A Fiber Optoacoustic Emitter with Controlled Ultrasound Frequency for Cell Membrane Sonoporation at Submillimeter Spatial Resolution

Abstract Focused ultrasound has attracted great attention in minimally invasive therapeutic and mechanism studies. Frequency below 1 MHz is identified preferable for high-efficiency bio-modulation. However, the poor spatial confinement of several millimeters and large device diameter of ∼25 mm of typical sub-MHz ultrasound technology suffered from the diffraction limit, severely hindering its further applications. To address it, a fiber-based optoacoustic emitter (FOE) is developed, serving as a miniaturized ultrasound point source, with sub-millimeter confinement, composed of an optical diffusion layer and an expansion layer on an optical fiber. By modifying acoustic damping and light absorption performance, controllable frequencies in the range of 0.083 MHz to 5.500 MHz are achieved and further induce cell membrane sonoporation with frequency dependent efficiency. By solving the problem of compromise between sub-MHz frequency and sub-millimeter precision via breaking the diffraction limit, the FOE shows a great potential in region-specific drug delivery, gene transfection and neurostimulation.