Majhi Amit Kumar, Thrivikraman Greeshma, Basu Bikramjit, Venkataraman V
Department of Physics, Indian Institute of Science, Bangalore, 560012, India.
Eur Biophys J. 2015 Feb;44(1-2):57-67. doi: 10.1007/s00249-014-1001-x. Epub 2014 Dec 13.
In order to study cell electroporation in situ, polymer devices have been fabricated from poly-dimethyl siloxane with transparent indium tin oxide parallel plate electrodes in horizontal geometry. This geometry with cells located on a single focal plane at the interface of the bottom electrode allows a longer observation time in both transmitted bright-field and reflected fluorescence microscopy modes. Using propidium iodide (PI) as a marker dye, the number of electroporated cells in a typical culture volume of 10-100 μl was quantified in situ as a function of applied voltage from 10 to 90 V in a series of ~2-ms pulses across 0.5-mm electrode spacing. The electric field at the interface and device current was calculated using a model that takes into account bulk screening of the transient pulse. The voltage dependence of the number of electroporated cells could be explained using a stochastic model for the electroporation kinetics, and the free energy for pore formation was found to be 45.6 ± 0.5 kT at room temperature. With this device, the optimum electroporation conditions can be quickly determined by monitoring the uptake of PI marker dye in situ under the application of millisecond voltage pulses. The electroporation efficiency was also quantified using an ex situ fluorescence-assisted cell sorter, and the morphology of cultured cells was evaluated after the pulsing experiment. Importantly, the efficacy of the developed device was tested independently using two cell lines (C2C12 mouse myoblast cells and yeast cells) as well as in three different electroporation buffers (phosphate buffer saline, electroporation buffer and 10% glycerol).
为了研究细胞原位电穿孔,已使用聚二甲基硅氧烷制造了聚合物装置,该装置带有水平几何结构的透明氧化铟锡平行板电极。这种细胞位于底部电极界面处单个焦平面上的几何结构,在透射明场和反射荧光显微镜模式下都能实现更长的观察时间。使用碘化丙啶(PI)作为标记染料,在0.5毫米电极间距上,以一系列约2毫秒的脉冲施加10至90伏的电压,对10 - 100微升典型培养体积中的电穿孔细胞数量进行了原位定量。利用考虑了瞬态脉冲体筛选的模型计算了界面处的电场和器件电流。电穿孔细胞数量的电压依赖性可以用一个电穿孔动力学的随机模型来解释,并且在室温下发现孔形成的自由能为45.6±0.5 kT。使用该装置,可以通过在施加毫秒级电压脉冲时原位监测PI标记染料的摄取来快速确定最佳电穿孔条件。还使用非原位荧光辅助细胞分选仪对电穿孔效率进行了定量,并在脉冲实验后评估了培养细胞的形态。重要的是,使用两种细胞系(C2C12小鼠成肌细胞和酵母细胞)以及三种不同的电穿孔缓冲液(磷酸盐缓冲盐水、电穿孔缓冲液和10%甘油)独立测试了所开发装置的功效。