Hierarchical AuNPs@BN@AgNR SERS sensor for ultrasensitive detection of bilirubin and biliverdin in saliva

AuNPs@BN@AgNR SERS sensor for ultrasensitive salivary BR/BV detection. • Ultra-low LODs of 5 × 10 −8  M for BR and 1 × 10 −7  M for BV in spiked saliva. • FDTD simulations confirm 5.54-fold electric field enhancement via LSPR coupling. • BN layer enables target enrichment and suppressed non-specific adsorption. Bilirubin (BR) and biliverdin (BV) are non-invasive biomarkers for hepatic function assessment. Their detection in saliva is limited by sub-micromolar concentrations and matrix interference. Conventional methods exhibit limits of detection (LODs) ≥ 10 −6  M. Herein, an AuNPs@BN@AgNR SERS sensor is fabricated via oblique angle deposition, wet chemical etching, and chemical reduction. FDTD simulations demonstrate a 5.54-fold local electric field enhancement in the x–z plane relative to the BN@AgNR bilayer, resulting from LSPR coupling between AuNPs and AgNRs. Experimentally, the substrate achieves enhancement factors up to 4.06 × 10 9 with a spatial relative standard deviation (RSD) of ≤7.00%. The sensor yields LODs of 1 × 10 −12  M (BPE), 2.5 × 10 −8  M (R6G), and 1 × 10 −6  M (CV). In spiked saliva, the sensor exhibits quantifiable concentration ranges of 5 × 10 −8  M to 1 × 10 −4  M for BR and 1 × 10 −7  M to 1 × 10 −4  M for BV, with corresponding LODs of 5 × 10 −8  M and 1 × 10 −7  M. This performance is attributed to BN-mediated electrostatic target enrichment and the suppression of non-specific protein adsorption. This study provides an analytical platform for the non-invasive trace analysis of hepatic biomarkers. Download: Download high-res image (112KB) Download: Download full-size image