Self-assembly of non-close-packed photonic crystal hydrogels enables robust point-of-care detection of microRNA in body fluids.

MicroRNA, especially microRNA-21 (miRNA-21), is a key oncogenic regulator, motivating the development of ultrasensitive and operationally simple detection strategies. Yet, existing approaches still rely on benchtop instrumentation and offer limited utility at the point of care. Here we report a point-of-care photonic crystal hydrogel (PCH) biosensor in which a self-assembled, non-close-packed colloidal lattice is coupled to a DNA-functionalized hydrogel matrix to convert miRNA-21 recognition into amplified photonic responses. The localized charge redistribution and volume-insertion effects through Watson-Crick base pairing elevate internal osmotic pressure, driving hydrogel swelling that increases the lattice spacing. The non-close-packed architecture provides large interstitial domains that facilitate rapid miRNA-21 penetration and magnify the resulting photonic response. The swelling-induced lattice expansion generates pronounced diffraction changes and structural-color transitions readily quantifiable by smartphone. The designed sensor achieves high sequence selectivity, a detection limit of 0.32 nM, and robust performance in saliva and serum. These results establish a mechanistically transparent, low-cost platform for portable nucleic-acid diagnostics and highlight the synergy between hydrogel ionodynamics and lattice photonics.