Engineering Microbubbles for Enhanced Non-linear Response: Modelling and Experimental Studies

气泡对声激励的非线性响应是生物医学和工程科学中的一个重要现象。例如，在医学超声成像中，微泡作为造影剂特别有用，因为它们具有非线性散射超声的能力。然而，增加非线性程度通常需要增加激励的幅度，这也可能导致剧烈的行为，如惯性空化和气泡破碎；这些影响可能是非常不受欢迎的，特别是在生物医学应用中。这项建议中描述的工作的目的是调查我们最近的初步研究结果，该结果表明，通过在微泡表面沉积纳米颗粒，可以在低激发幅度下显著增强其声学响应的非线性特征。我们建议建立一个理论模型来预测这一行为，并考察其对气泡稳定性的影响；并对纳米颗粒的尺寸、形状和浓度对微气泡的稳定性和声学响应的影响进行系统的实验研究，以验证理论工作。成功的结果将导致微泡制剂的开发，提高了成像和治疗应用的有效性和可预测性，这将为制药和保健行业、仪器制造商以及最终临床医生和患者带来重大好处。

The non-linear response of gas bubbles to acoustic excitation is an important phenomenon in both the biomedical and engineering sciences. In medical ultrasound imaging, for example, microbubbles are particularly useful as contrast agents on account of their ability to scatter ultrasound non-linearly. Increasing the degree of non-linearity, however, normally requires an increase in the amplitude of excitation and this may also result in violent behaviour such as inertial cavitation and bubble fragmentation; effects which may be highly undesirable, especially in biomedical applications. The aim of the work described in this proposal is to investigate the findings from our recent preliminary study which showed that by depositing nanoparticles on the surface of a microbubble, the non-linear character of its acoustic response can be increased significantly at low excitation amplitudes. We propose to develop a theoretical model to predict this behaviour and to examine the effect upon bubble stability; and to carry out systematic experimental investigations of the influence of nanoparticle size, shape and concentration upon the stability and acoustic response of microbubbles in order to verify the theoretical work. A successful outcome will lead to the development of microbubble agents with improved efficacy and predictability, for both imaging and therapeutic applications, that will offer significant benefits to the pharmaceutical and healthcare industries, instrumentation manufacturers and ultimately clinicians and patients.