神经元集群电信号探测用微电极阵列  

Microelectrode array for detecting electrical activities of neuron assemble

作　　者：潘海仙[1] 吕晓迎[1] 王志功[2] 王余峰[2] 陆慧琴[1] 沈洪妹[3] 

机构地区：[1]东南大学生物电子学国家重点实验室,南京210096 [2]东南大学射频与光电集成电路研究所,南京210096 [3]南通大学江苏省神经再生重点实验室,南通226001

出　　处：《东南大学学报（自然科学版）》2009年第3期468-472,共5页Journal of Southeast University：Natural Science Edition

基　　金：国家自然科学基金重点资助项目(90307013);国家自然科学基金创新群体基金资助项目(60121101)

摘　　要：介绍了一种用于神经元集群电信号探测的2×2微电极阵列芯片.该芯片集成了4个直径为20μm、中心间距为100μm的圆形微电极.4个电极点周围都布满地线作为参考电极,4个电极点与参考电极的间距分别为5,10,15和20μm.芯片版图设计及验证采用华大九天系统设计软件Zeni完成,并通过无锡CSMC公司的0.6μm DMDP CMOS标准工艺实现,芯片面积为0.28mm×0.40mm.对芯片进行了在晶圆电学测试,采用频率为10Hz～1MHz,幅度为50mV的正弦信号作为输入信号,分别测试4个电极点的阻抗特性.测试结果表明,在10kHz处4个电极点的等效阻抗模值在0.7～2.1MΩ之间,达到了细胞外电信号测量的要求.在芯片表面进行了L-929细胞和胎鼠海马神经元培养实验,结果表明芯片经过表面生物相容性修饰后可用于细胞外电信号测量.A 2×2 microelectrode array （MEA） for in-vitro detection of electrophysiological activities of neuron assemble is reported. It consists of four round electrodes with a diameter of 20μm each and a distance of 100 μm between the centers of electrodes. Ground plane was placed as a reference electrode around all the four electrodes, and the spaces between the reference electrode and each electrode center were respectively defined as 5, 10,15 and 20 μm. The layout design and verification was completed with Zeni tools （Huada Corp. , China）. It was realized in a standard 0. 6 μm DMDP CMOS technology of CSMC （Wuxi, China）. The final chip covers an area of 0. 28 mm × 0. 40 mm. Impedance measurements on wafer of the four electrodes were carded out with an 10 Hz to 1 MHz and 50 mV AC signal. The results show that the impedance of the electrodes lies in the range of 0. 7 - 2. 1 MΩ at about 10 kHz, which meets the requirements of extracellular recording. On-chip biological experiments with culturing hippocampal neurons of embryonic rats and L-929 cells are presented. The results show that the chip can be used in biological experiments after surface biocompatibility modification.

关 键 词：CMOS 微电极阵列 神经元集群 细胞外测量 

分 类 号：TN43[电子电信—微电子学与固体电子学]