BioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114.
Proc Natl Acad Sci U S A. 2018 Jul 24;115(30):7682-7687. doi: 10.1073/pnas.1721420115. Epub 2018 Jul 10.
Inertial microfluidics (i.e., migration and focusing of particles in finite Reynolds number microchannel flows) is a passive, precise, and high-throughput method for microparticle manipulation and sorting. Therefore, it has been utilized in numerous biomedical applications including phenotypic cell screening, blood fractionation, and rare-cell isolation. Nonetheless, the applications of this technology have been limited to larger bioparticles such as blood cells, circulating tumor cells, and stem cells, because smaller particles require drastically longer channels for inertial focusing, which increases the pressure requirement and the footprint of the device to the extent that the system becomes unfeasible. Inertial manipulation of smaller bioparticles such as fungi, bacteria, viruses, and other pathogens or blood components such as platelets and exosomes is of significant interest. Here, we show that using oscillatory microfluidics, inertial focusing in practically "infinite channels" can be achieved, allowing for focusing of micron-scale (i.e. hundreds of nanometers) particles. This method enables manipulation of particles at extremely low particle Reynolds number ( < 0.005) flows that are otherwise unattainable by steady-flow inertial microfluidics (which has been limited to > ∼10). Using this technique, we demonstrated that synthetic particles as small as 500 nm and a submicron bacterium, , can be inertially focused. Furthermore, we characterized the physics of inertial microfluidics in this newly enabled particle size and range using a Peclet-like dimensionless number (). We experimentally observed that >> 1 is required to overcome diffusion and be able to inertially manipulate particles.
惯性微流控(即在有限雷诺数微通道流中颗粒的迁移和聚焦)是一种被动、精确和高通量的微颗粒操纵和分选方法。因此,它已被应用于许多生物医学应用,包括表型细胞筛选、血液成分分离和稀有细胞分离。尽管如此,这项技术的应用仅限于较大的生物颗粒,如血细胞、循环肿瘤细胞和干细胞,因为较小的颗粒需要更长的惯性聚焦通道,这会增加压力要求和设备的占地面积,以至于系统变得不可行。较小的生物颗粒(如真菌、细菌、病毒和其他病原体或血小板和外泌体等血液成分)的惯性操纵具有重要意义。在这里,我们展示了使用振荡微流控技术,可以实现实际上“无限通道”中的惯性聚焦,从而实现微米级(即数百纳米)颗粒的聚焦。这种方法能够在极低的颗粒雷诺数(<0.005)下操纵颗粒,而稳态惯性微流控(其限制在>∼10)无法实现这一点。使用这种技术,我们证明了即使是 500nm 大小的合成颗粒和亚微米大小的细菌 也可以实现惯性聚焦。此外,我们使用类似于 Peclet 的无量纲数()来描述这种新方法在可实现的颗粒尺寸和范围内的惯性微流控物理特性。我们通过实验观察到,需要 >> 1 才能克服扩散并能够惯性地操纵颗粒。