A two-dimensional immunomagnetic nano-net for the efficient isolation of circulating tumor cells in whole blood

Abstract

An immunomagnetic “nano-net” was designed and synthesized for specifically capturing rare cells of interest from mixtures. The nano-net, Ab@Lipo-MNP-GO, consists of conjugated antibody molecules on a lipid coated magnetic nanoparticle–graphene oxide sheet complex. The magnetism, chemical composition, and the morphology of the construct and its precursors were characterized by SQUID, FTIR, TGA, DLS and SEM, to confirm the feasibility of the synthetic steps and the resulting properties suitable for solution phase immuno-recognition for cell capture. When applied to capturing circulating tumor cells (CTCs) in oral, colon and lung cancer clinical patients’ blood samples, the nano-net construct exhibited far superior ability whereas conventional immunomagnetic beads in some cases were unable to capture any CTCs, even by increasing the bead concentration. Confocal images showed that the nano-net wrapped around the CTCs while the immunomagnetic beads attached them with point contacts. A stable, patch-like multivalent matrix nano-net was demonstrated to tackle the shortcomings of single point contact of immunomagnetic beads to the target cell. This strategy is universal for any cell separation in complex fluids.