7 research outputs found

    Long-Term Stable Adhesion for Conducting Polymers in Biomedical Applications: IrOx and Nanostructured Platinum Solve the Chronic Challenge

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    Conducting polymers (CPs) have frequently been described as outstanding coating materials for neural microelectrodes, providing significantly reduced impedance or higher charge injection compared to pure metals. Usability has until now, however, been limited by poor adhesion of polymers like poly(3,4-ethylenedioxythiophene) (PEDOT) to metallic substrates, ultimately precluding long-term applications. The aim of this study was to overcome this weakness of CPs by introducing two novel adhesion improvement strategies that can easily be integrated with standard microelectrode fabrication processes. Iridium Oxide (IrOx) demonstrated exceptional stability for PEDOT coatings, resulting in polymer survival over 10 000 redox cycles and 110 days under accelerated aging conditions at 60 °C. Nanostructured Pt was furthermore introduced as a purely mechanical adhesion promoter providing 10-fold adhesion improvement compared to smooth Pt substrates by simply altering the morphology of Pt. This layer can be realized in a very simple process that is compatible with any electrode design, turning nanostructured Pt into a universal adhesion layer for CP coatings. By the introduction of these adhesion-promoting strategies, the weakness of CP-based neural probes can ultimately be eliminated and true long-term stable use of PEDOT on neural probes will be possible in future electrode generations

    Doctor of Philosophy

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    dissertationBy enabling neuroprosthetic technologies, neural microelectrodes can greatly improve diagnostic and treatment options for millions of individuals living with limb loss, paralysis, and sensory and autonomic neural disorders. However, clinical use of these devices is restricted by the limited functional lifetimes of implanted electrodes, which are commonly less than a few years. One cause is the evolution of damage to dielectric encapsulation that insulates microelectrodes from the physiological environment. Fluid penetration and exposure to an aggressive immunological response over time may weaken encapsulating films and cause electrical shunting. This reduces electrode impedance, diverts electrical signal away from target tissue, and causes multi-channel crosstalk. To date, no neural microelectrode encapsulating material or design approach has reliably resolved this issue. We employ the parylene C-encapsulated Utah Electrode Array (UEA), a silicon-micromachined neural interface FDA-cleared for human use, to execute three aims that address this challenge through investigations of new materials, electrode designs, and testing methods. We first evaluate a novel bilayer encapsulating film comprised of atomic layer deposited Al2O3 and parylene C, testing this film using UEAs and devices with UEA-relevant topography. Contrasting with previous work employing simplified planar structures, the incorporation of neural electrode features on test structures revealed failure modes pointing to the dissolution of Al2O3 over time. Our results emphasize the need for dielectric coatings resistant to water degradation as well as test methods that take electrode features into account. In our second aim, we show through finite element modeling and aggressive in vitro testing that use of degenerately doped silicon as a conductive neural electrode material can mitigate the consequences of encapsulation damage, owing to the high electrochemical impedance of silicon. Our final aim compares oxidative in vitro aging to long-term in vivo material damages and finds clear evidence that such in vitro testbeds may help predict certain in vivo damage modes. By pairing this testing with absorption and emission spectroscopic characterization modalities, we identify contributors to material damage and future design solutions. Our results will inform future material and testing choices, to improve the resilience of neural electrode dielectric encapsulation and enhance the longevity of neuroprostheses

    Electrochemical charaterization of PDMAAp/PEDOT coated electrodes for DC stimulation

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    Dissertação de mestrado em Biomedical EngineeringElectrotaxis or Galvanotaxis is the directed migration of cells in an electric field and constitutes a fundamental phenomenon in many biological mechanisms, for instance, cell division, wound healing, and embryonal development. It is caused by spontaneous endogenous electrical fields (EFs) due to ionic gradients. Multiple studies and experimental research have proven that applying an external electrical field (direct current DC) can originate an electrotactic response on the cells, since it resembles an endogenous EF. Besides fundamental understanding in biology, this form of artificial electrotaxis appears to be a promising alternative for wound healing treatment. The cell’s response and the mechanisms related to electrotaxis are still uncertain, and the properties of the electrode material hinder the advancements in cellular research and medical applications. A promising solution for this problem is the use of conductive polymer electrodes for DC stimulation. In this work, electrodes of different materials, IrOx, PEDOT/PSS, and PDMAAp/PEDOT, were developed, fabricated, and tested. The materials of the electrodes had different thicknesses that were tested and compared with each other. These electrodes were electrochemically characterized and used for DC stimulation. Due to their supercapacitive behavior, the electrodes were able to go through several DC stimulation cycles with different currents applied, without observable damage. A fluidic setup and an electronic readout system were designed and fabricated for pH measurements during different DC stimulations for all the electrodes materials. No changes in the pH value were observed in the medium surrounding the electrodes. Moreover, the electrodes materials were tested for cytotoxicity, and none could be observed. This work concludes that PDMAAp/PEDOT coated electrodes show excellent electrochemical properties and DC stimulation capabilities similar to PEDOT/PSS

    Doctor of Philosophy

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    dissertationBiomedical implantable devices have been developed for both research and clinical applications, to stimulate and record physiological signals in vivo. Chronic use of biomedical devices with thin-film-based encapsulation in large scale is impeded by their lack of long-term functionality and stability. Biostable, biocompatible, conformal, and electrically insulating coatings that sustain chronic implantation are essential for chip-scale implantable electronic systems. Even though many materials have been studied to for this purpose, to date, no encapsulation method has been thoroughly characterized or qualified as a broadly applicable long-term hermetic encapsulation for biomedical implantable devices. In this work, atomic layer deposited Al2O3 and Parylene C bi-layer was investigated as encapsulation for biomedical devices. The combination of ALD Al2O3 and CVD Parylene C encapsulation extended the lifetime of coated interdigitated electrodes (IDEs) to up to 72 months (to date) with low leakage current of ~ 15 pA. The long lifetime was achieved by significantly reducing moisture permeation due to the ALD Al2O3 layer. Moreover, the bi-layer encapsulation separates the permeated moisture (mostly at the Al2O3 and Parylene interface) from the surface contaminants (mostly at the device and Al2O3 interface), preventing the formation of localized electrolyte through condensation. Al2O3 works as an inner moisture barrier and Parylene works as an external ion barrier, preventing contact of AI2O3 with liquid water, and slowing the kinetics of alumina corrosion. Selective removal of encapsulation materials is required to expose the active sites for interacting with physiological environment. A self-aligned mask process with three steps was developed to expose active sites, composed of laser ablation, oxygen plasma etching, and BOE etching. Al2O3 layer was found to prevent the formation of microcracks in the iridium oxide film during laser ablation. Bi-layer encapsulated iridium oxide had higher charge injection capacity and similar electrochemical impedance compared with Parylene C coated iridium oxide film after deinsulation. The Al2O3 and Parylene C bi-layer encapsulation was applied to Utah electrode array (UEA)-based neural interfaces to study its long-term performance. The median tip impedance of the bi-layer encapsulated wired Utah electrode array increased slowly during the 960 days of equivalent soak testing at 37 °C. Impedance for Parylene coated UEA dropped 50% to 75% within 6 months. In addition, bi-layer coated fully integrated Utah array-based wireless neural interfaces had stable power-up frequencies at ~910 MHz and constant RF signal strength of -50 dBm during the 1044 days of equivalent soaking time at 37 °C. This is much longer than lifetime achieved with Parylene C coating, which was about one year at room temperature

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

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    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

    Comparison of Multiple Degrees of Electrode Surface Roughness: Impedance, Charge Storage Capacity, Biofouling and Biocompatibility

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    Devices called neural electrodes are generally used to record and / or stimulate neural activity whilst extracellularly interfacing with neurons. The ultimate goal of the field is to develop neural electrodes that can continuously record and / or stimulate neural activity for long periods of time (10+ years). Electrodes require low electrode impedance to enable good signal to noise ratio and a high capacity for chemically stable injection of charge (CSC) for stimulating neural activity. Electrode function typically deteriorates after a few months in-vivo due two factors: biofouling and local cellular response (glial scarring). Biofouling is theorised to be an accumulation of multiple proteins at the electrode surface. However this has only been backed up experimentally by single protein models in literature. Electrodes need to be able to combat the effects of biofouling and glial scarring. This study uses nanometre scale roughened gold (Au) electrodes. Electrode roughening has previously been shown to lower impedance, increase CSC and reduce glial response and the effects of biofouling. We compared multiple degrees of roughness with the aim of finding the optimal degree for improving impedance, CSC, biofouling and cellular response. We found that surface roughening increased impedance and only increased CSC for two only degrees of roughness. To find the optimal degree of roughness across conditions, we suspect a larger range of roughness may be necessary to lower impedance with our fabrication technique. This study is the first to use a multiprotein biofouling model. Contrary to literature, we found that incubation with protein decreased impedance, likely due to protein-protein interactions not accounted for in single protein models. Biocompatibility was improved for two degrees of Au roughness. Roughening of SU8, a polymer used to surround the electrodes, decreased biocompatibility. We also used artificial cerebral spinal fluid (aCSF) as an electrolyte, which is more chemically similar to in-vivo than commonly used phosphate buffered saline solution (PBS). The use aCSF as a medium was significant as the measures in aCSF were different from that in PBS

    Non-covalent interactions in organotin(IV) derivatives of 5,7-ditertbutyl- and 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine as recognition motifs in crystalline self- assembly and their in vitro antistaphylococcal activity

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    Non-covalent interactions are known to play a key role in biological compounds due to their stabilization of the tertiary and quaternary structure of proteins [1]. Ligands similar to purine rings, such as triazolo pyrimidine ones, are very versatile in their interactions with metals and can act as model systems for natural bio-inorganic compounds [2]. A considerable series (twelve novel compounds are reported) of 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) and 5,7-diphenyl- 1,2,4-triazolo[1,5-a]pyrimidine (dptp) were synthesized and investigated by FT-IR and 119Sn M\uf6ssbauer in the solid state and by 1H and 13C NMR spectroscopy, in solution [3]. The X-ray crystal and molecular structures of Et2SnCl2(dbtp)2 and Ph2SnCl2(EtOH)2(dptp)2 were described, in this latter pyrimidine molecules are not directly bound to the metal center but strictly H-bonded, through N(3), to the -OH group of the ethanol moieties. The network of hydrogen bonding and aromatic interactions involving pyrimidine and phenyl rings in both complexes drives their self-assembly. Noncovalent interactions involving aromatic rings are key processes in both chemical and biological recognition, contributing to overall complex stability and forming recognition motifs. It is noteworthy that in Ph2SnCl2(EtOH)2(dptp)2 \u3c0\u2013\u3c0 stacking interactions between pairs of antiparallel triazolopyrimidine rings mimick basepair interactions physiologically occurring in DNA (Fig.1). M\uf6ssbauer spectra suggest for Et2SnCl2(dbtp)2 a distorted octahedral structure, with C-Sn-C bond angles lower than 180\ub0. The estimated angle for Et2SnCl2(dbtp)2 is virtually identical to that determined by X-ray diffraction. Ph2SnCl2(EtOH)2(dptp)2 is characterized by an essentially linear C-Sn-C fragment according to the X-ray all-trans structure. The compounds were screened for their in vitro antibacterial activity on a group of reference staphylococcal strains susceptible or resistant to methicillin and against two reference Gramnegative pathogens [4] . We tested the biological activity of all the specimen against a group of staphylococcal reference strains (S. aureus ATCC 25923, S. aureus ATCC 29213, methicillin resistant S. aureus 43866 and S. epidermidis RP62A) along with Gram-negative pathogens (P. aeruginosa ATCC9027 and E. coli ATCC25922). Ph2SnCl2(EtOH)2(dptp)2 showed good antibacterial activity with a MIC value of 5 \u3bcg mL-1 against S. aureus ATCC29213 and also resulted active against methicillin resistant S. epidermidis RP62A
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