Low-Cost Polyphenol-Polypyrrole Molecularly Imprinted Sensor for Point-of-Care Alzheimer's Detection.

There is an urgent need for rapid, affordable diagnostics for Alzheimer's disease (AD), particularly those that can detect phosphorylated Tau 181 (p-tau181)─a key biomarker─directly in plasma. We present a scalable, label-free electrochemical biosensor fabricated on a printed circuit board platform, integrating a novel nanomolecularly imprinted polymer transducer based on a polyphenol red-polypyrrole composite. This platform enables sensitive detection of p-tau181 in undiluted plasma, serum, and clinical AD samples using a custom-designed potentiostat and machine learning-assisted classification. The sensor achieves a detection limit of 498 fg mL-1, a sensitivity of 8.99 μA/pg mL, and an area under the ROC curve (AUC) of 0.84 in clinical samples, comparable to the single molecule array (SIMOA) assay (AUC = 0.91), but at a fraction of the cost. This integrated platform, validated in real patient samples, demonstrates significant advancement toward accessible, point-of-care diagnostics for early AD detection.