Detecting circulating tumor cells (CTCs) is challenging due to their low presence and heterogeneity. Traditional methods using EpCAM-based separation struggle with CTCs that have undergone epithelial-mesenchymal transition, as this results in lower EpCAM expression. This study presents the use of silica-coated magnetic nanobeads functionalized with streptavidin for CTC capture. Using the FETCH magnetic separation system, we validated the capture efficiency of our beads on tumor cells with varying EpCAM expression. Our beads showed superior capture rates for LNCaP (97%), PC3-9 (91%), PC3 (23%), A549 (22%), and T24 (8%) cells compared to commercial MojoSort™ beads. Despite slightly higher nonspecific binding than CellSearch, our beads demonstrated improved sensitivity for EpCAMlow cells, suggesting they have promise for enhanced CTC capture.