CEA-LETI, Grenoble, France.
Biosens Bioelectron. 2010 Apr 15;25(8):1889-96. doi: 10.1016/j.bios.2010.01.001. Epub 2010 Jan 13.
Microelectrode arrays (MEAs) offer a powerful tool to both record activity and deliver electrical microstimulations to neural networks either in vitro or in vivo. Microelectronics microfabrication technologies now allow building high-density MEAs containing several hundreds of microelectrodes. However, dense arrays of 3D micro-needle electrodes, providing closer contact with the neural tissue than planar electrodes, are not achievable using conventional isotropic etching processes. Moreover, increasing the number of electrodes using conventional electronics is difficult to achieve into compact devices addressing all channels independently for simultaneous recording and stimulation. Here, we present a full modular and versatile 256-channel MEA system based on integrated electronics. First, transparent high-density arrays of 3D-shaped microelectrodes were realized by deep reactive ion etching techniques of a silicon substrate reported on glass. This approach allowed achieving high electrode aspect ratios, and different shapes of tip electrodes. Next, we developed a dedicated analog 64-channel Application Specific Integrated Circuit (ASIC) including one amplification stage and one current generator per channel, and analog output multiplexing. A full modular system, called BIOMEA, has been designed, allowing connecting different types of MEAs (64, 128, or 256 electrodes) to different numbers of ASICs for simultaneous recording and/or stimulation on all channels. Finally, this system has been validated experimentally by recording and electrically eliciting low-amplitude spontaneous rhythmic activity (both LFPs and spikes) in the developing mouse CNS. The availability of high-density MEA systems with integrated electronics will offer new possibilities for both in vitro and in vivo studies of large neural networks.
微电极阵列 (MEA) 为记录活动和向体外或体内神经网络提供电微刺激提供了强大的工具。微电子微制造技术现在允许构建包含数百个微电极的高密度 MEA。然而,使用传统的各向同性刻蚀工艺无法实现与平面电极相比更接近神经组织的密集 3D 微针电极阵列。此外,使用传统电子技术增加电极数量很难实现紧凑的设备,这些设备可以独立寻址所有通道,用于同时记录和刺激。在这里,我们展示了一种基于集成电子的全模块化和通用的 256 通道 MEA 系统。首先,通过报道在玻璃上的硅衬底的深反应离子刻蚀技术实现了透明高密度的 3D 形状微电极阵列。这种方法允许实现高电极纵横比和不同形状的尖端电极。接下来,我们开发了一种专用的模拟 64 通道专用集成电路 (ASIC),每个通道包括一个放大级和一个电流发生器,以及模拟输出多路复用。一个名为 BIOMEA 的全模块化系统已经设计出来,允许连接不同类型的 MEA(64、128 或 256 个电极)到不同数量的 ASIC,以实现所有通道的同时记录和/或刺激。最后,该系统通过在发育中的小鼠中枢神经系统中记录和电激发低幅度自发节律性活动(LFP 和尖峰)进行了实验验证。具有集成电子的高密度 MEA 系统的可用性将为体外和体内大型神经网络研究提供新的可能性。
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