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基于可调剪切速率共流微通道的粘性血液中 CTC 的直接分离和计数:原理验证研究。

Direct separation and enumeration of CTCs in viscous blood based on co-flow microchannel with tunable shear rate: a proof-of-principle study.

机构信息

Key Laboratory of Optoelectronic Technology and Systems, Ministry of Education & Key Disciplines Laboratory of Novel Micro-Nano Devices and System Technology, College of Optoelectronic Engineering, Chongqing University, Chongqing, 400044, China.

International R & D center of Micro-nano Systems and New Materials Technology, Chongqing University, Chongqing, 400044, China.

出版信息

Anal Bioanal Chem. 2022 Nov;414(26):7683-7694. doi: 10.1007/s00216-022-04299-7. Epub 2022 Sep 1.

DOI:10.1007/s00216-022-04299-7
PMID:36048191
Abstract

Circulating tumor cells (CTCs), which have extremely low density in whole blood, are an important indicator of primary tumor metastasis. Isolation and enumeration of these cells are critical for clinical applications. Separation of CTCs from massive blood cells without labeling and addition of synthetic polymers is challenging. Herein, a novel well-defined co-flow microfluidic device is presented and used to separate CTCs in viscous blood by applying both inertial and viscoelastic forces. Diluted blood without any synthetic polymer and buffer solution were used as viscoelastic fluid and Newtonian fluid, respectively, and they were co-flowed in the designed chip to form a sheath flow. The co-flow system provides the function of particle pre-focusing and creates a tunable shear rate region at the interface to adjust the migration of particles or cells from the sample solution to the buffer solution. Successful separation of CTCs from viscous blood was demonstrated and enumeration was also conducted by image recognition after separation. The statistical results indicated that a recovery rate of cancer cells greater than 87% was obtained using the developed method, which proved that the direct separation of CTCs from diluted blood can be achieved without the addition of any synthetic polymer to prepare viscoelastic fluid. This method holds great promise for the separation of cells in viscous biological fluid without either complicated channel structures or the addition of synthetic polymers.

摘要

循环肿瘤细胞(CTCs)在全血中的密度极低,是原发性肿瘤转移的一个重要指标。这些细胞的分离和计数对临床应用至关重要。在不进行标记和添加合成聚合物的情况下,从大量血细胞中分离 CTCs 具有挑战性。本文提出了一种新颖的、定义明确的共流微流控装置,并将其用于通过施加惯性力和粘弹性力来分离粘性血液中的 CTCs。稀释的血液和缓冲溶液分别用作粘弹性流体和牛顿流体,并在设计的芯片中共流以形成鞘流。共流系统提供了颗粒预聚焦的功能,并在界面处创建了一个可调剪切速率区域,以调节颗粒或细胞从样品溶液向缓冲溶液的迁移。成功地从粘性血液中分离出 CTCs,并在分离后通过图像识别进行了计数。统计结果表明,使用开发的方法可以获得大于 87%的癌细胞回收率,这证明了可以在不添加任何合成聚合物来制备粘弹性流体的情况下,直接从稀释血液中分离 CTCs。该方法有望用于分离粘性生物流体中的细胞,而无需复杂的通道结构或添加合成聚合物。

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Viscoelastic microfluidics: progress and challenges.粘弹性微流体学:进展与挑战
Microsyst Nanoeng. 2020 Dec 14;6:113. doi: 10.1038/s41378-020-00218-x. eCollection 2020.
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Cascaded contraction-expansion channels for bacteria separation from RBCs using viscoelastic microfluidics.用于通过粘弹性微流控技术从红细胞中分离细菌的级联收缩-扩张通道。
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Circulating Tumor Cell and Metabolites as Novel Biomarkers for Early-Stage Lung Cancer Diagnosis.
循环肿瘤细胞和代谢物作为早期肺癌诊断的新型生物标志物
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