Design and Clinical Application of an Integrated Microfluidic Device for Circulating Tumor Cells Isolation and...

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.