@article{becker_kuznetsov_2008, title={Thermal in vivo skin electroporation pore development and charged macromolecule transdermal delivery: A numerical study of the influence of chemically enhanced lower lipid phase transition temperatures}, volume={51}, ISSN={["1879-2189"]}, DOI={10.1016/j.ijheatmasstransfer.2007.06.010}, abstractNote={Electroporation is an approach used to enhance transdermal transport of large molecules in which the skin is exposed to a series of electric pulses. Electroporation temporarily destabilizes the structure of the outer skin layer, the stratum corneum, by creating microscopic pores through which agents, which ordinarily are unable to pass into the skin, are able to pass through this outer barrier. Long duration electroporation pulses can cause localized temperature rises which result in thermotropic phase transitions within the lipid bilayer matrix of the stratum corneum. Chemical agents applied to the skin can reduce the lipid phase transition temperatures. This paper studies the benefits of the combination of the chemical enhancer, terpene d-limonene with low voltage electroporation pulses in order to further aid in electroporation pore development resulting from fluidization of the lipid structures within the stratum corneum. A transient finite volume model is developed in which the thermal and electrical behavior associated with electroporation of in vivo human skin is analyzed and lipid phase transition is represented by a melting process. The Nernst–Planck model is used to represent the electrophoretic-assisted transport of large charged molecules through the skin. The results show that the lower lipid phase transition temperatures associated with the topical application of chemical enhancers to the skin allow for increased solute delivery and solute penetration of the skin reaching radial locations much further than in the untreated case. Solute transport solutions of both cases exhibit local accumulation of concentrations below the stratum corneum – epidermis interface which exceed concentration values initially contained within the applicator gel.}, number={7-8}, journal={INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER}, author={Becker, S. M. and Kuznetsov, A. V.}, year={2008}, month={Apr}, pages={2060–2074} } @article{becker_kunetsov_2007, title={Local temperature rises influence in vivo electroporation pore development: A numerical stratum corneum lipid phase transition model}, volume={129}, ISSN={["1528-8951"]}, DOI={10.1115/1.2768380}, abstractNote={Electroporation is an approach used to enhance transdermal transport of large molecules in which the skin is exposed to a series of electric pulses. Electroporation temporarily destabilizes the structure of the outer skin layer, the stratum corneum, by creating microscopic pores through which agents, ordinarily unable to pass into the skin, are able to pass through this outer barrier. Long duration electroporation pulses can cause localized temperature rises, which result in thermotropic phase transitions within the lipid bilayer matrix of the stratum corneum. This paper focuses on electroporation pore development resulting from localized Joule heating. This study presents a theoretical model of electroporation, which incorporates stratum corneum lipid melting with electrical and thermal energy equations. A transient finite volume model is developed representing electroporation of in vivo human skin, in which stratum corneum lipid phase transitions are modeled as a series of melting processes. The results confirm that applied voltage to the skin results in high current densities within the less resistive regions of the stratum corneum. The model captures highly localized Joule heating within the stratum corneum and subsequent temperature rises, which propagate radially outward. Electroporation pore development resulting from the decrease in resistance associated with lipid melting is captured by the lipid phase transition model. As the effective pore radius grows, current density and subsequent Joule heating values decrease.}, number={5}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Becker, S. M. and Kunetsov, A. V.}, year={2007}, month={Oct}, pages={712–721} } @article{becker_kuznetsov_2007, title={Numerical assessment of thermal response associated with in vivo skin electroporation: The importance of the composite skin model}, volume={129}, ISSN={["1528-8951"]}, DOI={10.1115/1.2720910}, abstractNote={Electroporation is an approach used to enhance transdermal transport of large molecules in which the skin is exposed to a series of electric pulses. The structure of the transport inhibiting outer layer, the stratum corneum, is temporarily destabilized due to the development of microscopic pores. Consequently agents that are ordinarily unable to pass into the skin are able to pass through this outer barrier. Of possible concern when exposing biological tissue to an electric field is thermal tissue damage associated with Joule heating. This paper shows the importance of using a composite model in calculating the electrical and thermal effects associated with skin electroporation. A three-dimensional transient finite-volume model of in vivo skin electroporation is developed to emphasize the importance of representing the skin's composite layers and to illustrate the underlying relationships between the physical parameters of the composite makeup of the skin and resulting thermal damage potential.}, number={3}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Becker, S. M. and Kuznetsov, A. V.}, year={2007}, month={Jun}, pages={330–340} } @article{becker_kuznetsov_2007, title={Thermal damage reduction associated with in vivo skin electroporation: A numerical investigation justifying aggressive pre-cooling}, volume={50}, ISSN={["1879-2189"]}, DOI={10.1016/j.ijheatmasstransfer.2006.06.030}, abstractNote={Electroporation is an approach used to enhance transdermal transport of large molecules in which the skin is exposed to a series of electric pulses. Electroporation temporarily destabilizes the structure of the outer skin layer, the stratum corneum, by creating microscopic pores through which agents, which ordinarily are unable to pass into the skin, are able to pass through this outer barrier. Of possible concern when exposing biological tissue to an electric field is thermal tissue damage associated with Joule heating. In order to find the electrical and transient thermal solutions associated with this process, this study develops a three-dimensional transient finite-volume composite model of in vivo skin electroporation. The electroporation process modeled consists of five 150 ms long DC square wave pulses administered at 1-s intervals with an applied voltage of 400 V. This paper finds that minor thermal influence of the electrode plate and the of a small presence blood vessel have a large impact on thermal damage. An aggressive pre-cooling technique is presented which is shown to dramatically reduce the risk of thermal damage.}, number={1-2}, journal={INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER}, author={Becker, S. M. and Kuznetsov, A. V.}, year={2007}, month={Jan}, pages={105–116} } @article{becker_kuznetsov_2006, title={Numerical modeling of in vivo plate electroporation thermal dose assessment}, volume={128}, ISSN={["1528-8951"]}, DOI={10.1115/1.2132375}, abstractNote={Electroporation is an approach used to enhance the transport of large molecules to the cell cytosol in which a targeted tissue region is exposed to a series of electric pulses. The cell membrane, which normally acts as a barrier to large molecule transport into the cell interior, is temporarily destabilized due to the development of pores in the cell membrane. Consequently, agents that are ordinarily unable enter the cell are able to pass through the cell membrane. Of possible concern when exposing biological tissue to an electric field is thermal tissue damage associated with joule heating. This paper explores the thermal effects of various geometric, biological, and electroporation pulse parameters including the blood vessel presence and size, plate electrode configuration, and pulse duration and frequency. A three-dimensional transient finite volume model of in vivo parallel plate electroporation of liver tissue is used to develop a better understanding of the underlying relationships between the physical parameters involved with tissue electroporation and resulting thermal damage potential.}, number={1}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Becker, SM and Kuznetsov, AV}, year={2006}, month={Feb}, pages={76–84} } @article{kuznetsov_becker_2004, title={Effect of the interface roughness on turbulent convective heat transfer in a composite porous/fluid duct}, volume={31}, ISSN={["0735-1933"]}, DOI={10.1016/s0735-1933(03)00197-0}, abstractNote={Flow over a finite porous medium is investigated using different interfacial conditions. In such configuration, a macroscopic interface is identified between the two media. In the first model, no diffusion-flux is considered when treating the statistical energy balance at the interface. The second approach assumes that diffusion fluxes of turbulent kinetic energy on both sides of the interface are unequal. Comparing these two models, this paper presents numerical solutions for such hybrid medium, considering here a channel partially filled with a porous layer through which fluid flows in turbulent regime. One unique set of transport equations is applied to both regions. Effects of Reynolds number, porosity, permeability and jump coefficient on mean and turbulence fields are investigated. Results indicate that depending on the value of the stress jump parameter, substantially dissimilar fields for the turbulence energy are obtained. Negative values for the stress jump parameter give results closer to experimental data for the turbulent kinetic energy at the interface.}, number={1}, journal={INTERNATIONAL COMMUNICATIONS IN HEAT AND MASS TRANSFER}, author={Kuznetsov, AV and Becker, SM}, year={2004}, month={Jan}, pages={11–20} } @article{becker_kuznetsov_avramenko_2004, title={Numerical modeling of a falling bioconvection plume in a porous medium}, volume={35}, ISSN={["1873-7005"]}, DOI={10.1016/j.fluiddyn.2004.07.003}, abstractNote={This paper considers a bioconvection plume in a fluid saturated porous medium. Bioconvection plumes may arise as a result of an unstable density stratification caused by up-swimming microorganisms. This unstable density stratification occurs when the microorganisms, heavier than water, accumulate in the upper regions of the fluid. The plume transports cells and oxygen from the upper fluid region to the lower fluid regions. This paper finds a numerical solution for the steady-state plume in a porous medium by utilizing an implicit finite difference method. The effects of varying pertinent parameters are investigated. A similarity solution of the plume is also obtained for comparison purposes.}, number={5}, journal={FLUID DYNAMICS RESEARCH}, author={Becker, SM and Kuznetsov, AV and Avramenko, AA}, year={2004}, month={Nov}, pages={323–339} }