Hafizovic S, Heer F, Ugniwenko T, Frey U, Blau A, Ziegler C, Hierlemann A
Physical Electronics Laboratory, ETH Zurich, Wolfgang-Pauli Str. 16, 8093 Zurich, Switzerland.
J Neurosci Methods. 2007 Aug 15;164(1):93-106. doi: 10.1016/j.jneumeth.2007.04.006. Epub 2007 Apr 19.
We report on the system integration of a CMOS chip that is capable of bidirectionally communicating (stimulation and recording) with electrogenic cells such as neurons or cardiomyocytes and that is targeted at investigating electrical signal propagation within cellular networks in vitro. The overall system consists of three major subunits: first, the core component is a 6.5 mm x 6.5 mm CMOS chip, on top of which the cells are cultured. It features 128 bidirectional electrodes, each equipped with dedicated analog filters and amplification stages and a stimulation buffer. The electrodes are sampled at 20 kHz with 8-bit resolution. The measured input-referred circuitry noise is 5.9 microV root mean square (10 Hz to 100 kHz), which allows to reliably detect the cell signals ranging from 1 mVpp down to 40 microVpp. Additionally, temperature sensors, a digital-to-analog converter for stimulation, and a digital interface for data transmission are integrated. Second, there is a reconfigurable logic device, which provides chip control, event detection, data buffering and an USB interface, capable of processing the 2.56 million samples per second. The third element includes software that is running on a standard PC performing data capturing, processing, and visualization. Experiments involving the stimulation of neurons with two different spatio-temporal patterns and the recording of the triggered spiking activity have been carried out. The response patterns have been successfully classified (83% correct) with respect to the different stimulation patterns. The advantages over current microelectrode arrays, as has been demonstrated in the experiments, include the capability to stimulate (voltage stimulation, 8 bit, 60 kHz) spatio-temporal patterns on arbitrary sets of electrodes and the fast stimulation reset mechanism that allows to record neuronal signals on a stimulating electrode 5 ms after stimulation (instantaneously on all other electrodes). Other advantages of the overall system include the small number of needed electrical connections due to the digital interface and the short latency time that allows to initiate a stimulation less than 2 ms after the detection of an action potential in closed-loop configurations.
我们报告了一种CMOS芯片的系统集成，该芯片能够与神经元或心肌细胞等电活性细胞进行双向通信（刺激和记录），旨在研究体外细胞网络内的电信号传播。整个系统由三个主要子单元组成：首先，核心组件是一个6.5毫米×6.5毫米的CMOS芯片，细胞在其顶部培养。它具有128个双向电极，每个电极都配备有专用的模拟滤波器、放大级和刺激缓冲器。电极以20 kHz的采样频率和8位分辨率进行采样。测得的输入参考电路噪声为5.9微伏均方根（10 Hz至100 kHz），这使得能够可靠地检测从1 mVpp到40 microVpp的细胞信号。此外，还集成了温度传感器、用于刺激的数模转换器和用于数据传输的数字接口。其次，有一个可重构逻辑器件，它提供芯片控制、事件检测、数据缓冲和一个USB接口，能够每秒处理256万个样本。第三个元件包括在标准PC上运行的软件，用于执行数据捕获、处理和可视化。已经进行了涉及用两种不同时空模式刺激神经元并记录触发的尖峰活动的实验。针对不同的刺激模式，响应模式已成功分类（正确率83%）。实验表明，与当前的微电极阵列相比，其优势包括能够在任意电极组上刺激（电压刺激，8位，60 kHz）时空模式，以及快速刺激复位机制，该机制允许在刺激后5毫秒在刺激电极上记录神经元信号（在所有其他电极上即时记录）。整个系统的其他优势包括由于数字接口而所需的电连接数量少，以及在闭环配置中检测到动作电位后不到2毫秒即可启动刺激的短延迟时间。
