MULTI-SCALE NUMERICAL STUDY OF NANOPARTICLE TRANSPORT IN DEFORMABLE TISSUES DURING AN INFUSION PROCESS

Nanoparticles have attracted growing research interest in novel hyperthermia treatments of cancers due to their ability to generate impressive levels of heat when excited by an external alternating magnetic field. Intratumoral injection by means of needle is an important method to deliver nanoparticles in tumors, and the resulting distribution of the particles is a critical factor determining the distribution of temperature elevations. In order to maximize the outcome of magnetic nanoparticle hyperthermia treatment, it is essential to acquire knowledge and understanding of the transport of nanoparticles and nanofluid in biological tissues during and after an infusion process. A multiscale model is developed in this dissertation that consists of a macroscale model for nanofluid flow, tissue deformation, nanoparticle convection and diffusion, as well as nanoparticle deposition in porous tissues, and a particle trajectory tracking model that considers particle-surface interactions and the resulting effect of particle deposition. The integration of these two models at different scales enables the study of the behavior of nanoparticle deposition on the cellular structure, the formation of backflow and the variation of tissue porosity induced by an infusion, the spreading shape of nanofluid, and the transport mechanism of nanoparticles in a tumor. The particle deposition rate coefficient, the shapes of nanofluid distribution volume, the length of backflow, and the distribution of nanoparticle concentration are predicted for a wide range of injection conditions. The results show that tissue deformation and particle binding to the cell surface are leading mechanisms that substantially affect the particle concentration distribution and the nanofluid spreading shape after an intratumoral injection. Infusion-induced tissue deformation results in backflow that causes nanofluid to flow back and infiltrate along the needles track, thus leading to an irregular shape of the nanofluid spreading. Tissue deformation also alters the pore size near the injection site, and thereby facilitates particle penetration through the tissue. Particle binding to the cellular structure, which reduces the particle concentration in the fluid phase, is found to be the leading mechanism causing the non-uniform distribution of the nanoparticles after an injection. The rate of particle binding to the cellular structure can be reduced by increasing the local interstitial fluid velocity, tissue porosity, and surface charge of the particles. Simulations are also performed under various infusion conditions, and the effects of injection rate, needle sizes, tissue elastic properties, and injection amounts on the spatial distribution of nanoparticles in tumors are quantified