Transition metal doping boosting paper-based photoelectrochemical immunosensing for neurofilament light chain protein detection

Early diagnosis of neurodegenerative diseases relies on highly sensitive detection of their specific biomarkers. However, existing photoelectrochemical (PEC) sensing technologies, despite the promising prospects, exhibit significant limitations in detection stability, photoelectric conversion efficiency, and portability. This work reported an innovative approach integrating transition metal doping modification with paper-based electrodes to construct a highly sensitive and low-cost paper-based sensing platform for detecting neurofilament light chain protein (NEFL). Fe-doped TiO₂ nanomaterials were synthesized <i>via</i> a homogeneous thermal treatment method. Fe substitution within the TiO₂ lattice constructed an intermediate energy level, optimizing the bandgap to 2.17 eV. This expanded the photoresponse range into the visible spectrum, enhancing the photocurrent intensity by 31-fold compared to pure TiO₂. A printed carbon paper triple-electrode system was fabricated <i>via</i> a template method, demonstrating excellent stability and reproducibility. Based on an immuno-sandwich model, the presence of target NEFL triggered glucose oxidase conjugated Au nanoparticle (GOx@Au NP)-labeled signal antibodies to catalyze glucose into hydrogen peroxide, further sensitizing the photocurrent response of Fe-TiO₂ to achieve wide range (0.01-200 ng mL^-1) detection of NEFL. This work enhances the PEC efficiency <i>via</i> Fe-doped TiO₂ and solves portability with paper-based electrodes, enabling sensitive NEFL detection, which supports early diagnosis of neurodegenerative diseases and provides an innovative technical solution for rapid point-of-care diagnosis of neurodegenerative diseases, while also offering theoretical and experimental references for the modification of wide band gap semiconductor materials and the development of paper-based sensing platforms.