Continuous in vivo monitoring of biomarkers remains challenging due to limited sensitivity, integration, and biocompatibility. Here, we report an integrated microneedle-based electrochemiluminescence device (MN-ECLD) for real-time detection of protein biomarkers in interstitial fluid. Leveraging hydrogen-bonded organic frameworks with ultrabright, biocompatible electrochemiluminescence, the emitters were incorporated into porous gold-coated microneedle arrays and regulated via interface-specific Y-shaped probes, enabling efficient coreactant-free signal generation. The device achieved ultrasensitive protein detection in vitro with a linear range of 100 fg/mL to 10 ng/mL, a detection limit of 21.3 fg/mL, and stability over 12 days, delivering an 87-fold sensitivity enhancement over conventional emitters. In vivo, MN-ECLD enabled real-time monitoring of cardiac biomarkers, achieving early warning of acute myocardial infarction in rats and pigs, with biomarker trends consistent with serum ELISA. This work establishes a versatile platform for continuous in vivo diagnostics of acute cardiovascular and metabolic disorders.
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