Monitoring the Formation of Fibrin Clots as Part of the Coagulation Cascade Using Fluorescent Single-Walled Carbon Nanotubes

Abstract

Blood coagulation is a critical defense mechanism against bleeding that results in the conversion of liquid blood into a solid clot through a complicated cascade, which involves multiple clotting factors. One of the final steps in the coagulation pathway is the conversion of fibrinogen to insoluble fibrin mediated by thrombin. Because coagulation disorders can be life-threatening, the development of novel methods for monitoring the coagulation cascade dynamics is of high importance. Here, we use near-infrared (NIR)-fluorescent single-walled carbon nanotubes (SWCNTs) to image and monitor fibrin clotting in real time. Following the binding of fibrinogen to a tailored SWCNT platform, thrombin transforms the fibrinogen into fibrin monomers, which start to polymerize. The SWCNTs are incorporated within the clot and can be clearly visualized in the NIR-fluorescent channel, where the signal-to-noise ratio is improved compared to bright-field imaging in the visible range. Moreover, the diffusion of individual SWCNTs within the fibrin clot gradually slows down after the addition of thrombin, manifesting a coagulation rate that depends on both fibrinogen and thrombin concentrations. Our platform can open new opportunities for coagulation disorder diagnostics and allow for real-time monitoring of the coagulation cascade with a NIR optical signal output in the biological transparency window.