Supramolecular Hydrogel Microneedle Platform for In Situ Melatonin Monitoring

Supramolecular interactionsincluding host–guest inclusion and nucleic acid self-assembly—offer reversible and specific recognition motifs for designing functional materials. Herein, we report a supramolecular hydrogel microneedle platform that synergistically integrates β-cyclodextrin (β-CD) host–guest chemistry with hybridization chain reaction (HCR) self-assembly for in situ melatonin monitoring in skin interstitial fluid (ISF). β-CD functions as a supramolecular capture unit: its hydrophobic cavity selectively enriches melatonin via host–guest complexation, while its peripheral hydroxyl groups form dense hydrogen bonds with the polymer network, creating physical crosslinks that enhance swelling kinetics (equilibrium ratio 181.20%) and mechanical robustness (fracture force ~0.8 N/needle). A triggerable aptamer pre-encapsulated in the microneedle undergoes a conformational switch upon melatonin binding, initiating an HCR cascade—a dynamic supramolecular self-assembly process that generates exponential fluorescence amplification. This integrated platform requires no sample pretreatment, achieves a detection limit of 10 pM, and exhibits excellent selectivity and biocompatibility. In a living rat model, the sensor faithfully captured circadian melatonin fluctuations, correlating well with ELISA and LC-MS/MS (R2 > 0.95). This work establishes a supramolecular materials design strategy for minimally invasive, in situ monitoring of hydrophobic biomarkers.