Simultaneous on-chip isolation and characterization of circulating tumor cell sub-populations

The diagnosis of tumor metastasis using circulating tumor cells (CTCs) has been considered an important developmental target for several decades but remains a formidable challenge because of the rarity and heterogeneity of CTCs. Additional downstream analysis is required after isolating CTCs on-chip for subtype verification. To solve those problems, we have developed microfluidic based integrated system which uses magnetic field gradient and immune-fluorescence differences to on-chip isolation and discrimination of CTCs simultaneously. The system presented in the present study can isolate CTCs with an efficiency of >99% by utilizing magnetic nanoparticles conjugated to CTC membranes. Furthermore, the statuses of three biomarkers can be determined on-chip simultaneously. The devised microfluidic system can differentiate eight different subtypes of heterogenic CTCs by on-chip isolation and based on the statuses of three biomarkers (HER2, ER, and PR) which are critical variables to five-year overall survivals for breast cancer patients.