GHz Ultrasonic Chip-Scale Device Induces Ion Channel Stimulation in Human Neural Cells
GHz Ultrasonic Chip-Scale Device Induces Ion Channel Stimulation in Human Neural Cells
复制标题
DOI：
10.1038/s41598-020-58133-0
复制
发表时间：
2020-02-20
影响因子：
4.6
通讯作者：
Lal, Amit
中科院分区：
文献类型：
--
作者：
Balasubramanian, Priya S.;Singh, Ankur;Lal, Amit
神经义肢设备发展的新趋势集中在建立刺激定位，通过免疫兼容性提高寿命，降低能量需求，以及在设备中嵌入主动控制。超声刺激可以单枪匹马地解决这些挑战。在100 kHz ~ 10 MHz范围内对神经元进行超声刺激，具有穿透性强、局部性差的特点。本文设计了一种由压电氮化铝超声换能器组成的芯片级装置，用于向人体神经细胞传递千兆赫（GHz）的超声波刺激。这些器件为互补金属氧化物半导体（CMOS）集成到完全可控的神经器件提供了一条途径。在GHz频率下，水中的超声波波长为几微米，吸收深度为10-20 μ m。这种能量限制可用于控制单个神经元内的刺激量。这篇论文是第一个概念验证研究，证明GHz超声波可以在体外刺激神经元。通过利用光学钙成像，记录指示动作电位发生的钙离子通量，本文证明，应用无毒剂量的GHz超声波（>= 0.05 W/cm(2)），钙瞬态的平均归一化荧光强度记录>1.40。由于芯片级超声传输引起的电效应被认为是刺激的唯一机制，所有强度和对照组之间的效应测试均为α = 0.01，具有统计学意义。光学记录的离子瞬态被证实是由离子通道介导的，实验数据表明，对刺激的热贡献不显著，预测1.2 W/cm时增加0.03℃(2)。本文为进一步探索芯片级轴突和神经元特异性神经刺激奠定了实验框架，并将其应用于神经修复、芯片级神经工程以及不同组织和细胞类型。
Emergent trends in the device development for neural prosthetics have focused on establishing stimulus localization, improving longevity through immune compatibility, reducing energy requirements, 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 mu m. 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 (>= 0.05 W/cm(2)) 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 alpha = 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 degrees C for 1.2 W/cm(2). 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.