Electrokinetic Transport Process in Nanopores Generated on Cell Membrane during Electroporation

In this thesis, underlying concepts of transport phenomena through generated nanopores on a cell membrane during electroporation were studied. A comprehensive literature review was performed to find the pros and cons of the previous works and consequently extensive studies were accomplished to explain shortcomings of the former studies on this topic. The membrane permeabilization of the single cell located in the microchannel was studied, and the effects of microchannel’s wall and electrode size were investigated on cell electroporation. It was studied how the electrical (e.g., strength of the electric pulse) and geometrical parameters (e.g., microchannel height and electrode size) affect size, location, and number of created hydrophilic pores on the cell membrane. Because of a transmembrane potential, the electrokinetic effects have decisive influence on the transport process through the created nanopores. A comprehensive study was performed to explain the electrokinetic transport through the nanochannels. Effects of surface electric charge and radius of the nanochannel on the electric potential, liquid flow, and ionic transport were investigated. Unlike microchannels, the electric potential field, ionic concentration field, and velocity field are strongly size-dependent in the nanochannels. They are also affected by the surface electric charge of the nanochannel. More counter ions than co-ions are transported through the nanochannel. The ionic concentration enrichment at the entrance and the exit of the nanochannel is completely evident from the simulation results. The study also shows that the fluid velocity in the nanochannel is higher when the surface electric charge is stronger, or the radius of the nanochannel is larger. The obtained model of the electrokinetic effects in the nanochannels was utilized to examine the ionic mass transfer and the fluid flow through the generated hydrophilic nanopores of the cell membrane during electroporation. The results showed how the electric potential, velocity field, and ionic concentration vary with the size and angular position of the generated nanopores of the cell membrane. It was also shown that, in the presence of the electric pulse, the electrokinetic effects (the electroosmosis and the electrophoresis) had significant influences on the ionic mass transfer through the nanopores, while the effect of diffusion on the ionic mass flux was negligible in comparison with the electrokinetics. Increasing the radius of the nanopores intensified the effect of convection (electroosmosis) in comparison with the electrophoresis on the ionic flux. Furthermore, the electrokinetic motion of the nanoparticle through the nanochannel was investigated to mimic inserting the nanoscale biological samples, such as QDots and DNAs, through the created nanopores on the cell membrane. It was proved that, because of the large applied electric field over the nanochannel, the impact of the Brownian force was negligible in comparison with the electrophoretic and the hydrodynamic forces. It was demonstrated that increasing the bulk ionic concentration or the surface charge of the nanochannel will increase the electroosmotic flow, and hence affect the particle’s motion. It was also shown that, unlike the microchannels with thin EDL, the change in the nanochannel size will change the EDL field and the ionic concentration field in the nanochannel, affecting the particle’s motion. If the nanochannel size is fixed, a larger particle will move faster than a smaller particle under the same conditions. Finally, it was examined how the nanoscale biological samples (nanoparticles) reach openings of the generated nanopores on the cell membrane during electroporation. It was examined what forces (electrophoresis, diffusion, and convection) brings the nanoparticles into the nanopores and how the size and the surface electric charge of the nanoparticle affect its transport to the opening of the nanopores.1 yea