Development of a Three Dimensional Neural Sensing Device by a Stacking Method

This study reports a new stacking method for assembling a 3-D microprobe array. To date, 3-D array structures have usually been assembled with vertical spacers, snap fasteners and a supporting platform. Such methods have achieved 3-D structures but suffer from complex assembly steps, vertical interconnection for 3-D signal transmission, low structure strength and large implantable opening. By applying the proposed stacking method, the previous techniques could be replaced by 2-D wire bonding. In this way, supporting platforms with slots and vertical spacers were no longer needed. Furthermore, ASIC chips can be substituted for the spacers in the stacked arrays to achieve system integration, design flexibility and volume usage efficiency. To avoid overflow of the adhesive fluid during assembly, an anti-overflow design which made use of capillary action force was applied in the stacking method as well. Moreover, presented stacking procedure consumes only 35 minutes in average for a 4 × 4 3-D microprobe array without requiring other specially made assembly tools. To summarize, the advantages of the proposed stacking method for 3-D array assembly include simplified assembly process, high structure strength, smaller opening area and integration ability with active circuits. This stacking assembly technique allows an alternative method to create 3-D structures from planar components

Carbon Fiber Microelectrode Arrays for Neuroprosthetic and Neuroscience Applications.

The aim of this work is to develop, validate, and characterize the insertion mechanism, tissue response, and recording longevity of a new high-density carbon fiber microelectrode array. This technology was designed to significantly improve the field of penetrating microelectrodes while simultaneously accommodating the variable needs of both neuroscientists and neural engineers. The first study presents the fabrication and insertion dynamics of a high-density carbon fiber electrode array using a dual sided printed circuit board platform. The use of this platform has pushed electrode density to limits not seen in other works. This necessitated the use of an encapsulation method that served to temporarily stiffen the fibers during insertion, but did not enter the brain as many other shuttles do for other probe designs. The initial findings in this work informed the development of an even higher density array using a silicon support structure as a backbone. The second study reports on the tissue reaction of chronically implanted carbon fiber electrode arrays as compared to silicon electrodes. Due to their smaller footprint, the reactive response to carbon fibers should be greatly attenuated, if not non-existent. Results show a scarring response to the implanted silicon electrode with elevated astrocyte and microglia activity coupled to a local decrease in neuronal density. The area implanted with the carbon fiber electrodes showed a varied response, from no detectable increase in astrocytic or microglial activity to an elevated activation of both cell types, but with no detectable scars. Neuronal density in the carbon fiber implant region was unaffected. The data demonstrates that the small carbon fiber profile, even in an array configuration, shows an attenuated reactive response with no visible scaring. The final study reports on the viability of chronically implanted high-density carbon fiber arrays as compared to more traditional silicon planar arrays with comparable site sizes. While most new probe technologies or designs are able to demonstrate proof of concept functionality in acute preparations, very few show the ability to record chronic unit activity. This study aims to provide a comprehensive analysis of electrophysiology data collected over implant durations ranging from 3 – 5 months.PhDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111557/1/parasp_1.pd

Fabrication and applications of dopamine-sensitive electrode

The neurotransmitter dopamine has shown to be of central importance to difference brain functions, such as movement, reward, and addiction. A biosensor for the detection of dopamine in the brain should have a fast time response to monitor concentration changes which happen on a subsecond time scale. Furthermore, the sensor should have a high sensitivity to dopamine, because the physiological concentrations of dopamine were found to be in the range form nanomolar to lower micromolar. High selectivity is also necessary to distinguish the desired signal from electrochemical interferences in the brain such as ascorbic acid. Fast scan cyclic voltammetry at glass-encased carbon fiber microelectrodes has been shown to fulfill these requirements and is therefore often used for measurements of easily oxidizable neurotransmitters like dopamine. In this dissertation, some drawbacks of the technique and the sensor are addressed and improved. Chapter 1 contains an overview of electrochemical methods that have been used to detect various neurotransmitters in the brain. Chapter 2 explains a method to increase the sensitivity and selectivity for dopamine of carbon fiber microelectrodes by covalent attachment of a cation-exchange layer to the electrode surface. A method utilizing tungsten microwires as substrate for the construction of flexible gold, platinum, and carbon microelectrodes is described in Chapter 3 and 4. Carbon-coated tungsten microwires have then been examined for use as in vivo dopamine sensor. The microwires showed the same electrochemical properties as conventional glass-encased carbon fiber microelectrodes. In chapters 5 and 6 a novel instrumental method to subtract of the large background current, which occurs during application of fast scan rates, is presented. This method has then been used to examine the changes in this background current and account for these changes. This enabled us to expand the time course for fast scan voltammetric measurements 20-fold. Furthermore, the origin of these background changes was examined. In the last chapter tungsten based microelectrodes were used to evaluate changes in dopamine concentrations and pH of the extracellular fluid in a primate brain during reward delivery

Microeléctrodos de diamante para estudos de corrosão

Doutoramento em Ciência e Engenharia de MateriaisEste trabalho teve como objetivos a produção, caracterização e aplicação de microelétrodos (MEs) de diamante como sensores amperométricos e potenciométricos em sistemas de corrosão nos quais a agressividade do meio e a presença de produtos de corrosão, constituem obstáculos que podem diminuir o desempenho, ou inviabilizar a utilização, de outros tipos de sensores. Os microeléctrodos são baseados em filmes finos de diamante dopado com boro (BDD – Boron Doped Diamond) depositados sobre fios de tungsténio afiados, através do método de deposição química a partir da fase vapor, assistida por filamento quente (HFCVD – Hot Filament Chemical Vapor Deposition). A otimização das diversas etapas de fabricação dos MEs deu origem ao desenvolvimento de um novo sistema de afiamento eletroquímico para obtenção destes fios e a várias opções para a obtenção dos filmes de diamante condutor e seu isolamento com resinas para exposição apenas da ponta cilíndrica. A qualidade cristalina dos filmes de diamante foi avaliada por espectroscopia de Raman. Esta informação foi complementada com uma caracterização microestrutural dos filmes de diamante por microscopia eletrónica de varrimento (SEM), em que se fez a identificação da tipologia dos cristais como pertencendo às gamas de diamante nanocristalino ou microcristalino. Os filmes de BDD foram utilizados na sua forma não modificada, com terminações em hidrogénio e também com modificação da superfície através de tratamentos de plasma RF de CF4 e O2 indutores de terminações C-F no primeiro caso e de grupos C=O, C-O-C e C-OH no segundo, tal como determinado por XPS. A caracterização eletroquímica dos MEs não modificados revelou uma resposta voltamétrica com elevada razão sinal/ruído e baixa corrente capacitiva, numa gama de polarização quasi-ideal com extensão de 3 V a 4 V, dependente dos parâmetros de crescimento e pós-tratamentos de superfície. Estudou-se a reversibilidade de algumas reações heterogéneas com os pares redox Fe(CN)6 3-/4- e FcOH0/+ e verificou-se que a constante cinética, k0, é mais elevada em elétrodos com terminações em hidrogénio, nos quais não se procedeu a qualquer modificação da superfície. Estes MEs não modificados foram também testados na deteção de Zn2+ onde se observou, por voltametria cíclica, que a detecção da redução deste ião é linear numa escala log-log na gama de 10-5-10-2 M em 5 mM NaCl. Realizaram-se também estudos em sistemas de corrosão modelares, em que os microeléctrodos foram usados como sensores amperométricos para mapear a distribuição de oxigénio e Zn2+ sobre um par galvânico Zn-Fe, com recurso a um sistema SVET (Scanning Vibrating Electrode Technique). Foi possível detetar, com resolução lateral de 100 μm, um decréscimo da concentração de O2 junto a ambos os metais e produção de catiões de zinco no ânodo. Contudo verificou-se uma significativa deposição de zinco metálico na superfície dos ME utilizados. Os MEs com superfície modificada por plasma de CF4 foram testados como sensores de oxigénio dissolvido. A calibração dos microeléctrodos foi efetuada simultaneamente por voltametria cíclica e medição óptica através de um sensor de oxigénio comercial. Determinou-se uma sensibilidade de ~0.1422 nA/μM, com um limite de deteção de 0.63 μM. Os MEs modificados com CF4 foram também testados como sensores amperométricos com os quais se observou sensibilidade ao oxigénio dissolvido em solução, tendo sido igualmente utilizados durante a corrosão galvânica de pares Zn-Fe. Em alguns casos foi conseguida sensibilidade ao ião Zn2+ sem que o efeito da contaminação superficial com zinco metálico se fizesse sentir. Os microeléctrodos tratados em plasma de CF4 permitem uma boa deteção da distribuição de oxigénio, exibindo uma resposta mais rápida que os não tratados além de maior estabilidade de medição e durabilidade. Nos MEs em que a superfície foi modificada com plasma de O2 foi possível detetar, por cronopotenciometria a corrente nula, uma sensibilidade ao pH de ~51 mV/pH numa gama de pH 2 a pH 12. Este comportamento foi associado à contribuição determinante de grupos C-O e C=O, observados por XPS com uma razão O/C de 0,16. Estes MEs foram igualmente testados durante a corrosão galvânica do par Zn-Fe onde foi possível mapear a distribuição de pH associada ao desenvolvimento de regiões alcalinas causadas pela redução do oxigénio, acima da região catódica, e de regiões ácidas decorrentes da dissolução anódica do ânodo de zinco. Com o par galvânico imerso em 50 mM NaCl registou-se uma variação de pH aproximadamente entre 4,8 acima do ânodo de zinco a 9,3 sobre o cátodo de ferro. A utilização pioneira destes MEs como sensores de pH é uma alternativa promissora aos elétrodos baseados em membranas seletivas.This work was dedicated to the production, characterization and application of diamond microelectrodes (MEs) in corrosion systems as amperometric and potentiometric sensors in which the aggressive media and the presence of corrosion products can affect the performance, or even impede the use of other types of sensors. The MEs are based in boron doped diamond (BDD) thin films grown by HFCVD (Hot Filament Chemical Vapor Deposition) on top of sharp tungsten filaments. The optimization of the various ME fabrication steps gave origin to a novel electrochemical etching technique for the production of sharp metal wires and to multiple options for the growth of diamond films and their insulation with resins in order to expose only the cylindrical tip. The crystalline quality of the diamond films was evaluated with Raman spectroscopy. Complementary microstructural information was gathered by scanning electron microscopy (SEM), to identify the microcrystalline or nanocrystalline nature of the diamond coatings. The BDD films were used in the as-grown form, with hydrogen terminated surface and also with surface modification, by RF-plasma, using CF4 and O2 for inducing different surface terminations, C-F bonds in the first case and C=O, CO- C and C-OH in the second, as detected by XPS. The electrochemical characterization of the MEs revealed a voltammetric response with high signal-to-noise ratio and low capacitive current. The potential range of water stability varied from 3 V to 4V, depending on the growth parameters and surface treatments. Heterogeneous electron transfer kinetics were measured using the Fe(CN)6 3-/4- and FcOH0/+ redox couples and it was verified that the kinetic constant, k0, is higher for the as-grown MEs than for the modified ones. The as-grown MEs were used for the detection of Zn2+ exhibiting a log-log linear response in the range of 10-5-10-2 M in 5 mM NaCl, by cyclic voltammetry. Studies in model corrosion systems were also performed in which the MEs were used as amperometric sensors to map the distribution of oxygen and Zn2+ above a corroding galvanic Zn-Fe couple, by using a SVET (Scanning Vibrating Electrode Technique) system. It was possible to detect with a lateral resolution of 100 μm, a decrease in O2 concentration above both metals and the release of zinc cations above the anode. However, a significant zinc deposition at the surface of the electrodes was observed. The MEs modified by CF4 plasma were tested as dissolved oxygen sensors. The calibration of the microelectrodes was performed simultaneously by cyclic voltammetry and optical measurement with a commercial oxygen sensor. A sensitivity of ~0.1422 nA/μM was determined, with a detection limit of 0.63 μM. The fluorinated MEs were also tested during galvanic corrosion of Zn-Fe couples. In some cases sensitiveness to Zn2+ was also achieved without zinc contamination. The CF4 plasma treated MEs allow a good oxygen mapping, showing a faster response than the as-grown MEs, as well as higher measurement stability and longer lifetime. For the O2 plasma treated MEs it was possible to detect, by zero-current chronopotentiometry, a pH sensitivity of ~51 mV/pH in a pH 2 to pH 12 range. This behavior was attributed to the contribution of the C-O and C=O groups, observed by XPS with an O/C ratio of 0.16. These MEs were also tested during the galvanic corrosion of a Zn-Fe couple where it was possible to map the pH distribution deriving from the development of alkaline regions caused by oxygen reduction, above the cathode, and of acidic regions resulting from the anodic dissolution of zinc. With the galvanic couple immersed in 50 mM NaCl a pH variation was registered from ca. 4.8 above the zinc anode to 9.3 above the cathode. The innovative use of these MEs as pH sensors is a promising alternative to the selective membrane based MEs

Neuroengineering Tools/Applications for Bidirectional Interfaces, Brain–Computer Interfaces, and Neuroprosthetic Implants – A Review of Recent Progress

The main focus of this review is to provide a holistic amalgamated overview of the most recent human in vivo techniques for implementing brain–computer interfaces (BCIs), bidirectional interfaces, and neuroprosthetics. Neuroengineering is providing new methods for tackling current difficulties; however neuroprosthetics have been studied for decades. Recent progresses are permitting the design of better systems with higher accuracies, repeatability, and system robustness. Bidirectional interfaces integrate recording and the relaying of information from and to the brain for the development of BCIs. The concepts of non-invasive and invasive recording of brain activity are introduced. This includes classical and innovative techniques like electroencephalography and near-infrared spectroscopy. Then the problem of gliosis and solutions for (semi-) permanent implant biocompatibility such as innovative implant coatings, materials, and shapes are discussed. Implant power and the transmission of their data through implanted pulse generators and wireless telemetry are taken into account. How sensation can be relayed back to the brain to increase integration of the neuroengineered systems with the body by methods such as micro-stimulation and transcranial magnetic stimulation are then addressed. The neuroprosthetic section discusses some of the various types and how they operate. Visual prosthetics are discussed and the three types, dependant on implant location, are examined. Auditory prosthetics, being cochlear or cortical, are then addressed. Replacement hand and limb prosthetics are then considered. These are followed by sections concentrating on the control of wheelchairs, computers and robotics directly from brain activity as recorded by non-invasive and invasive techniques

New Generation of Electrochemical Sensors for Nitric Oxide;Ruthenium/Carbon-Based Nanostructures and Colloids as Electrocatalytic Platforms

Nitric oxide (NO) is an important intercellular messenger that acts in many tissues to regulate a diverse range of physiological and pathological processes. The physiologically implications of NO function are far from being completely understood. The multifaceted reactivity of NO prompted the need for accurate determination of the concentration of this molecule. However, it is difficult to detect nitric oxide, particularly in biological media and near live cells due to its short half-life, a result of its reactivity and the low levels of NO produced in vivo. As a result, the accurate and reliable detection of NO under varying experimental conditions has always posed a challenging task. The main goal was to develop ultra-sensitive electrocatalytic sensors for accurate quantification of NO. We report the fabrication and characterization of improved NO sensors based on electrocatalytic platforms such as ruthenium (colloids, nanoparticles, and nanotubes) and carbon (pastes and nanotubes), acting as catalytic sites for NO oxidation. These sensors are characterized using various surface analytical tools. The electrocatalytic oxidation of NO is assessed by cyclic voltammetry and amperometry both in solution phase and gas phase. Excellent sensitivity and linearity are observed for our modified electrodes towards NO quantification. Our new NO detection sensors also show superior limit of detection and selectivity against common interference species. Our NO sensors are tested for various applications including in the measurement of NO released from human umbilical vein endothelial cells (HUVECs

New Generation of Electrochemical Sensors for Nitric Oxide;Ruthenium/Carbon-Based Nanostructures and Colloids as Electrocatalytic Platforms

Nitric oxide (NO) is an important intercellular messenger that acts in many tissues to regulate a diverse range of physiological and pathological processes. The physiologically implications of NO function are far from being completely understood. The multifaceted reactivity of NO prompted the need for accurate determination of the concentration of this molecule. However, it is difficult to detect nitric oxide, particularly in biological media and near live cells due to its short half-life, a result of its reactivity and the low levels of NO produced in vivo. As a result, the accurate and reliable detection of NO under varying experimental conditions has always posed a challenging task. The main goal was to develop ultra-sensitive electrocatalytic sensors for accurate quantification of NO. We report the fabrication and characterization of improved NO sensors based on electrocatalytic platforms such as ruthenium (colloids, nanoparticles, and nanotubes) and carbon (pastes and nanotubes), acting as catalytic sites for NO oxidation. These sensors are characterized using various surface analytical tools. The electrocatalytic oxidation of NO is assessed by cyclic voltammetry and amperometry both in solution phase and gas phase. Excellent sensitivity and linearity are observed for our modified electrodes towards NO quantification. Our new NO detection sensors also show superior limit of detection and selectivity against common interference species. Our NO sensors are tested for various applications including in the measurement of NO released from human umbilical vein endothelial cells (HUVECs

New Generation of Electrochemical Sensors for Nitric Oxide;Ruthenium/Carbon-Based Nanostructures and Colloids as Electrocatalytic Platforms

Nitric oxide (NO) is an important intercellular messenger that acts in many tissues to regulate a diverse range of physiological and pathological processes. The physiologically implications of NO function are far from being completely understood. The multifaceted reactivity of NO prompted the need for accurate determination of the concentration of this molecule. However, it is difficult to detect nitric oxide, particularly in biological media and near live cells due to its short half-life, a result of its reactivity and the low levels of NO produced in vivo. As a result, the accurate and reliable detection of NO under varying experimental conditions has always posed a challenging task. The main goal was to develop ultra-sensitive electrocatalytic sensors for accurate quantification of NO. We report the fabrication and characterization of improved NO sensors based on electrocatalytic platforms such as ruthenium (colloids, nanoparticles, and nanotubes) and carbon (pastes and nanotubes), acting as catalytic sites for NO oxidation. These sensors are characterized using various surface analytical tools. The electrocatalytic oxidation of NO is assessed by cyclic voltammetry and amperometry both in solution phase and gas phase. Excellent sensitivity and linearity are observed for our modified electrodes towards NO quantification. Our new NO detection sensors also show superior limit of detection and selectivity against common interference species. Our NO sensors are tested for various applications including in the measurement of NO released from human umbilical vein endothelial cells (HUVECs

Rapid and Sensitive Detection of Foodborne Pathogens Using Bio-Nanocomposites Functionalized Electrochemical Immunosensor with Dielectrophoretic Attraction.

Ph.D. Thesis. University of Hawaiʻi at Mānoa 2017