Neuromodulation by ultrasound has recently received attention due to its noninvasive stimulation capability for treating brain diseases. Although there have been several studies related to ultrasonic neuromodulation, these studies have suffered from poor spatial resolution of the ultrasound and low repeatability with a fixed condition caused by conventional and commercialized ultrasound transducers. In addition, the underlying physics and mechanisms of ultrasonic neuromodulation are still unknown. To determine these mechanisms and accurately modulate neural circuits, researchers must have a precisely controllable ultrasound transducer to conduct experiments at the cellular level. Herein, we introduce a new MEMS ultrasound stimulation system for modulating neurons or brain slices with high spatial resolution. The piezoelectric micromachined ultrasonic transducers (pMUTs) with small membranes (sub-mm membranes) generate enough power to stimulate neurons and enable precise modulation of neural circuits. We designed the ultrasound transducer as an array structure to enable localized modulation in the target region. In addition, we integrated a cell culture chamber with the system to make it compatible with conventional cell-based experiments, such as in vitro cell cultures and brain slices. In this work, we successfully demonstrated the functionality of the system by showing that the number of responding cells is proportional to the acoustic intensity of the applied ultrasound. We also demonstrated localized stimulation capability with high spatial resolution by conducting experiments in which cocultured cells responded only around a working transducer.

超声波的神经调节由于其用于治疗脑部疾病的无创刺激能力而最近受到关注。虽然已经有几项与超声神经调节相关的研究，但这些研究都受到了超声空间分辨率差和传统和商业化超声换能器在固定条件下的低可重复性的影响。此外，超声神经调节的基本物理原理和机制仍然未知。为了确定这些机制并准确地调节神经回路，研究人员必须有一个精确可控的超声换能器来在细胞水平上进行实验。在此，我们介绍了一种新的 MEMS 超声刺激系统，用于调制具有高空间分辨率的神经元或脑切片。带有小膜（亚毫米膜）的压电微机械超声换能器 (pMUT) 产生足够的能量来刺激神经元并实现神经回路的精确调制。我们将超声换能器设计为阵列结构，以实现目标区域的局部调制。此外，我们将细胞培养室与系统集成，使其与传统的基于细胞的实验兼容，例如体外细胞培养和脑切片。在这项工作中，我们通过显示响应细胞的数量与应用超声的声强度成正比，成功地证明了系统的功能。我们还通过进行共培养细胞仅在工作传感器周围响应的实验证明了具有高空间分辨率的局部刺激能力。