Clinical application of serological Alzheimer's disease diagnosis using a highly sensitive biosensor with hydrogel-enhanced dielectrophoretic force

Abstract

Analysis of a ratio between amyloid beta 1-40 and 1-42 (A beta(1-40) and A beta(1-42)) presented in plasm enables a highly accurate diagnosis of Alzheimer's disease (AD). However, the analysis of plasma A beta s is not routinely conducted because of the lack of A beta detection techniques sensitive enough to specifically detect A beta 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 A beta 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 A beta s and removed the non-specific plasma proteins. Consequently, our sensor achieved a limit of detection (LOD) of approximately similar to 0.15 pg/mL for both A beta(1-40) and A beta(1-42) in the standard plasma. Finally, comparing the ratio between A beta(1-40) and A beta(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).