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Focused ultrasound has attracted great attention in minimally invasivetherapy, gene delivery, brain stimulation, etc. Frequency below 1 MHz has beenidentified preferable for high-efficacy drug delivery, gene transfection andneurostimulation due to minimized tissue heating and cell fragmentation.However, the poor spatial resolution of several millimeters and the largedevice diameter of ~25 mm of current sub-MHz ultrasound technology severelyhinders its further applications for effective, precise, safe and wearablebiomedical studies and clinical use. To address this issue, we report thedevelopment of a novel fiber-based optoacoustic emitter (FOE). The FOE, a newminiaturized ultrasound source, is composed of an optical diffusion coatinglayer and an expansion coating layer at an optical fiber distal end with adiameter of approximately 500 microns. Taking advantage of the fiber size anddiffusive nanoparticles introduced, the ultrasound generated by the FOEs showeda spatial confinement of sub-millimeter. The optoacoustic conversion efficiencywas maximized through choosing absorbing nanomaterials and thermal expansionmatrix. Controllable frequencies in the range of 0.083 MHz to 5.500 MHz wereachieved through using the diffusion layer as a damping material or modifyingthe nano-composition in the expansion layer. This sub-MHz frequencycontrollability allows FOEs to be used as a localized ultrasound source forprecise cell modulation. We demonstrated optoacoustic cell membranesonoporation with a localization of sub-millimeter and negligible heatdeposition, implicating its broad biomedical applications, includingregion-specific drug delivery, gene transfection as well as localized neuronstimulation.

A Fiber Optoacoustic Emitter with Maximized Conversion Efficiency and Controlled Ultrasound Frequency for Biomedical Applications