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Research

Background

Ultrasound (US) cavitation, sono-cavitation or acoustic cavitation (referred to simply as cavitation hereafter) applications have extended use in biomedical and industrial fields; Figure 1 shows representative images of a simulated and an actual cavitation cloud forming during ultrasound operation. A non-exhaustive list of cutting edge applications includes kidney stone lithotripsy, cancer cell histotripsy, cell sonoporation, drug and even DNA delivery and micro-streaming. Cavitation may be used to achieve sono-thrombolysis, drug delivery, cell destruction, dental cleaning, Blood-Brain Barrier (BBB) opening, neuro-stimulation and even to provide contrast with application in medical imaging. In the field of cell membrane permeabilization and drug delivery, cavitation is commonly used as a means to produce sonoporation. The induced jetting phenomena can directly create pores in membranes/tissues. Careful adjustments of ultrasound intensity can lead to sonoporation of specific cell types, thus enhancing drug delivery to targeted cells only, a requirement for permeabilization without causing permanent damage to tissues/cells, especially in delicate organs. In addition, High Intensity Focused Ultrasound (HIFU) may also be used directly to induce heat or cavitation for tissue destruction.

 

Figure 1

The cavitational destruction mode is also referred to as histotripsy. Moreover, ultrasounds are used for surface cleaning, material and food processing (e.g. homogenization, emulsification, dispersion, cutting, extraction, inactivation of microorganisms). Interactions of bubbles/shock waves with soft matter also occur in animal species that have evolved to stun or kill prey (snapping and mantis shrimps).

On a microscale, the common denominator for all these applications is the generation of shockwaves induced during the collapse of cavitation micro-bubbles, occurring simultaneously with high pressure/temperatures developing at the epicentres of collapse and inducing significant heating/stresses in the surroundings. In extreme cases, such events can induce chemical reactions and the production of free radicals, which can be linked to biochemical reactions. Even almost 40 years since the pioneering simulations of Plesset and Chapman and the experiments of Lauterborn and Bolle on bubble collapse mechanisms, there is still large disparity between the theoretical predictions of various experiments and models from different researchers, ranging from 10-10K to 50,000K or even less. Vast prediction discrepancies also exist in the bubble collapse shape, depending on model assumptions. On a macroscale, bubble nucleation in fluids/tissues and bubble cloud interaction with shockwaves and the deformable boundaries of soft matter (tissues, membranes and blood cells), remain unexplored. Despite the significance of these topics, well-controlled experiments and computational models able to resolve the underlying physical processes and thus, support the development of new technologies/treatment protocols, are largely absent.

Motivation

Three unknown, unexplored and long-lasting open problems in the field of shockwave and bubble/soft matter interactions have driven the research proposed here: (1) Can fundamental experimental studies be designed which allow the temperatures developing during bubble collapse be quantified by measurement/simulation in order to provide a definite answer to this relevant long-standing question? (2) Can new state-of-the-art, experimentally validated, computational models which couple fluid dynamics, chemistry and soft material mechanics, simulate the interactions of shockwaves, cavitating bubbles and soft matter in the aforementioned applications? (3) What is the cavitation threshold of tissues and how can we control cavitation in Tissue Mimicking Materials (TMM) that will allow the relevant experiments to be conducted in vitro? In order to answer these questions, new experiments which address the onset of cavitation in TMM, ultrasound assisted drug delivery techniques, bubble cleaning and fundamental bubble dynamics are scheduled; these will provide better understanding of the relevant processes and greatly assist validation of the relevant models. At a theoretical/numerical level, development and validation of new state-of-the-art tools for US cavitation modelling in tissues/TMM, heterogeneous bubble nucleation at walls, shockwave/bubble interaction (including deformable surfaces/cell membranes and chemical reactions inside collapsing bubbles) can help in the understanding of the applications mentioned above, and thus be essential in improving their efficacy.