Liquid Flooded Flow-Focusing Microfluidic Device for in situ Generation of Monodisperse Microbubbles.

Liquid Flooded Flow-Focusing Microfluidic Device for in situ Generation of Monodisperse Microbubbles.
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DOI:
10.1007/s10404-012-1064-x
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发表时间:
2013-03-01
影响因子:
2.8
通讯作者:
Hossack JA
Hossack JA
中科院分区:
工程技术3区
文献类型:
--
作者:
Dhanaliwala AH;Chen JL;Wang S;Hossack JA

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当前的基于微泡的超声对比剂被静脉内施用,导致对比度的损失,全身分布以及微泡寿命的严格要求,而不是直径的大小微流体设备(FFMD)是一种有前途的技术,用于实现原位生产,因为它们可以生产具有精确控制直径的微泡实时。虽然微流体芯片很小,因此添加了进气口和互连以大大增加这些设备的足迹,从而阻止了FFMD的小型化,以兼容。我们引入了一种将液体(壳)相的新方法供应消除笨重的互连的FFMD。 FFMD,我们称其为洪水的FFMD。以450,000个微泡(MB/s)的生产速率实现±0.3μm。先前报道的结果也简化了平行化,最高670,000 MB/s的生产率是使用洪水的FFMD并行的。获得了超声对比度成像装置。原位微泡产生和实时成像。利用原位产生的微泡以对比度增强了对脉管系统的超声成像和药物递送的对比度。
Current microbubble-based ultrasound contrast agents are administered intravenously resulting in large losses of contrast agent, systemic distribution, and strict requirements for microbubble longevity and diameter size. Instead we propose in situ production of microbubbles directly within the vasculature to avoid these limitations. Flow focusing microfluidic devices (FFMDs) are a promising technology for enabling in situ production as they can produce microbubbles with precisely controlled diameters in real-time. While the microfluidic chips are small, the addition of inlets and interconnects to supply the gas and liquid phase greatly increases the footprint of these devices preventing the miniaturization of FFMDs to sizes compatible with medium and small vessels. To overcome this challenge, we introduce a new method for supplying the liquid (shell) phase to an FFMD that eliminates bulky interconnects. A pressurized liquid-filled chamber is coupled to the liquid inlets of an FFMD, which we term a flooded FFMD. The microbubble diameter and production rate of flooded FFMDs were measured optically over a range of gas pressures and liquid flow rates. The smallest FFMD manufactured measured 14.5 × 2.8 × 2.3 mm. A minimum microbubble diameter of 8.1 ± 0.3 μm was achieved at a production rate of 450,000 microbubbles/s (MB/s). This represents a significant improvement with respect to any previously reported result. The flooded design also simplifies parallelization and production rates of up to 670,000 MB/s were achieved using a parallelized version of the flooded FFMD. In addition, an intravascular ultrasound (IVUS) catheter was coupled to the flooded FFMD to produce an integrated ultrasound contrast imaging device. B-mode and IVUS images of microbubbles produced from a flooded FFMD in a gelatin phantom vessel were acquired to demonstrate the potential of in situ microbubble production and real-time imaging. Microbubble production rates of 222,000 MB/s from a flooded FFMD within the vessel lumen provided a 23 dB increase in B-mode contrast. Overall, the flooded design is a critical contribution towards the long- term goal of utilizing in situ produced microbubbles for contrast enhanced ultrasound imaging of, and drug delivery to, the vasculature.
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