Soumi Roy Kang, Sarang Choi, Kyu Yeong Lee, Kun Ho Shin, Keyong-Sik Kang, Ji Yoon 2024-01-12T06:30:06Z 2024-01-12T06:30:06Z 2024-01-09 2024-03 0956-5663 https://pubs.kist.re.kr/handle/201004/79656 Alzheimer&apos;s Disease (AD) is one of the most common neurodegenerative disorders in elderly people. It is diagnosed by detecting amyloid beta (Aβ) protein in cerebrospinal fluid (CSF) obtained by lumbar puncture or through expensive positron emission tomography (PET) imaging. Although blood-based diagnosis of AD offers a less invasive and cost-effective alternative, the quantification of Aβ is technically challenging due to its low abundance in peripheral blood. To address this, we developed a compact yet highly sensitive microwell-based electrochemical sensor with a densely packed microelectrode array (20 by 20) for enhancing sensitivity. Employing microwells on the working and counter electrodes minimized the leakage current from the metallic conductors into the assay medium, refining the signal fidelity. We achieved a detection limit <10 fg/mL for Aβ by elevating the signal-to-noise ratio, thus capable of AD biomarker quantification. Moreover, the microwell structure maintained the performance irrespective of variations in bead number, indicative of the sensor&apos;s robustness. The sensor&apos;s efficacy was validated through the analysis of Aβ concentrations in plasma samples from 96 subjects, revealing a significant distinction between AD patients and healthy controls with an area under the receiver operating characteristic curve (AUC) of 0.85. Consequently, our novel microwell-based electrochemical biosensor represents a highly sensitive platform for detecting scant blood-based biomarkers, including Aβ, offering substantial potential for advancing AD diagnostics. English Pergamon Press Ltd. Implementation of an ultra-sensitive microwell-based electrochemical sensor for the detection of Alzheimer’s disease Article 10.1016/j.bios.2023.115898 1 Biosensors and Bioelectronics, v.247 Biosensors and Bioelectronics 247 N scie scopus 001157336500001 Biophysics Biotechnology & Applied Microbiology Chemistry, Analytical Electrochemistry Nanoscience & Nanotechnology Biophysics Biotechnology & Applied Microbiology Chemistry Electrochemistry Science & Technology - Other Topics Article DIAGNOSIS STABILITY ARRAYS Microwell-based electrochemical sensor Limits of Detection (LOD) Magnetic beads Alzheimer &apos s disease Amyloid Beta Patient plasma sample