Paper-based sensors for visual detection of alkaline phosphatase and alpha-fetoprotein via the distance readout

The development of paper-based sensors with the distance readout is particularly attractive for the point-of-care testing (POCT) of biomarkers. Herein, we report a paper-based sensor that can convert the viscosity change caused by the hydrogel degradation into the variance of water flow distance on the paper. The detection of alkaline phosphatase (ALP) and alpha-fetoprotein (AFP) is demonstrated as examples. Copper alginate (Cu-Alg) hydrogel can be formed when mixing the aqueous solutions of Cu2+ and alginate. The introduction of pyrophosphate ion (PPi) induces the gel-sol transition due to the high affinity between Cu2+ and PPi. However, in the presence of ALP, the gel-sol transition is prevented due to the hydrolysis of PPi by ALP. In these processes, the viscosity changes of the hydrogels are translated into the differences of the flow distances on the pH test papers. In addition, the tilt of the papers can increase the accuracy of detection. The detection of AFP is also fulfilled via the construction of the paper-based immunosensor using the ALP-linked AFP detection antibody. The developed paper-based sensors show excellent performance for the quantitative detection of biomarkers in real samples with remarkable selectivity. Overall, this convenient method has great potential in POCT applications.