Alzheimer’s disease (AD), a heterogeneous pathological process representing the most common causes of dementia worldwide, has required early and accurate diagnostic tools. Neuropathological hallmar...

Amyloid beta (aβ) 1-42, a peptide that is 1-42 amino acids long, is a major component of senile plaques in the brains of patients with Alzheimer’s disease. Aβ detection has become an essential antecedence to predict the declining mental abilities of patients. In this paper, a probeless capacitive biosensor for the non-Faradaic detection of aβ 1-42 peptide was developed by immobilizing a specific anti-aβ antibody onto a self-assembled monolayer functionalized interdigitated chain-shaped electrode (anti-aβ/SAM/ICE). The novelty and difference of this article from previous studies is the direct detection of aβ peptide with no redox probe ((Fe(CN)₆)^3−/4−), which can avoid the denaturation of the protein caused by the metallization (binding of aβ to metal ion Fe which is presented in the redox couple). The direct detection of aβ with no redox probe is performed by non-Faradaic capacitive measurement, which is greatly different from the Faradaic measurement of the charge transfer resistance of the redox probe. The detection of various aβ 1-42 peptide concentrations in human serum (HS) was performed by measuring the relative change in electrode interfacial capacitance due to the specific antibody-aβ binding. Capacitance change in the anti-aβ/SAM/ICE biosensor showed a linear detection range between 10 pg mL⁻¹ and 10⁴ pg mL⁻¹, and a detection limit of 7.5 pg mL⁻¹ in HS, which was much lower than the limit of detection for CSF aβ 1-42 (~500 pg mL⁻¹) and other biosensors. The small dissociation constant K_d of the antibody-antigen interaction was also found to be 0.016 nM in HS, indicating the high binding affinity of the anti-aβ/SAM/ICE biosensor in the recognizing of aβ 1-42. Thus, the developed sensor can be used for label-free and direct measurement of aβ 1-42 peptide and for point-of-care diagnosis of Alzheimer’s disease without redox probe.