Adhesion-based tumor cell capture using nanotopography

Circulating tumor cells (CTCs) shed from primary tumors, transport through the blood stream to distant sites, and cause 90% of cancer deaths. Although different techniques have been developed to isolate CTCs for cancer detection, diagnosis and treatment, the heterogeneity of expression of the target antigen and the significant size variance in CTCs limit clinical applications of antibody- and size-based isolation techniques. Cell adhesion using nanotopography has been suggested as a promising approach to isolate CTCs independent of surface marker expression or size of CTCs. However, the nanotopographies studied are mainly nanopillars; the influence of other nanotopography such as nanogratings and their dimensions on tumor cell capture remains to be investigated. This study examined capture performance of several cancer cell lines of different types, surface marker expression and metastatic status on nanotopographies of various geometries and dimensions without antibody conjugation. The cancer cells exhibited differential capture performance on the nanotopographies with an efficiency up to 52%. Compared with flat surfaces and isotropic, discrete nanopillars, nanogratings favored cancer cell adhesion, thus improving the capture efficiency. The influence of nanotopography height studied, on the other hand, was less significant. This study provides useful information to optimize nanotopography for further improvement of CTC capture efficiency.