Department of Mechanical Engineering, University of California, Berkeley, USA; Berkeley Sensor and Actuators Center, USA; Department of Biological Systems Engineering, Virginia Tech, USA; Hangzhou Institute of Advanced Transducing Technology, Wahaha R&D Academe, Hangzhou, China.
School of Optometry and Vision Science Program, University of California, Berkeley, USA; Department of Materials Science and Engineering, National Cheng Kung University, Tainan, Taiwan.
Biosens Bioelectron. 2020 Feb 15;150:111900. doi: 10.1016/j.bios.2019.111900. Epub 2019 Nov 16.
Isolation of circulating tumor cells (CTCs) from blood samples has important prognostic and therapeutic implications for cancer treatments, but the process is very challenging due to the low concentration of CTCs. In this study, we report a novel 3D printed microfluidic device functionalized with anti-EpCAM (epithelial cell adhesion molecule) antibodies to isolate CTCs from human blood samples. A 3D printing technology was utilized with specially designed interior structures to fabricate a microfluidic device with high surface area and fluid flow manipulation, increasing capture efficiency of tumor cells. These devices with the optimal flow rate (1 mL/h) and channel length (2 cm) were demonstrated to test three kinds of EpCAM positive cancer cell lines (MCF-7 breast cancer, SW480 colon cancer, and PC3 prostate cancer), and one kind of EpCAM negative cancer cell line (293T kidney cancer). Experimentally, the capture efficiency higher than 90% has been achieved, and the isolation of MCF-7 tumor cells from spiked human blood samples has also been demonstrated. Combined with DNA-based detection (e.g. polymerase chain reaction or DNA sequencing), the detection and analysis of released DNAs from captured tumor cells could be another future direction for clinical diagnosis and cancer treatment.
从血液样本中分离循环肿瘤细胞 (CTCs) 对癌症治疗具有重要的预后和治疗意义,但由于 CTCs 的浓度很低,因此该过程极具挑战性。在这项研究中,我们报告了一种新型的 3D 打印微流控装置,该装置用抗上皮细胞黏附分子 (EpCAM) 抗体功能化,用于从人血样中分离 CTCs。使用专门设计的内部结构的 3D 打印技术制造了一种具有高表面积和流体流动控制的微流控装置,提高了肿瘤细胞的捕获效率。这些具有最佳流速 (1 mL/h) 和通道长度 (2 cm) 的设备已被证明可用于测试三种 EpCAM 阳性癌细胞系 (乳腺癌 MCF-7、结肠癌 SW480 和前列腺癌 PC3) 和一种 EpCAM 阴性癌细胞系 (肾癌细胞 293T)。实验中,捕获效率高于 90%,并且已经证明可以从掺杂的人血样中分离 MCF-7 肿瘤细胞。结合基于 DNA 的检测(例如聚合酶链反应或 DNA 测序),从捕获的肿瘤细胞中释放的 DNA 的检测和分析可能是临床诊断和癌症治疗的另一个未来方向。