Immunomagnetic separation in a novel cavity-added serpentine microchannel structure for the selective isolation of lung adenocarcinoma cells

Abstract

The manipulation and separation of circulating tumor cells (CTCs) in continuous fluidic flows play an essential role in various biomedical applications, particularly the early diagnosis and treatment of diseases. Recent advances in magnetic bead development have provided promising solutions to the challenges encountered in CTC manipulation and isolation. In this study, we proposed a biomicrofluidic platform for specifically isolating human lung carcinoma A549 cells in microfluidic channels. The principle of separation was based on the effect of the magnetic field on aptamer-conjugated magnetic beads, also known as immunomagnetic beads, in a serpentine microchannel with added cavities (SMAC). The magnetic cell separation performance of the proposed structure was modeled and simulated by using COMSOL Multiphysics. The experimental procedures for aptamer molecular conjugation on 1.36 µm-diameter magnetic beads and magnetic bead immobilization on A549 cells were also reported. The lung carcinoma cell-bead complexes were then experimentally separated by an external magnetic field. Separation performance was also confirmed by optical microscopic observations and fluorescence analysis, which showed the high selectivity and efficiency of the proposed system in the isolation and capture of A549 cells in our proposed SMAC. At the flow rate of 5 µL/s, the capture rate of human lung carcinoma cells exceeded 70% in less than 15 min, whereas that of the nontarget cells was approximately 4%. The proposed platform demonstrated its potential for high selectivity, portability, and facile operation, which are suitable considerations for developing point-of-care applications for various biological and clinical purposes.

Keywords: Aptamer; CTCs; Immunomagnetic separation; Microfluidic flow.