An integrated microfluidic chip for one-step isolation of circulating tumor cells

Abstract

The presence of circulating tumor cells (CTCs) in blood of cancer patients is thought to be an important indicator of disease progression and survival. Due to the rarity of CTCs in the bloodstream, CTCs must be enriched for molecular and cellular analyses for clinical use. Current CTC detection methods mostly rely on epithelial cell adhesion molecule (EpCAM); however, these methods may underestimate CTC number and potentially miss a critical subpopulation because of large heterogeneity among CTCs. We describe an integrated microfluidic chip, termed the μ-MixMACS chip, that can negatively exclude background cells from a CTC population. It comprises a micromixer that generates multivortexing flows to enhance mixing, which increasing binding between white blood cells and magnetic nanoparticles coated CD45 antibody, and a magnetic sorter to remove magnet-coated cells and minimize interference from white blood cells during subsequent CTC analysis. As all processes were carried out continuous manner, any CTC loss during isolation was minimized. Blood samples from 10 patients with adjuvant breast cancer were analyzed. CTCs were sorted as unfixed cells in solution. CTCs were isolated from 5 of 10 blood samples, 1?3 CTCs were found in each of these 5 samples. The proposed μ-MixMACS chip is expected to be useful for isolating CTCs from a variety of tumor types without any changes.