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通过基于介电电泳的收缩-扩张惯性微流控通道进行连续循环肿瘤细胞分离

Continuous CTC separation through a DEP-based contraction-expansion inertial microfluidic channel.

作者信息

Islam Md Sadiqul, Chen Xiaolin

机构信息

School of Engineering and Computer Science, Washington State University, 14204 NE Salmon Creek Ave, Vancouver, Washington, 98686, USA.

出版信息

Biotechnol Prog. 2023 Jul-Aug;39(4):e3341. doi: 10.1002/btpr.3341. Epub 2023 Mar 27.

Abstract

The efficient isolation of viable and intact circulating tumor cells (CTCs) from blood is critical for the genetic analysis of cancer cells, prediction of cancer progression, development of drugs, and evaluation of therapeutic treatments. While conventional cell separation devices utilize the size difference between CTCs and other blood cells, they fail to separate CTCs from white blood cells (WBCs) due to significant size overlap. To overcome this issue, we present a novel approach that combines curved contraction-expansion (CE) channels with dielectrophoresis (DEP) and inertial microfluidics to isolate CTCs from WBCs regardless of size overlap. This label-free and continuous separation method utilizes dielectric properties and size variation of cells for the separation of CTCs from WBCs. The results demonstrate that the proposed hybrid microfluidic channel can effectively isolate A549 CTCs from WBCs regardless of their size with a throughput of 300 μL/min, achieving a high separation distance of 233.4 μm at an applied voltage of 50 V . The proposed method allows for the modification of cell migration characteristics by controlling the number of CE sections of the channel, applied voltage, applied frequency, and flow rate. With its unique features of a single-stage separation, simple design, and tunability, the proposed method provides a promising alternative to the existing label-free cell separation techniques and may have a wide range of applications in biomedicine.

摘要

从血液中有效分离出有活力且完整的循环肿瘤细胞(CTC)对于癌细胞的基因分析、癌症进展预测、药物研发以及治疗效果评估至关重要。传统的细胞分离装置利用CTC与其他血细胞之间的大小差异,但由于大小存在显著重叠,它们无法将CTC与白细胞(WBC)分离。为克服这一问题,我们提出了一种新颖的方法,该方法将弯曲的收缩 - 扩张(CE)通道与介电电泳(DEP)和惯性微流体相结合,以实现无论大小重叠与否都能从WBC中分离出CTC。这种无标记且连续的分离方法利用细胞的介电特性和大小差异来从WBC中分离CTC。结果表明,所提出的混合微流体通道能够以300 μL/min的通量有效分离出A549 CTC与WBC,在50 V的施加电压下实现233.4 μm的高分离距离。所提出的方法可通过控制通道的CE段数量、施加电压、施加频率和流速来改变细胞迁移特性。凭借其单级分离、设计简单和可调节性的独特特点,该方法为现有的无标记细胞分离技术提供了一种有前景的替代方案,并且可能在生物医学中有广泛的应用。

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