Rational aspect ratio and suitable antibody coverage of gold nanorod for ultra-sensitive detection of a cancer biomarker

We report a simple, ultra-sensitive, and straightforward method for non-labeling detection of a cancer biomarker, using Rayleigh light scattering spectroscopy of the individual nanosensor based on antibody-antigen recognition and localized surface plasmon resonance (LSPR) λ_max shifts. By experimentally measuring the refractive index sensitivity of Au nanorods, the Au nanorod with an aspect ratio of ∼3.5 was proven optimal for the LSPR sensing. To reduce the steric hindrance effect as well as to immobilize a large amount of ligand on the nanoparticle surface, various mixtures containing different molar ratios of HS(CH₂)₁₁(OCH₂CH ₂)₆OCH₂COOH and HS(CH₂) ₁₁(OCH₂CH₂)₃OH were applied to form different self-assembled monolayer surfaces. The results showed that the best molar ratio for antibody conjugation was 1:10. When using individual Au nanorod sensors for the detection of prostate specific antigen (PSA), the lowest concentration recorded was ∼1 aM (∼6 × 10⁵ molecules), corresponding to LSPR λ_max shifts of ∼4.2 nm. These results indicate that sensor miniaturization down to the nanoscale level, the reduction of steric hindrance, and optimization of size, shape, and aspect ratio of nanorods have led to a significant improvement in the detection limit of sensors.