Design and Clinical Application of an Integrated Microfluidic Device for Circulating Tumor Cells Isolation and Single-Cell Analysis

• Main Authors: Mingxin Xu, Wenwen Liu, Kun Zou, Song Wei, Xinri Zhang, Encheng Li, Qi Wang
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: Micromachines
• Subjects: CTC-isolation; microfluidics; single-cell analysis; high-throughput sequencing; lung cancer
• Online Access: https://www.mdpi.com/2072-666X/12/1/49

Circulating tumor cells (CTCs) have been considered as an alternative to tissue biopsy for providing both germline-specific and tumor-derived genetic variations. Single-cell analysis of CTCs enables in-depth investigation of tumor heterogeneity and individualized clinical assessment. However, common CTC enrichment techniques generally have limitations of low throughput and cell damage. Herein, based on micropore-arrayed filtration membrane and microfluidic chip, we established an integrated CTC isolation platform with high-throughput, high-efficiency, and less cell damage. We observed a capture rate of around 85% and a purity of 60.4% by spiking tumor cells (PC-9) into healthy blood samples. Detection of CTCs from lung cancer patients demonstrated a positive detectable rate of 87.5%. Additionally, single CTCs, ctDNA and liver biopsy tissue of a representative advanced lung cancer patient were collected and sequenced, which revealed comprehensive genetic information of CTCs while reflected the differences in genetic profiles between different biological samples. This work provides a promising tool for CTCs isolation and further analysis at single-cell resolution with potential clinical value.