Clinical application of serological Alzheimer's disease diagnosis using a highly sensitive biosensor with...

Analysis of a ratio between amyloid beta 1-40 and 1-42 (Aβ_1-40 and Aβ_1-42) presented in plasm enables a highly accurate diagnosis of Alzheimer's disease (AD). However, the analysis of plasma Aβs is not routinely conducted because of the lack of Aβ detection techniques sensitive enough to specifically detect Aβ from thousands of biomaterials present in the plasma. We developed a hydrogel-patterned spiral microelectrode sensor combined with a hopping dielectrophoretic (DEP) force, combining the negative DEP and positive DEP forces, for Aβ detection. The hydrogel effectively increased the number of immobilized fragmented antibodies in the reaction region of the sensor and enabled size-exclusive passive filtration of non-specific plasma proteins from that region. The hopping DEP force further concentrated the Aβs and removed the non-specific plasma proteins. Consequently, our sensor achieved a limit of detection (LOD) of approximately ∼ 0.15 pg/mL for both Aβ_1-40 and Aβ_1-42 in the standard plasma. Finally, comparing the ratio between Aβ_1-40 and Aβ_1-42 signals, we distinguished AD patients from cognitively normal subjects with 95.83% accuracy and 92.31% precision (n = 24, p < 0.0001, One-way ANOVA).