Real-Time and Rapid Fibrinolysis Analysis Based on Fibrin-Loaded Tubular SiO2–TiO2 Hybrid Inverse Opal

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Abstract
The fibrinolytic system serves as the core mechanism for maintaining vascular patency and cardiovascular homeostasis, and precise, rapid fibrinolysis analysis is crucial for the clinical prediction of thrombosis or bleeding. In this study, the fibrin-loaded fibrinolytic responsive interference layer was constructed using tubular SiO2–TiO2 hybrid inverse opal (IO) as the scaffold and was combined with ordered porous layer interferometry (OPLI) technology for real-time and rapid fibrinolysis analysis. The tubular IO prepared by the sol–gel co-growth method can load more fibrin and endow them with optical interference effects. The fibrinolysis triggered by the model enzyme nattokinase leads to the migration of the interference fringes of the interference layer, which could be reflected by optical thickness changes (ΔOT) tracked in real-time by the OPLI system. Compared with the silica colloidal crystal film with opal structure, the tubular SiO2–TiO2 hybrid IO exhibited higher sensitivity and shorter detection times in fibrinolysis analysis. Furthermore, the introduction of lysine into the fibrinolytic responsive interference layer can further shorten the detection time of fibrinolytic activity of nattokinase to 10 min. Importantly, both the fibrinolytic interference sensing models with and without lysine adsorption demonstrated high reliability in fibrinolysis analysis of nattokinase-spiked whole blood samples. A parallel comparison with the thromboelastography method further validated the accuracy of this method.
Funding Information
  • Jiangsu Provincial Key Research and Development Program (BE2021355)
  • Leading Talent Program for Gusu Innovation and Entrepreneurship in Suzhou (ZXL2022635)

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