Paper-based origami assisted and enhanced electroanalytical detection of β-Amyloid peptide in plasma samples

In this novel work, we demonstrate how the analytical performance towards β-amyloid (Aβ(1–42) detection can be easily improved by using a printed label-free electrochemical immunosensor coupled to an external paper-based origami. Coupling the immunosensor with a customized foldable origami allows for an increase of resulting sensitivity towards the detection of Aβ(1–42) in both standard and biological samples. The exceptional features of paper are fundamental for the analysis of Aβ(1–42), recognized as a central indicator of Alzheimer’s pathology, considering the low levels in plasma associated with early-stage disease. The proposed strategy highlights up to a 5-fold signal enhancement in both buffer and plasma at low Aβ(1–42) concentrations, bringing the platform’s performance toward clinical requirements. The immunoplatform has been systematically optimized through electrochemical characterization and parameter tuning, achieving limits of detection of 2.7 ng/mL in buffer and 4.7 ng/mL in undiluted plasma, with a linear range up to 1 μg/mL. The platform shows satisfactory repeatability (<10%) and excellent selectivity in the presence of interfering plasma proteins. Overall, this work offers a promising foundation for the development of accessible and scalable tools for early Alzheimer's disease screening. • Label-free immunosensor detects Aβ(1–42) in buffer and undiluted plasma. • Paper-based origami enables 4–5× signal boost at low Aβ(1–42) levels. • Device shows excellent selectivity against common plasma proteins. • Rapid, low-cost platform suitable for point-of-care Alzheimer’s screening.