Determining the Role of Microbubbles in Sonoporation through Numerical Simulations

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For over 100 years the damaging capabilities of collapsing bubbles and cavities have been known. Originally, the focus of research was on maritime applications, but today the fields of interest are far more wide ranging. In recent years, there has been a great deal of interest in sonoporation - the process of increasing cell permeability through the application of ultrasound to enable the delivery of large molecules, such as genes and drugs, to cells for the purposes of gene therapy or cancer treatment. A number of benefits over other therapeutic techniques have been proposed, and, consequently, a large body of experimental research (both in vitro and in vivo) continues to make progress in understanding and developing the procedure. It is well-known that the presence of microbubbles in the treatment region greatly enhances the efficacy of the procedure. However, the precise role of the microbubbles is poorly understood. Indeed, a detailed study of the interaction of multiple bubbles with adjacent cellular matter is extremely difficult to perform experimentally, especially within in vivo environments. To aid a complete understanding of the fluid mechanical processes involved, a computational modelling tool is needed to provide accurate simulations which can be controlled in a precise and cost-effective manner unavailable to experiment. However, the complexity of these processes is such that many of the popular computational and mathematical modelling approaches fall short in providing accurate predictions of the dynamics. With this in mind, this research project will develop a computational modelling tool capable of providing robust and accurate quantitative predictions of bubble dynamics relevant to the sonoporation process (specifically, multi-bubble dynamics near a deformable biological surface). This work will extend a pre-existing mathematical model and numerical method developed by the author and collaborators for solving multiphase viscoelastic flow problems. The overall aim is to ascertain (in a quantitative sense) the relative importance of the various fluid mechanical mechanisms that occur during microbubble-enhanced sonoporation. This investigation addresses the dearth of mathematical and computational research in this area, and will facilitate a complete understanding of the sonoporation process. The important insights and output from this project will play a fundamental role in the long-term development of a viable clinical procedure.