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

PI: renn, Steven / Sarkar， kausik提案号：1603007 / 1602884提议的研究重点是研究液滴内微泡的行为。当微泡被脂质包裹，然后嵌套在充满水的细胞中时，微泡就会变得稳定。这种安排可以应用于生物领域，如药物输送技术和通过气泡声响应成像进行诊断。包覆微泡在超声造影中已经很有用了。将它们嵌套在携带药物的囊泡中，作为“治疗”载体具有巨大的潜力，这意味着它们可以用于治疗和诊断应用。同时，嵌套可以保护微气泡不受气体扩散的影响，将它们的寿命从几分钟延长到几小时。然而，嵌套微泡会导致微泡声学活动和由此产生的流体动力学（包括声学微流）发生剧烈变化。巢形概念在几年前才首次被实验证明，而巢形影响声微流的机制尚不清楚；关于嵌套微气泡的实验和理论研究都很少。这就是这个合作方案的目标。研究小组将对各种嵌套配方进行系统和详尽的一系列声学和物理化学测试，同时推导出考虑嵌套壳的数学和计算流体动力学模型，并与实验结果一致。有三个具体目的：1)计算嵌套结构中的流线，并计算沿嵌套磷脂双层内层小叶的剪切应力分布；2)确定响应微流产生的应力的双层结构自身重组的机制；3)量化微流的灵敏度和双分子层对超声输入参数和化学衍生嵌套膜性质的响应。所提出的工作的更广泛影响是开发一种可用于超声成像和/或药物输送的治疗载体。最终应用可能是在实际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性不足的少数民族学生，并为高中生、本科生和研究生开展教育活动。

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.