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从全血中高回收率分选癌细胞的周期性聚焦惯性微流控芯片

High-recovery sorting of cancer cells from whole blood periodic-focusing inertial microchip.

机构信息

Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX, 79409, USA.

出版信息

Analyst. 2022 Oct 10;147(20):4536-4546. doi: 10.1039/d2an01310j.

Abstract

Inertial microfluidic devices continue to show promise for label-free separation of cells from liquid biopsies and other biological samples. Serpentine-channel microfluidic devices capitalizing on inertial forces such as Dean flow have been demonstrated for cell separation, but are limited in performance due to the magnitude of the inertial lift and drag force gradients across the separation channel. We have developed a new flow design that uses periodic channel contractions to enhance the magnitude of the force gradient. Separation recover was 97% with the final sorter output consisting of 78% target cells. Separation efficiency was 87% for whole blood, which could be increased to 97% if the sample was diluted prior to sorting. The enrichment of cancer cells was over 1000-fold, and sorted cancer cells maintained a viability of 93.8% for 96 hours after sorting. In the analysis of blood plasma, breast cancer cells from a clinical patient were enriched 20×. The incorporation of periodic channel contractions in a Dean flow circuit resulted in an increase in Dean flow gradient according to simulation, resulting in sorting of small-diameter cancer cells in blood samples.

摘要

惯性微流控装置在从液体活检和其他生物样本中无标记分离细胞方面继续显示出前景。利用惯性力(如迪恩流)的蛇形通道微流控装置已被证明可用于细胞分离,但由于分离通道内惯性升力和阻力梯度的幅度,其性能受到限制。我们开发了一种新的流动设计,使用周期性的通道收缩来增强力梯度的幅度。最终分拣器的分离回收率为 97%,输出的目标细胞占 78%。全血的分离效率为 87%,如果在分拣前稀释样本,分离效率可提高到 97%。癌细胞的富集超过 1000 倍,分拣后的癌细胞在分拣后 96 小时内保持 93.8%的活力。在对血浆的分析中,从临床患者中分离出的乳腺癌细胞富集了 20 倍。根据模拟,在迪恩流回路中加入周期性的通道收缩,导致迪恩流梯度增加,从而在血液样本中分拣出小直径的癌细胞。

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