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

• Published in: Sensors and actuators. B, Chemical Vol. 238; pp. 1144 - 1150
• Main Authors: Lee, Tae Yoon, Hyun, Kyung-A, Kim, Seung-Il, Jung, Hyo-Il
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier B.V 01.01.2017; Elsevier Science Ltd
• Subjects: Blood; Blood circulation; Cancer; Cell adhesion; Cell adhesion & migration; Chips; Circulating tumor cells (CTCs); Heterogeneity; Leukocytes; Metastasis; Microfluidic magnetic activated cell sorter (micro-MACS); Microfluidics; Multivortex micromixer; Negative enrichment; Patients; Tumors; White blood cells; Negative enrichment; Multivortex micromixer; Microfluidic magnetic activated cell sorter (micro-MACS); Circulating tumor cells (CTCs)
• ISSN: 0925-4005; 1873-3077
• DOI: 10.1016/j.snb.2016.05.163

•We introduce a fully integrated microfluidic chip designed for one-step CTC isolation.•Multi-voltex micromixer improves the binding between WBCs and MNPs coated with CD45 antibody.•Continuous manner from sample preparation to isolation makes minimization of CTC loss.•One to 3 CTCs were isolated from 5 of 10 blood samples from adjuvant breast cancer patients. 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.