Copper Vacancy-Doped Cu_2-xSe Activating Nanozyme Sensor Arrays for Multiprotein Discrimination and Cancer Screening

Given the complexity and interrelated nature of biological activities, acquiring multitarget information is crucial for accurate cancer diagnosis. In this study, we developed a cross-reactive sensor array using peroxidase-like nonstoichiometric copper selenide nanoparticles (Cu_2-xSe), which featured varying copper vacancies, for multiplex protein detection and cancer screening. The Cu_2-xSe nanoparticles demonstrated outstanding peroxidase-like activity that can be modulated to varying degrees in the presence of multiple proteins with varying isoelectric points and compositions, generating fingerprint outputs. By integrating pattern recognition method principal component analysis with linear discriminant analysis (PCA-LDA), the sensor array effectively discriminated among six proteins and was further applied to cells and clinical samples, attaining 100% accuracy in differentiating cancer patients from healthy individuals, as well as in identifying specific cancer types, namely, liver and prostate cancers. Moreover, as a proof-of-concept, the partial least-squares regression (PLSR) approached the accurate detection of AFP and PSA within the range of 0.1-2.0 μg/L in the complex biological matrix. These results highlighted the practical potential of multitarget sensing and clinical diagnosis by the nanozyme-based chemical nose strategies.