The Design of a CMOS Nanoelectrode Array with 4096 Current-Clamp/Voltage-Clamp Amplifiers for Intracellular Recording/Stimulation of Mammalian Neurons.
The Design of a CMOS Nanoelectrode Array with 4096 Current-Clamp/Voltage-Clamp Amplifiers for Intracellular Recording/Stimulation of Mammalian Neurons.
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DOI：
10.1109/jssc.2020.3005816
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发表时间：
2020-09
影响因子：
5.4
通讯作者：
Ham D
中科院分区：
文献类型：
--
作者：
Abbott J;Ye T;Krenek K;Qin L;Kim Y;Wu W;Gertner RS;Park H;Ham D
CMOS微电极阵列（MEA）可以并行记录大量神经元的电生理活动，但只能在细胞外进行，信噪比低。膜片钳电极可以进行高信噪比的细胞内记录，但只能对少数神经元进行平行记录。最近，我们已经开发和报告了一种神经电子接口，结合了并行的CMOS MEA和细胞内的膜片钳的灵敏度。在这里，我们报告的CMOS集成电路（IC），神经电子接口的关键组成部分的设计和表征。该IC采用0.18 μm技术制造，其表面上有4，096个铂黑（PtB）纳米电极阵列，间距为20 μm，包含4，096个有源像素电路。每个有源像素电路均由一个新型开关电容电流注入器（能够注入±15 pA至±0.7 μA电流，分辨率为5 pA）和一个运算放大器组成，具有高度可配置性。当配置为电流钳模式时，像素在细胞内记录膜电位，包括阈下活动，输入参考噪声为1.23 μVrms，同时注入电流进行同步刺激。当配置为电压钳位模式时，像素变成具有101 pArms输入参考噪声的开关电容跨导放大器，并且在施加电压以进行同时刺激的同时在细胞内记录离子通道电流。这种电压/电流钳细胞内记录/刺激是以前只有膜片钳方法才可能实现的壮举。同时，作为一个阵列，IC克服了膜片钳方法缺乏并行性的缺点，并行测量数千个哺乳动物神经元，在9.4 kHz下进行全帧细胞内记录/刺激。
CMOS microelectrode arrays (MEAs) can record electrophysiological activities of a large number of neurons in parallel but only extracellularly with low signal-to-noise ratio. Patch clamp electrodes can perform intracellular recording with high signal-to-noise ratio but only from a few neurons in parallel. Recently we have developed and reported a neuroelectronic interface that combines the parallelism of the CMOS MEA and the intracellular sensitivity of the patch clamp. Here, we report the design and characterization of the CMOS integrated circuit (IC), a critical component of the neuroelectronic interface. Fabricated in 0.18-μm technology, the IC features an array of 4,096 platinum black (PtB) nanoelectrodes spaced at a 20 μm pitch on its surface and contains 4,096 active pixel circuits. Each active pixel circuit, consisting of a new switched-capacitor current injector—-capable of injecting from ±15 pA to ±0.7 μA with a 5 pA resolution—-and an operational amplifier, is highly configurable. When configured into current-clamp mode, the pixel intracellularly records membrane potentials including subthreshold activities with ∼23 μVrms input referred noise while injecting a current for simultaneous stimulation. When configured into voltage-clamp mode, the pixel becomes a switched-capacitor transimpedance amplifier with ∼1 pArms input referred noise, and intracellularly records ion channel currents while applying a voltage for simultaneous stimulation. Such voltage/current-clamp intracellular recording/stimulation is a feat only previously possible with the patch clamp method. At the same time, as an array, the IC overcomes the lack of parallelism of the patch clamp method, measuring thousands of mammalian neurons in parallel, with full-frame intracellular recording/stimulation at 9.4 kHz.
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影响因子：
4.3
作者：
Obien ME;Deligkaris K;Bullmann T;Bakkum DJ;Frey U
通讯作者：
Frey U
影响因子：
38.3
作者：
通讯作者：
--
影响因子：
10.8
作者：
Dipalo M;Amin H;Lovato L;Moia F;Caprettini V;Messina GC;Tantussi F;Berdondini L;De Angelis F
通讯作者：
De Angelis F
影响因子：
6.1
作者：
Berdondini, Luca;Imfeld, Kilian;Martinoia, Sergio
通讯作者：
Martinoia, Sergio
DOI：
10.1073/pnas.1016051108
发表时间：
2011-03-29
影响因子：
11.1
作者：
Perin, Rodrigo;Berger, Thomas K.;Markram, Henry
通讯作者：
Markram, Henry