Highly sensitive detection of different aggregation stages of Aβ1-42 -amyloid peptide in urine-like samples by auto-fluorescence

Several studies demonstrated that the fibrillation process of β-amyloid peptides, including Aβ1-42, can be toxic at different stages. Such process is involved in the formation of plaques in the brains of patients affected by neurodegenerative diseases, such as Alzheimer's or Parkinson's disease. Therefore, detecting different stages of β-amyloid aggregation in a sample of body fluid poses a significant challenge to evaluate the stadiation of an eventual neurodegenerative pathology and hence to achieve a certain diagnosis in the very first stages of the disease. Nowadays, techniques like mass spectroscopy or analytical centrifugation are available for studying amyloid aggregations, but they remain expensive and time-consuming and hence, not suitable for routine clinical practice. Here, we show the development of a novel sensor designed to detect low abundant aggregates of Aβ1-42 in a body fluid that mimics human urine. This sensor utilizes an innovative technique that exploits the accumulation efficiency of an electric field generated by the pyroelectric effect to concentrate tiny volumes of sample onto a reaction slide. This concentration allows for the detection of the auto-fluorescent signal of the aggregates. This method, which we refer to as a ‘pyro-electrohydrodynamic jet ' or p-jet, uses the intrinsic electric field of a ferroelectric material without external electrodes, resulting in a more compact and streamlined electro-hydrodynamic extraction of tiny droplets. A label-free, rapid, and sensitive classification of amyloids and their aggregation stages is achievable. Demonstrating picogram-level sensitivity for β-amyloid aggregates in urine-like samples, this method significantly outperforms common spectroscopic techniques.