Distance-based β-amyloid protein detection on PADs for the scanning and subsequent follow-up of Alzheimer’s disease in human urine samples

We report on the first development of a simple distance-based β-amyloid (Aβ) protein quantification using
a paper-based device (dPAD) to screen for Alzheimer’s disease (AD) and to subsequently follow up on its
influence, i.e., clinical dementia. This sensor method is based on the transformation of a free acid form
and its binding with a basic form of bromocresol purple (BCP) through its electrostatic interaction with an
Aβ protein. This sensor can measure the length of color change from yellow to blue-green on a paper
strip, with this change proportional to the amount of Aβ protein level. We found that the linearity for Aβ
protein monitoring was in the range from 0.50 to 10.0 ng mL−1, and the subsequent naked-eye detection
limit for Aβ was 0.20 ng mL−1. This system also provided high reproducibility and with no apparent interference
effect for Aβ protein analysis in human urine samples. Furthermore, our developed dPAD constituted
an accurate and effective device to precisely determine an Aβ protein concentration in real samples,
with percentage recoveries in the range of 97–103%, and with the highest relative standard deviation of
5.41%. Subsequently, the validation of our assay was assessed by comparison with a commercial ELISA
approach, with favorable results. Finally, the proposed dPAD was successfully applied to the determination
of an Aβ protein in human urine samples and showed more benefits for the unskilled user, such as costefficiency,
simplicity, low reagent usage, and low time consumption. It is also suitable for point-of-care
monitoring.