Gold Nanoparticle-Based Optical Biosensing Platform for Ultrasensitive Glucose Monitoring

Abstract

Accurate quantification of glucose is essential for diabetes management, particularly within low-concentration ranges where early hypoglycemia detection remains clinically challenging. Existing optical nanobiosensors frequently rely on single-channel readouts, resulting in baseline drift, limited sub-millimolar resolution, and inconsistent reproducibility across synthesis batches. To address these limitations, we developed a gold nanoparticle (AuNP)-based optical biosensing platform integrating dual-channel signal acquisition with glucose oxidase (GOx) chromogenic amplification and batch-normalized calibration. The system simultaneously records LSPR wavelength shift (Δλ) and scattering intensity ratio (I540/I620), improving sensitivity and measurement stability relative to single-mode detection. Across 1,200 serum samples (0-20 mM), the platform achieved a limit of detection of 18.6±2.3 µM, mean absolute error of 0.21±0.03 mM compared with clinical analyzers, and spectral linearity of R² = 0.98. Ablation testing confirmed functional necessity of the enzymatic amplification pathway (LoD increased to 78.6±7.9 µM when GOx was removed), while batch-calibration reduced inter-fabrication drift. Stability evaluation demonstrated minimal 14-day signal attenuation (4.3±0.5%) with <1.8 nm wavelength drift, and cross-institution validation showed no significant performance decline (p > 0.05). These results demonstrate a reproducible and sensitive optical route to glucose detection, with practical applicability to future point-of-care or minimally invasive monitoring frameworks.