Abstract
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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Acknowledgements
Figures 1c, 3a, 4a, b, l, and 5a, o, were provided by Servier Medical Art (https://smart.servier.com), licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). We gratefully acknowledge the financial support by the Young Top-Notch Talents of the Ten-Thousand Talents Program (QWH1615018), Shanghai Scientific and Technological Innovation Action Plan (23ZR1403200, 22S31901900), National Natural Science Foundation of China (22374029 and 22174024 to X.F.; 22174022 and 22127806 to J.K.; 82472962 to W.W.; 82272174 and 81827901 to H.S.), and Natural Science Foundation of Shanghai (24ZR1459800 to W.W.).
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All authors have given approval to the final version of the manuscript. Huiwen Xiong conducted the initial conceptualization and finalized the manuscript drafts. Huiwen Xiong and Chenxin Zhu finished the establishment and verification of instruments, and undertook the whole test. Ashraf Ghazala performed in-depth revision of the manuscript, improving its technical clarity, narrative structure, and scientific rigor. Xiaopeng Guo and Lin Liu contributed to the synthesis of nanomaterials. Haonan Wang help undertake the animal experiments. Hui Chen assisted in the methodology. Wenhao Weng supervised the clinical experiments. Huali Shen supervised the establishment of instruments. Jilie Kong provided the funding support. Xueen Fang was responsible for overseeing the entire project and supervised the study. All the authors provided constructive and valuable feedback on the manuscript.
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Xiong, H., Zhu, C., Ashraf, G. et al. In situ electrochemiluminescence microneedle device for real-time biomarker monitoring in vivo. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70686-8
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DOI: https://doi.org/10.1038/s41467-026-70686-8
