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 TiO 2 nanomaterials were synthesized via a homogeneous thermal treatment method. Fe substitution within the TiO 2 lattice constructed an intermediate energy level, optimizing the bandgap to 2.17 eV. This expanded the photoresponse range into the visible spectrum, enhancing photocurrent intensity by 31-fold compared to pure TiO 2 . A printed carbon paper triple-electrode system was fabricated via a template method, demonstrating excellent stability and reproducibility. Based on an immunosandwich model, the presence of target NEFL triggered glucose oxidase conjugated Au nanoparticles (GOx@Au NP)-labeled signal antibodies to catalyze glucose into hydrogen peroxide, further sensitizing the photocurrent response of Fe-TiO 2 to achieve wide-range (0.01-200 ng mL -1 ) detection of NEFL. This work enhances PEC efficiency via Fe-doped TiO 2 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.