Oxygen-enriching triphase platform for reliable sensing of femtomolar Alzheimer's neurofilament lights.

Accurate quantification of neurofilament lights (NfLs), a prognostic blood biomarker, is highly required to predict neurodegeneration in the presymptomatic stages of Alzheimer's disease. Here, we report self-oxygen-enriching coral structures with triphase interfaces for the label-free photocathodic detection of NfLs in blood plasma with femtomolar sensitivities and high reliability. In conventional photocathodic immunoassays, the poor solubility and sluggish diffusion rate of the dissolved oxygen serving as electron acceptors have necessitated the incorporation of additional electron acceptors or aeration procedures. To address the challenge, we designed the coral-like copper bismuth oxides (CBO) with robust solid-liquid-air contact boundaries that enrich the interfacial oxygen levels without an external aeration source. By optimally assembling the perfluorododecyltrichlorosilane (FTCS) and platinum (Pt) co-catalysts into the silver-doped CBO (Ag:CBO), the stable solid-liquid-air contact boundaries were formed within the sensor interfaces, which allowed for the abundant supply of air phase oxygen through an air pocket connected to the atmosphere. The Pt/FTCS-Ag:CBO exhibited the stable background signals independent of the dissolved oxygen fluctuations and amplified photocurrent signals by 1.76-fold, which were attributed to the elevated interfacial oxygen levels and 11.15 times-lowered mass transport resistance. Under the illumination of white light-emitting diode, the oxygen-enriching photocathodic sensor composed of Pt/FTCS-Ag:CBO conjugated with NfLs-specific antibodies precisely quantified the NfLs in plasma with a low coefficient of variation (≤2.97%), a high degree of recovery (>97.0%), and a limit of detection of 40.38 fg/mL, which was 140 times lower than the typical photocathodic sensor with diphase interfaces.