1328 IEEE TRANSACTIONS ON NANOTECHNOLOGY, VOL. 10, NO. 6, NOVEMBER 2011 Investigation of Extracellular Signal Shapes Recorded by Planar Metal Microelectrodes Covered With Carbon Nanotubes: Modeling and Simulations Giuseppe Massobrio, Paolo Massobrio, Member, IEEE, and Sergio Martinoia, Member, IEEE Abstract—Bundles of carbon nanotubes (CNTs) arranged in ver- tical alignment and in normal direction to the surface of a pla- nar metal microelectrode were used to interface neurons and the recording microtransducer. A model of such a hybrid system was developed and implemented in HSPICE to simulate and analyze the electrical interactions and the induced extracellularly recorded neuronal electrical activity as a function of the neuroelectronic junction and CNTs bundle parameters. The results pointed out carbon nanotubes, as electrical interfaces to neurons, act both on the amplitude and the shape of the recorded signals. Index Terms—Carbon nanotube, extracellular signal record- ing, HSPICE simulation, microelectrode, neuroelectronic junction, neuron. I. INTRODUCTION R ECORDING systems based on multielectrodes array (MEA) have long been demonstrated as powerful tools for recording the electrical activity of networks of neurons cultured in vitro [1]–[3]. Under this experimental condition, neurons are directly connected to microelectrodes by a neuroelectronic junction, and the neuronal electrical activity is extracellularly recorded. Despite their advantages, a fundamental drawback of the mi- croelectrodes is their relatively high specific impedance that leads to increased noise levels. MEAs recording performances are also limited by the neuron-to-microelectrode coupling which is mainly characterized by neuron-to-microelectrode attach- ment and sealing. These parameters play an important role in determining the accuracy of the recorded signal [4]. In order to improve the recording performances of MEAs, re- searchers have been working extensively on improving neuron- to-microelectrode coupling [5], as well as on reducing the impedance of the microelectrode [6]. Manuscript received November 12, 2010; revised March 16, 2011; accepted March 23, 2011. Date of publication April 7, 2011; date of current version November 9, 2011. The review of this paper was arranged by Associate Editor B. Yu. G. Massobrio and P. Massobrio are with the Neuroengineering and Bio- NanoTechnology Laboratory, Department of Biophysical and Electronic En- gineering, University of Genova, Genova 16145, Italy (e-mail: giuseppe. massobrio@unige.it; paolo.massobrio@unige.it). S. Martinoia is with the Neuroengineering and Bio-NanoTechnology Lab- oratory, Department of Biophysical and Electronic Engineering, University of Genova, Genova 16145, Italy, and also with the Neurosciences and Brain Technologies Department, Italian Institute of Technology, Genova 16145, Italy (e-mail: sergio.martinoia@unige.it). Color versions of one or more of the figures in this paper are available online at http://ieeexplore.ieee.org. Digital Object Identifier 10.1109/TNANO.2011.2138716 Carbon nanotubes (CNTs) [7] offer a new emerging way to further improve the performances of MEAs and to solve many of the aforementioned drawbacks, because of their properties, such as mechanical stability, chemical durability, large electrical conductivity, current carrying capabilities, and biocompatibil- ity [8]. CNTs were proposed as a possible replacement for metal interconnects [9]–[12], and studies showed that CNTs can pro- vide an excellent surface for neuronal cell adhesion and growth, either on uniform surfaces [13] or on isolated CNT [14]. More- over, it was shown that CNT substrates may even boost neuronal electrical signaling [15]. However, despite the widespread use of experimental tools, there is still a lack of appropriate models and simulation tools for a better understanding and for a more accurate interpretation of signals recorded extracellularly from populations of neurons [16]. In this study, we present a model of a hybrid neuroelectronic junction consisting of interfacing neurons and metal microelec- trodes by means of CNTs, to investigate the capability of such a system to efficiently record the electrophysiological neuronal activity, as sketched in the schematic of Fig. 1. The system model includes a neuronal cell membrane (simulated by means of a “silicon neuron”), and a metal microelectrode that incor- porates a bundle of individual CNTs vertically grown and in normal direction to the microelectrode surface, in such a way that the neuronal cell membrane is in close contact with the nanotubes. Simulations of the recorded extracellular neuronal signals obtained from the neuron-CNTs-microelectrode system (see Fig. 1, left) were carried out, and the results were com- pared with those obtained by the neuron-CNTs-free microelec- trode system (see Fig. 1, right). The influence of the equivalent circuit elements of the neuron-(CNTs)-microelectrode system, with respect to their physical meanings, was investigated. To this goal, the general-purpose electronic network-analysis program HSPICE was used with ad hoc developed and modified models of the neuron, CNT, microelectrode, and neuroelectronic junc- tion. We showed that, by varying the parameters of the electrical equivalents of the models, different shapes of the recorded ex- tracellular signals can be obtained for a given input (i.e., for a given simulated action potential); moreover, the obtained results pointed out carbon nanotubes, as electrical interfaces to neurons, act both on the amplitude and the shape of the recorded signals and promote an increase in the efficacy of neuronal signal trans- mission. Intriguing limit behaviors of the extracellular signals shape, resembling the intracellular membrane action potential, under specific operating conditions, were found. 1536-125X/$26.00 © 2011 IEEE