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尺寸可调的微涡旋捕获稀有细胞。

Size-tunable microvortex capture of rare cells.

机构信息

Department of Bioengineering and University of California, Los Angeles, CA 90055, USA.

出版信息

Lab Chip. 2017 Jul 25;17(15):2542-2549. doi: 10.1039/c7lc00355b.

DOI:10.1039/c7lc00355b
PMID:28613306
Abstract

Inertial separation of particles and cells based on their size has advanced significantly over the last decade. However, size-based inertial separation methods require precise tuning of microfluidic device geometries to adjust the separation size of particles or cells. Here, we show a passive capture method that targets a wide size range of cells by controlling the flow conditions in a single device geometry. This multimodal capture device is designed to generate laminar vortices in lateral cavities that branch from long rectangular channels. Micro-vortices generated at lower Reynolds numbers capture and stabilize large particles in equilibrium orbits or limit cycles near the vortex core. Other smaller particles or cells orbit near the vortex boundaries and they are susceptible to exiting the cavity flow. In the same cavity, however, at higher Reynolds number, we observe small particles migrating inward. This evolution in limit cycle trajectories led to a corresponding evolution in the average size of captured particles, indicating that the outermost orbits are less stable. We identify three phases of capture as a function of Reynolds number that give rise to unique particle orbit trajectories. Flow-based switching overcomes a major engineering challenge to automate capture and release of polydisperse cell subpopulations. The approach can expand clinical applications of label free trapping in isolating and processing a larger subset of rare cells like circulating tumor cells (CTCs) from blood and other body fluids.

摘要

基于颗粒和细胞大小的惯性分离技术在过去十年中取得了显著进展。然而,基于大小的惯性分离方法需要精确调整微流控器件的几何形状,以调整颗粒或细胞的分离大小。在这里,我们展示了一种被动捕获方法,通过控制单个器件几何形状中的流动条件,针对广泛的细胞大小范围进行目标捕获。这种多模态捕获器件旨在在从长矩形通道分支的横向腔中产生层流涡流。在较低雷诺数下产生的微涡流捕获并稳定大颗粒处于平衡轨道或涡核附近的极限环中。其他较小的颗粒或细胞在涡边界附近盘旋,容易离开腔流。然而,在同一腔中,在较高的雷诺数下,我们观察到小颗粒向内迁移。这种极限环轨迹的演变导致捕获颗粒的平均尺寸相应变化,表明最外层轨道不太稳定。我们确定了作为雷诺数函数的三个捕获阶段,这些阶段产生了独特的颗粒轨道轨迹。基于流动的切换克服了一个主要的工程挑战,即实现了对多分散细胞亚群的自动捕获和释放。该方法可以扩展无标记捕获在从血液和其他体液中分离和处理更大比例的稀有细胞(如循环肿瘤细胞(CTC))的临床应用。

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