Bioelectric effects of intense ultrashort pulses

Models for electric field interactions with biological cells predict that pulses with durations shorter than the charging time of the outer membrane can affect intracellular structures. Experimental studies in which human cells were exposed to pulsed electric fields of up to 300 kV/cm amplitude, with durations as short as 10 ns, have confirmed this hypothesis. The observed effects include the breaching of intracellular granule membranes without permanent damage to the cell membrane, abrupt rises in intracellular free calcium levels, enhanced expression of genes, cytochrome c release, and electroporation for gene transfer and drug delivery. At increased electric fields, the application of nanosecond pulses induces apoptosis (programmed cell death) in biological cells, an effect that has been shown to reduce the growth of tumors. Possible applications of the intracellular electroeffects are enhancing gene delivery to the nucleus, controlling cell functions that depend on calcium release (causing cell immobilization), and treating tumors. Such nanosecond electrical pulses have been shown to successfully treat melanoma tumors by using needle arrays as pulse delivery systems. Reducing the pulse duration of intense electric field pulses even further into the subnanosecond range will allow for the use of wideband antennas to deliver the electromagnetic fields into tissue with a spatial resolution in the centimeter range. This review carefully examines the above concepts, provides a theoretical basis, and modeling results based on both continuum approaches and atomistic molecular dynamics methods. Relevant experimental data are also presented, and some of the many potential bioengineering applications discussed.