(386c) Graduate Student Award Session: Enhanced Capture and Release of Circulating Tumor Cells Using Hollow Glass Microspheres with Nanostructured Surface

Circulating tumor cells (CTCs), derived from primary tumor sites, can spread through the bloodstream to distant organs, which cause metastasis and cancer related death. Therefore, isolation and analysis of CTCs has attracted great attention for cancer prognosis and personalized medicine. Recently, self-floating hollow glass microspheres (HGMS) modified with tumor-specific antibodies have been developed for capture CTCs in resource-limited settings, and it has demonstrated effective cell isolation and good viability of isolated cancer cells when the concentration of spiked cells is larger than 10,000 cells/mL. However, capture efficiency dramatically decreases if the spiked cell concentration in blood is below 5,000 cell/mL, probably due to the weak interactions between HGMS and cancer cells. In order to apply the HGMS approach for CTC isolation to clinically relevant samples, it is ideal to create nanostructures on the surface of HGMSs to enhance cell-surface interactions. However, current microfabrication methods for generating nanostructured surface are not feasible for coating on the surface of microparticles. In this work, we have developed a new type of HGMS with controlled nanotopograpghical structure (^NSHGMS) on its surface and demonstrated its remarkable performance of isolation and recovery of rare cancer cells. ^NSHGMS was achieved by applying layer-by-layer (LbL) assembly of negatively charged SiO₂ nanoparticles and positively charged poly-L-arginine; then the surface was sheathed with an enzymatically degradable LbL film made from biotinylated alginate and poly-L-arginine, and then capping with anti-EpCAM antibodies and anti-fouling molecules. Comparing to HGMS with smooth surface, ^NSHGMS showed shorter isolation time (< 20 min), enhanced capture efficiency (> 95%) and lower detection limit (< 50 cells/mL) for various commonly used metastatic cancer cell lines (MCF7, SK-BR-3, PC3, A549). This ^NSHGMS-based CTC isolation method requires neither specialized lab equipment nor any form of external power source, which can be adapted for separation of other types of targeted cells from blood or other body fluid, especially in a resource-limited environment.