Peyman Sally A, McLaughlan James R, Abou-Saleh Radwa H, Marston Gemma, Johnson Benjamin R G, Freear Steven, Coletta P Louise, Markham Alexander F, Evans Stephen D
School of Physics and Astronomy, University of Leeds, LS2 9JT, UK.
Lab Chip. 2016 Feb 21;16(4):679-87. doi: 10.1039/c5lc01394a. Epub 2015 Dec 22.
Micron-sized lipid-stabilised bubbles of heavy gas have been utilised as contrast agents for diagnostic ultrasound (US) imaging for many years. Typically bubbles between 1 and 8 μm in diameter are produced to enhance imaging in US by scattering sound waves more efficiently than surrounding tissue. A potential area of interest for Contrast Enhanced Ultrasound (CEUS) are bubbles with diameters <1 μm or 'nanobubbles.' As bubble diameter decreases, ultrasonic resonant frequency increases, which could lead to an improvement in resolution for high-frequency imaging applications when using nanobubbles. In addition, current US contrast agents are limited by their size to the vasculature in vivo. However, molecular-targeted nanobubbles could penetrate into the extra-vascular space of cancerous tissue providing contrast in regions inaccessible to traditional microbubbles. This paper reports a new microfluidic method for the generation of sub-micron sized lipid stabilised particles containing perfluorocarbon (PFC). The nanoparticles are produced in a unique atomisation-like flow regime at high production rates, in excess of 10(6) particles per s and at high concentration, typically >10(11) particles per mL. The average particle diameter appears to be around 100-200 nm. These particles, suspected of being a mix of liquid and gaseous C4F10 due to Laplace pressure, then phase convert into nanometer sized bubbles on the application of US. In vitro ultrasound characterisation from these nanoparticle populations showed strong backscattering compared to aqueous filled liposomes of a similar size. The nanoparticles were stable upon injection and gave excellent contrast enhancement when used for in vivo imaging, compared to microbubbles with an equivalent shell composition.
微米级重气脂质稳定气泡作为诊断超声（US）成像的造影剂已被使用多年。通常会产生直径在1至8微米之间的气泡，通过比周围组织更有效地散射声波来增强超声成像。对比增强超声（CEUS）的一个潜在感兴趣领域是直径<1微米的气泡或“纳米气泡”。随着气泡直径减小，超声共振频率增加，这可能会在使用纳米气泡进行高频成像应用时提高分辨率。此外，目前的超声造影剂在体内受其大小限制只能进入脉管系统。然而，分子靶向纳米气泡可以渗透到癌组织的血管外空间，在传统微气泡无法到达的区域提供对比。本文报道了一种新的微流控方法，用于生成含有全氟化碳（PFC）的亚微米级脂质稳定颗粒。这些纳米颗粒以独特的类似雾化的流动方式以高生产率产生，每秒超过10^6个颗粒，且浓度很高，通常每毫升>10^11个颗粒。平均颗粒直径似乎在100 - 200纳米左右。由于拉普拉斯压力，这些颗粒被怀疑是液态和气态C4F10的混合物，然后在施加超声时相转变为纳米级气泡。与类似大小的水填充脂质体相比，这些纳米颗粒群体的体外超声表征显示出强烈的反向散射。与具有等效壳组成的微气泡相比，这些纳米颗粒在注射后稳定，用于体内成像时能提供出色的对比增强效果。
