Artificial Wet Neuronal Networks from Compartmentalised Excitable Chemical Media (NEUNEU)

This document is a guide to the results of the NEUNEU research program, which is concerned with the development of mass- producible chemical information processing components and their interconnection into functional architectures.This document is a guide to the results of the NEUNEU research program, which is concerned with the development of mass- producible chemical information processing components and their interconnection into functional architectures

Brain-inspired nanophotonic spike computing:challenges and prospects

Nanophotonic spiking neural networks (SNNs) based on neuron-like excitable subwavelength (submicrometre) devices are of key importance for realizing brain-inspired, power-efficient artificial intelligence (AI) systems with high degree of parallelism and energy efficiency. Despite significant advances in neuromorphic photonics, compact and efficient nanophotonic elements for spiking signal emission and detection, as required for spike-based computation, remain largely unexplored. In this invited perspective, we outline the main challenges, early achievements, and opportunities toward a key-enabling photonic neuro-architecture using III-V/Si integrated spiking nodes based on nanoscale resonant tunnelling diodes (nanoRTDs) with folded negative differential resistance. We utilize nanoRTDs as nonlinear artificial neurons capable of spiking at high-speeds. We discuss the prospects for monolithic integration of nanoRTDs with nanoscale light-emitting diodes and nanolaser diodes, and nanophotodetectors to realize neuron emitter and receiver spiking nodes, respectively. Such layout would have a small footprint, fast operation, and low power consumption, all key requirements for efficient nano-optoelectronic spiking operation. We discuss how silicon photonics interconnects, integrated photorefractive interconnects, and 3D waveguide polymeric interconnections can be used for interconnecting the emitter-receiver spiking photonic neural nodes. Finally, using numerical simulations of artificial neuron models, we present spike-based spatio-temporal learning methods for applications in relevant AI-based functional tasks, such as image pattern recognition, edge detection, and SNNs for inference and learning. Future developments in neuromorphic spiking photonic nanocircuits, as outlined here, will significantly boost the processing and transmission capabilities of next-generation nanophotonic spike-based neuromorphic architectures for energy-efficient AI applications. This perspective paper is a result of the European Union funded research project ChipAI in the frame of the Horizon 2020 Future and Emerging Technologies Open programme.</p

Iron-Catalyzed Belousov-Zhabotinsky Hydrogels and Liquid Crystals

Reducing stress is an important goal in poultry production. The Saccharomyces cerevisiae-derived yeast fermentation product Original XPC (XPC, Diamond V Mills, Cedar Rapids, IA, United States) has been shown to reduce the severity of enteric infection and reduce measures of stress in poultry exposed to acute or chronic stress. However, the effect of dietary supplementation of yeast fermentate on other physiological parameters and its mode of action in reducing stress remains unclear. This work aimed to investigate the effects of supplementing XPC or its liquid equivalent, AviCare (Diamond V Mills), on measures of stress susceptibility, health and well-being in poultry exposed to acute and chronic stressors. Three consecutive experiments were conducted to evaluate the effects of yeast fermentate supplementation on measures of stress, growth and feed efficiency in Cobb 500 male broilers exposed to acute and rearing stressors. Both XPC and AviCare consistently and equally reduced measures of short- and long-term stress across all 3 experiments, although trends in body weight gain and feed efficiency were inconsistent. A fourth experiment investigated the effects of XPC and AviCare on measures of stress, plasma biochemistry, cecal microbiome and expression of stress- and immune-related genes in Cobb 500 male broilers. Both XPC and AviCare reduced stress by reducing expression of the ACTH receptor, and modulated immune activity by reducing IL10 and CYP1A2 gene expression as well as plasma IL- The Belousov-Zhabotinsky (BZ) reaction is one of the most studied nonlinear dynamic chemical systems due to its autonomous periodic oscillations. It represents a suitable model for various oscillatory phenomena in Nature such as neuron synapsis, cardiac muscle beating and/or tachycardia, cellular formation cycle in molds, and other types of live-organism morphogenesis. The complexity of the BZ reaction chemical mechanism led to the creation of the Fields-Koros-Noyes model (FKN) that allows for studies via theoretical and mathematical models. Thus, experimental studies of this reaction are necessary to create 3D and life-like models. To bring these models into a more naturalistic setting, we researched the BZ reaction through hydrogels containing iron because of its natural occurrence and relevance. Chemically, the BZ reaction requires a catalyst based on iron (Fe), ruthenium (Ru) or cerium (Ce), and most of the current reports employ Ru. Alternatively, we employed Fe complexes as the catalyst due to their lower toxicity compared to Ru. The Fe-based catalyst was incorporated into polymer matrices (PNIPAM-co-PAAm, gelatin + kappa-carrageenan, and gelatin) to obtain hydrogels that exhibited pattern-rich, self-oscillatory response. Hence, the hydrogels served as models to investigate the effect of liquid crystalline structures on oscillations, the effect of geometry on the wave pattern of 3D-printed hydrogels, and the autonomous motion of hydrogels. Overall, these results open the door for future research on BZ reaction systems with low-toxicity. Furthermore, they contribute to the creation of new 3D locomotive hydrogels and to the development of realistic 3D models that could mimic Nature more efficiently.. However, cecal microbiome and antioxidative capacity were not affected after 42 d. Finally, 2 consecutive experiments were conducted to evaluate the effect of XPC and AviCare on measures of intestinal health in Cobb 500 male broilers and mixed-sex Pekin ducks exposed to cyclic heat stress during the last 14 d of growth. In both experiments yeast fermentate attenuated the negative effects of heat stress on villus length and villus/crypt ratio but not goblet cell density. Yeast fermentate also affected metabolism but did not improve electrolyte balance. In conclusion, adding yeast fermentate to the feed or drinking water reduced stress susceptibility by reducing glucocorticoid production, supported intestinal cell survival during cyclic heat stress, and modulated inflammatory processes in poultry exposed to rearing stress but not cyclic heat stress

Transcriptional Regulation of Arrhythmia: from Mouse to Human

In the last two decades, our understanding of cardiac arrhythmias has been accelerated immensely by the development of genetically engineered animals. Transgenic and knockout mice have been the “gold standard” platforms for delineating disease mechanisms. Much of our understanding of the pathogenesis of atrial and ventricular arrhythmias is gained from mouse models that alter the expression of specific ion channels or other proteins. However, cardiac arrhythmias such as atrial fibrillation are heterogeneous diseases with numerous distinct conditions that could not be explained exclusively by the disruption of ionic currents. Increasing evidence suggests disruption of signaling pathways in the pathogenesis of cardiac arrhythmias. Although crucial for studying disease mechanisms, animal models often fail to predict human response to treatments due to inter-species genetic and physiological differences. Cardiac slices obtained from human hearts have been demonstrated as an accurate model that more faithfully recapitulates human cardiac physiology. However, the use of the human cardiac slices for evaluating the transcriptional regulation of arrhythmia is hampered by tissue remodeling and dedifferentiation in long-term culture of the slices. The first part of this dissertation aims to elucidate one of the potential mechanisms of sick sinus syndrome and atrial fibrillation induced by transient reactivation of Notch, a critical transcription factor during cardiac development and has been shown to be reactivated in the adult heart following cardiac injury. When Notch is transiently reactivated in the adult mice to mimic the injury response, the animals exhibits slowed heart rate, increased heart rate variability, frequent sinus pauses, and slowed atrial conduction. The electrical remodeling of the atrial myocardium results in increased susceptibility to atrial fibrillation. The transient reactivation of Notch also significantly altered the atrial gene expression profile, with many of the disrupted genes associated with cardiac arrhythmias by genome-wide association study. The second part of this dissertation aims to address the lack the translation from animal research to human therapies by extending the human cardiac slice viability in culture. With the optimized culture parameters, human cardiac slices obtained from the left ventricular free wall remained electrically viable for up to 21 days in vitro and routinely maintained normal electrophysiology for up to 4 days. To genetically alter the human cardiac slices, a localized gene delivery technique was evaluated and optimized. The third part of the dissertation aims to further improve long-term culture of human cardiac slices and to increase the availability of human tissue for research by developing a self-contained heart-on-a-chip system for automated culture of human cardiac slices. The system maintains optimal culture conditions and provides electrical stimulation and mechanical anchoring to minimize tissue dedifferentiation. The work allows for accelerated optimization of long-term culturing of human cardiac slice, which will enable study of arrhythmia mechanisms on human cardiac tissue via targeted control of transcription factors

Enhancing all-in-one bioreactors by combining interstitial perfusion, electrical stimulation, on-line monitoring and testing within a single chamber for cardiac constructs

Tissue engineering strategies have been extensively exploited to generate functional cardiac patches. To maintain cardiac functionality in vitro, bioreactors have been designed to provide perfusion and electrical stimulation, alone or combined. However, due to several design limitations the integration of optical systems to assess cardiac maturation level is still missing within these platforms. Here we present a bioreactor culture chamber that provides 3D cardiac constructs with a bidirectional interstitial perfusion and biomimetic electrical stimulation, allowing direct cellular optical monitoring and contractility test. The chamber design was optimized through finite element models to house an innovative scaffold anchoring system to hold and to release it for the evaluation of tissue maturation and functionality by contractility tests. Neonatal rat cardiac fibroblasts subjected to a combined perfusion and electrical stimulation showed positive cell viability over time. Neonatal rat cardiomyocytes were successfully monitored for the entire culture period to assess their functionality. The combination of perfusion and electrical stimulation enhanced patch maturation, as evidenced by the higher contractility, the enhanced beating properties and the increased level of cardiac protein expression. This new multifunctional bioreactor provides a relevant biomimetic environment allowing for independently culturing, real-time monitoring and testing up to 18 separated patches

Tracking the mind's image in the brain : combining evidence from fMRI and rTMS

Die Dissertation kombiniert die Methode der funktionellen Magnetresonanztomographie (fMRT) zur genauen räumlichen Lokalisation aufgabenkorrelierter parietaler Aktivierungen mit Transkranieller Magnetstimulation (TMS) zur systematischen Untersuchung der funktionellen Relevanz dieser Aktivierungen für die tatsächliche Leistungsfähigkeit. Die experimentelle Kombination beider Methoden ermöglichte die gezielte Stimulation der im tMRT identifizierten, mit visuospatialen Fähigkeiten assoziierten Hirnareale. Durch die systematische Auswertung der TMS-induzierten visuospatialen Leistungsveränderungen wurde die spezifische funktionelle Bedeutung dieser Hirnareale für visuospatiale Leistungen experimentell untersucht. Der zugrunde gelegte Versuchsplan umfasste sowohl visuospatiale Leistungen auf der Grundlage visuell dargebotener als auch mental vorgestellter Aufgaben. Dies ermöglichte die systematische Untersuchung, ob und inwieweit mentale visuospatiale Informationsverarbeitung die gleichen oder ähnliche Aktivierungsmuster im fMRT aufweist wie visuospatiale Verarbeitung visuell dargebotener Stimuli, und ob sich diese Aktivierungsmuster vorgestellter Stimuli unter dem Einfluss von rTMS in gleicher Weise als funktionell relevant erweisen. Aufgrund der separaten unilateralen Stimulation beider Hemisphären konnten darüber hinaus die unterschiedlichen behavioralen Auswirkungen einer Aktivierungsunterdrückung des linken und rechten Parietalkortex systematisch untersucht werden. Obwohl die Ausführung visuospatialer Aufgaben, sowohl auf der Grundlage visuell dargebotener als auch mental vorgestellter Stimuli, im fMRT mit einer bilateralen Aktivierung im Parietalkortex korrelierte, führte lediglich die TMS-induzierte temporäre Unterbrechung der neuronalen Aktivierung im rechten Parietalkortex zu einer signifikanten Verschlechterung in der Leistungsfähigkeit der damit assoziierten visuospatialen Aufgaben. Auf der Grundlage dieser Ergebnisse wurde ein modulares Modell der visuospatialen Imagination formuliert, in welchem den aufgabenkorrelierten bilateralen Aktivierungen aufgrund ihrer raum-zeitlichen Separierbarkeit unterschiedliche mentale Prozesse und aufgrund der mit TMS aufgezeigten funktionellen hemisphärischen Asymmetrie parietaler Aktivierung für visuospatiale Informationsverarbeitung unterschiedliche Kompensationsmechanismen zugeordnet wurden

Neuromorphic nanophotonic systems for artificial intelligence

Over the last decade, we have witnessed an astonishing pace of development in the field of artificial intelligence (AI), followed by proliferation of AI algorithms into virtually every domain of our society. While modern AI models boast impressive performance, they also require massive amounts of energy and resources for operation. This is further fuelling the research into AI-specific, optimised computing hardware. At the same time, the remarkable energy efficiency of the brain brings an interesting question: Can we further borrow from the working principles of biological intelligence to realise a more efficient artificial intelligence? This can be considered as the main research question in the field of neuromorphic engineering. Thanks to the developments in AI and recent advancements in the field of photonics and photonic integration, research into light-powered implementations of neuromorphic hardware has recently experienced a significant uptick of interest. In such hardware, the aim is to seize some of the highly desirable properties of photonics not just for communication, but also to perform computation. Neurons in the brain frequently process information (compute) and communicate using action potentials, which are brief voltage spikes that encode information in the temporal domain. Similar dynamical behaviour can be elicited in some photonic devices, at speeds multiple orders of magnitude higher. Such devices with the capability of neuron-like spiking are of significant research interest for the field of neuromorphic photonics. Two distinct types of such excitable, spiking systems operating with optical signals are studied and investigated in this thesis. First, a vertical cavity surface emitting laser (VCSEL) can be operated under a specific set of conditions to realise a high-speed, all-optical excitable photonic neuron that operates at standard telecom wavelengths. The photonic VCSEL-neuron was dynamically characterised and various information encoding mechanisms were studied in this device. In particular, a spiking rate-coding regime of operation was experimentally demonstrated, and its viability for performing spiking domain conversion of digital images was explored. Furthermore, for the first time, a joint architecture utilising a VCSEL-neuron coupled to a photonic integrated circuit (PIC) silicon microring weight bank was experimentally demonstrated in two different functional layouts. Second, an optoelectronic (O/E/O) circuit based upon a resonant tunnelling diode (RTD) was introduced. Two different types of RTD devices were studied experimentally: a higher output power, µ-scale RTD that was RF coupled to an active photodetector and a VCSEL (this layout is referred to as a PRL node); and a simplified, photosensitive RTD with nanoscale injector that was RF coupled to a VCSEL (referred to as a nanopRL node). Hallmark excitable behaviours were studied in both devices, including excitability thresholding and refractory periods. Furthermore, a more exotic resonate and-fire dynamical behaviour was also reported in the nano-pRL device. Finally, a modular numerical model of the RTD was introduced, and various information processing methods were demonstrated using both a single RTD spiking node, as well as a perceptron-type spiking neural network with physical models of optoelectronic RTD nodes serving as artificial spiking neurons.Over the last decade, we have witnessed an astonishing pace of development in the field of artificial intelligence (AI), followed by proliferation of AI algorithms into virtually every domain of our society. While modern AI models boast impressive performance, they also require massive amounts of energy and resources for operation. This is further fuelling the research into AI-specific, optimised computing hardware. At the same time, the remarkable energy efficiency of the brain brings an interesting question: Can we further borrow from the working principles of biological intelligence to realise a more efficient artificial intelligence? This can be considered as the main research question in the field of neuromorphic engineering. Thanks to the developments in AI and recent advancements in the field of photonics and photonic integration, research into light-powered implementations of neuromorphic hardware has recently experienced a significant uptick of interest. In such hardware, the aim is to seize some of the highly desirable properties of photonics not just for communication, but also to perform computation. Neurons in the brain frequently process information (compute) and communicate using action potentials, which are brief voltage spikes that encode information in the temporal domain. Similar dynamical behaviour can be elicited in some photonic devices, at speeds multiple orders of magnitude higher. Such devices with the capability of neuron-like spiking are of significant research interest for the field of neuromorphic photonics. Two distinct types of such excitable, spiking systems operating with optical signals are studied and investigated in this thesis. First, a vertical cavity surface emitting laser (VCSEL) can be operated under a specific set of conditions to realise a high-speed, all-optical excitable photonic neuron that operates at standard telecom wavelengths. The photonic VCSEL-neuron was dynamically characterised and various information encoding mechanisms were studied in this device. In particular, a spiking rate-coding regime of operation was experimentally demonstrated, and its viability for performing spiking domain conversion of digital images was explored. Furthermore, for the first time, a joint architecture utilising a VCSEL-neuron coupled to a photonic integrated circuit (PIC) silicon microring weight bank was experimentally demonstrated in two different functional layouts. Second, an optoelectronic (O/E/O) circuit based upon a resonant tunnelling diode (RTD) was introduced. Two different types of RTD devices were studied experimentally: a higher output power, µ-scale RTD that was RF coupled to an active photodetector and a VCSEL (this layout is referred to as a PRL node); and a simplified, photosensitive RTD with nanoscale injector that was RF coupled to a VCSEL (referred to as a nanopRL node). Hallmark excitable behaviours were studied in both devices, including excitability thresholding and refractory periods. Furthermore, a more exotic resonate and-fire dynamical behaviour was also reported in the nano-pRL device. Finally, a modular numerical model of the RTD was introduced, and various information processing methods were demonstrated using both a single RTD spiking node, as well as a perceptron-type spiking neural network with physical models of optoelectronic RTD nodes serving as artificial spiking neurons

On the development of slime mould morphological, intracellular and heterotic computing devices

The use of live biological substrates in the fabrication of unconventional computing (UC) devices is steadily transcending the barriers between science fiction and reality, but efforts in this direction are impeded by ethical considerations, the field’s restrictively broad multidisciplinarity and our incomplete knowledge of fundamental biological processes. As such, very few functional prototypes of biological UC devices have been produced to date. This thesis aims to demonstrate the computational polymorphism and polyfunctionality of a chosen biological substrate — slime mould Physarum polycephalum, an arguably ‘simple’ single-celled organism — and how these properties can be harnessed to create laboratory experimental prototypes of functionally-useful biological UC prototypes. Computing devices utilising live slime mould as their key constituent element can be developed into a) heterotic, or hybrid devices, which are based on electrical recognition of slime mould behaviour via machine-organism interfaces, b) whole-organism-scale morphological processors, whose output is the organism’s morphological adaptation to environmental stimuli (input) and c) intracellular processors wherein data are represented by energetic signalling events mediated by the cytoskeleton, a nano-scale protein network. It is demonstrated that each category of device is capable of implementing logic and furthermore, specific applications for each class may be engineered, such as image processing applications for morphological processors and biosensors in the case of heterotic devices. The results presented are supported by a range of computer modelling experiments using cellular automata and multi-agent modelling. We conclude that P. polycephalum is a polymorphic UC substrate insofar as it can process multimodal sensory input and polyfunctional in its demonstrable ability to undertake a variety of computing problems. Furthermore, our results are highly applicable to the study of other living UC substrates and will inform future work in UC, biosensing, and biomedicine

Rolle der Kopplungsbedingungen für die Musterbildung in anregbaren Medien: Studie von Vorhofflimmermechanismen und Oszillatorarrays in der Belousov-Zhabotinsky-Reaktion

Diese Arbeit beschäftigt sich mit dem Übergang zwischen regulären und irregulären Mustern in Reaktions-Diffusions (RD)-Systemen. Hierbei lag der Fokus der Untersuchung auf der Rolle der Kopplungsbedingungen zwischen mehreren Oszillatoren für das Auftreten des Übergangs und der Systemspezifität der zugrundeliegenden Mechanismen. Zwei RD-Systeme wurden hierfür gewählt: (i) das Herz im Vorhofflimmer(VF)-zustand und (ii) die Belousov-Zhabotinsky-Reaktion (BZR). Numerische Simulationen dieser Systeme basierten auf einem Standard-RD-Modell, dem Fitzhugh-Nagumo-Modell, und verschiedenen systemspezifischen Modellen. Ergebnisse der Simulationen wurden mit selbstdurchgeführten Experimenten der BZR auf Silikatgelen sowie mit Literaturdaten zu medizinischen Studien des VF verglichen. Zwei Mechanismen für den Übergang zu irregulären Mustern wurden studiert. Der erste, von mir vorgeschlagene Mechanismus basiert auf der Wechselwirkung zweier aktiver Quellen, welche räumlich separiert sind. In Abhängigkeit des Frequenzverhältnisses der Quellen konnten verschiedene Typen von irregulären Mustern identifiziert werden: ein generischer Typ und drei weitere Typen, welche nur im allgemeinen oder den systemspezifischen Modellen auftraten. Der vorgeschlagene Mechanismus kann das episodische Auftreten von VF erklären, indem Änderungen einer Quellenfrequenz das System in den Zustand irregulärer Muster bringen. Dieser neue Mechanismus ist nicht nur für VF sondern auch für RD-Systeme (BZR, Nervenzellen) relevant. Der zweite untersuchte Mechanismus basiert auf der diffusiven Kopplung vieler Oszillatoren. In dieser Arbeit wurden irreguläre Muster im Bereich schwacher Kopplung gefunden, für welche als Ursache einerseits die reduzierte Kohärenz zwischen den gekoppelten Oszillatoren identifiziert wurde und andererseits die aufgrund der Kopplung veränderte Dynamik im Falle von anregbaren Einheiten. Ein weiterer Typ irregulärer Muster wird durch das Aufbrechen von Wellenfronten an den Oszillatoren verursacht. Der Einfluss der Größe, Form und Kopplungsstärke auf das Auftreten der irregulären Muster wurde untersucht sowie die Eigenschaften der Muster. Aufgrund der Generalität der identifizierten Mechanismen sind diese auch für andere chemische und biologische RD-Systeme wie PEM-Brennstoffzellen oder Herz-, Nerven- oder Bauchspeicheldrüsenzellen von Bedeutung.In this work, the transition between regular and irregular patterns was studied in reaction-diffusion (RD) systems with the ability of pattern formation. The focus of this work lies on the role of the coupling conditions between two or more oscillators for the occurrence of the irregular states and the system-specificity of the mechanisms. To address this issue, two specific RD systems were chosen: (i) the heart during atrial fibrillation (AF) and (ii) the Belousov-Zhabotinsky reaction (BZR). Numerical simulations of these systems have been performed on the basis of a standard generic model, the FitzHugh-Nagumo model, and system-specific models. Results are compared to experiments of the BZR on silica gels with spatially structured catalyst patterns and medical data from literature for AF studies. Two mechanisms were studied, which are suggested to yield irregular patterns. The first mechanism, proposed by myself, consists of the interaction of two active sources located in separate regions. In dependence of the relation between the frequencies of the active sources, irregular patterns of different types occurred. One type is a general one, while three other types occurred only in either the generic model or the system-specific one. The proposed mechanism can explain the often episodic occurrence of AF, when considering frequency changes of one active source, which can move the system into the range of irregular patterns. The novel mechanism is relevant also for other RD systems where similar effects situations like detachment of waves and conduction blocks occur. The second mechanism is based on the diffusive coupling of multiple oscillators. In this case, either a reduced coupling or heterogeneity are thought to cause irregular patterns. Irregular patterns were found in the weak coupling regime due to clusters of synchronized oscillators and the modified dynamics of coupled excitable units. Another type consists of wavefront break-up at the spot centers. The influence of the size, shape and coupling strength of the coupled units on the irregularities was investigated as well as the properties of the irregularities itself. These mechanisms are relevant also for chemical RD systems (e.g. PEM fuel cells) and biological systems as, e.g., the nerve, heart or pancreatic beta cells

Ultra-sensitive bioelectronic transducers for extracellular electrophysiological studies

Extracellular 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.A atividade elétrica extracelular das células é geralmente medida usando matrizes de micro-elétrodos (MEA) planares. A tecnologia MEA foi otimizada para medir sinais gerados por células excitáveis, como os neurónios. Essas células produzem sinais conhecidos como potenciais de ação. No entanto, todas as células produzem potenciais de membrana. Em contraste com os potenciais de ação, os sinais elétricos gerados por células não excitáveis ou não eletrogénicas, não são “spikes”, mas sinais que variam lentamente e que podem mudar ao longo de períodos de vários minutos com amplitudes de apenas alguns microvolts. Estes sinais desempenham funções importantes nos mecanismos de sinalização que controlam a proliferação, a diferenciação e a migração celular. Medir e entender esses sinais é importante na biologia do desenvolvimento, na medicina regenerativa e no desenvolvimento de novas terapias para combater células cancerosas. O objetivo desta tese é fabricar e caracterizar transdutores para medir in vitro a atividade de células não eletrogénicas. Como esses sinais são da ordem de alguns microvolts, os elétrodos devem ter um limite de detecção na ordem de centenas de nanovolts. Para enfrentar este desafio, foi desenvolvida uma metodologia para analisar a forma como os sinais se acoplam à superfície do sensor. A metodologia baseia-se na descrição da interface de detecção por um circuito eléctrico equivalente. Procedimentos para extração dos parâmetros de circuito e a relação com as propriedades do material e o desenho geométrico foi estabelecida. Este conhecimento foi usado para estabelecer diretrizes para otimização dos transdutores. Em primeiro lugar a metodologia foi usada para interpretar as medidas de sinais usando elétrodos de ouro, posteriormente estendida para analisar superfícies de polímeros condutores (PEDOT: PSS) e, finalmente, para compreender o funcionamento de transístores. Os resultados desta tese contribuíram para o avanço do conhecimento em transdutores bioeletrónicos nos seguintes aspectos: (i) Detecção de sinais produzidos por uma importante classe de células neurais, astrócitos e gliomas, que tem permanecido inacessíveis usando elétrodos extracelulares. (ii) Desenvolvimento de um método eletrofisiológico para medir a migração de células cancerosas e o estabelecimento de conexões entre células. (ii) Estudo das limitações dos transístores para medir sinais eletrofisiológicos rápidos.The work developed in this thesis was carried out within the framework of the project entitled: “Implantable Organic Devices for Advanced Therapies (INNOVATE)”, ref. PTDC/EEI-AUT/5442/2014, financed by Fundação para a Ciência e Tecnologia (FCT).This project was carried out at the laboratories of the “ Instituto de Telecomunicações (IT) UID/Multi/04326/2013” at the University of the Algarve. The PhD study period received full scholarship under European EM program, “Erasmus Mundus Action 2 (EMA2)” coordinated by University of Warsaw