Engineering Caged Microbubbles for Controlled Acoustic Cavitation and Pressure Sensing

Acoustic microbubbles (MBs) are an important class of biomaterials that play an increasingly prominent role in advanced applications such as contrast and super-resolution imaging, sonoporation, drug delivery, microrobotics, and biosensors. The ability to control and regulate acoustic cavitation of MBs by ultrasound (US) pulses is fundamental to achieve these applications. However, most MBs are coated with a soft shell that may undergo alteration (e.g., rupture or dissolution) under insonification and result in unintended acoustic responses. This work introduces a system of stable polymeric caged MBs in which the gas core is encapsulated within a rigid but nanoporous shell, so that their acoustic response is regulated by both shell compressibility and metastructure (i.e., porosity), thus permitting high control over their cavitation behaviors via pulse manipulation. These caged MBs are fabricated via a method of interfacial nanoprecipitation. Fabrication parameters can be varied to manipulate shell elasticity and porosity and subsequently control a wide range of acoustic properties such as tuning resonance frequency, controlling modes of nonlinear cavitation. Furthermore, the cavitation of caged MBs can be manipulated to develop tunable acoustic pressure sensors. These caged MBs offer insight of the acoustic–material relationship to design acoustic biomaterials for US-guided diagnostic and therapeutic technologies.