1.33V/cm的电场强度。在高电场实验中，细胞会经历电穿孔。在肿瘤治疗电场低电场强度的实验中，细胞的有丝分裂时间从典型的80 - 90分钟延长到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电场强度的重要性。与迄今为止报道的使用绝缘电极的替代方案相比，这里开发的具有未绝缘电极的热塑性微流控生物反应器为细胞研究提供了一个新的、通用的和耐用的平台，有助于改进包括个性化治疗在内的抗癌疗法。
