Detection of β-amyloid peptide aggregates by quartz crystal microbalance based on dual-aptamer assisted signal amplification

Abstract

β-amyloid peptide (Aβ) aggregates are regarded as a typical neuropathology hallmark for the diagnosis of Alzheimer's disease (AD). Aβ₄₀ aggregates include soluble oligomers (Aβ₄₀O) and insoluble fibrils (Aβ₄₀F). Both of them can simultaneously bind to two different kinds of its aptamer (Apt1 and Apt2). As a mass-sensitive sensing platform, quartz crystal microbalance (QCM) converts changes in mass on the Au chip surface into frequency shift. Here, a dual-aptamer assisted Aβ₄₀ aggregates assay was developed. Taking Aβ₄₀O detection as an example, Apt2 was modified on the surface of Au chip by Au-S bond. Subsequently, the solution consisted of Aβ₄₀O and gold nanoparticles-Apt1 (AuNPs-Apt1) were injected into the QCM chamber. As a result, Aβ₄₀O was specifically recognized and captured by Apt2. AuNPs-Apt1 were also combined on the surface of the Au chip because Aβ₄₀O can simultaneously bind to Apt1. Then, a significant frequency shift occurred because of the large weight of AuNPs. Similarly, this procedure can be used to detect Aβ₄₀F. This QCM biosensor was able to detect Aβ₄₀O with a range of 0.2-10 pM with a detection limit of 0.11 pM, while the linear range for Aβ₄₀F was 0.1-10 pM with a detection limit of 0.02 pM. This QCM biosensor was simple and highly sensitive, which provided a new method for Aβ₄₀ aggregates detection.

Keywords: Alzheimer disease; Aβ(40) aggregates; Gold nanoparticles; Quartz crystal microbalance; β-amyloid peptide.