Determining the Role of Microbubbles in Sonoporation through Numerical Simulations

100多年来，人们已经知道破裂气泡和空洞的破坏性能力。最初，研究的重点是海上应用，但今天感兴趣的领域要广泛得多。近年来，人们对声孔化非常感兴趣--这是一种通过应用超声波来增加细胞渗透性的过程，能够将大分子，如基因和药物，输送到细胞中，用于基因治疗或癌症治疗。与其他治疗技术相比，已经提出了许多好处，因此，大量的实验研究(包括体外和体内)在理解和开发该程序方面继续取得进展。众所周知，治疗区域中微泡的存在极大地提高了该程序的效果。然而，人们对微泡的确切作用知之甚少。事实上，对多个气泡与相邻细胞物质相互作用的详细研究很难在实验中进行，特别是在活体环境中。为了帮助全面了解所涉及的流体力学过程，需要一种计算建模工具来提供精确的模拟，这些模拟可以以实验无法获得的精确和经济的方式进行控制。然而，这些过程的复杂性使得许多流行的计算和数学建模方法无法提供对动态的准确预测。考虑到这一点，这一研究项目将开发一种计算建模工具，能够对与声旋分离过程相关的气泡动力学(具体地说，可变形生物表面附近的多气泡动力学)提供稳健和准确的定量预测。这项工作将扩展作者和合作者为解决多相粘弹性流动问题而建立的已有的数学模型和数值方法。总体目标是确定(在定量意义上)在微泡增强声学手术过程中发生的各种流体机械机制的相对重要性。这项研究解决了这一领域中数学和计算研究的匮乏问题，并将有助于全面了解声旋切术过程。该项目的重要见解和成果将在可行的临床程序的长期发展中发挥基础性作用。

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.