Lu Qing, Guo Feng, Zhang Zhinan, Ding Xianting
State Key Laboratory of Mechanical System and Vibration, Shanghai Jiao Tong University, Shanghai, 200240, China.
Department of Plastic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200025, China.
Biosens Bioelectron. 2025 Jun 15;278:117359. doi: 10.1016/j.bios.2025.117359. Epub 2025 Mar 11.
Circulating tumor cells (CTCs) are rare cells detaching from metastasis or primary tumor and flowing into bloodstream, which has been a promising biomarker for non-invasive cancer monitoring and diagnosis. Although CTC separating techniques have been widely reported, few platforms practically realize high-throughput and precise isolation of multiple types of CTCs directly from undiluted human blood due to complex flow behavior and interference from high concentration of blood cells. Herein, we present a rapid and label-free cascaded viscoelastic microfluidics (CVEM) composed of blood cells depletion module (BCDM) and CTCs isolation module (CIM). BCDM is used to filter out blood cells from samples, and remaining two types of CTCs (A549 and MCF-7) are isolated in CIM. To systematically reveal the separation mechanism, particle trajectory prediction model including criterion of crossing interface and particle dynamics equation is constructed, and the theoretical results are verified by polystyrene (PS) particle separation experiments. Further, the performance of CVEM is tested with four PS particles mixture solution and human blood spiked with A549 and MCF-7, respectively. 1 mL undiluted blood can be processed within 40 min, and both types of CTCs have high purity (≥81.27%) and recovery rate (≥82.15%). CVEM represents a powerful platform for sorting multiple types of CTCs from directly collected blood, demonstrating significant clinical application potential. Furthermore, particle trajectory prediction model provides a solid theoretical basis for optimizing viscoelastic microfluidics (VEM), and permits rapid iterative design according to different separating requirements, thereby realizing the flexible extension of VEM to other fields.
循环肿瘤细胞（CTCs）是从转移灶或原发肿瘤脱离并流入血液循环的稀有细胞，它已成为一种用于非侵入性癌症监测和诊断的有前景的生物标志物。尽管CTCs分离技术已被广泛报道，但由于复杂的流动行为和高浓度血细胞的干扰，很少有平台能够实际实现从未稀释的人体血液中直接高通量、精确地分离多种类型的CTCs。在此，我们提出了一种由血细胞去除模块（BCDM）和CTCs分离模块（CIM）组成的快速、无标记的级联粘弹性微流控系统（CVEM）。BCDM用于从样品中滤出血细胞，剩余的两种类型的CTCs（A549和MCF - 7）在CIM中被分离。为了系统地揭示分离机制，构建了包括穿越界面准则和粒子动力学方程的粒子轨迹预测模型，并通过聚苯乙烯（PS）粒子分离实验验证了理论结果。此外，分别用四种PS粒子混合溶液和添加了A549和MCF - 7的人体血液对CVEM的性能进行了测试。1 mL未稀释血液可在40分钟内处理完毕，两种类型的CTCs均具有高纯度（≥81.27%）和回收率（≥82.15%）。CVEM是一个从直接采集的血液中分选多种类型CTCs的强大平台，具有显著的临床应用潜力。此外，粒子轨迹预测模型为优化粘弹性微流控系统（VEM）提供了坚实的理论基础，并允许根据不同的分离要求进行快速迭代设计，从而实现VEM在其他领域的灵活扩展。
