Capacitive coupling increases the accuracy of cell-specific tumour disruption by electric fields

Abstract

Irreversible electroporation holds great potential for cell-specific lysis due to the size-dependent susceptibility of cells to externally imposed electric fields. Previous attempts at selective cell lysis lead to significant overlap between affected populations and struggle with inconsistent biological outcome. We propose that charge transfer at the electrode-liquid interface is responsible by inducing multifactorial effects originating from both the electric field and electrochemical reactions. A promising remedy is the coating of electrodes with a high-k dielectric layer. The resulting capacitive coupling restores the selective potential of electric field mediated lysis in a microfluidic setup. Initial experiments show the consistent depletion of erythrocytes from whole blood while leaving leukocytes intact. The same is true for the reproducible and selective depletion of Jurkat and MCF-7 cells in a mixture with leukocytes. Unexpectedly, the observed order of lysis cannot be correlated with cell size. This implies that the cellular response to capacitive coupling features a selective characteristic that is different from conventional lysis configurations..

Recent Advances in Microscale Electroporation

“…Thus, >10 μm mammalian cells require approximately 10× lower electric field strengths than ∼1 μm bacteria to achieve EP. Experiments show that this correlation holds true, although not on a linear scale . The induced TMP is also affected by cell shape and interactions with adjacent cells .…”

“…A SiO 2 -passivated device did not display such effects under the same conditions and had increased cell viability after EP. TiO 2 has also been proposed as a suitable dielectric material for titanium electrodes. ,, This layer limits the passage of off-target currents through the electrolyte solution. Wimberger et al found that passivated electrodes led to more consistent cell inactivation at different electric field strengths than exposed electrodes because stochastic electrolysis effects were minimized (Figure A) .…”

“…Cancer cells were positioned closer than blood cells to locally amplified electric fields, so only the cancer cells were lysed with 57% efficiency. Interestingly, Wimberger et al found that the relationship between cell size and threshold EP voltage did not always correlate when lysing blood cells, possibly due to differences in cell shape . Cancer cell lines whose diameters were >10 μm were lysed at 13 V, and nonspherical ∼7.8 μm erythrocytes were lysed at ∼17 V. 6–10 μm leukocytes required the harshest conditions of ∼36 V for cell lysis.…”