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

• Published in: Biosensors & bioelectronics Vol. 195; p. 113668
• Main Authors: Kim, Hye Jin, Choi, Woongsun, San Lee, Jin, Choi, Jungkyu, Choi, Nakwon, Hwang, Kyo Seon
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.01.2022
• Subjects: Alzheimer disease; Alzheimer's disease; amyloid; Amyloid-beta; biocompatible materials; biosensors; detection limit; dielectrophoresis; disease diagnosis; filtration; Hopping dielectrophoretic force; hydrogels; Plasma-based diagnosis; Porosity-tunable hydrogel; Porosity-tunable hydrogel; Plasma-based diagnosis; Hopping dielectrophoretic force; Alzheimer's disease; Amyloid-beta
• ISSN: 0956-5663; 1873-4235; 1873-4235
• DOI: 10.1016/j.bios.2021.113668

Analysis of a ratio between amyloid beta 1–40 and 1–42 (Aβ1-40 and Aβ1-42) 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 Aβ1-40 and Aβ1-42 in the standard plasma. Finally, comparing the ratio between Aβ1-40 and Aβ1-42 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). •Plasma levels of Aβ1-40 and Aβ1-42 represent a risk of Alzheimer's disease.•Hydrogel-patterned SME sensor with a hopping DEP force allowed for analyzing Aβs.•Hydrogel's 3D mesh structure filters non-specific plasma proteins larger than Aβs.•Hopping DEP force concentrates Aβs and removes non-specific plasma proteins.•Ratiometric analysis of Aβ1-40 and Aβ1-42 enables highly accurate diagnosis of AD.