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In this study, we present a miniaturized, silicon-based electrochemical sensor for sequential detection of two AD salivary biomarkers, lactoferrin (Lf) and amyloid \u03b2-protein 1-42 (A\u03b21-42), on a single reusable electrode. The sensor features a three-electrode system fabricated by sputter-coating a quartz substrate with gold (Au) sensing electrodes, which are further modified with gold nanoparticles (AuNPs) to form 3D dendritic structures that enhance surface area and electron transfer. To improve specificity, immunomagnetic beads (MBs) are employed to selectively capture and isolate target biomarkers from saliva samples. These MB\u2013biomarker complexes are introduced into a polydimethylsiloxane chamber aligned with Au sensing electrodes, where a detachable magnet localizes the complexes onto the electrode surface to amplify redox signals. The AuNPs\/MBs sensor achieves detection limits of 2 \u03bcg\/mL for Lf and 0.1 pg\/mL for A\u03b21-42, outperforming commercial ELISA kits (37.5 pg\/mL for A\u03b21-42) and covering physiological salivary concentrations. After the MBs capture the biomarkers, the sensor can output the result within one minute. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) measurements confirm enhanced electron transfer kinetics on AuNP-decorated surfaces, while linear correlations (R2 &gt; 0.95) validate quantitative accuracy across biomarker ranges. The compact and integrated design eliminates reliance on bulky instrumentation and enables user-friendly operation, establishing a promising platform for portable, cost-effective AD screening and monitoring.<\/jats:p>","DOI":"10.3390\/s25134088","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T12:10:31Z","timestamp":1751285431000},"page":"4088","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["AuNP\/Magnetic Bead-Enhanced Electrochemical Sensor Toward Dual Saliva Alzheimer\u2019s Biomarkers Detection"],"prefix":"10.3390","volume":"25","author":[{"given":"Pengcheng","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian 116000, China"},{"name":"State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieyu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian 116000, China"},{"name":"State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongju","family":"Mao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China"},{"name":"Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China"},{"name":"Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China"},{"name":"Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxing","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Science and Technology, Shanghai Open University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng","family":"Sun","sequence":"additional","affiliation":[{"name":"Lin Gang Laboratory, Shanghai 201306, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianan","family":"Hui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China"},{"name":"Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"Shanghai Frontier Innovation Research Institute, Shanghai, 201108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowu","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian 116000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.jalz.2016.02.002","article-title":"Preclinical Alzheimer\u2019s disease: Definition, natural history, and diagnostic criteria","volume":"12","author":"Dubois","year":"2016","journal-title":"Alzheimers Dement."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/S1474-4422(21)00066-1","article-title":"Clinical diagnosis of Alzheimer\u2019s disease: Recommendations of the International Working Group","volume":"20","author":"Dubois","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"110017","DOI":"10.1016\/j.ejrad.2021.110017","article-title":"Integrated Positron Emission Tomography\/Magnetic Resonance Imaging in clinical diagnosis of Alzheimer\u2019s disease","volume":"145","author":"Gao","year":"2021","journal-title":"Eur. 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