Electrical detection of β-amyloid (1-40) using scanning tunneling microscopy

Numerous studies have shown that the presence of β-amyloid (1-40) in cerebrospinal fluid can be used as a potential biomarker for Alzheimerʹs disease. Identifying biomarkers for Alzheimerʹs disease is highly important because these biomarkers could be used to establish the diagnosis before the disease reaches clinical severity. In this study, a vertically configured electrical detection system associated with scanning tunneling microscopy (STM) was used to characterize antigen–antibody binding interactions. The proposed technique can be easily utilized to construct a multiple measurement system in a protein chip. The immunocomplexes used in the model protein comprise β-amyloid (1-40), corresponding antibody fragments, and gold nanoparticle–antibody conjugates. The electrical tunneling current between the STM tip and these complexes exhibited a peak-like pulse, where the frequency of these pulses was dependent on the surface density of bound complexes. Hence, a quantitative measurement of β-amyloid concentration from a periodogram analysis of peak frequency was successfully achieved at concentrations as low as 1 fg/mL.