Özkayar Gürhan, Mutlu Ege, Şahin Şebnem, Demircan Yalçın Yağmur Demircan, Töral Taylan, Külah Haluk, Yıldırım Ender, Zorlu Özge, Özgür Ebru
Mikro Biyosistemler A.Ş., ODTÜ Teknokent MET Yerleskesi, No:280/B/10, 06530 Ankara, Turkey.
Department of Electrical and Electronics Engineering, Middle East Technical University (METU), 06530 Ankara, Turkey.
Micromachines (Basel). 2020 Oct 30;11(11):981. doi: 10.3390/mi11110981.
Being one of the major pillars of liquid biopsy, isolation and characterization of circulating tumor cells (CTCs) during cancer management provides critical information on the evolution of cancer and has great potential to increase the success of therapies. In this article, we define a novel strategy to effectively enrich CTCs from whole blood based on size, utilizing a spiral microfluidic channel embedded with a hydrofoil structure at the downstream of the spiral channel. The hydrofoil increases the distance between the streams of CTCs and peripheral blood cells, which are already distributed about two focal axes by the spiral channel, thereby improving the resolution of the separation. Analytical validation of the system has been carried out using Michigan Cancer Foundation-7 (MCF7) breast cancer cell lines spiked into blood samples from healthy donors, and the performance of the system in terms of white blood cell (WBC) depletion, CTC recovery rate and cell viability has been shown in single or two-step process: by passing the sample once or twice through the microfluidic chip. Single step process yielded high recovery (77.1%), viable (84.7%) CTCs. When the collected cell suspension is re-processed by the same chip, recovery decreases to 65.5%, while the WBC depletion increases to 88.3%, improving the purity. Cell viability of >80% was preserved after two-step process. The novel microfluidic chip is a good candidate for CTC isolation applications requiring high recovery rate and viability, including functional downstream analyses for variety of cancer types.
作为液体活检的主要支柱之一,在癌症管理过程中循环肿瘤细胞(CTC)的分离和表征提供了有关癌症演变的关键信息,并具有极大的潜力来提高治疗的成功率。在本文中,我们定义了一种基于尺寸从全血中有效富集CTC的新策略,利用在螺旋通道下游嵌入水翼结构的螺旋微流控通道。水翼增加了CTC流与外周血细胞流之间的距离,而外周血细胞已经由螺旋通道围绕两个焦轴分布,从而提高了分离分辨率。使用掺入健康供体血样中的密歇根癌症基金会-7(MCF7)乳腺癌细胞系对该系统进行了分析验证,并且该系统在白细胞(WBC)去除、CTC回收率和细胞活力方面的性能已在单步或两步过程中得到展示:使样品一次或两次通过微流控芯片。单步过程产生了高回收率(77.1%)、有活力(84.7%)的CTC。当收集的细胞悬液通过同一芯片重新处理时,回收率降至65.5%,而白细胞去除率增加到88.3%,提高了纯度。两步过程后细胞活力保持在80%以上。这种新型微流控芯片是CTC分离应用的良好候选者,这些应用需要高回收率和活力,包括对多种癌症类型的功能性下游分析。