Self‐Recognizing L‐Glutamine‐Conjugated Manganese Oxide Sensors for Salivary Microdroplet Analysis

Early detection of Alzheimer's disease (AD) remains a critical challenge in neurodiagnostics that necessitates the development of noninvasive, cost‐effective, and reliable biosensing platforms. Herein, a self‐recognizing L‐glutamine‐conjugated manganese oxide (Gln‐MnO 2 )‐modified electrode is developed for the electrochemical detection of L‐glutamine (Gln) in a microdroplet of human saliva, a potential biomarker for early‐stage AD. The biofunctionalized MnO 2 interface facilitates hydrogen bonding and electrostatic interactions with Gln, eliminating the need for enzymatic recognition elements while enhancing its sensitivity. Electrochemical characterization demonstrates a reversible, adsorption‐controlled redox process with an electroactive surface area of 0.225 cm 2 , high sensitivity (3.16 µA cm −2 nM −1 ), and a low detection limit (69.7 pM). Real saliva analysis confirms its practical utility, with measured Gln concentrations (6.70 ± 0.93 µM) aligning with reported physiological levels. Furthermore, standard addition experiments yield a recovery of 94.67 ± 5.14%, which also validates its accuracy. The Gln‐MnO 2 sensor exhibits excellent operational stability over 15 days, with minimal signal loss afterward due to nonspecific adsorption in complex biofluids. The developed platform offers a cost‐effective, enzyme‐free, and disposable sensing approach for AD biomarker detection, with potential applications in metabolic monitoring and point‐of‐care diagnostics.