Cohen Ariel, Shappir Joseph, Yitzchaik Shlomo, Spira Micha E
Department of Neurobiology, The Life Sciences Institute, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Biosens Bioelectron. 2008 Jan 18;23(6):811-9. doi: 10.1016/j.bios.2007.08.027. Epub 2007 Sep 12.
The employment of standard CMOS technology to produce semiconductor chips for recording neuronal activity or for its future use to link neurons and transistors under in vivo conditions, suffers from a low signal to noise ratio. Using Aplysia neurons cultured on CMOS floating gate field effect transistors, we report here that minor mechanical pressure applied to restricted neuronal compartment that face the sensing pad induces two independent alterations: (a) increase in the seal resistance formed between the neuron's membrane and the sensing pad, and (b) increase the conductance of the membrane patch that faces the sensing pad. These alterations (from approximately 0.5 to approximately 1.2 MOmega and 75 to approximately 600 nS correspondingly), are sufficient to transform the low capacitive coupling between a neuron and a transistor to Ohmic coupling, which is manifested by semi-intracellular recordings of APs with amplitudes of up to 30 mV. The semi-intracellular recordings could be maintained for hours. As a number of compression and decompression cycles could be applied to a single cell without causing significant alterations in its excitable properties, we conclude that the mechanical damage inflicted to the neurons by local compression are reversible. Based on these observations, we suggest that the application of minimal local pressure or suction forces could be used to transform conventional extracellular field potential recordings into quasi-intracellular recording, and thereby dramatically improve both the signal to noise ratio and the quality of recordings from neurons cultured on CMOS semiconductors chips.
采用标准互补金属氧化物半导体(CMOS)技术生产用于记录神经元活动的半导体芯片,或用于未来在体内条件下连接神经元和晶体管,但存在信噪比低的问题。我们在此报告,利用培养在CMOS浮栅场效应晶体管上的海兔神经元,对面向传感垫的受限神经元区室施加微小机械压力会引发两种独立变化:(a)神经元膜与传感垫之间形成的封接电阻增加;(b)面向传感垫的膜片电导增加。这些变化(相应地从约0.5兆欧增加到约1.2兆欧,从75纳西门子增加到约600纳西门子)足以将神经元与晶体管之间的低电容耦合转变为欧姆耦合,这表现为动作电位(AP)的半细胞内记录,其幅度高达30毫伏。半细胞内记录可持续数小时。由于可以对单个细胞施加多个压缩和减压循环而不会显著改变其兴奋性特性,我们得出结论,局部压缩对神经元造成的机械损伤是可逆的。基于这些观察结果,我们建议施加最小的局部压力或吸力可用于将传统的细胞外场电位记录转变为准细胞内记录,从而显著提高信噪比以及在CMOS半导体芯片上培养的神经元的记录质量。