Abstract: Depression, the most prevalent global psychiatric disorder, heavily relies on subjective clinical assessments that are prone to diagnostic inaccuracies, necessitating the development of reliable and objective detection systems. Kynurenine, a neuroactive metabolite with well-established pathophysiological links to depression, has emerged as a promising depression biomarker. Herein, we report a d-band-modulated PtCo alloy nanozyme synergistically integrated with molecularly imprinted polymers (MIPs), achieving ultrasensitive kynurenine detection for depression screening. The PtCo nanozyme demonstrated a 4.28-fold enhancement in oxidase-mimetic activity compared to monometallic Pt. This exceptional performance is mechanistically attributed to Co-induced modulation of Pt d-band center that optimizes oxygen adsorption and activation dynamics, as rigorously validated by density functional theory calculations and in situ spectroscopic characterizations. Molecular imprinting on the PtCo surface generates kynurenine-specific recognition cavities, enabling selective target binding while preserving catalytic functionality. The resulting PtCo@MIP paper-based biosensor achieves a detection limit of 0.382 μM in serum with a broad linear response (4.8-960 μM) and exceptional anti-interference performance. When integrated into paper-based biochips with smartphone-enabled RGB colorimetric readout, the platform demonstrates high recovery rates (107.6%-109.7%) in clinical samples, outperforming commercial kits in terms of precision. This study establishes a pretreatment-free, cost-effective diagnostic paradigm that bridges advanced nanozymes with high-performance biosensors, offering a foundation for next-generation depression diagnostics.

Key words: PtCo nanozymes, d-band center, Depression, Colorimetric sensing, Molecular imprinting