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

Micromachines

Wenwen Liu¹  Kun Zou²  Song Wei³  Encheng Li³  Qi Wang³  Mingxin Xu³  Xinri Zhang⁴ 

[1] Cancer Translational Medicine Research Center, The Second Hospital Affiliated to Dalian Medical University, No. 467 Zhongshan Road, Dalian 116023, China;Department of Radiation Oncology, The First Hospital Affiliated to Dalian Medical University, No. 222 Zhongshan Road, Dalian 116011, China;Department of Respiratory Medicine, The Second Hospital Affiliated to Dalian Medical University, No. 467 Zhongshan Road, Dalian 116023, China;Department of Respiratory and Critical Care Medicine, The First Hospital, Shanxi Medical University, No. 85 Jiefang South Road, Taiyuan 030001, China;

关键词: CTC-isolation;    microfluidics;    single-cell analysis;    high-throughput sequencing;    lung cancer;   

DOI  :  10.3390/mi12010049

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown