Visual Ratiometric Fluorescent Capsule for Ultralow Detection of Indoxyl Sulfate: A Paradigm Shift in Point-of-Care Chronic Kidney Disease Diagnostics

Indoxyl sulfate (IS), a protein-bound uremic toxin implicated in chronic kidney disease (CKD) progression and extrarenal pathologies, necessitates the development of accessible monitoring tools for point-of-care diagnostics. To address this challenge, we engineered a portable fluorescent capsule device by encapsulating an antenna-effect-enhanced europium metal-organic gel (EuMOG) within a biocompatible alginate matrix. This innovative sensor exhibits specific ratiometric fluorescence modulation toward IS via a photoinduced electron transfer (PET) mechanism, wherein IS binding triggers a distinct emission shift: quenching of Eu³⁺ red emission (619 nm) with concurrent 29-fold enhancement of ligand-centered blue emission (393 nm). Significantly, the capsule achieves ultrasensitive detection with record-low detection limits of 1.9 ppb in urine and 43.61 ppm in serum─surpassing conventional methods by orders of magnitude─while maintaining selectivity against structurally similar metabolites (e.g., uric acid, creatinine) and physiological interferents in complex matrices. The visually discernible pink-to-blue transition under UV light enables instrument-free, real-time semiquantification within 16 min, as validated by linear ratiometric responses across clinically relevant IS concentrations (1-900 μM, R² = 0.996). The integration of room-temperature synthesis, dynamic capsule dissolution kinetics, and PET-driven specificity establishes a paradigm shift toward deployable CKD diagnostics, particularly for resource-limited settings.