Binding properties of flowing fibrin-targeted microbubbles evaluated with a thrombus-embedded microchannel

Fibrin is found in both arterial and venous thrombi, which provides an important target for thrombus-targeted microbubbles (MBs) used in MB-enhanced ultrasound imaging and sonothrombolysis. A fibrin-targeted peptide, Cys-Arg-Glu-Lys-Ala (CREKA), is used to modify the commercially available SonoVue ultrasound contrast agent using a conjugation method, and the binding capacity and binding strength of the fibrin-targeted CREKA-modified SonoVue MBs are evaluated with a thrombus-embedded microchannel at a typical shear rate range of venous and arterial blood flow. The experimental results indicate that the targeted MBs bind firmly to the thrombus surface when they flow along the microchannel at a wall shear rate of up to 1000 s^-1. This work not only provides an effective method for the fabrication of fibrin-targeted MBs based on commercially available SonoVue MBs but also demonstrates an approach for evaluation of the binding properties of flowing targeted MBs under well-controlled flow conditions.