Gregory T. Martin

Theoretical analysis of localized heating in human skin subjected to high voltage pulses

Electroporation, the increase in the permeability of bilayer lipid membranes by the application of high voltage pulses, has the potential to serve as a mechanism for transdermal drug delivery. However, the associated current flow through the skin will increase the skin temperature and might affect nearby epidermal cells, lipid structure or even transported therapeutic molecules. Here, thermal conduction and thermal convection models are used to provide upper and lower bounds on the local temperature rise, as well as the thermal damage, during electroporation from exponential voltage pulses (70 V maximum) with a 1 ms and a 10 ms pulse time constant. The peak temperature rise predicted by the conduction model ranges from 19 degrees C for a 1 ms time constant pulse to 70 degrees C for the 10 ms time constant pulse. The convection (mass transport) model predicts a 18 degrees C peak rise for 1 ms time constant pulses and a 51 degrees C peak rise for a 10 ms time constant pulse. The convection model compares more favorably with previous experimental studies and companion observations of the local temperature rise during electroporation. Therefore, it is expected that skin electroporation can be employed at a level which is able to transport molecules transdermally without causing significant thermal damage to the tissue.

Biological Effects Due to Weak Electric and Magnetic Fields: The Temperature Variation Threshold

A large number of epidemiological and experimental studies suggest that prolonged (>100 s) weak 50-60-Hz electric and magnetic field (EMF) exposures may cause biological effects(NIEHS Working Group, NIH, 1998; Bersani, 1999). We show, however, that for typical temperature sensitivities of biochemical processes, realistic temperature variations during long exposures raise the threshold exposure by two to three orders of magnitude over a fundamental value, independent of the biophysical coupling mechanism. Temperature variations have been omitted in previous theoretical analyses of possible weak field effects, particularly stochastic resonance (Bezrukov and Vodyanoy 1997a. Nature. 385:319-321; Astumian et al., 1997 Nature. 338:632-633; Bezrukov and Vodyanoy, 1997b. Nature. 338:663; Dykman and McClintock, 1998. Nature. 391:344; McClintock, 1998;. Gammaitoni et al., 1998. Rev. Mod. Phys. 70:223-287). Although sensory systems usually respond to much shorter (approximately 1 s) exposures and can approach fundamental limits (Bialek, 1987 Annu. Rev. Biophys. Biophys. Chem. 16:455-468; Adair et al, 1998. Chaos. 8:576-587), our results significantly decrease the plausibility of effects for nonsensory biological systems due to prolonged, weak-field exposures.

Kinetics of the temperature rise within human stratum corneum during electroporation and pulsed high-voltage iontophoresis

Electroporation is believed to be a nonthermal phenomenon at the membrane level. However, the effects of associated processes, such as Joule heating, should be considered. Because electroporation of skin, specifically the stratum corneum (SC), occurs at highly localized sites, the heating is expected to conform locally to the sites of electroporation. Significant localized heating was found to be strongly dependent on the voltage and duration of the high-voltage pulses. Specifically, a localized temperature rise was predicted theoretically and confirmed by experiments, with only a small rise (about 17 degrees C) for short, large pulses (1 ms, 100 V across the SC), but was increased (about 54 degrees C) for long, large pulses (300 ms, 60 V across the SC). The latter case appears to result in irreversible structural changes like vesicularization of the lipid lattice. These results support the hypothesis that electroporation occurs within the SC and that additional processes, such as localized heating, may be important.

The temperature distribution in a semi-infinite body due to surface absorption of laser radiation

Abstract An exact steady state and transient solution for the temperature distribution in a semi-infinite body with a Gaussian distribution heat source at the body surface is developed and presented. This solution has direct application to steady state laser heating for target materials which have a high absorption coefficient at the laser wavelength. The solution also provides an upper bound for the case of pulsed laser heating. Approximate solutions for the steady and transient cases are used for comparison and it is shown that the exact solutions are the asymptotic limit of the approximate solutions.

A transient spherical source method to determine thermal conductivity of liquids and gels

Abstract A method developed for the measurement of tissue blood flow is modified to measure the thermal conductivity of liquids and silica gels. The method controls a thermistor temperature at a set point above the baseline and determines conductivity from the power as a function of time. Natural convection in the liquids is suppressed by reducing the measurement time to 10 s and by reducing the temperature step, thus decreasing the magnitude of buoyancy. Conductivities were measured in six aqueous liquids and in gels constituted from these liquids with various amounts of silica. The technique determined the conductivity with a 95% confidence interval to less than 1% in nearly all cases. It was found that conductivity varied 0.3% per 1% silica for gels made from a CuSO 4 solution and 1% per 1% silica for gels made from a Cu(BF 4 ) 2 solution.

Model and solution for the thermal response of blood-perfused tissue during laser hyperthermia

The monitoring and control of the thennal dose in non-contact laser hyperthermia treatment of tumors requires a model and solution of the lasertissue interaction. Presented are two models for the thermal response of tissue during continuous wave, noncontact, laser hyperthermia treatment of tumors. The first model is where all the laser energy is absorbed at the surface of the tissue and the second model is where the laser energy penetrates into the tissue before absorption. Both models include the effect of blood perfusion in the solution for the temperature rise. It is shown that perfusion has a negligible affect on the temperature distribution for the surface absorption of laser energy. However, in the case of laser energy penetration, perfusion has a significant effect which increases with increasing optical penetration.

Molecular Transport across Stratum Corneum due to Electric Pulses:Behavior of Localized Transport Regions (LTRS)

Investigations of the response of human skin to “high voltage” (HV) pulsing have been motivated by the prospect of significantly improved transdermal drug delivery and analyte extraction for noninvasive sensing. Previous experimental studies1–10 have shown that large increases in ionic and molecular transport take place if the HV pulses result in the transdermal voltage reaching Uskin≈ 50 to 10O V.