Cellulose-based hydrogel SERS sensor for label-free detection and identification of antithyroid drugs.

Antithyroid drugs, while essential for the management of hyperthyroidism, can induce adverse reactions detrimental to patient health. Therefore, developing a rapid, quantitative method for monitoring therapeutic drug levels in blood is critical for the effective diagnosis and treatment of thyroid disorders. In this study, we fabricated a three-dimensional (3D) porous Ag NPs/C-CNF/PNIPAM hydrogel as a sensor for surface-enhanced Raman spectroscopy (SERS). Specifically, silver nanoparticles (Ag NPs) were stabilized within a poly(N-isopropylacrylamide) (PNIPAM) network using carboxylated cellulose nanofibers (C-CNF). Notably, this hydrogel facilitates the rapid separation and enrichment of methimazole (MMI) and 2-Thiouracil (2-TU) directly from plasma, obviating the need for complex sample pretreatment. The method achieved limits of detection (LOD) as low as 7.48 × 10-9 M for MMI and 2.35 × 10-8 M for 2-TU. Furthermore, by integrating SERS with machine learning, the proposed method precisely discriminates between MMI and 2-TU in spiked blood samples, achieving 100% accuracy and an area under the receiver operating characteristic curve (AUC) of 1 for both compounds. This hydrogel-based platform offers a reliable solution for the rapid detection of antithyroid drugs, holding significant potential for clinical applications in therapeutic monitoring.