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Fluorescent Microscope System to Monitor Real-Time Interactions between Focused Ultrasound Echogenic Drug Delivery Vehicles and Live Cell Membranes

机译:荧光显微镜系统以活细胞的膜聚焦超声显示器之间的实时交互回声增强药物递送载体和

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摘要

Rapid development in the field of ultrasound triggered drug delivery has made it essential to study the real-time interaction between the membranes of live cells and the membranes of echogenic delivery vehicles under exposure to focused ultrasound. The objective of this work was to design an analysis system that combined fluorescent imagining, high speed videography, and definable pulse sequences of focused ultrasound to allow for real time observations of both cell and vehicle membranes. Documenting the behavior of the membranes themselves has not previously been possible due to limitations with existing optical systems used to understand the basic physics of microbubble/ultrasound interaction and the basic interaction between microbubbles and cells. The performance of this new system to monitor membrane behavior was demonstrated by documenting the modes of vehicle fragmentation at different ultrasound intensity levels. At 1.5 MPa the membranes were shown to completely fragment while at intensities below 1 MPa there is a popping and slow unfolding. The interaction between these vehicles and cell membranes was also documented by the removal of fluorescent particles from the surfaces of live cells out to 20 μm from the microbubble location. The fluid flow created by microstreaming around ensonated microbubbles was documented at video recording speeds from 60 to 18,000 frames per second. This information about membrane behavior allows the chemical and physical properties of the drug delivery vehicle to be designed along with the ultrasound pulse sequence to cause the most efficient drug delivery.
机译:超声波触发药物递送领域的快速发展使得研究活细胞膜与接触聚焦超声的回声递送载体的膜之间的实时相互作用是必要的。这项工作的目的是设计一种分析系统,将荧光图像组合,高速摄像机和可定心的超声脉冲序列组合,以允许对细胞和车辆膜的实时观察。记录膜本身的行为之前尚未实现,因为用于了解微泡/超声相互作用的基本物理学和微泡和细胞之间的基本相互作用的现有光学系统的限制。通过在不同的超声强度水平下记录车辆碎片模式来证明了这种新系统来监测膜行为的性能。在1.5MPa下,膜被显示为完全片段,而在低于1MPa的强度下,有一个突然和缓慢的展开。通过从微泡位置从活细胞表面从活细胞的表面除去荧光颗粒,还记录了这些车辆和细胞膜之间的相互作用。通过综合微泡的微晶产生的流体流量以每秒60至18,000帧的视频记录速度记录在视频记录速度下。关于膜行为的该信息允许药物输送载体的化学和物理性质与超声脉冲序列一起设计,以引起最有效的药物递送。

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