Wearable electroencephalography for long-term monitoring and diagnostic purposes

Truly Wearable EEG (WEEG) can be considered as the future of ambulatory EEG units, which are the current standard for long-term EEG monitoring. Replacing these short lifetime, bulky units with long-lasting, miniature and wearable devices that can be easily worn by patients will result in more EEG data being collected for extended monitoring periods. This thesis presents three new fabricated systems, in the form of Application Specific Integrated Circuits (ASICs), to aid the diagnosis of epilepsy and sleep disorders by detecting specific clinically important EEG events on the sensor node, while discarding background activity. The power consumption of the WEEG monitoring device incorporating these systems can be reduced since the transmitter, which is the dominating element in terms of power consumption, will only become active based on the output of these systems. Candidate interictal activity is identified by the developed analog-based interictal spike selection system-on-chip (SoC), using an approximation of the Continuous Wavelet Transform (CWT), as a bandpass filter, and thresholding. The spike selection SoC is fabricated in a 0.35 μm CMOS process and consumes 950 nW. Experimental results reveal that the SoC is able to identify 87% of interictal spikes correctly while only transmitting 45% of the data. Sections of EEG data containing likely ictal activity are detected by an analog seizure selection SoC using the low complexity line length feature. This SoC is fabricated in a 0.18 μm CMOS technology and consumes 1.14 μW. Based on experimental results, the fabricated SoC is able to correctly detect 83% of seizure episodes while transmitting 52% of the overall EEG data. A single-channel analog-based sleep spindle detection SoC is developed to aid the diagnosis of sleep disorders by detecting sleep spindles, which are characteristic events of sleep. The system identifies spindle events by monitoring abrupt changes in the input EEG. An approximation of the median frequency calculation, incorporated as part of the system, allows for non-spindle activity incorrectly identified by the system as sleep spindles to be discarded. The sleep spindle detection SoC is fabricated in a 0.18 μm CMOS technology, consuming only 515 nW. The SoC achieves a sensitivity and specificity of 71.5% and 98% respectively.Open Acces

Design and Evaluation of a Hardware System for Online Signal Processing within Mobile Brain-Computer Interfaces

Brain-Computer Interfaces (BCIs) sind innovative Systeme, die eine direkte Kommunikation zwischen dem Gehirn und externen Geräten ermöglichen. Diese Schnittstellen haben sich zu einer transformativen Lösung nicht nur für Menschen mit neurologischen Verletzungen entwickelt, sondern auch für ein breiteres Spektrum von Menschen, das sowohl medizinische als auch nicht-medizinische Anwendungen umfasst. In der Vergangenheit hat die Herausforderung, dass neurologische Verletzungen nach einer anfänglichen Erholungsphase statisch bleiben, die Forscher dazu veranlasst, innovative Wege zu beschreiten. Seit den 1970er Jahren stehen BCIs an vorderster Front dieser Bemühungen. Mit den Fortschritten in der Forschung haben sich die BCI-Anwendungen erweitert und zeigen ein großes Potenzial für eine Vielzahl von Anwendungen, auch für weniger stark eingeschränkte (zum Beispiel im Kontext von Hörelektronik) sowie völlig gesunde Menschen (zum Beispiel in der Unterhaltungsindustrie). Die Zukunft der BCI-Forschung hängt jedoch auch von der Verfügbarkeit zuverlässiger BCI-Hardware ab, die den Einsatz in der realen Welt gewährleistet. Das im Rahmen dieser Arbeit konzipierte und implementierte CereBridge-System stellt einen bedeutenden Fortschritt in der Brain-Computer-Interface-Technologie dar, da es die gesamte Hardware zur Erfassung und Verarbeitung von EEG-Signalen in ein mobiles System integriert. Die Architektur der Verarbeitungshardware basiert auf einem FPGA mit einem ARM Cortex-M3 innerhalb eines heterogenen ICs, was Flexibilität und Effizienz bei der EEG-Signalverarbeitung gewährleistet. Der modulare Aufbau des Systems, bestehend aus drei einzelnen Boards, gewährleistet die Anpassbarkeit an unterschiedliche Anforderungen. Das komplette System wird an der Kopfhaut befestigt, kann autonom arbeiten, benötigt keine externe Interaktion und wiegt einschließlich der 16-Kanal-EEG-Sensoren nur ca. 56 g. Der Fokus liegt auf voller Mobilität. Das vorgeschlagene anpassbare Datenflusskonzept erleichtert die Untersuchung und nahtlose Integration von Algorithmen und erhöht die Flexibilität des Systems. Dies wird auch durch die Möglichkeit unterstrichen, verschiedene Algorithmen auf EEG-Daten anzuwenden, um unterschiedliche Anwendungsziele zu erreichen. High-Level Synthesis (HLS) wurde verwendet, um die Algorithmen auf das FPGA zu portieren, was den Algorithmenentwicklungsprozess beschleunigt und eine schnelle Implementierung von Algorithmusvarianten ermöglicht. Evaluierungen haben gezeigt, dass das CereBridge-System in der Lage ist, die gesamte Signalverarbeitungskette zu integrieren, die für verschiedene BCI-Anwendungen erforderlich ist. Darüber hinaus kann es mit einer Batterie von mehr als 31 Stunden Dauerbetrieb betrieben werden, was es zu einer praktikablen Lösung für mobile Langzeit-EEG-Aufzeichnungen und reale BCI-Studien macht. Im Vergleich zu bestehenden Forschungsplattformen bietet das CereBridge-System eine bisher unerreichte Leistungsfähigkeit und Ausstattung für ein mobiles BCI. Es erfüllt nicht nur die relevanten Anforderungen an ein mobiles BCI-System, sondern ebnet auch den Weg für eine schnelle Übertragung von Algorithmen aus dem Labor in reale Anwendungen. Im Wesentlichen liefert diese Arbeit einen umfassenden Entwurf für die Entwicklung und Implementierung eines hochmodernen mobilen EEG-basierten BCI-Systems und setzt damit einen neuen Standard für BCI-Hardware, die in der Praxis eingesetzt werden kann.Brain-Computer Interfaces (BCIs) are innovative systems that enable direct communication between the brain and external devices. These interfaces have emerged as a transformative solution not only for individuals with neurological injuries, but also for a broader range of individuals, encompassing both medical and non-medical applications. Historically, the challenge of neurological injury being static after an initial recovery phase has driven researchers to explore innovative avenues. Since the 1970s, BCIs have been at one forefront of these efforts. As research has progressed, BCI applications have expanded, showing potential in a wide range of applications, including those for less severely disabled (e.g. in the context of hearing aids) and completely healthy individuals (e.g. entertainment industry). However, the future of BCI research also depends on the availability of reliable BCI hardware to ensure real-world application. The CereBridge system designed and implemented in this work represents a significant leap forward in brain-computer interface technology by integrating all EEG signal acquisition and processing hardware into a mobile system. The processing hardware architecture is centered around an FPGA with an ARM Cortex-M3 within a heterogeneous IC, ensuring flexibility and efficiency in EEG signal processing. The modular design of the system, consisting of three individual boards, ensures adaptability to different requirements. With a focus on full mobility, the complete system is mounted on the scalp, can operate autonomously, requires no external interaction, and weighs approximately 56g, including 16 channel EEG sensors. The proposed customizable dataflow concept facilitates the exploration and seamless integration of algorithms, increasing the flexibility of the system. This is further underscored by the ability to apply different algorithms to recorded EEG data to meet different application goals. High-Level Synthesis (HLS) was used to port algorithms to the FPGA, accelerating the algorithm development process and facilitating rapid implementation of algorithm variants. Evaluations have shown that the CereBridge system is capable of integrating the complete signal processing chain required for various BCI applications. Furthermore, it can operate continuously for more than 31 hours with a 1800mAh battery, making it a viable solution for long-term mobile EEG recording and real-world BCI studies. Compared to existing research platforms, the CereBridge system offers unprecedented performance and features for a mobile BCI. It not only meets the relevant requirements for a mobile BCI system, but also paves the way for the rapid transition of algorithms from the laboratory to real-world applications. In essence, this work provides a comprehensive blueprint for the development and implementation of a state-of-the-art mobile EEG-based BCI system, setting a new benchmark in BCI hardware for real-world applicability

OPTIMIZATION OF TIME-RESPONSE AND AMPLIFICATION FEATURES OF EGOTs FOR NEUROPHYSIOLOGICAL APPLICATIONS

In device engineering, basic neuron-to-neuron communication has recently inspired the development of increasingly structured and efficient brain-mimicking setups in which the information flow can be processed with strategies resembling physiological ones. This is possible thanks to the use of organic neuromorphic devices, which can share the same electrolytic medium and adjust reciprocal connection weights according to temporal features of the input signals. In a parallel - although conceptually deeply interconnected - fashion, device engineers are directing their efforts towards novel tools to interface the brain and to decipher its signalling strategies. This led to several technological advances which allow scientists to transduce brain activity and, piece by piece, to create a detailed map of its functions. This effort extends over a wide spectrum of length-scales, zooming out from neuron-to-neuron communication up to global activity of neural populations. Both these scientific endeavours, namely mimicking neural communication and transducing brain activity, can benefit from the technology of Electrolyte-Gated Organic Transistors (EGOTs). Electrolyte-Gated Organic Transistors (EGOTs) are low-power electronic devices that functionally integrate the electrolytic environment through the exploitation of organic mixed ionic-electronic conductors. This enables the conversion of ionic signals into electronic ones, making such architectures ideal building blocks for neuroelectronics. This has driven extensive scientific and technological investigation on EGOTs. Such devices have been successfully demonstrated both as transducers and amplifiers of electrophysiological activity and as neuromorphic units. These promising results arise from the fact that EGOTs are active devices, which widely extend their applicability window over the capabilities of passive electronics (i.e. electrodes) but pose major integration hurdles. Being transistors, EGOTs need two driving voltages to be operated. If, on the one hand, the presence of two voltages becomes an advantage for the modulation of the device response (e.g. for devising EGOT-based neuromorphic circuitry), on the other hand it can become detrimental in brain interfaces, since it may result in a non-null bias directly applied on the brain. If such voltage exceeds the electrochemical stability window of water, undesired faradic reactions may lead to critical tissue and/or device damage. This work addresses EGOTs applications in neuroelectronics from the above-described dual perspective, spanning from neuromorphic device engineering to in vivo brain-device interfaces implementation. The advantages of using three-terminal architectures for neuromorphic devices, achieving reversible fine-tuning of their response plasticity, are highlighted. Jointly, the possibility of obtaining a multilevel memory unit by acting on the gate potential is discussed. Additionally, a novel mode of operation for EGOTs is introduced, enabling full retention of amplification capability while, at the same time, avoiding the application of a bias in the brain. Starting on these premises, a novel set of ultra-conformable active micro-epicortical arrays is presented, which fully integrate in situ fabricated EGOT recording sites onto medical-grade polyimide substrates. Finally, a whole organic circuitry for signal processing is presented, exploiting ad-hoc designed organic passive components coupled with EGOT devices. This unprecedented approach provides the possibility to sort complex signals into their constitutive frequency components in real time, thereby delineating innovative strategies to devise organic-based functional building-blocks for brain-machine interfaces.Nell’ingegneria elettronica, la comunicazione di base tra neuroni ha recentemente ispirato lo sviluppo di configurazioni sempre più articolate ed efficienti che imitano il cervello, in cui il flusso di informazioni può essere elaborato con strategie simili a quelle fisiologiche. Ciò è reso possibile grazie all'uso di dispositivi neuromorfici organici, che possono condividere lo stesso mezzo elettrolitico e regolare i pesi delle connessioni reciproche in base alle caratteristiche temporali dei segnali in ingresso. In modo parallelo, gli ingegneri elettronici stanno dirigendo i loro sforzi verso nuovi strumenti per interfacciare il cervello e decifrare le sue strategie di comunicazione. Si è giunti così a diversi progressi tecnologici che consentono agli scienziati di trasdurre l'attività cerebrale e, pezzo per pezzo, di creare una mappa dettagliata delle sue funzioni. Entrambi questi ambiti scientifici, ovvero imitare la comunicazione neurale e trasdurre l'attività cerebrale, possono trarre vantaggio dalla tecnologia dei transistor organici a base elettrolitica (EGOT). I transistor organici a base elettrolitica (EGOT) sono dispositivi elettronici a bassa potenza che integrano funzionalmente l'ambiente elettrolitico attraverso lo sfruttamento di conduttori organici misti ionici-elettronici, i quali consentono di convertire i segnali ionici in segnali elettronici, rendendo tali dispositivi ideali per la neuroelettronica. Gli EGOT sono stati dimostrati con successo sia come trasduttori e amplificatori dell'attività elettrofisiologica e sia come unità neuromorfiche. Tali risultati derivano dal fatto che gli EGOT sono dispositivi attivi, al contrario dell'elettronica passiva (ad esempio gli elettrodi), ma pongono comunque qualche ostacolo alla loro integrazione in ambiente biologico. In quanto transistor, gli EGOT necessitano l'applicazione di due tensioni tra i suoi terminali. Se, da un lato, la presenza di due tensioni diventa un vantaggio per la modulazione della risposta del dispositivo (ad esempio, per l'ideazione di circuiti neuromorfici basati su EGOT), dall'altro può diventare dannosa quando gli EGOT vengono adoperati come sito di registrazione nelle interfacce cerebrali, poiché una tensione non nulla può essere applicata direttamente al cervello. Se tale tensione supera la finestra di stabilità elettrochimica dell'acqua, reazioni faradiche indesiderate possono manifestarsi, le quali potrebbero danneggiare i tessuti e/o il dispositivo. Questo lavoro affronta le applicazioni degli EGOT nella neuroelettronica dalla duplice prospettiva sopra descritta: ingegnerizzazione neuromorfica ed implementazione come interfacce neurali in applicazioni in vivo. Vengono evidenziati i vantaggi dell'utilizzo di architetture a tre terminali per i dispositivi neuromorfici, ottenendo una regolazione reversibile della loro plasticità di risposta. Si discute inoltre la possibilità di ottenere un'unità di memoria multilivello agendo sul potenziale di gate. Viene introdotta una nuova modalità di funzionamento per gli EGOT, che consente di mantenere la capacità di amplificazione e, allo stesso tempo, di evitare l'applicazione di una tensione all’interfaccia cervello-dispositivo. Partendo da queste premesse, viene presentata una nuova serie di array micro-epicorticali ultra-conformabili, che integrano completamente i siti di registrazione EGOT fabbricati in situ su substrati di poliimmide. Infine, viene proposto un circuito organico per l'elaborazione del segnale, sfruttando componenti passivi organici progettati ad hoc e accoppiati a dispositivi EGOT. Questo approccio senza precedenti offre la possibilità di filtrare e scomporre segnali complessi nelle loro componenti di frequenza costitutive in tempo reale, delineando così strategie innovative per concepire blocchi funzionali a base organica per le interfacce cervello-macchina

Conformable transistors for bioelectronics

The diversity of network disruptions that occur in patients with neuropsychiatric disorders creates a strong demand for personalized medicine. Such approaches often take the form of implantable bioelectronic devices that are capable of monitoring pathophysiological activity for identifying biomarkers to allow for local and responsive delivery of intervention. They are also required to transmit this data outside of the body for evaluation of the treatment’s efficacy. However, the ability to perform these demanding electronic functions in the complex physiological environment with minimum disruption to the biological tissue remains a big challenge. An optimal fully implantable bioelectronic device would require each component from the front-end to the data transmission to be conformable and biocompatible. For this reason, organic material-based conformable electronics are ideal candidates for components of bioelectronic circuits due to their inherent flexibility, and soft nature. In this work, first an organic mixed-conducting particulate composite material (MCP) able to form functional electronic components and non-invasively acquire high–spatiotemporal resolution electrophysiological signals by directly interfacing human skin is presented. Secondly, we introduce organic electrochemical internal ion-gated transistors (IGTs) as a high-density, high-amplification sensing component as well as a low leakage, high-speed processing unit. Finally, a novel wireless, battery-free strategy for electrophysiological signal acquisition, processing, and transmission that employs IGTs and an ionic communication circuit (IC) is introduced. We show that the wirelessly-powered IGTs are able to acquire and modulate neurophysiological data in-vivo and transmit them transdermally, eliminating the need for any hard Si-based electronics in the implant

Pluripotent Stem Cell Biology

Pluripotent stem cells have the potential to revolutionize treatment options for a range of diseases and conditions. This book presents recent advances in our understanding of the biological mechanisms of stem cell self-renewal, reprograming and regeneration. Also covered are novel methodological advances in the culture, purification and use of stem cells, as well as the ethical and moral dilemmas of embryo donation and adoption. These advances will shape the utilization of stem cells for future basic and applied applications

WOFEX 2021 : 19th annual workshop, Ostrava, 1th September 2021 : proceedings of papers

The workshop WOFEX 2021 (PhD workshop of Faculty of Electrical Engineer-ing and Computer Science) was held on September 1st September 2021 at the VSB – Technical University of Ostrava. The workshop offers an opportunity for students to meet and share their research experiences, to discover commonalities in research and studentship, and to foster a collaborative environment for joint problem solving. PhD students are encouraged to attend in order to ensure a broad, unconfined discussion. In that view, this workshop is intended for students and researchers of this faculty offering opportunities to meet new colleagues.Ostrav

A Closed-Loop Bidirectional Brain-Machine Interface System For Freely Behaving Animals

A brain-machine interface (BMI) creates an artificial pathway between the brain and the external world. The research and applications of BMI have received enormous attention among the scientific community as well as the public in the past decade. However, most research of BMI relies on experiments with tethered or sedated animals, using rack-mount equipment, which significantly restricts the experimental methods and paradigms. Moreover, most research to date has focused on neural signal recording or decoding in an open-loop method. Although the use of a closed-loop, wireless BMI is critical to the success of an extensive range of neuroscience research, it is an approach yet to be widely used, with the electronics design being one of the major bottlenecks. The key goal of this research is to address the design challenges of a closed-loop, bidirectional BMI by providing innovative solutions from the neuron-electronics interface up to the system level. Circuit design innovations have been proposed in the neural recording front-end, the neural feature extraction module, and the neural stimulator. Practical design issues of the bidirectional neural interface, the closed-loop controller and the overall system integration have been carefully studied and discussed.To the best of our knowledge, this work presents the first reported portable system to provide all required hardware for a closed-loop sensorimotor neural interface, the first wireless sensory encoding experiment conducted in freely swimming animals, and the first bidirectional study of the hippocampal field potentials in freely behaving animals from sedation to sleep. This thesis gives a comprehensive survey of bidirectional BMI designs, reviews the key design trade-offs in neural recorders and stimulators, and summarizes neural features and mechanisms for a successful closed-loop operation. The circuit and system design details are presented with bench testing and animal experimental results. The methods, circuit techniques, system topology, and experimental paradigms proposed in this work can be used in a wide range of relevant neurophysiology research and neuroprosthetic development, especially in experiments using freely behaving animals