Renewable and Switchable Biofunctional Modification of Poly(dimethylsiloxane) Surfaces via Host–Guest Interactions for Enhanced Capture of Circulating Tumor Cells in Microfluidics

Circulating tumor cells (CTCs) are crucial for understanding cancer metastasis. Poly(dimethylsiloxane) (PDMS) microfluidic chips utilizing aptamers (APTs) effectively separate CTCs, but the hydrophobicity of PDMS causes issues with nonspecific adsorption and reduces cell viability. Therefore, it is imperative to develop innovative surface modification techniques for PDMS to enhance its biocompatibility and optimize its performance in microfluidic applications. In this study, oligo(ethylene glycol) methacrylate (OEGMA) and adamantane-modified OEGMA were copolymerized onto an initiator-containing PDMS surface. Poly(OEGMA) prevents nonspecific adsorption, and biotin-modified β-cyclodextrin (β-CD) was introduced through host-guest interaction between β-CD and adamantane. By using the biotin-streptavidin interaction, streptavidin and biotin-modified aptamers (TD05 APT and Sgc8 APT) were sequentially immobilized on the copolymer-grafted PDMS substrate. The data indicate that the PDMS substrate functionalized with TD05 APT achieved a capture efficiency of 91% and a selectivity of 30.2 for Ramos cells, while the substrate functionalized with Sgc8 APT achieved a capture efficiency of 93% and a selectivity of 33.3 for CEM cells. Furthermore, treating the APT-functionalized surfaces with sodium dodecyl sulfate released the β-CD component, allowing for the regeneration and switching of the surface biofunctionality by reimmobilizing TD05 APT or Sgc8 APT. Finally, the PDMS microfluidic chips modified using this strategy achieved high capture efficiency (96% for Ramos cells, 93% for CEM cells) and high selectivity (11.4 for Ramos cells, 9.2 for CEM cells). The host-guest chemistry endows the modified PDMS substrate with renewable and switchable biofunctionality, offering insights into the potential applications in the isolation and enrichment of CTCs.