Portable non-enzymatic electrochemical biosensor based on caffeine for Alzheimer's disease diagnosis

Caffeine and its derivatives can effectively bind amyloid beta 16–22 (Aβ_16–22) fragment of amyloid beta 1–42 (Aβ_1–42), a biomarker for the early diagnosis of Alzheimer's disease (AD), by means of conformation selection, π–π stacking, van der Waals forces, and hydrogen bonding, so as to achieve high specificity and quantitative detection of Aβ_1–42. In this study, 3-mercaptopropionic acid (MPA), conductive polymer poly(thiophene-3-acetic acid) (PTAA), and pine-like/Au pine PTAA (pine PTAA) were applied to modify the electrodes, and the non-enzymatic caffeine was used as specific biorecognition element to study the analytical performance of the electrochemical sensor platform for Aβ_1–42 oligomer (AβO). It was found that caffeine/pine PTAA-based sensor with large surface area, high active sites, and excellent electrical conductivity demonstrated the widest linear range (10⁻⁸ to 100 nM) and highest sensitivity (743.77 Ω/log nM) in comparison. The prepared caffeine-based sensor was afterward applied to cerebrospinal fluid and blood tests for real sample analysis, demonstrating its potential for practical use in detecting AβO at the attomolar level. Furthermore, the non-enzymatic caffeine was constructed on the pine-like PTAA-modified screen-printed electrodes for the rapid detection of AβO using portable meter.