title: Electroporation on microchips: the harmful effects of pH changes and scaling down.
abstract: Electroporation has been widely used in delivering foreign biomolecules into cells, but there is still much room for improvement, such as cell viability and integrity. In this manuscript, we investigate the distribution and the toxicity of pH changes during electroporation, which significantly decreases cell viability. A localized pH gradient forms between anode and cathode leading to a localized distribution of cell death near the electrodes, especially cathodes. The toxicity of hydroxyl ions is severe and acute due to their effect in the decomposition of phospholipid bilayer membrane. On the other hand, the electric field used for electroporation aggravates the toxicity of hydroxyl because the electropermeabilization of cell membrane makes bilayer structure more loosen and vulnerable. We also investigate the side effects during scaling down the size of electrodes in electroporation microchips. Higher percentage of cells is damaged when the size of electrodes is smaller. At last, we propose an effective strategy to constrain the change of pH by modifying the composition of electroporation buffer. The modified buffer decreases the changes of pH, thus enables high cell viability even when the electric pulse duration exceeds several milliseconds. This ability has potential advantage in some applications that require long-time electric pulse stimulation.
authors.affiliation: Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: National Key Laboratory of Science and Technology on Micro/Nano Fabrication, Institute of Microelectronics, Peking University, Beijing 100871, China.|Department of Engineering Science and Mechanics, The Pennsylvania State University, State College, PA 16801, USA.
authors.forename: Mengxi
authors.initials: M
authors.lastname: Wu
authors.affiliation: Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Deyao
authors.initials: D
authors.lastname: Zhao
authors.affiliation: National Center for Nanoscience and Technology, Beijing 100190, China.
authors.forename: Zewen
authors.initials: Z
authors.lastname: Wei
authors.affiliation: National Key Laboratory of Science and Technology on Micro/Nano Fabrication, Institute of Microelectronics, Peking University, Beijing 100871, China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Zicai
authors.initials: Z
authors.lastname: Liang
authors.affiliation: National Key Laboratory of Science and Technology on Micro/Nano Fabrication, Institute of Microelectronics, Peking University, Beijing 100871, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Li
mesh_terms: D002021:Buffers; D002460:Cell Line; D002470:Cell Survival; D004566:Electrodes; D018274:Electroporation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D046228:Microarray Analysis
chemical_list: D002021:Buffers