A New Chitosan-Modified Paper-Based SERS Glucose Sensor with Enhanced Reproducibility, Stability, and Sensitivity for Non-Enzymatic Label-Free Detection

We have fabricated a new highly reproducible, stable, and sensitive cellulose paper-based Surfaced-enhanced Raman scattering (SERS) sensor substrate for non-enzymatic label-free glucose detection. To enhance reproducibility, stability, and sensitivity, the cellulose paper (CP) substrate has been modified with a naturally derived biocompatible polymer, chitosan (CS), followed by depositing enormous amount of plasmonic silver nanoparticles (AgNPs) on CP/CS and finally forming a self-assembling monolayer of 4-mercaptophenyl boronic acid (MPBA) on CP/CS/AgNPs (CP/CS/AgNPs/MPBA). The SERS sensor substrate is characterized by scanning electron microscopy (SEM), energy dispersive X-ray (EDX), Fourier transform infrared (FT-IR), and X-ray diffraction (XRD) spectroscopy techniques. The glucose sensing is achieved by monitoring the SERS intensity of C-S and B-O stretching vibrations at 1072 cm^-1 in MPBA, which is gradually increased with increasing concentration of glucose due to the increasing orientation change of MPBA on AgNPs. The results show that the proposed glucose paper-based SERS sensor exhibits a high analytical enhancement factor (AEF) (3.4 × 10⁷), enhanced reproducibility (<7%), improved stability (>5 weeks), excellent selectivity towards other metabolic compounds, and high sensitivity with a limit of detection (LOD) of 0.74 mM and a linear dynamic range between 1.0 and 7.0 mM. The practical application of this SERS sensor is examined in real spiked and non-spiked human blood serum samples for the detection of glucose, and satisfactory recovery results have been obtained, demonstrating the potentiality of the present paper-based SERS sensor for non-enzymatic label-free glucose detection in real biological samples.