72
Electromagnetic Fields in Biological Systems
contrast, the application of high-intensity electric fields does not present such difficulties. Short exposures of cells and tissues to strong fields represent an important subset of
high voltage external excitation. The fields involved are larger in the order of magnitude
and so can readily pass the conceptual tests based on signal-to-noise ratio (SNR) criteria
in spite of the short exposure times.
Models of electric field interactions with biological cells predict that pulses with durations shorter than the charging time of the outer membrane can penetrate and 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 be beneficial in reducing the growth
of tumors (Nuccitelli et al. 2006). Such nanosecond electrical pulses have been shown
to successfully treat melanoma tumors by using needle arrays as pulse delivery systems.
Besides treating tumors, possible applications of the intracellular electrical effects are
enhancing gene delivery to the nucleus, controlling calcium release and cell functions,
and cell immobilization. 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 (EM) fields into tissue with a spatial resolution in the centimeter range.
This chapter primarily examines the concepts of electric field interactions in cells,
though some treatment of tissues has also been included. The focus is on ultrashort
(∼10–100 ns), pulsed high-intensity fields (∼100 kV/cm). A theoretical basis for evaluating field strengths and penetrating into single cells is given, together with modeling
results as appropriate. Continuum approaches are discussed for electric field evaluations
that can then form the basis for subsequent methods of molecular dynamics or structural bioinformatics for analyzing cellular electrical responses. The time-dependent
and spatially dependent electric field E(r,t) can then yield important parameters such
as the specific absorption rate (SAR) and total absorbed dose (AD). For example, from
the knowledge of the local density (ρ) and the electrical conductivity (σ), the SAR can
be obtained as σ E(r,t) 2 /ρ. The present discussions have an important bearing on microdosimetry, that is, the quantitative evaluation of the electric fields and voltages across
the cell membrane leading to energy absorption. Microdosimetry can also be extremely
useful in developing more effective Micro-Second Pulsed Electric Field (μsPEF) waveforms and in designing innovative pulse applicators. Here, both simple and complicated
cell models are discussed. The role of the dielectric properties of biological cells is also
outlined because these parameters affect the development and magnitude of electric
field generation within the biosystem. It is argued that the frequency-dependent dielectric response can be used in designing shorter pulses that would have greater bioeffects.
Finally, some of the experimental techniques pertinent to the measurement of dielectric
properties are briefly considered.
Electromagnetic Fields in Biological Systems
contrast, the application of high-intensity electric fields does not present such difficulties. Short exposures of cells and tissues to strong fields represent an important subset of
high voltage external excitation. The fields involved are larger in the order of magnitude
and so can readily pass the conceptual tests based on signal-to-noise ratio (SNR) criteria
in spite of the short exposure times.
Models of electric field interactions with biological cells predict that pulses with durations shorter than the charging time of the outer membrane can penetrate and 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 be beneficial in reducing the growth
of tumors (Nuccitelli et al. 2006). Such nanosecond electrical pulses have been shown
to successfully treat melanoma tumors by using needle arrays as pulse delivery systems.
Besides treating tumors, possible applications of the intracellular electrical effects are
enhancing gene delivery to the nucleus, controlling calcium release and cell functions,
and cell immobilization. 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 (EM) fields into tissue with a spatial resolution in the centimeter range.
This chapter primarily examines the concepts of electric field interactions in cells,
though some treatment of tissues has also been included. The focus is on ultrashort
(∼10–100 ns), pulsed high-intensity fields (∼100 kV/cm). A theoretical basis for evaluating field strengths and penetrating into single cells is given, together with modeling
results as appropriate. Continuum approaches are discussed for electric field evaluations
that can then form the basis for subsequent methods of molecular dynamics or structural bioinformatics for analyzing cellular electrical responses. The time-dependent
and spatially dependent electric field E(r,t) can then yield important parameters such
as the specific absorption rate (SAR) and total absorbed dose (AD). For example, from
the knowledge of the local density (ρ) and the electrical conductivity (σ), the SAR can
be obtained as σ E(r,t) 2 /ρ. The present discussions have an important bearing on microdosimetry, that is, the quantitative evaluation of the electric fields and voltages across
the cell membrane leading to energy absorption. Microdosimetry can also be extremely
useful in developing more effective Micro-Second Pulsed Electric Field (μsPEF) waveforms and in designing innovative pulse applicators. Here, both simple and complicated
cell models are discussed. The role of the dielectric properties of biological cells is also
outlined because these parameters affect the development and magnitude of electric
field generation within the biosystem. It is argued that the frequency-dependent dielectric response can be used in designing shorter pulses that would have greater bioeffects.
Finally, some of the experimental techniques pertinent to the measurement of dielectric
properties are briefly considered.