A Low-Noise, Modular, and Versatile Analog Front-End Intended for ProcessingIn VitroNeuronal Signals Detected by Microelectrode Arrays

Giulia Regalia,Emilia Biffi,Alessandra Pedrocchi,Giancarlo Ferrigno

doi:10.1155/2015/172396

Giulia Regalia, Emilia Biffi + Show 2 more

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https://doi.org/10.1155/2015/172396

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Abstract

The collection of good quality extracellular neuronal spikes from neuronal cultures coupled to Microelectrode Arrays (MEAs) is a binding requirement to gather reliable data. Due to physical constraints, low power requirement, or the need of customizability, commercial recording platforms are not fully adequate for the development of experimental setups integrating MEA technology with other equipment needed to perform experiments under climate controlled conditions, like environmental chambers or cell culture incubators. To address this issue, we developed a custom MEA interfacing system featuring low noise, low power, and the capability to be readily integrated inside an incubator-like environment. Two stages, a preamplifier and a filter amplifier, were designed, implemented on printed circuit boards, and tested. The system is characterized by a low input-referred noise (<1 μV RMS), a high channel separation (>70 dB), and signal-to-noise ratio values of neuronal recordings comparable to those obtained with the benchmark commercial MEA system. In addition, the system was successfully integrated with an environmental MEA chamber, without harming cell cultures during experiments and without being damaged by the high humidity level. The devised system is of practical value in the development of in vitro platforms to study temporally extended neuronal network dynamics by means of MEAs.

Highlights

At the present time, the in vitro study of neuronal network electrical activity under physiological or pathological conditions largely relies on Microelectrode Arrays (MEA), which are substrate-integrated extracellular electrode matrices kept permanently in contact with neurons in culture [1,2,3,4,5]
Features of typical extracellular spikes detected by standard MEAs are (i) amplitude ranging from 30 μV to 1 mV peak-to-peak, (ii) frequency content ranging between a few hundred Hz and a few kHz, (iii) overlapping microelectrode thermal and background biological noise ∼20 μV peak-to-peak (∼3-4 μV root-mean-squared noise levels (RMS)), and (iv) microelectrode offset in the order of few hundred mV [24, 25]
Compared to commercial devices well-established in MEAbased research, main strengths of the system are modularity, compactness, low power consumption, and resistance to high humidity levels, which are advantageous in the development of prototypal setups, such as stand-alone MEA chambers [19], or in the customization of existing equipment, like the case of setups integrated inside cell incubators [17, 18, 20]

Summary

Introduction

The in vitro study of neuronal network electrical activity under physiological or pathological conditions largely relies on Microelectrode Arrays (MEA), which are substrate-integrated extracellular electrode matrices kept permanently in contact with neurons in culture [1,2,3,4,5]. Commercial solutions do not always meet some demanding needs, such as low power, compactness, compatibility with experimental setup constraints (e.g., size, environmental conditions), flexibility (e.g., easiness to change component values if needed), or cost-effectiveness. For this reason, some researchers have resorted to the utilization of in-house designed MEA interfacing electronics [7,8,9,10,11,12,13,14]

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