Enhanced functional DNA biosensor for distance-based read-by-eye quantification of various analytes based on starch-hydrolysis-adjusted wettability change in paper devices.

Low-cost, equipment-free and quantitative detection of a wide range of analytes of interest at home and in the field holds the potential to revolutionize disease diagnosis, environmental pollution monitoring, and food safety analysis. Herein, we describe a functional DNA biosensor for the first time that integrates analyte-directed assembly of enzyme-coated microbead probes for robust yet efficient signal amplification with a simple quantitative detection motif of distance measurement on portable paper devices based on starch-hydrolysis-adjusted wettability change of paper. Its utility is well demonstrated with highly sensitive and specific detection of model analytes ranging from adenosine (an important small biomolecule; 1.6 μM detection limit) to interferon-γ (a protein marker; 0.3 nM detection limit) and Pb (a highly toxic metal ion; 0.5 nM detection limit) by simply using an inexpensive, ubiquitous ruler. The developed general method with the distance-measuring readout should be easily tailored for the portable, read-by-eye, quantitative detection of many other types of analytical targets by taking advantage of their specific functional DNA partners like aptamers and DNAzymes.