Collaborative Research: Acoustic micro-streaming in the aqueous core of bubble-containing liposomes for controlled release via shear-induced bilayer reorganization

PI：Wrenn，Steven/Sarkar，Kausik建议编号：1603007/1602884拟议的研究重点是研究液滴中微泡的行为。当微泡被脂类包裹，然后嵌套在充满水的细胞中时，微泡变得稳定。这种布置可以具有生物学意义的应用，例如药物输送技术和通过对气泡的声学响应进行成像的诊断。涂层微泡已经用于对比增强超声成像。将它们嵌套在一个带药物的囊泡中，可以作为“治疗”的载体，这意味着它们既可以用于治疗，也可以用于诊断。同时，筑巢可以保护微泡不受气体扩散的影响，将它们的寿命从几分钟提高到几小时。然而，嵌套微气泡会导致微气泡的声学活动和由此产生的流体动力学(包括声学微流)发生巨大变化。就在几年前，嵌套的概念首次在实验上得到证明，但嵌套影响声学微流的机制尚未详细了解；涉及嵌套微泡的实验和理论研究都很少。这就是这项合作提案的目标。研究小组将对各种嵌套配方进行系统和详尽的声学和物理化学测试，同时推导出解释巢壳的数学和计算流体力学模型，并与实验结果相一致。有三个具体的目标：1)计算嵌套构型中的流线和计算沿着嵌套磷脂双层的内叶产生的剪切应力分布；2)确定双层根据微流产生的应力进行自我重组的机制(S)；以及3)量化微流的敏感性和双层对超声输入参数和化学派生的嵌套膜特性的响应。这项拟议工作的更广泛影响是开发一种可用于超声成像和/或药物输送的治疗工具。最终的应用可能是在实际的临床环境中使用嵌套微泡。该提案还包括一项计划，积极从摩根州立大学招收代表不足的少数族裔学生，以及针对高中、本科生和研究生的教育活动。

PI: Wrenn, Steven / Sarkar, KausikProposal Number: 1603007 / 1602884The proposed research is focused on the study of the behavior of microbubbles inside a liquid drop. The microbubbles become stable when coated with lipids and then nested in a cell that is filled with water. This arrangement can have applications with biological interest, such as drug delivery techniques and diagnostics through imaging of the acoustic response of the bubbles. Coated microbubbles are already useful for contrast enhanced ultrasound imaging. Nesting them inside a drug bearing vesicle confers great potential as "theranostic" vehicles, meaning they can be used for both therapeutic and diagnostic applications. At the same time, nesting can protect microbubbles against gas diffusion, enhancing their life time from minutes to hours. However, nesting a microbubble leads to dramatic changes in microbubble acoustical activity and the resulting fluid dynamics, including acoustic microstreaming. The nesting concept was demonstrated experimentally for the first time just a few years ago, and the mechanism by which nesting impacts acoustic microstreaming is not yet known in detail; both experimental and theoretical studies involving nested microbubbles are scant. This is the objective of this collaborative proposal. The research team will perform a systematic and exhaustive series of acoustic and physicochemical tests of various nested formulations, while simultaneously deriving mathematical and computational fluid dynamics models that account for the nesting shell and agree with the experimental results. There are three specific aims: 1) compute the streamlines in a nested configuration and calculate the resulting shear stress profile along the inner leaflet of the nesting phospholipid bilayer; 2) identify the mechanism(s) by which the bilayer restructures itself in response to the stresses produced by microstreaming; and 3) quantify the sensitivity of microstreaming and the bilayer response to ultrasonic input parameters and chemically derived nesting membrane properties. The broader impact of the proposed work is to develop a theranostic vehicle that can be used for ultrasound imaging and/or drug delivery. The end application could be the use of nested micro-bubbles in actual clinical environments. The proposal also includes a plan to actively recruit underrepresented minority students from Morgan State, as well as educational activities for high school, undergraduate and graduate students.