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Determining the Role of Microbubbles in Sonoporation through Numerical Simulations

通过数值模拟确定微泡在声孔作用中的作用

基本信息

批准号：
EP/L011549/1
负责人：
Steven Lind
金额：
$ 12.16万
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2014
资助国家：
英国
起止时间：
2014 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FL011549%2F1
关键词：
Determining Role Microbubbles Sonoporation through

项目摘要

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.

100多年来，人们已经知道气泡和空腔破裂的破坏能力。最初，研究的重点是海事应用，但今天感兴趣的领域更加广泛。近年来，人们对声致孔作用产生了极大的兴趣，声致孔作用是通过应用超声来增加细胞渗透性的过程，从而能够将大分子（例如基因和药物）递送到细胞中，以用于基因治疗或癌症治疗的目的。已经提出了许多优于其他治疗技术的好处，因此，大量的实验研究（体外和体内）继续在理解和开发该程序方面取得进展。众所周知，治疗区域中微泡的存在极大地增强了手术的功效。然而，微泡的确切作用知之甚少。事实上，多个气泡与相邻细胞物质的相互作用的详细研究在实验上是非常困难的，特别是在体内环境中。为了帮助全面了解所涉及的流体机械过程，需要一种计算建模工具来提供精确的模拟，这种模拟可以以一种精确且具有成本效益的方式进行控制，而这种方式是实验无法实现的。然而，这些过程的复杂性是这样的，许多流行的计算和数学建模方法在提供准确的动态预测方面存在不足。考虑到这一点，该研究项目将开发一种计算建模工具，能够提供与声孔过程相关的气泡动力学（特别是可变形生物表面附近的多气泡动力学）的稳健和准确的定量预测。这项工作将扩展一个预先存在的数学模型和数值方法开发的作者和合作者解决多相粘弹性流动问题。总的目的是确定（在定量意义上）的相对重要性，在微泡增强声致穿孔过程中发生的各种流体力学机制。这项调查解决了在这一领域的数学和计算研究的缺乏，并将促进一个完整的了解声穿孔过程。该项目的重要见解和产出将在可行的临床程序的长期开发中发挥重要作用。