Tetrahedron DNA-Encapsulated Gold Nanoparticles Inhibit Nanolayer Aggregation on Ω-shaped Fiber-Optic Surface for LSPR-based biosensor with Merit of Molar Ratio-dependent Sensitivity

Gold nanoparticles (AuNPs) are widely used in fiber-optic (FO) local surface plasmon resonance (LSPR) biosensors due to their ease of modification, high dielectric constant, and biocompatibility. However, salt ions and cross-linking agents often cause AuNPs aggregation during modification, which significantly degrades the sensing sensitivity of FO-based LSPR. Herein, tetrahedron DNA-encapsulated AuNPs (TDN-AuNPs) were served as a new nanolayer on FO surface for a sensitive biosensor. TDN improved the salt-resistance and cross-linking agent-resistance, also served as a gap to hinder the nanolayer close to each other, which could avoid the AuNPs aggregation on the FO surface. Further, a significant merit of molar ratio-dependent refractive index sensitivity was found in the FO-based LSPR through the three kinds of modification methods, namely self-assembled monolayer (SAM)-based, ployA-based, and complementary strand (CS)-based methods. Further, CS-based method maintained strong chemical stability under weak acid or neutral environment and exhibited stronger binding stability and long-term stability compared to the other two methods. Finally, the CS-based method also showed a new merit of molar ratio-dependent sensing sensitivity. The mole ratio of TDN: AuNPs played a vital role in sensing sensitivity. Under the optimal conditions, the lowest limit of detection of 12 cells/mL was obtained within 50 min. Since high stability, sensitivity, and selectivity for cancer cell sensing, FO-based LSPR biosensor via CS-based method had great potential for cancer diagnosis in the early stage.