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Design of a microfluidic device for immunoaffinity-based isolation of circulating tumor cells with minimal clogging
Sensors and Actuators Reports Pub Date : 2023-07-13 , DOI: 10.1016/j.snr.2023.100169
Begum Sen-Dogan , Ender Yildirim , Sebnem Sahin , Ebru Ozgur , Ozge Zorlu , Haluk Kulah

Combining bioaffinity-based techniques with microfluidics is an effective strategy for the selective isolation of rare circulating tumor cells (CTCs) among peripheral blood cells. In this scope, designing a microfluidic channel with high cell-surface interaction is crucial, which can be realized by increasing surface area via micropillars. In such microfluidic channels, the interpillar distance represents a critical design parameter, and the value is decided considering the trade-off between the possibility of clogging and CTC capture efficiency. In this study, a curvilinear microfluidic channel with a wide (150 µm) interpillar distance was developed to prevent clogging while maintaining high CTC capture efficiency. Computational fluid dynamics was used to compare the residence time of particles in the designed channels. For the proof-of-concept study, microfabricated channels were biofunctionalized for immunoaffinity-based isolation of CTCs, using anti-EpCAM antibodies. Enhanced CTC capture was enabled through the micropillars inside the channels helping the increased encounters between the cells and the antibody-functionalized surface. The curvilinear channel effectively isolated cells from MCF-7 breast cancer cell line among white blood cells, with more than 85% capture efficiency. The rate of non-specific binding of white blood cells remained below 20%. This study demonstrated the ability to increase the interactions between particles and surfaces without requiring a dense layout of the micropillars inside the microchannel, therefore minimizing the clogging possibility of the channel without sacrificing performance.



中文翻译:

设计一种微流体装置,用于基于免疫亲和力的循环肿瘤细胞分离,且堵塞最少

将基于生物亲和力的技术与微流体相结合是选择性分离外周血细胞中稀有循环肿瘤细胞(CTC)的有效策略。在此范围内,设计具有高细胞表面相互作用的微流体通道至关重要,这可以通过增加表面积来实现微柱。在这种微流体通道中,柱间距离是一个关键的设计参数,其值是在考虑堵塞可能性和CTC捕获效率之间的权衡后确定的。在本研究中,开发了一种具有较宽 (150 µm) 柱间距离的曲线微流体通道,以防止堵塞,同时保持高 CTC 捕获效率。使用计算流体动力学来比较颗粒在设计通道中的停留时间。在概念验证研究中,使用抗 EpCAM 抗体对微加工通道进行生物功能化,以基于免疫亲和力分离 CTC。通道内的微柱增强了 CTC 捕获,有助于增加细胞与抗体功能化表面之间的接触。曲线通道有效分离白细胞中MCF-7乳腺癌细胞系的细胞,捕获效率超过85%。白细胞非特异性结合率保持在20%以下。这项研究证明了增强颗粒和表面之间相互作用的能力,而不需要在微通道内密集布局微柱,从而在不牺牲性能的情况下最大限度地减少通道的堵塞可能性。

更新日期:2023-07-13
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