BioSystems 87 (2007) 150–155 PhotoMEA: An opto-electronic biosensor for monitoring in vitro neuronal network activity Diego Ghezzi a,* , Alessandra Pedrocchi a,1 , Andrea Menegon b,2 , Sara Mantero a,3 , Flavia Valtorta b,4 , Giancarlo Ferrigno a,5 a Bioengineering Department, Politecnico di Milano, p.zza Leonardo da Vinci 32, 20133 Milano, Italy b Department of Neuroscience, San Raffaele Scientific Institute and “Vita-Salute” University, via Olgettina 60, 20132 Milano, Italy Received 28 February 2005; received in revised form 8 July 2006; accepted 15 July 2006 Abstract PhotoMEA is a biosensor useful for the analysis of an in vitro neuronal network, fully based on optical methods. Its function is based on the stimulation of neurons with caged glutamate and the recording of neuronal activity by Voltage-Sensitive fluorescent Dyes (VSD). The main advantage is that it will be possible to stimulate even at sub-single neuron level and to record with high resolution the activity of the entire network in the culture. A large-scale view of neuronal intercommunications offers a unique opportunity for testing the ability of drugs to affect neuronal properties as well as alterations in the behaviour of the entire network. The concept and a prototype for validation is described here in detail. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Neuronal information processing; Technology for neuropharmacology; Neural-based biosensor; Bio-information processing system; Computational biology 1. Introduction The most important function of neurons and neuronal networks is to process, modulate and transmit informa- tion through electrical signals (i.e. spikes). Our ability in eliciting, modulating and recording this activity is fun- * Corresponding author. Tel.: +39 02 23999506; fax: +39 02 23993360. E-mail addresses: diego.ghezzi@polimi.it (D. Ghezzi), alessandra.pedrocchi@polimi.it (A. Pedrocchi), menegon.andrea@hsr.it (A. Menegon), sara.mantero@polimi.it (S. Mantero), valtorta.flavia@hsr.it (F. Valtorta), giancarlo.ferrigno@polimi.it (G. Ferrigno). 1 Tel.: +39 02 23993371; fax: +39 02 23993360. 2 Tel.: +39 02 26434868; fax: +39 02 26434813. 3 Tel.: +39 02 23993376; fax: +39 02 23993360. 4 Tel.: +39 02 26434826; fax: +39 02 26434813. 5 Tel.: +39 02 23993371; fax: +39 02 23993360. damental for understanding the mechanisms that govern the central nervous system (CNS) functions. Therefore, one of the most relevant topic in neuroscience is the bet- ter understanding of the functional dynamics that govern the complex network properties. There are two possible approaches in studying neu- ronal functions. On one hand, a large-scale approach aims at understanding a more or less synchronized activ- ity of the whole neuronal system. On the other hand, a micro-scale approach studies detailed behavioural mod- els of the neuron, and also of the complex molecular systems which actively contribute to the generation and modulation of the whole neuronal activity. Brain functions originate from the coordinate activity of many neurons, acting in several regions involved in information processing. Thus, the study of the modula- tion of neuronal physiology that regulates neuronal activ- ity must necessarily be inserted into a large-scale view 0303-2647/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.biosystems.2006.09.008