Highly Sensitive Phase-Engineered Copper Sulfide Interfaces for Nonenzymatic Electrochemical Creatinine Sensing in Human Urine

Herein, we report for the first time the exploration of PVP-modulated copper sulfide for a high-performance electrochemical nonenzymatic sensor for noninvasive creatinine sensing. A controlled coprecipitation route in the presence of polyvinylpyrrolidone (PVP) yields phase-pure Cu 7 S 4, while synthesis without PVP results in a heterogeneous mixture of Cu 6 S 6, Cu 7 S 4, and secondary phases (Cu x S). Electrochemical evaluation by cyclic voltammetry demonstrates that the phase-engineered PVP-modulated Cu 7 S 4 sensor exhibits a stable, well-defined cathodic complexation response, in contrast to Cu x S-based sensor. Mechanistic understanding was further advanced through high-resolution XPS at potentials associated with redox transitions and Copper–Creatinine complexation, confirming the role of surface Cu 2+ species and the C═N group of creatinine in facilitating electron transfer. The sensor demonstrated exceptional analytical figures of merit, including a wide linear range of 0–300 μM, encompassing the entire physiological and pathological range, a low detection limit of 1.196 μM, and a high sensitivity of 541.83 μA mM –1 cm –2 . Furthermore, the sensor exhibited splendid specificity, effectively mitigating uric acid interference through simple 100-fold dilution, and maintained remarkable stability with a 96.68% signal retention over 26 days. Crucially, validation using clinical human urine samples showed excellent agreement with the gold standard test ( P > 0.05). The PXRD, FTIR, Raman spectroscopy, UV–visible, FESEM, HR-TEM, Zeta potential, and XPS were performed for comprehensive material characterization, which revealed crucial phase engineering and functionalization influencing electrocatalytic activity. This study establishes phase-engineered PVP-modulated Cu 7 S 4 as a robust and reproducible nonenzymatic sensing material offering mechanistic insights that can guide the design of next-generation point-of-care creatinine sensors.