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具有凹截面的螺旋微通道用于增强癌细胞的惯性分离。

Spiral microchannels with concave cross-section for enhanced cancer cell inertial separation.

机构信息

College of Mechanical and Electrical Engineering, Hohai University, Changzhou, 213200, China.

Department of Chemistry, School of Science, Tokyo Institute of Technology, Tokyo, 152-8550, Japan.

出版信息

Mikrochim Acta. 2024 Sep 30;191(10):634. doi: 10.1007/s00604-024-06724-3.

DOI:10.1007/s00604-024-06724-3
PMID:39347843
Abstract

Inertial microfluidic technologies have proven effective for particle focusing and separation in many microchannels, typically the channels with the rectangular and trapezoidal shapes. To advance particle focusing in complex channels, we propose a spiral channel combining rectangular and concave cross-sections for high-resolution particle and cell focusing and separation. Numerical simulations were conducted to illustrate the effects of channel geometry on secondary flow distribution and particle focusing positions. The simulation shows the concave cross-section generates two asymmetrical Dean vortices skewing towards the inner and outer channel walls, resulting to stronger flow velocity magnitudes near the walls than the channel center. Consequently, larger particles focus near the inner wall, while smaller particles are trapped closer to the outer wall under the influence of the stronger velocity magnitude near the walls. A microfluidic chip with the proposed channel geometry, along with a traditional rectangular channel, was fabricated by 3D printing and PDMS casting. Fluorescent microbeads were used to investigate inertial focusing and separation behaviors in the microfluidic chips. Experimental results show that the concave channel facilitates particle focusing or trapping much closer to the walls than the traditional rectangular channel, achieving better separation resolution. Finally, the proposed channel was applied to separate lung cancer A549 cells from human blood, achieving a cancer cell recovery rate of ~ 84.78% (enrichment ratio over 820-fold) and a blood cell rejection rate of ~ 99.88%. This innovative channel design in inertial microfluidics offers new insights for enhanced particle focusing and holds significant promise for cell manipulation with improved separation resolution.

摘要

惯性微流控技术已被证明在许多微通道中,尤其是矩形和梯形通道中,对颗粒聚焦和分离非常有效。为了在复杂通道中推进颗粒聚焦,我们提出了一种结合矩形和凹形横截面的螺旋通道,用于实现高分辨率的颗粒和细胞聚焦和分离。进行了数值模拟,以说明通道几何形状对二次流分布和颗粒聚焦位置的影响。模拟表明,凹形横截面会产生两个不对称的Dean 涡旋,向通道的内、外壁倾斜,导致靠近壁面的流速比通道中心的流速更大。因此,较大的颗粒在靠近内壁的位置聚焦,而较小的颗粒在靠近外壁的位置被捕获,这是由于靠近壁面的流速较大的影响。使用 3D 打印和 PDMS 铸造技术制造了具有所提出通道几何形状的微流控芯片,以及传统的矩形通道。使用荧光微球研究了在微流控芯片中的惯性聚焦和分离行为。实验结果表明,凹形通道比传统的矩形通道更有利于颗粒聚焦或捕获靠近壁面的位置,从而实现更好的分离分辨率。最后,将所提出的通道应用于从人血中分离肺癌 A549 细胞,实现了约 84.78%的癌细胞回收率(富集倍数超过 820 倍)和约 99.88%的血细胞拒绝率。这种惯性微流控中的创新通道设计为增强颗粒聚焦提供了新的思路,并为提高分离分辨率的细胞操作提供了很大的前景。

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本文引用的文献

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Elasto-inertial focusing and particle migration in high aspect ratio microchannels for high-throughput separation.用于高通量分离的高纵横比微通道中的弹性惯性聚焦和颗粒迁移。
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High-throughput and simultaneous inertial separation of tumor cells and clusters from malignant effusions using spiral-contraction-expansion channels.使用螺旋收缩-扩张通道从恶性积液中高通量同步惯性分离肿瘤细胞和细胞团。
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从未经治疗的恶性胸腔和腹腔积液中对恶性肿瘤细胞进行级联弹性惯性分离。
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A curved expansion-contraction microfluidic structure for inertial based separation of circulating tumor cells from blood samples.一种基于弯曲伸缩的微流控结构,用于从血液样本中基于惯性的分离循环肿瘤细胞。
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Advancements and Limitations in 3D Printing Materials and Technologies: A Critical Review.3D打印材料与技术的进展与局限:批判性综述
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New Generation Dielectrophoretic-Based Microfluidic Device for Multi-Type Cell Separation.新一代基于电润湿的微流控芯片用于多类型细胞分离
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Novel size-based design of spiral microfluidic devices with elliptic configurations and trapezoidal cross-section for ultra-fast isolation of circulating tumor cells.用于超快速分离循环肿瘤细胞的具有椭圆形结构和梯形横截面的基于尺寸的新型螺旋微流控装置设计。
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Tuning particle inertial separation in sinusoidal channels by embedding periodic obstacle microstructures.通过嵌入周期性障碍物微结构来调节正弦通道中的粒子惯性分离
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