To achieve high efficiency of electroporation and to minimize unwanted side effects, the electric field parameters must be optimized. Recently, it was suggested that biphasic high-frequency irreversible electroporation (H-FIRE) pulses reduce muscle contractions. However, it was also shown for sub-microsecond biphasic pulses that the opposite polarity phase of the pulse cancels the effect of the first phase if the interphase delay is short enough. We investigated the effect of interphase and interpulse delay (ranging from 0.5 to 10,000 µs) of 1 µs biphasic H-FIRE pulses on cell membrane permeabilization, on survival of four mammalian cell lines and determined metal release from aluminum, platinum and stainless steel electrodes. Biphasic H-FIRE pulses were compared to 8 × 100 µs monophasic pulses. We show that a longer interphase and interpulse delay results in lower cell survival, while the effects on cell membrane permeabilization are ambiguous. The cancellation effect was observed only for the survival of one cell line. Application of biphasic H-FIRE pulses results in lower metal release from electrodes but the interphase and interpulse delay does not have a large effect. The electrode material, however, importantly influences metal release - the lowest release was measured from platinum and the highest from aluminum electrodes.

中文翻译：

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高频不可逆电穿孔脉冲的相间和脉冲间延迟对细胞存活，膜通透性和电极材料释放的影响。

为了实现高效率的电穿孔并最大程度地减少不良副作用，必须优化电场参数。最近，有人建议双相高频不可逆电穿孔（H-FIRE）脉冲减少肌肉收缩。但是，对于亚微秒双相脉冲，还表明，如果相间延迟足够短，则脉冲的相反极性的相位会抵消第一相的影响。我们研究了1 µs双相H-FIRE脉冲的相间和脉冲间延迟（0.5到10,000 µs）对细胞膜通透性的影响，对四种哺乳动物细胞系的存活以及确定的铝，铂和不锈钢电极金属释放的影响。将双相H-FIRE脉冲与8×100 µs单相脉冲进行比较。我们表明较长的相间和脉冲间延迟导致较低的细胞存活率，而对细胞膜通透性的影响是模棱两可的。仅在一种细胞系的存活中观察到消除作用。施加双相H-FIRE脉冲可降低电极中的金属释放量，但相间和脉冲间的延迟影响不大。然而，电极材料对金属的释放有重要影响-铂释放量最低，而铝电极释放量最高。施加双相H-FIRE脉冲可降低电极中的金属释放量，但相间和脉冲间延迟的影响不大。但是，电极材料对金属的释放有重要影响-铂释放量最低，而铝电极释放量最高。施加双相H-FIRE脉冲可降低电极中的金属释放量，但相间和脉冲间延迟的影响不大。但是，电极材料对金属的释放有重要影响-铂释放量最低，而铝电极释放量最高。