IEEE Trans Ultrason Ferroelectr Freq Control. 2018 Apr;65(4):570-581. doi: 10.1109/TUFFC.2018.2803137.
Ultrasound in the presence of gas-filled microbubbles can be used to enhance local uptake of drugs and genes. To study the drug delivery potential and its underlying physical and biological mechanisms, an in vitro vessel model should ideally include 3-D cell culture, perfusion flow, and membrane-free soft boundaries. Here, we propose an organ-on-a-chip microfluidic platform to study ultrasound-mediated drug delivery: the OrganoPlate. The acoustic propagation into the OrganoPlate was determined to assess the feasibility of controlled microbubble actuation, which is required to study the microbubble-cell interaction for drug delivery. The pressure field in the OrganoPlate was characterized non-invasively by studying experimentally the well-known response of microbubbles and by simulating the acoustic wave propagation in the system. Microbubble dynamics in the OrganoPlate were recorded with the Brandaris 128 ultrahigh-speed camera (17 million frames/s) and a control experiment was performed in an OptiCell, an in vitro monolayer cell culture chamber that is conventionally used to study ultrasound-mediated drug delivery. When insonified at frequencies between 1 and 2 MHz, microbubbles in the OrganoPlate experienced larger oscillation amplitudes resulting from higher local pressures. Microbubbles responded similarly in both systems when insonified at frequencies between 2 and 4 MHz. Numerical simulations performed with a 3-D finite-element model of ultrasound propagation into the OrganoPlate and the OptiCell showed the same frequency-dependent behavior. The predictable and homogeneous pressure field in the OrganoPlate demonstrates its potential to develop an in vitro 3-D cell culture model, well suited to study ultrasound-mediated drug delivery.
超声在充满气体的微泡存在下可用于增强药物和基因的局部摄取。为了研究药物传递的潜力及其潜在的物理和生物学机制，理想的体外血管模型应包括 3D 细胞培养、灌注流动和无膜软边界。在这里，我们提出了一种用于研究超声介导药物传递的器官芯片微流控平台：OrganoPlate。为了评估控制微泡致动的可行性，需要对 OrganoPlate 中的声传播进行确定，这对于研究用于药物传递的微泡-细胞相互作用是必需的。通过实验研究微泡的已知响应并模拟系统中的声波传播，对 OrganoPlate 中的压力场进行了非侵入性表征。使用 Brandaris 128 超高帧率相机（1700 万帧/秒）记录了 OrganoPlate 中的微泡动力学，并在 OptiCell 中进行了对照实验，OptiCell 是一种传统上用于研究超声介导药物传递的体外单层细胞培养室。当在 1 至 2 MHz 之间的频率下进行激励时，OrganoPlate 中的微泡由于更高的局部压力而经历更大的振荡幅度。当在 2 至 4 MHz 之间的频率下进行激励时，两个系统中的微泡表现出相似的响应。使用 OrganoPlate 和 OptiCell 的超声传播的 3D 有限元模型进行的数值模拟显示出相同的频率相关行为。OrganoPlate 中可预测且均匀的压力场表明其具有开发适合研究超声介导药物传递的体外 3D 细胞培养模型的潜力。
