School of Electrical and Computer Engineering, Cornell University, Ithaca, 14853, NY, USA.
Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, 14853, NY, USA.
Sci Rep. 2020 Feb 20;10(1):3075. doi: 10.1038/s41598-020-58133-0.
Emergent trends in the device development for neural prosthetics have focused on establishing stimulus localization, improving longevity through immune compatibility, reducing energy re-quirements, and embedding active control in the devices. Ultrasound stimulation can single-handedly address several of these challenges. Ultrasonic stimulus of neurons has been studied extensively from 100 kHz to 10 MHz, with high penetration but less localization. In this paper, a chip-scale device consisting of piezoelectric Aluminum Nitride ultrasonic transducers was engineered to deliver gigahertz (GHz) ultrasonic stimulus to the human neural cells. These devices provide a path towards complementary metal oxide semiconductor (CMOS) integration towards fully controllable neural devices. At GHz frequencies, ultrasonic wavelengths in water are a few microns and have an absorption depth of 10-20 µm. This confinement of energy can be used to control stimulation volume within a single neuron. This paper is the first proof-of-concept study to demonstrate that GHz ultrasound can stimulate neurons in vitro. By utilizing optical calcium imaging, which records calcium ion flux indicating occurrence of an action potential, this paper demonstrates that an application of a nontoxic dosage of GHz ultrasonic waves [Formula: see text] caused an average normalized fluorescence intensity recordings >1.40 for the calcium transients. Electrical effects due to chip-scale ultrasound delivery was discounted as the sole mechanism in stimulation, with effects tested at α = 0.01 statistical significance amongst all intensities and con-trol groups. Ionic transients recorded optically were confirmed to be mediated by ion channels and experimental data suggests an insignificant thermal contributions to stimulation, with a predicted increase of 0.03 C for [Formula: see text] This paper paves the experimental framework to further explore chip-scale axon and neuron specific neural stimulation, with future applications in neural prosthetics, chip scale neural engineering, and extensions to different tissue and cell types.
神经修复体的设备开发出现了一些新趋势，这些趋势集中于实现刺激定位、通过免疫兼容性提高设备寿命、降低能量需求，并在设备中嵌入主动控制。超声刺激可以单独解决其中的一些挑战。人们已经从 100kHz 到 10MHz 的范围内广泛研究了神经元的超声刺激，这种刺激具有较高的穿透性但定位效果较差。在本文中，设计了一种由压电氮化铝超声换能器组成的芯片级设备，用于向人类神经细胞提供千兆赫兹 (GHz) 超声刺激。这些设备为向完全可控的神经设备进行互补金属氧化物半导体 (CMOS) 集成提供了一条途径。在 GHz 频率下，水中的超声波波长为数微米，吸收深度为 10-20μm。这种能量的限制可以用于控制单个神经元内的刺激体积。本文是第一个证明概念的研究，证明了 GHz 超声可以在体外刺激神经元。通过利用光学钙成像技术，该技术记录表明动作电位发生的钙离子通量，本文证明了应用无毒剂量的 GHz 超声波 [Formula: see text] 可使钙瞬变的平均归一化荧光强度记录值 >1.40。由于芯片级超声传输引起的电效应被排除为刺激的唯一机制，在所有强度和对照组中，以 α = 0.01 的统计显著性进行了测试。通过光学记录证实了离子瞬变是由离子通道介导的，实验数据表明刺激的热贡献可以忽略不计，对于 [Formula: see text] 预测会增加 0.03°C。本文为进一步探索芯片级轴突和神经元特定的神经刺激铺平了实验框架，未来可应用于神经修复体、芯片级神经工程以及不同组织和细胞类型的扩展。
