Acoustically driven micro/nanobubbles: from fundamental mechanisms to biomedical applications.

Abstract

Acoustically driven micro/nanobubbles, as a bridge between macroscopic acoustic fields and microscopic biological machinery, have shown considerable promise due to their non-contact actuation, tunable mechanical responses, and favorable biocompatibility. Recent advances in bubble formulation and acoustic control have further expanded their capabilities, enabling targeted membrane permeabilization, enhanced molecular transport, and precise manipulation at the microscale. In this review, we summarize the fundamental mechanisms linking bubble dynamics to biologically relevant effects under ultrasound and establish quantitative design criteria that govern the coupling between acoustic parameters, bubble behavior, and therapeutic performance. We then organize biomedical applications across scales, spanning single-cell manipulation, tissue-level barrier modulation, and organ-scale imaging and therapeutic interventions. Particular attention is given to how acoustic modes and bubble configurations translate into measurable performance metrics, as well as the limitations that constrain reproducibility and safety in complex biological environments. Finally, we discuss key challenges for practical translation from an engineering perspective and propose strategies for improving controllability, standardization, and system integration. By providing a framework to overcome the inherent randomness of bubble-acoustic interactions in clinical translation, this review outlines a roadmap toward reliable and programmable mechano-bio platforms for closed-loop, patient-adaptive interventions.