Poly(ethylene oxide) Concentration Gradient-Based Microfluidic Isolation of Circulating Tumor Cells

作者：Yangchang Cheng, Shaohua Zhang, Lili Qin, Junxiang Zhao, Hua Song, Yang Yuan, Jiashu Sun, Fei Tian, Chao Liu · 发表于：Analytical Chemistry · 年份：2023 · DOI：10.1021/acs.analchem.2c05257 · 被引用次数：41 · 研究领域：Microfluidic and Bio-sensing Technologies、Cancer Cells and Metastasis、3D Printing in Biomedical Research

Circulating tumor cells (CTCs) have emerged as promising circulating biomarkers for non-invasive cancer diagnosis and management. Isolation and detection of CTCs in clinical samples are challenging due to the extreme rarity and high heterogeneity of CTCs. Here, we describe a poly(ethylene oxide) (PEO) concentration gradient-based microfluidic method for rapid, label-free, highly efficient isolation of CTCs directly from whole blood samples. Stable concentration gradients of PEO were formed within the microchannel by co-injecting the side fluid (blood sample spiked with 0.025% PEO) and center fluid (0.075% PEO solution). The competition between the elastic lift force and the inertial lift force enabled size-based separation of large CTCs and small blood cells based on their distinct migration patterns. The microfluidic device could process 1 mL of blood sample in 30 min, with a separation efficiency of >90% and an enrichment ratio of >700 for tumor cells. The isolated CTCs from blood samples were enumerated by immunofluorescence staining, allowing for discrimination of breast cancer patients from healthy donors with an accuracy of 84.2%. The concentration gradient-based microfluidic separation provides a powerful tool for label-free isolation of CTCs for a wide range of clinical applications.