Generation of ultrasound using the optoacoustic effect has received increasing attention in the field of imaging and translational medicine. However, none of the current optoacoustic converters has been used for neural modulation. Here, we developed a miniaturized Fiber-Optoacoustic Converter (FOC), which has a diameter of 600 μm, and can convert nano-second laser pulses into acoustic waves through the optoacoustic effect. The ball shaped FOC is composed of one ZnO /epoxy based diffusion layer and two graphite/epoxy based absorption layer. The radiofrequency spectrum of the generated US frequency ranges from 0.1-5 MHz, with multiple frequencies peaks at 0.5, 1 and 3MHz. Compared to traditional ultrasound transducers, the FOC system has the advantages of miniaturized size, superior spatial resolution, and produces omnidirectional propagating acoustic wave. Using this FOC system, we show that ultrasound can directly activate individual cortical neuron in vitro with a radius of 500 μm around the FOC tip, and generate intracellular Ca2+ transient without neural damage. Neural activation is the consequence of mechanical disturbance of neuronal membrane, rather than direct laser or photothermal stimulation. Finally, we combine FOC neural modulation with electrophysiology, and achieve direct and spatially confined neural stimulation in vivo. The FOC system opens new possibilities to use optoacoustic effect as a new method for precise neural modulation.
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