Gold Nanoparticle-Based Optical Biosensing Platform for Ultrasensitive Glucose Monitoring
Keywords:
gold nanoparticles, optical biosensing, glucose monitoring, dual-channel plasmonic detection, enzymatic amplificationAbstract
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.References
1. E. W. Gregg, J. Buckley, M. K. Ali, J. Davies, D. Flood, R. Mehta, and Z. Zhumadilov, "Improving health outcomes of people with diabetes: target setting for the WHO Global Diabetes Compact," the lancet, vol. 401, no. 10384, pp. 1302-1312, 2023. doi: 10.1016/s0140-6736(23)00001-6
2. T. Saha, R. Del Caño, K. Mahato, E. De la Paz, C. Chen, S. Ding, and J. Wang, "Wearable electrochemical glucose sensors in diabetes management: a comprehensive review," Chemical Reviews, vol. 123, no. 12, pp. 7854-7889, 2023. doi: 10.1021/acs.chemrev.3c00078
3. Q. Wang, Z. A. Zhao, K. Y. Yao, Y. L. Cheng, D. S. H. Wong, D. W. C. Wong, and J. C. W. Cheung, "The Versatility of Biological Field-Effect Transistor-Based Biosensors (BioFETs) in Point-of-Care Diagnostics: Applications and Future Directions for Peritoneal Dialysis Monitoring," Biosensors, vol. 15, no. 3, p. 193, 2025.
4. N. Shukla, A. Chanderiya, R. Das, E. A. Mukhanova, A. V. Soldatov, and S. Belbekhouche, "Au QDs in Advanced Biomedicine: Fluorescent, Biocompatible, and Multifunctional Nanoprobes for Imaging, Diagnostics, and Targeted Drug Delivery," Journal of Nanotheranostics, vol. 6, no. 3, p. 25, 2025. doi: 10.3390/jnt6030025
5. J. Chen, X. Liu, G. Zheng, W. Feng, P. Wang, J. Gao, and Q. Wang, "Detection of glucose based on noble metal nanozymes: mechanism, activity regulation, and enantioselective recognition," Small, vol. 19, no. 8, p. 2205924, 2023. doi: 10.1002/smll.202205924
6. J. Lee, and S. Lee, "Non-invasive, reliable, and fast quantification of DNA loading on gold nanoparticles by a one-step optical measurement," Analytical chemistry, vol. 95, no. 3, pp. 1856-1866, 2023. doi: 10.1021/acs.analchem.2c03378
7. E. Ferrari, "Gold nanoparticle-based plasmonic biosensors," Biosensors, vol. 13, no. 3, p. 411, 2023. doi: 10.3390/bios13030411
8. M. Tadesse, and Y. Liu, "Recent Advances in Enzyme Immobilization: The Role of Artificial Intelligence, Novel Nanomaterials, and Dynamic Carrier Systems," Catalysts, vol. 15, no. 6, p. 571, 2025. doi: 10.3390/catal15060571
9. S. Das, R. Devireddy, and M. R. Gartia, "Surface plasmon resonance (SPR) sensor for cancer biomarker detection," Biosensors, vol. 13, no. 3, p. 396, 2023. doi: 10.3390/bios13030396
10. A. Soliman, C. Williams, R. Hopper, F. Udrea, H. Butt, and T. D. Wilkinson, "HighTransmission MidInfrared Bandpass Filters using Hybrid MetalDielectric Metasurfaces for CO2 Sensing," Advanced Optical Materials, vol. 13, no. 8, p. 2402603, 2025.
11. Y. Chen, K. X. Fu, R. Cotton, Z. Ou, J. W. Kwak, J. C. Chien, and H. Tom Soh, "A biochemical sensor with continuous extended stability in vivo," Nature Biomedical Engineering, pp. 1-14, 2025.
12. H. Cao, E. F. Oghenemaro, A. Latypova, M. K. Abosaoda, G. S. Zaman, and A. Devi, "Advancing clinical biochemistry: addressing gaps and driving future innovations," Frontiers in Medicine, vol. 12, p. 1521126, 2025. doi: 10.3389/fmed.2025.1521126
13. J. Bai, D. Liu, X. Tian, Y. Wang, B. Cui, Y. Yang, and S. Zhang, "Coin-sized, fully integrated, and minimally invasive continuous glucose monitoring system based on organic electrochemical transistors," Science Advances, vol. 10, no. 16, p. eadl1856, 2024. doi: 10.1126/sciadv.adl1856
14. M. Xie, J. Jiang, and J. Chao, "DNA-based gold nanoparticle assemblies: From structure constructions to sensing applications," Sensors, vol. 23, no. 22, p. 9229, 2023. doi: 10.3390/s23229229
15. C. D. Flynn, D. Chang, A. Mahmud, H. Yousefi, J. Das, K. T. Riordan, and S. O. Kelley, "Biomolecular sensors for advanced physiological monitoring," Nature Reviews Bioengineering, vol. 1, no. 8, pp. 560-575, 2023. doi: 10.1038/s44222-023-00067-z

