Degradable Zinc-Phosphate-Based Hierarchical Nanosubstrates for Capture and Release of Circulating Tumor Cells

Circulating tumor cells (CTCs) play a significant role in cancer diagnosis and personalized therapy, and it is still a significant challenge to efficiently capture and gently release CTCs from clinical samples for downstream manipulation and molecular analysis. Many CTC devices incorporating various nanostructures have been developed for CTC isolation with sufficient capture efficiency, however, fabricating such nanostructured substrates often requires elaborate design and complicated procedures. Here we fabricate a degradable zinc-phosphate-based hierarchical nanosubstrate (HZnPNS), and we demonstrate its excellent CTC-capture performance along with effective cell-release capability for downstream molecular analysis. This transparent hierarchical architecture prepared by a low-temperature hydrothermal method, enables substantially enhanced capture efficiency and convenient imaging. Biocompatible sodium citrate could rapidly dissolve the architecture at room temperature, allowing that 88 ± 4% of captured cells are gently released with a high viability of 92 ± 1%. Furthermore, antiepithelial cell adhesion molecule antibody functionalized HZnPNS (anti-EpCAM/HZnPNS) was successfully applied to isolate CTCs from whole blood samples of cancer patients, as well as release CTCs for global DNA methylation analysis, indicating it will serve as a simple and reliable alternative platform for CTC detection.