UltraSensitive, SelfCalibrating Cortisol Immunosensor Enabled by Dual-Modal CuMOF-PEI@AuNPs@HRP Immunoreceptor

Accurate cortisol monitoring is essential for stress assessment and health management, yet reliable quantification remains challenging because signal fluctuations and matrix effects can compromise the performance of conventional single-mode immunosensors. Herein, we developed a fluorescence-colorimetric (FL-CL) dual-modal immunosensor based on a CuMOF-PEI@AuNPs@HRP (CPA) immunoreceptor for cortisol determination. The integrated sensing architecture generates correlated fluorescence and colorimetric responses from the same recognition event, which are combined through a normalized dual-signal output to improve calibration reliability. Under optimized conditions, the proposed sensor exhibited a detection limit of 0.22 ng/mL and a linear range of 3.1-200 ng/mL, covering physiologically relevant cortisol concentrations in saliva. Compared with single-modal assays and commercial kits, the proposed platform demonstrates enhanced sensitivity, improved correlation, good stability, and batch reproducibility. By integrating signal amplification, dual-modal readout, and simplified immunoreceptor fabrication within a single sensing platform, this work provides a reliable strategy for cortisol monitoring and offers potential for extension to other biomarker detection systems.