Target-induced click hydrogel paper-based analytical device: A rapid and sensitive approach for multi-analyte detection

Paper-based analytical devices (PADs) have revolutionized environmental monitoring, food safety and disease diagnosis due to their inherent portability, simplicity, and cost-efficiency. Among these, distance-based PADs enable instrument-free quantitative detection by translating target concentration into measurable flow distance. Stimuli-responsive hydrogels, whose viscosity can be altered by target-triggered sol-gel transitions, are widely used in distance-based PADs, among which click-chemistry hydrogels stand out by virtue of their efficient and stable covalent bonding. Such stable covalent networks provide click hydrogels with strong anti-swelling and anti-degradation properties, crucial for reliable performance in on-site environments. In this study, we present a novel distance-based PAD approach that integrates target-induced click hydrogels, establishing a highly stable, versatile, and sensitive platform for multi-analyte detection. This innovative PAD makes use of copper-catalyzed azide-alkyne cycloaddition click chemistry to craft hydrogels from polyethylene glycol derivatives. Notably, specific target analytes like Cu²⁺, ascorbic acid, alkaline phosphatase, and pyrophosphate finely modulate the hydrogel crosslinking degree, causing noticeable changes in its viscosity. These viscosity variations are then translated into measurable flow distances on pH test papers, providing a direct and quantitative visual readout without the need for complex instrumentation or extensive operation. The entire detection process, from sample loading to result readout, can be accomplished within approximately 5 min, demonstrating the rapid analysis capability of this approach. This work offers stable, rapid, sensitive, and cost-effective multi-target detection, significantly advancing instrument-free PAD technology and expanding the scope of versatile analyte detection.