Krasovitski Boris, Kislev Hanoch, Kimmel Eitan
Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Ultrasonics. 2007 Dec;47(1-4):90-101. doi: 10.1016/j.ultras.2007.08.004. Epub 2007 Aug 28.
Previous experimental studies showed that powerful heating of nanoparticles by a laser pulse using energy density greater than 100 mJ/cm(2), could induce vaporization and generate microbubbles. When ultrasound is introduced at the same time as the laser pulse, much less laser power is required. For therapeutic applications, generation of microbubbles on demand at target locations, e.g. cells or bacteria can be used to induce hyperthermia or to facilitate drug delivery. The objective of this work is to develop a method capable of predicting photothermal and acoustic parameters in terms of laser power and acoustic pressure amplitude that are needed to produce stable microbubbles; and investigate the influence of bubble coalescence on the thresholds when the microbubbles are generated around nanoparticles that appear in clusters. We develop and solve here a combined problem of momentum, heat and mass transfer which is associated with generation and growth of a microbubble, filled with a mixture of non-vaporized gas (air) and water vapor. The microbubble's size and gas content vary as a result of three mechanisms: gas expansion or compression, evaporation or condensation on the bubble boundary, and diffusion of dissolved air in the surrounding water. The simulations predict that when ultrasound is applied relatively low threshold values of laser and ultrasound power are required to obtain a stable microbubble from a single nanoparticle. Even lower power is required when microbubbles are formed by coalescence around a cluster of 10 nanoparticles. Laser pulse energy density of 21 mJ/cm(2) is predicted for instance together with acoustic pressure of 0.1 MPa for a cluster of 10 or 62 mJ/cm(2) for a single nanoparticle. Those values are well within the safety limits, and as such are most appealing for targeted therapeutic purposes.
先前的实验研究表明,使用能量密度大于100 mJ/cm²的激光脉冲对纳米颗粒进行强力加热,可诱导汽化并产生微气泡。当在激光脉冲的同时引入超声波时,所需的激光功率要少得多。对于治疗应用,在目标位置(如细胞或细菌)按需产生微气泡可用于诱导热疗或促进药物递送。这项工作的目的是开发一种方法,能够根据产生稳定微气泡所需的激光功率和声压幅度来预测光热和声参数;并研究当微气泡在成簇出现的纳米颗粒周围产生时,气泡聚并对阈值的影响。我们在此开发并解决了一个与微气泡的产生和生长相关的动量、热量和质量传递的组合问题,该微气泡填充有未汽化气体(空气)和水蒸气的混合物。由于三种机制,微气泡的大小和气体含量会发生变化:气体膨胀或压缩、气泡边界上的蒸发或凝结以及溶解在周围水中的空气的扩散。模拟预测,当施加超声波时,从单个纳米颗粒获得稳定微气泡所需的激光和超声波功率阈值相对较低。当微气泡通过围绕10个纳米颗粒的簇聚并形成时,所需功率甚至更低。例如,对于10个纳米颗粒的簇,预测激光脉冲能量密度为21 mJ/cm²,声压为0.1 MPa,对于单个纳米颗粒则为62 mJ/cm²。这些值完全在安全范围内,因此对于靶向治疗目的极具吸引力。