Continuous labeling of circulating tumor cells with microbeads using a vortex micromixer for highly selective isolation

• Published in: Biosensors & bioelectronics Vol. 40; no. 1; pp. 63 - 67
• Main Authors: Lin, Ming Xian, Hyun, Kyung-A, Moon, Hui-Sung, Sim, Tae Seok, Lee, Jeong-Gun, Park, Jae Chan, Lee, Soo Suk, Jung, Hyo-Il
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Kidlington Elsevier B.V 15.02.2013; Elsevier
• Subjects: Biological and medical sciences; Biotechnology; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Separation - instrumentation; Cell Tracking - instrumentation; Circulating tumor cells; EpCAM antibody; Equipment Design; Equipment Failure Analysis; Fundamental and applied biological sciences. Psychology; Humans; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Microbeads; Microfluidic Analytical Techniques - instrumentation; Microspheres; Miniaturization; Staining and Labeling - instrumentation; Vortex micromixer; Microbeads; Vortex micromixer; Circulating tumor cells; EpCAM antibody; Continuous process; Antibody; Tagging; Isolation; Selectivity; Circulating tumor cell
• ISSN: 0956-5663; 1873-4235
• DOI: 10.1016/j.bios.2012.06.016

Circulating tumor cells (CTCs) are identified in transit within the blood stream of cancer patients and have been proven to be a main cause of metastatic disease. Current approaches for the size-based isolation of CTCs have encountered technical challenges as some of the CTCs have a size similar to that of leukocytes and therefore CTCs are often lost in the process. Here, we propose a novel strategy where most of the CTCs are coated by a large number of microbeads to amplify their size to enable complete discrimination from leukocytes. In addition, all of the microbead labeling processes are carried out in a continuous manner to prevent any loss of CTCs during the isolation process. Thus, a microfluidic mixer was employed to facilitate the efficient and selective labeling of CTCs from peripheral blood samples. By generating secondary vortex flows called Taylor–Gortler vortices perpendicular to the main flow direction in our microfluidic device, CTCs were continuously and successfully coated with anti-epithelial cell adhesion molecule-conjugated beads. After the continuous labeling, the enlarged CTCs were perfectly trapped in a micro-filter whereas all of the leukocytes escaped.