Multifunctional Amyloid-Like Porous Nanofilm-Decorated Transistor-Based Biosensor for Accurate Detection of Alzheimer’s Disease Biomarker

The high sensitivity of field-effect transistor (FET) biosensors has made them a valuable tool for detecting low abundance biomarkers in AD diagnosis, but it faces ongoing challenges, particularly in their susceptibility to interference from complex sample matrices. Here, an amyloid-like nanofilm was introduced as an intermediate layer to enhance the antifouling ability and sensitivity of FET biosensors in complex systems. This nanofilm serves a dual purpose: due to the size-selective mechanism of the amyloid-like nanofilm, which prevents interference from nonspecific proteins, the proposed biosensor exhibited enhanced stability and antifouling capability in complex samples (nonspecific response of less than 5%). Weakening Debye shielding through its undulating porous structure enabled the highly sensitive detection of biomarkers even in solutions with high ionic strength. The biosensor successfully detected Alzheimer's disease (AD) biomarker P-tau181 with a low limit of detection down to 0.1 fg/mL and achieved a remarkable 100% diagnostic accuracy across 25 serum samples. This study provides a highly stable and sensitive FET biosensor that is expected to be used for early screening of AD.