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结合超声和毛细血管嵌入 T 型微流控装置,通过声致破碎技术扩大窄径微泡的产量。

Combining Ultrasound and Capillary-Embedded T-Junction Microfluidic Devices to Scale Up the Production of Narrow-Sized Microbubbles through Acoustic Fragmentation.

机构信息

Chemical Engineering, Indian Institute of Technology Gandhinagar, Palaj, Gandhinagar 382355, Gujarat, India.

Department of Mechanical Engineering, University College London (UCL), London WC1E 7JE, U.K.

出版信息

Langmuir. 2022 Aug 23;38(33):10288-10304. doi: 10.1021/acs.langmuir.2c01676. Epub 2022 Aug 9.

Abstract

Microbubbles are tiny gas-filled bubbles that have a variety of applications in ultrasound imaging and therapeutic drug delivery. Microbubbles can be synthesized using a number of techniques including sonication, amalgamation, and saline shaking. These approaches can produce highly concentrated microbubble suspensions but offer minimal control over the size and polydispersity of the microbubbles. One of the simplest and effective methods for producing monodisperse microbubbles is capillary-embedded T-junction microfluidic devices, which offer great control over the microbubble size. However, lower production rates (∼200 bubbles/s) and large microbubble sizes (∼300 μm) limit the applicability of such devices for biomedical applications. To overcome the limitations of these technologies, we demonstrate in this work an alternative approach to combine a capillary-embedded T-junction device with ultrasound to enhance the generation of narrow-sized microbubbles in aqueous suspensions. Two T-junction microfluidic devices were connected in parallel and combined with an ultrasonic horn to produce lipid-coated SF core microbubbles in the size range of 1-8 μm. The rate of microbubble production was found to increase from 180 microbubbles/s in the absence of ultrasound to (6.5 ± 1.2) × 10 bubble/s in the presence of ultrasound (100% ultrasound amplitude). When stored in a closed environment, the microbubbles were observed to be stable for up to 30 days, with the concentration of the microbubble suspension decreasing from ∼2.81 × 10/mL to ∼2.3 × 10/mL and the size changing from 1.73 ± 0.2 to 1.45 ± 0.3 μm at the end of 30 days. The acoustic response of these microbubbles was examined using broadband attenuation spectroscopy, and flow phantom imaging was performed to determine the ability of these microbubble suspensions to enhance the contrast relative to the surrounding tissue. Overall, this approach of coupling ultrasound with microfluidic parallelization enabled the continuous production of stable microbubbles at high production rates and low polydispersity using simple T-junction devices.

摘要

微泡是一种充满气体的微小气泡,在超声成像和治疗药物输送中有多种应用。微泡可以通过多种技术合成,包括超声处理、汞齐化和盐水摇动。这些方法可以产生高度浓缩的微泡悬浮液,但对微泡的大小和多分散性的控制能力有限。产生单分散微泡的最简单有效的方法之一是使用带有嵌入式毛细管的 T 型结微流控装置,该装置可以对微泡大小进行很好的控制。然而,较低的生产速度(约 200 个/秒)和较大的微泡尺寸(约 300μm)限制了此类设备在生物医学应用中的适用性。为了克服这些技术的局限性,我们在这项工作中展示了一种替代方法,即将带有嵌入式毛细管的 T 型结装置与超声相结合,以增强在水悬浮液中生成窄尺寸微泡的能力。两个 T 型结微流控装置并联连接,并与超声换能器结合,以在 1-8μm 的范围内产生包被脂质的 SF 核微泡。发现微泡的生成速度从无超声时的 180 个/秒增加到有超声时的(6.5±1.2)×10 个/秒(超声幅度为 100%)。当储存在封闭环境中时,微泡在长达 30 天的时间内观察到稳定,微泡悬浮液的浓度从约 2.81×10 个/ml 降低到 30 天后约 2.3×10 个/ml,并且尺寸从 1.73±0.2μm 变化到 1.45±0.3μm。使用宽带衰减光谱法对这些微泡的声响应进行了检查,并进行了流动体模成像,以确定这些微泡悬浮液相对于周围组织增强对比度的能力。总的来说,这种将超声与微流控并行化相结合的方法能够使用简单的 T 型结装置以高生产速度和低多分散性连续生产稳定的微泡。

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