Amyloid beta detection by faradaic electrochemical impedance spectroscopy using interdigitated microelectrodes

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.