Nanomechanical characterization of soft bioelectronic interfaces via modeling-informed atomic force microscopy

The field of bioelectronics involves the use of electrodes to exchange electrical signals with biological systems for diagnostic and therapeutic purposes in biomedical devices and healthcare applications. However, the mechanical compatibility of implantable devices with the human body has been a challenge, particularly with long-term implantation into target organs. Current rigid bioelectronics can trigger inflammatory responses and cause unstable device functions due to the mechanical mismatch with the surrounding soft tissue. Recent advances in flexible and stretchable electronics have shown promise in making bioelectronic interfaces more biocompatible. To fully achieve this goal, material science and engineering of soft electronic devices must be combined with quantitative characterization and modeling tools to understand the mechanical issues at the interface between electronic technology and biological tissue. Local mechanical characterization is crucial to understand the activation of failure mechanisms and optimizing the devices. Experimental techniques for testing mechanical properties at the nanoscale are emerging, and the Atomic Force Microscope (AFM) is a good candidate for in situ local mechanical characterization of soft bioelectronic interfaces. In this work, in situ experimental techniques with solely AFM supported by interpretive models for the characterization of planar and three-dimensional devices suitable for in vivo and in vitro biomedical experimentations are reported. The combination of the proposed models and experimental techniques provides access to the local mechanical properties of soft bioelectronic interfaces. The study investigates the nanomechanics of hard thin gold films on soft polymeric substrates (Poly(dimethylsiloxane) PDMS) and 3D inkjet-printed micropillars under different deformation states. The proposed characterization methods provide a rapid and precise determination of mechanical properties, thus giving the possibility to parametrize the microfabrication steps and investigate their impact on the final device

Electronic dura mater soft, multimodal neural interfaces:technology, integration and implementation to surface implants

Neuroprosthetic devices are engineered to study, support or replace impaired functions of the nervous system. The neural interface is an essential element of neuroprosthetic systems as it allows for transduction of signals and stimuli of desired functions (recording, stimulation, neuromodulation). A persistent challenge for translating neuroprosthetics from the laboratory to the clinic is the lack of long-term biointegration of neural interfaces. This thesis aims at improving biointegration of neural interfaces by reducing the mechanical mismatch between implant and neural tissue. In this thesis, the design, fabrication and characterization of soft surface neural interfaces is described. These soft neural interfaces, termed electronic dura mater or e-dura, were designed to mimic the mechanical properties of dura mater. In contrast with conventional neural technologies, e-dura neural interfaces were made of soft and compliant materials. They conform to the circumvolutions of the brain and spinal cord and follow their dynamic deformation without damaging the surrounding neural tissues. These soft multimodal neural interfaces were fabricated on silicone substrates using techniques imported from the microfabrication industry and incorporate compliant electrodes, stretchable electrical interconnects and a micro-catheter for drug delivery. Evaluation of the e-dura biointegration with spinal tissues demonstrated reduced foreign body reaction, compared to stiff polyimide based implants. Additionally, mechanical tests on an in-vitro spinal surrogate provided insights on the complex biomechanical coupling between implants and neural tissue. E-dura interfaces, implanted in rodents, maintained their functionality over extended periods and provided high-resolution neuronal recordings and concurrent delivery of electrical and chemical neuromodulation. Eventually, the use of gallium thin films was explored to create highly conductive and stretchable interconnects for integration of active electronic components in e-dura neural interfaces

Poly (3,4-ethylenedioxythiophene) (PEDOT) Coatings for High Quality Electromyography Recording

Les revêtements en polymère conducteur sur les électrodes métalliques constituent une solution efficace pour améliorer l'enregistrement et la stimulation des signaux neuronaux en raison de leurs conductivités électronique et ionique ainsi que de leur biocompatibilité. Cependant, très peu d’études ont été réalisées sur les revêtements de polymères conducteurs sur des fils métalliques pour l'enregistrement du signal musculaire. Ces travaux traitent surtout les électrodes pour l'enregistrement chronique sous anesthésie. L'enregistrement chronique du signal musculaire chez les animaux en mouvement pose un de défis pour les revêtements d'électrode, en raison des déplacements musculaires qui peuvent provoquer un délaminage du revêtement et une défaillance du dispositif. De plus, la faible adhérence des polymères conducteurs à certains substrats inorganiques et la dégradation de leurs propriétés électrochimiques après des traitements sévères tels que la stérilisation ou pendant l'implantation, limitent davantage leur utilisation pour les applications biomédicales. Dans ce travail, nous avons développé des électrodes invasives électrochimiquement stables pour l'enregistrement de signaux musculaires chez les petits animaux à base de fils multibrins en acier inoxydable revêtus du polymère conducteur poly(3,4-ethylenedioxythiophene) (PEDOT). La stabilité électrochimique et mécanique a été obtenue en ajustant les conditions d'électropolymérisation. Le PEDOT, dopé par des anions ClO4 - , a été électropolymérisé de manière galvanostatique sur des fils d'acier inoxydable en utilisant trois solvants différents: le carbonate de propylène (organique), l'acétonitrile (organique) et l'eau (inorganique). L’adhérence du revêtement au substrat métallique a été testée par ultrasonication et la stabilité électrochimique a été évaluée par vieillissement accéléré dans une solution tampon de phosphate salin et par stérilisation à l’autoclave. Le solvant a joué un rôle clé dans l’adhérence du revêtement PEDOT. Les solvants organiques offraient la meilleure stabilité mécanique. Les électrodes préparées avec ces solvants possédaient une excellente stabilité électrochimique et survivaient à la stérilisation et au trempage prolongé sans changement majeur des propriétés électrochimiques. Des électrodes en acier inoxydable sans revêtements de polymères conducteurs et d’autres revêtues de PEDOT ont été implantées dans le muscle acromiotrapezius de cinq souris pour l'enregistrement du signal musculaire durant une période de 6 semaines. Le revêtement PEDOT a amélioré les propriétés électrochimiques des électrodes en acier inoxydable, abaissant l'impédance, ce qui a permis d'améliorer le rapport signal / bruit lors de l'enregistrement du signal musculaire in vivo par rapport aux électrodes sans polymère.----------ABSTRACT Conductive polymer coatings on metal electrodes are an efficient solution to improve neural signal recording and stimulation due to their mixed electronic-ionic conduction and biocompatibility. To date only a few studies have been reported on conductive polymer coatings on metallic wire electrodes for muscle signal recording. These studies mainly deal with testing of electrodes for acute recording during anaesthesia. Chronic muscle signal recording in free-walking animals offers more challenges for the electrode coatings, due to the muscle displacements which may cause coating delamination and device failure. The poor adhesion of conductive polymers to some inorganic substrates and the possible degradation of their electrochemical properties after harsh treatments, such as sterilization, or during implantation still limit their use for biomedical applications. In this work, we developed mechanically and electrochemically stable invasive electrodes for muscle signal recording in small animals based on stainless steel multi-stranded wires coated with the conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT). The electrochemical and mechanical stability was achieved by tuning the electropolymerization conditions. PEDOT doped with ClO4 - anions was galvanostatically electropolymerized using three different solvents: propylene carbonate (organic), acetonitrile (organic) and water (inorganic). The coating’s adhesion to the metallic substrate was tested through ultrasonication and the electrochemical stability was evaluated through accelerated ageing in phosphate buffer solution and autoclave sterilization. The solvent played a key role in the adhesion of the PEDOT coating, with organic solvents giving the best mechanical stability. Electrodes prepared with these solvents possessed excellent electrochemical stability, and survived sterilization and prolonged soaking without major changes in electrochemical properties. PEDOT-coated and bare electrodes were implanted in the acromiotrapezius muscle of five mice for muscle signal recording during a period of 6 weeks. The PEDOT coating improved the electrochemical properties of the stainless steel electrodes, lowering the impedance, which resulted in enhanced signal to noise ratio during in vivo muscle signal recording compared to bare electrodes

Advances in materials strategies, circuit designs, and informatics for wearable, flexible and stretchable electronics with medical and robotic applications

The future of medical electronics should be flexible, stretchable and skin-integrated. While modern electronics become increasing smaller, faster and energy efficient, the designs remain bulky and rigid due to materials and processing limitations. The miniaturization of health monitoring devices in wearable form resembles a significant progress towards the next-generation medical electronics. However, there are still key challenges in these wearable electronics associated with medical-grade sensing precision, reliable wireless powering, and materials strategy for skin-integration. Here, I present a series of systematic studies from materials strategies, circuit design to signal processing on skin-mounted electronic wearable devices. Several types of Epidermal Electronic Systems (EES) develop applications in dermatology, cardiology, rehabilitation, and wireless powering. For skin hydration measurement, fundamental studies of electrode configurations and skin-electrode impedance reveal the optimal sensor design. Furthermore, wireless operation of hydration sensor was made possible with direct integration on skin, and on porous substrates that collect and analyze sweats. Additionally, I present an epidermal multi-functional sensing platform that could provide a control-feedback loop through electromyogram and current stimulation; and a mechano-acoustic device that could capture vibrations from muscle, heart, and throat as diagnostic tools or human-machine interface. I developed a modularized epidermal radio-frequency energy transfer epidermal device to eliminate batteries and power cables for wearable electronics. Finally, I present a clinical study that validates a commercialized ESS on patients with nerve disorders for electromyography monitoring during peripheral nerve and spinal cord surgeries

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

De animais a máquinas : humanos tecnicamente melhores nos imaginários de futuro da convergência tecnológica

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Sociais, Departamento de Sociologia, 2020.O tema desta investigação é discutir os imaginários sociais de ciência e tecnologia que emergem a partir da área da neuroengenharia, em sua relação com a Convergência Tecnológica de quatro disciplinas: Nanotecnologia, Biotecnologia, tecnologias da Informação e tecnologias Cognitivas - neurociências- (CT-NBIC). Estas áreas desenvolvem-se e são articuladas por meio de discursos que ressaltam o aprimoramento das capacidades físicas e cognitivas dos seres humanos, com o intuito de construir uma sociedade melhor por meio do progresso científico e tecnológico, nos limites das agendas de pesquisa e desenvolvimento (P&D). Objetivos: Os objetivos nesse cenário, são discutir as implicações éticas, econômicas, políticas e sociais deste modelo de sistema sociotécnico. Nos referimos, tanto as aplicações tecnológicas, quanto as consequências das mesmas na formação dos imaginários sociais, que tipo de relações se estabelecem e como são criadas dentro desse contexto. Conclusão: Concluímos na busca por refletir criticamente sobre as propostas de aprimoramento humano mediado pela tecnologia, que surgem enquanto parte da agenda da Convergência Tecnológica NBIC. No entanto, as propostas de melhoramento humano vão muito além de uma agenda de investigação. Há todo um quadro de referências filosóficas e políticas que defendem o aprimoramento da espécie, vertentes estas que se aliam a movimentos trans-humanistas e pós- humanistas, posições que são ao mesmo tempo éticas, políticas e econômicas. A partir de nossa análise, entendemos que ciência, tecnologia e política estão articuladas, em coprodução, em relação às expectativas de futuros que são esperados ou desejados. Ainda assim, acreditamos que há um espaço de diálogo possível, a partir do qual buscamos abrir propostas para o debate público sobre questões de ciência e tecnologia relacionadas ao aprimoramento da espécie humana.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The subject of this research is to discuss the social imaginaries of science and technology that emerge from the area of neuroengineering in relation with the Technological Convergence of four disciplines: Nanotechnology, Biotechnology, Information technologies and Cognitive technologies -neurosciences- (CT-NBIC). These areas are developed and articulated through discourses that emphasize the enhancement of human physical and cognitive capacities, the intuition it is to build a better society, through the scientific and technological progress, at the limits of the research and development (R&D) agendas. Objectives: The objective in this scenery, is to discuss the ethic, economic, politic and social implications of this model of sociotechnical system. We refer about the technological applications and the consequences of them in the formation of social imaginaries as well as the kind of social relations that are created and established in this context. Conclusion: We conclude looking for critical reflections about the proposals of human enhancement mediated by the technology. That appear as a part of the NBIC technologies agenda. Even so, the proposals of human enhancement go beyond boundaries that an investigation agenda. There is a frame of philosophical and political references that defend the enhancement of the human beings. These currents that ally to the transhumanism and posthumanism movements, positions that are ethic, politic and economic at the same time. From our analysis, we understand that science, technology and politics are articulated, are in co-production, regarding the expected and desired futures. Even so, we believe that there is a space of possible dialog, from which we look to open proposals for the public discussion on questions of science and technology related to enhancement of human beings

In Vivo Imaging to Characterize Dynamic Tissue Responses after Neural Electrode Implantation

Implantable neural electrodes are promising technologies to restore motor, sensory, and cognitive function in many neural pathologies through brain-computer interfacing (BCI). Many BCI applications require electrode implantation within neural tissue to resolve and/or modulate the physiological activity of individual neurons via electrical recording and stimulation. This invasive implantation leads to acute and long-term deterioration of both the electrode device as well as the neurons surrounding the device. Ultimately, damage to the electrode and neural tissue results in electrode recording failure within the first years after implantation. Many strategies to improve BCI longevity focus on mitigating tissue damage through improving neuronal survival or reducing inflammatory activity around implants. Despite incremental improvements, electrode failure persists as an obstacle to wide-spread clinical deployment of BCIs. This can be partly attributed to an incomplete understanding of the biological correlates of recording performance. These correlates have largely been identified through post-mortem histological staining, which cannot capture dynamic changes in cellular physiology and morphology. In the following dissertation, we use longitudinal two-photon in vivo imaging to quantify how neurons, microglia, and meningeal immune cells are affected by an intracortical electrode during and after implantation in mouse cortex. We go beyond conventional histological techniques to show the time-course of neuronal injury and microglial recruitment after implantation. Neuronal injury occurs instantaneously, with prolonged, high calcium levels evident in neurons within 100 µm of implants. Microglial activation occurs within minutes of implantation and subsequent microglial encapsulation of electrodes can be modulated by bioactive surface coatings. Within the first day post-implant, there is high trafficking of peripheral immune cells through venules at the surface of the brain as well as along the electrode’s shank at the surface of the brain. Over the next month, calcium activity in neurons increases while the collagenous meningeal tissues at the surface of the brain thicken. We further show that meningeal thickening can have profound implications for devices implanted into non-human primates as well. In sum, these results define new potential therapeutic targets and windows that could improve the longevity of implantable neural electrodes

Designing a Clinically Viable Brain Computer Interface for the Control of Neuroprosthetics

Currently no brain computer interfaces exist that can control the individual fingers of a hand prosthesis and is suitable for permanent implantation in and individual with a single limb amputation. Within this thesis a design for a novel minimally invasive brain computer interface system is proposed that would be relatively low risk, allow for control of a prosthesis using existing cortical structures and be suitable for patients with loss of a single limb. The early stage development and proof of concept work has been done taking into account relevant regulatory requirements, so that a finalised version of the design would be suitable for regulatory certification. This novel design is found to be worth pursuing and may in turn open up new research opportunities

The 2nd International Electronic Conference on Applied Sciences

This book is focused on the works presented at the 2nd International Electronic Conference on Applied Sciences, organized by Applied Sciences from 15 to 31 October 2021 on the MDPI Sciforum platform. Two decades have passed since the start of the 21st century. The development of sciences and technologies is growing ever faster today than in the previous century. The field of science is expanding, and the structure of science is becoming ever richer. Because of this expansion and fine structure growth, researchers may lose themselves in the deep forest of the ever-increasing frontiers and sub-fields being created. This international conference on the Applied Sciences was started to help scientists conduct their own research into the growth of these frontiers by breaking down barriers and connecting the many sub-fields to cut through this vast forest. These functions will allow researchers to see these frontiers and their surrounding (or quite distant) fields and sub-fields, and give them the opportunity to incubate and develop their knowledge even further with the aid of this multi-dimensional network