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- Ultra-sensitive bioelectronic transducers for extracellular electrophysiological studiesPublication . Asgarifar, Sanaz; Gomes, Henrique L.; Ruano, M. GraçaExtracellular electrical activity of cells is commonly recorded using microelectrode arrays (MEA) with planar electrodes. MEA technology has been optimized to record signals generated by excitable cells such as neurons. These cells produce spikes referred to as action potentials. However, all cells produce membrane potentials. In contrast to action potentials, electrical signals produced by non-excitable or non-electrogenic cells, do not exhibit spikes, rather smooth potentials that can change over periods of several minutes with amplitudes of only a few microvolts. These bioelectric signals serve functional roles in signalling pathways that control cell proliferation, differentiation and migration. Measuring and understanding these signals is of high priority in developmental biology, regenerative medicine and cancer research. The objective of this thesis is to fabricate and characterise bioelectronic transducers to measure in vitro the bioelectrical activity of non-electrogenic cells. Since these signals are in the order of few microvolts the electrodes must have an unrivaled low detection limit in the order of hundreds of nanovolts. To meet this challenge a methodology to analyze how bioelectrical signals are coupled into sensing surfaces was developed. The methodology relies on a description of the sensing interface by an equivalent circuit. Procedures for circuit parameter extraction are presented. Relation between circuit parameters, material properties and geometrical design was established. This knowledge was used to establish guidelines for device optimization. The methodology was first used to interpret recordings using gold electrodes, later it as extended to conducting polymers surfaces (PEDOT:PSS ) and finally to graphene electrolyte-gated transistors. The results of this thesis have contributed to the advance of the knowledge in bioelectronic transducers in the following aspects: (i) Detection of signals produced by an important class of neural cells, astrocyte and glioma that thus far had remained inaccessible using conventional extracellular electrodes. (ii) Development of an electrophysiological quantitative method for in vitro monitoring of cancer cell migration and cell-to-cell connections. (iii)An understanding of the limitations of electrolyte-gated transistors to record high frequency signals.