  Focused ultrasound has attracted great attention in minimally invasive
therapy, gene delivery, brain stimulation, etc. Frequency below 1 MHz has been
identified preferable for high-efficacy drug delivery, gene transfection and
neurostimulation due to minimized tissue heating and cell fragmentation.
However, the poor spatial resolution of several millimeters and the large
device diameter of ~25 mm of current sub-MHz ultrasound technology severely
hinders its further applications for effective, precise, safe and wearable
biomedical studies and clinical use. To address this issue, we report the
development of a novel fiber-based optoacoustic emitter (FOE). The FOE, a new
miniaturized ultrasound source, is composed of an optical diffusion coating
layer and an expansion coating layer at an optical fiber distal end with a
diameter of approximately 500 microns. Taking advantage of the fiber size and
diffusive nanoparticles introduced, the ultrasound generated by the FOEs showed
a spatial confinement of sub-millimeter. The optoacoustic conversion efficiency
was maximized through choosing absorbing nanomaterials and thermal expansion
matrix. Controllable frequencies in the range of 0.083 MHz to 5.500 MHz were
achieved through using the diffusion layer as a damping material or modifying
the nano-composition in the expansion layer. This sub-MHz frequency
controllability allows FOEs to be used as a localized ultrasound source for
precise cell modulation. We demonstrated optoacoustic cell membrane
sonoporation with a localization of sub-millimeter and negligible heat
deposition, implicating its broad biomedical applications, including
region-specific drug delivery, gene transfection as well as localized neuron
stimulation.
