The overall objective of this dissertation is to study the biotransport dynamics and their applications in several topics of the life sciences, including human transdermal absorption, cartilage/synovial fluid interaction in a joint, blood flowing through stenosis, leukocyte locomotion within a lab-on-a-chip. To accomplish these goals, computational modeling, Lab-on-Chip fabrication, hormone transdermal absorption testing were applied.
We first started by looking into the problem of transdermal absorption phenomenon. Transdermal drug delivery is a common approach for administration of chemical therapeutic agents. Transdermal absorption is a transport process of drugs through the skin, a multi-laminar structure from the pharmaceutical patch to stratum corneum (SC), then to the viable epidermis and dermis, and finally penetrating into the blood. The process becomes complicated because of the flux barriers between the interfaces (patch/SC, SC/viable epidermis). The finite element method was used in this study to develop a contact algorithm with a computational element to account for both the influence of the interface barrier and the chemical absorption mechanisms during such a transdermal drug delivery process. The discontinuity at the layer boundary could be overcome in the algorithm by adopting the temperature-concentration diffusion analogy to assure the continuity across the interfaces.
We then conducted some experimental work by using radioactive 17 /?-estradiol to detect the absorptions in stratum corneum, viable epidermis and dermis respectively. Such transdermal parameters as lag time, permeability and diffusion coefficients between the skin and drug were derived. In transdermal absorption, the partition coefficients vary in stratum corneum, epidermis and dermis.
The next focus is on the blood flow problem. The hemodynamic shear stress acts as a prevailing factor responsible for arteriosclerosis and thrombosis in blood vessels. We integrated several complex issues including the fluid and structural interaction (FSI), turbulence and non-Newtonian flow into a numerical axisymmetric model for predicting the shear stress and vessel deformation during the blood flow. The leukocyte transportation in a PDMS-microchip was investigated, and a steady laminar CFD (computational fluid dynamics) solution was used to predict the particle collision and deposition, whereas the FSI algorithm was applied to a vacuum-seal PDMS microfluidic channel for leukocytes locomotion over an engineered substrate. Finally, The FSI method was also applied to a joint cartilage model, including both the articular cartilage and subchondral bone, and the synovial fluid. Simulations predicted the shear stress on the articular cartilage by synovial fluid while the subchondral bone experiences forces during movement.