We developed an interdigitated microelectrode (IME) sensor system for blood-based Alzheimer’s disease (AD) diagnosis based on impedimetric detection of amyloid-β (Aβ) protein, which is a representative candidate biomarker for AD. The IME sensing device was fabricated using a surface micromachining process. For highly sensitive detection of several tens to hundreds of picogram/mL of Aβ in blood, medium change from plasma to PBS buffer was utilized with signal cancellation and amplification processing (SCAP) system. The system demonstrated approximately 100-folds higher sensitivity according to the concentrations. A robust antibody-immobilization process was used for stability during medium change. Selectivity of the reaction due to the affinity of Aβ to the antibody and the sensitivity according to the concentration of Aβ were also demonstrated. Considering these basic characteristics of the IME sensor system, the medium change was optimized in relation to the absolute value of impedance change and differentiated impedance changes for real plasma based Aβ detection. Finally, the detection of Aβ levels in transgenic and wild-type mouse plasma samples was accomplished with the designed sensor system and the medium-changing method. The results confirmed the potential of this system to discriminate between patients and healthy controls, which would enable blood-based AD diagnosis.

We compared levels of Aβ by self-standard in plasma using an interdigitated microelectrode sensor to detect Alzheimer disease.

Faradaic electrochemical impedance spectroscopy (f-EIS) in the presence of redox reagent, e.g., [Fe(CN)₆]^3−/4−, is widely used in biosensors owing to its high sensitivity. However, in sensors detecting amyloid beta (Aβ), the redox reagent can cause the aggregation of Aβ, which is a disturbance factor in accurate detection. Here, we propose an interdigitated microelectrode (IME) based f-EIS technique that can alleviate the aggregation of Aβ and achieve high sensitivity by buffer control. The proposed method was verified by analyzing three different EIS-based sensors: non-faradaic EIS (nf-EIS), f-EIS, and the proposed f-EIS with buffer control. We analyzed the equivalent circuits of nf-EIS and f-EIS sensors. The dominant factors of sensitivity were analyzed, and the impedance change rates via Aβ reaction was compared. We measured the sensitivity of the IME sensors based on nf-EIS, f-EIS, and the proposed f-EIS. The results demonstrate that the proposed EIS-based IME sensor can detect Aβ with a sensitivity of 7.40-fold and 10.93-fold higher than the nf-EIS and the f-EIS sensors, respectively.