基于瞬态空化效应的低频超声皮肤增透机制研究

In order to solve the dosage control problems in transdermal interstitial fluid extraction and transdermal drug delivery by low-frequency sonophoresis, and extend the clinical application of low-frequency ultrasound-based technology for skin permeabilization, a method to study the microscopic mechanism of skin permeabilization by low-frequency sonophoresis is innovatively proposed in this project. In this method, the high speed, high resolution, high precision, and direct observation of the transient variation process of cavitation bubble in micron scale will be carried out by combining the microfluidic chip technology with highly precise photoelectric measurement methods. In addition, multiphysics coupling analysis will be performed utilizing finite element method and boundary element method to study and build the theoretical model of the mechanism of skin permeabilization by low-frequency sonophoresis. The contents of this project include: (1) observe the dynamic process of a single transient cavitation bubble collapsing near the measured surface under different ultrasound conditions, identify the style of transient cavitation, and determine the position of cavitation; (2) measure and analyze the relationship between the transient cavitation style, position, and variations of pressure and temperature caused by transient cavitation; (3) measure and analyze the effect of ultrasound conditions and skin surface properties on the distribution of transient cavitation near skin surface; (4) theoretical analyze, numerical simulate, and experimental validate the mechanism of skin permeabilization by low-frequency sonophoresis.

为了解决低频超声皮肤增透技术中实现组织液透皮抽取和药物透皮导入的定量化问题，进而推广低频超声皮肤增透技术的临床应用，项目原创性的提出了一种研究低频超声皮肤增透微观机制的方法。该方法通过微流控芯片技术和光电精密测试测量方法的有机结合，实现微米尺度内空化气泡瞬时变化过程的高速、高分辨率、精确、直接观测，并辅之以多物理场耦合的有限元和边界元分析技术，来研究和建立低频超声皮肤增透机制的理论模型。项目的研究内容包括：（1）观测不同超声作用条件下被测表面附近，单个瞬态空化气泡崩溃的动力学过程，辨识瞬态空化方式，确定空化位置；（2）测量和分析瞬态空化方式和空化位置，与伴随瞬态空化发生的压强和温度变化之间的关系；（3）测量和分析超声作用条件和皮肤表面特性对皮肤表面瞬态空化分布的影响；（4）对低频超声皮肤增透机制进行理论分析、数值模拟和实验验证。

为了解决低频超声皮肤增透技术中实现组织液透皮抽取和药物透皮导入的高效性和安全性问题，进而推广低频超声皮肤增透技术的临床应用，项目提出了一种研究低频超声皮肤增透微观机制的方法。本项目通过微流控芯片技术和光电精密测试测量方法的有机结合，实现了微米尺度内空化气泡瞬时变化过程的高速、高分辨率、精确、直接观测，建立了瞬态空化气泡崩溃的数值模型，并对低频超声皮肤增透的微观机制进行了探讨。项目的研究内容包括：（1）观测和分析了不同超声作用条件下被测表面附近，单个瞬态空化气泡崩溃的动力学过程；（2）建立了瞬态空化气泡崩溃的动力学过程的数值模型，结合观测结果验证了模型的有效性；（3）测量和分析了超声作用条件和皮肤表面特性对皮肤表面瞬态空化分布的影响；（4）研究了低频超声皮肤增透的微观机制，给出了优化低频超声皮肤增透效果的基本原则。