Nihon Kikai Gakkai ronbunshu (Mar 2021)

Numerical analysis of cell membrane perforation in on-chip microdroplet-based electroporation (Membrane perforation characteristics when electrodes are placed on the same plane)

  • Kenji NAKASHIMA,
  • Fuminori MATSUYAMA,
  • Yuuki JOHNO,
  • Miho ISHII-TESHIMA,
  • Takayuki SHIBATA

DOI
https://doi.org/10.1299/transjsme.20-00446
Journal volume & issue
Vol. 87, no. 896
pp. 20-00446 – 20-00446

Abstract

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On-chip microdroplet-based electroporation is a newly developed process that enables droplet electroporation in a microfluidic device. If the process is to be realized at low cost, the electrode pair should be installed on the same plane. On the other hand, the electrode pair is installed as parallel plates in electroporation process with ordinary cuvettes. When the electroporation process is converted to a microfluidic device, the effect of electrode placement must be investigated because the electrode placement pattern is different from that of conventional electroporation. Therefore, numerical analysis of cell membrane perforation in micro rectangular channels was performed to support the design of an on-chip microdroplet-based electroporation system. The calculated geometry was given a state in which one cell was located in the center of the droplet. Since membrane perforation by a voltage pulse is a 1 μs time scale phenomenon, a numerical method was applied in which the electric field formation and membrane perforation are calculated in the same time step. The current conservation equation and the asymptotic Smoluchowski equation were coupled by the transmembrane voltage to calculate the time dependence. The calculation results showed that the position of high pore density on the cell membrane was slightly shifted compared to the case of electroporation by cuvette, but the position was almost ideal. And the pore density, electric field strength and transmembrane voltage distribution on the membrane showed accurate perforation locations and mechanisms. In addition, numerical analysis was also performed on the ideal parallel plane electrode assuming electroporation with a cuvette. It was shown that although the parallel planar electrode enables more efficient electroporation, the same planar electrode can also perforate the cell membrane at almost the same position. Finally, based on the results of 81 different calculations, the transitions in pore density and transmembrane voltage when cell is translocated are shown. The computing software COMSOL Multiphysics 5.4 on Windows OS was used on the workstation HP Z8 (CPU: Intel Xeon Gold 6128×2, Main memory: 96 GB).

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