Controlling fluid flow rate to separate leukocytes and cancer cells based on stiffness differences

IF 5.3 2区 化学 Q1 CHEMISTRY, ANALYTICAL
Gaolin Li, Huan Liu, Shiyu Wang, Enxia Mao, Xuye Zhuang
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Abstract

Microfluidic techniques for label-free sorting of circulating tumor cells (CTCs) from peripheral blood are generally based on physical characteristic differences between blood cells and cancer cells, especially size differences. However, because the diameter ranges of some leukocytes and CTCs overlap, size-based sorting can certainly be disturbed by leukocytes. This study proposes a microfluidic sorting strategy based on cell stiffness differences, which achieves efficient separation of cells with overlapping sizes by precisely controlling the fluid flow rate. A quantitative relationship model between critical inlet flow rate, cell diameter, and Young’s modulus was established based on the cell deformation effect, and its accuracy was verified through fluid dynamics simulation and experiments. The results showed that when the flow rate was between the critical flow rates of leukocytes and CTCs, high-stiffness leukocytes could be captured by the slit, while low-stiffness CTCs passed smoothly, with a separation resolution of 0.3 µm. This method can serve as a supplement to existing size-based sorting techniques, significantly improving the purity of CTCs.

Graphical Abstract

根据硬度差异控制流体流速以分离白细胞和癌细胞
用于外周血循环肿瘤细胞(CTCs)无标记分选的微流控技术通常基于血细胞和癌细胞之间的物理特性差异,特别是大小差异。然而,由于一些白细胞和CTCs的直径范围重叠,基于大小的分选肯定会受到白细胞的干扰。本研究提出了一种基于细胞刚度差异的微流体分选策略,通过精确控制流体流速,实现对大小重叠的细胞的高效分离。基于胞体变形效应,建立了临界进口流量、胞体直径与杨氏模量之间的定量关系模型,并通过流体动力学仿真和实验验证了模型的准确性。结果表明,当流速在白细胞和CTCs的临界流速之间时,高刚度的白细胞可以被狭缝捕获,而低刚度的CTCs则可以顺利通过,分离分辨率为0.3µm。该方法可以作为现有基于粒度的分选技术的补充,显著提高ctc的纯度。图形抽象
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来源期刊
Microchimica Acta
Microchimica Acta 化学-分析化学
CiteScore
9.80
自引率
5.30%
发文量
410
审稿时长
2.7 months
期刊介绍: As a peer-reviewed journal for analytical sciences and technologies on the micro- and nanoscale, Microchimica Acta has established itself as a premier forum for truly novel approaches in chemical and biochemical analysis. Coverage includes methods and devices that provide expedient solutions to the most contemporary demands in this area. Examples are point-of-care technologies, wearable (bio)sensors, in-vivo-monitoring, micro/nanomotors and materials based on synthetic biology as well as biomedical imaging and targeting.
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