Enhancing thrombolysis efficiency using acoustic vortex tweezers and microbubbles: a microscale mechanistic study with experimental validation

Abstract

Previous research has shown that acoustic vortex tweezers (AVT) combined with microbubbles (MBs) and tissue plasminogen activator (t-PA) can enhance thrombolytic efficiency. However, due to varying evaluation methods, an objective framework for investigating its mechanisms is lacking. This study establishes a standardized thrombolysis evaluation protocol to compare AVT, t-PA, and MBs with mainstream sonothrombolysis and to explore their thrombolytic mechanisms. A miniature ultrasound transducer capable of generating an AVT field was applied to fluorescent fibrin clots. The MB penetration and fibrin structure changes were observed using a high-speed camera and confocal microscopy. The drug permeability, thrombolytic efficiency, fragment size, and quantity were then quantified to assess the efficacy and safety of AVT. The results showed that AVT with MBs produced deeper (up to 30 μm) and wider MBs channels and increased fibrin looseness by 32.6 %, significantly enhancing t-PA penetration and fibrin clot dissolution. Within 30 min, the dissolution area in the AVT + t-PA + MBs group was 43.6 % larger than the t-PA only group, without creating excessive or oversized fragments. These findings confirm the potential of AVT for promoting fibrin disruption and drug penetration. Future validation using ex vivo vascular models and animal studies may position AVT as an important adjunct therapy in clinical thrombolysis.