High-Throughput, Label-Free Isolation of Cancer Stem Cells on the Basis of Cell Adhesion Capacity

Herein we report a microfluidics method that enriches cancer stem cells (CSCs) or tumor-initiating cells on the basis of cell adhesion properties. In our on-chip enrichment system, cancer cells were driven by hydrodynamic forces to flow through microchannels coated with basement membrane extract. Highly adhesive cells were captured by the functionalized microchannels, and less adhesive cells were collected from the outlets. Two heterogeneous breast cancer cell lines (SUM-149 and SUM-159) were successfully separated into enriched subpopulations according to their adhesive capacity, and the enrichment of the cancer stem cells was confirmed by flow cytometry biomarker analysis and tumor-formation assays. Our findings show that the less adhesive phenotype is associated with a higher percentage of CSCs, higher cancer-cell motility, and higher resistance to chemotherapeutic drugs.