From Submicrosecond to Subnanosecond Pulses - Entering a New Domain of Electric Field-Cell Interactions

Summary form only given. By reducing the duration of electrical pulses from microseconds into the nanosecond range, the electric field-cell interactions shift increasingly from the plasma (cell) membrane to subcellular structures. Yet another domain of pulsed electric field interactions with cell structures and functions opens when the pulse duration is reduced to values such that membrane charging becomes negligible, and direct electric field-molecule effects determine the biological mechanisms. For mammalian cells, this holds for a pulse duration of less than one nanosecond. In addition to entering a new domain of electric field-cell interactions, entering the subnanosecond temporal range will allow us to use near-field-focusing, wideband antennas, rather than needle or plate electrodes, to generate large pulsed electric fields with reasonable spatial resolution in tissue. Modeling results indicate that electric field intensities of tens (up to perhaps hundreds) of kV/cm with a spatial resolution of a few mm can be generated with prolate-spheroidal reflectors with TEM wave-launching structures, and using state-of-the-art pulsed power technology. In order to study the biological effect of subnanosecond pulses, we have developed a sub-ns pulse generator capable of delivering 250 kV into a high impedance load. The pulse width is approximately 600 ps with a voltage rise of up to 1 MV/ns. The pulses have been applied to B16 (murine melanoma) cells, and the plasma membrane integrity was studied by means of trypan blue exclusion. The results show that temporary nanopores in the plasma membrane are generated, allowing the uptake of drugs or nanoparticles without affecting the viability of the cells.