Advances in nanomaterials integration in CMOS-based electrochemical sensors: a review

The monolithic integration of electrochemical sensors with instrumentation electronics on semiconductor technology is a promising approach to achieve sensor scalability, miniaturization and increased signal to noise ratio. Such an integration requires post-process modification of microchips (or wafers) fabricated in standard semiconductor technology (e.g. CMOS) to develop sensitive and selective sensing electrodes. This review focuses on the post-process fabrication techniques for addition of nanomaterials to the electrode surface, a key component in the construction of electrochemical sensors that has been widely used to achieve surface reactivity and sensitivity. Several CMOS-compatible techniques are summarized and discussed in this review for the deposition of nanomaterials such as gold, platinum, carbon nanotubes, polymers and metal oxide/nitride nanoparticles. These techniques include electroless deposition, electro-chemical deposition, lift-off, micro-spotting, dip-pen lithography, physical adsorption, self-assembly and hydrothermal methods. Finally, the review is concluded and summarized by stating the advantages and disadvantages of these deposition methods

Amino acids, peptides, and proteins:Implications for nanotechnological applications in biosensing and drug/gene delivery

Over various scientific fields in biochemistry, amino acids have been highlighted in research works. Protein, peptide- and amino acid-based drug delivery systems have proficiently transformed nanotechnology via immense flexibility in their features for attaching various drug molecules and biodegradable polymers. In this regard, novel nanostructures including carbon nanotubes, electrospun carbon nanofibers, gold nanoislands, and metal-based nanoparticles have been introduced as nanosensors for accurate detection of these organic compounds. These nanostructures can bind the biological receptor to the sensor surface and increase the surface area of the working electrode, significantly enhancing the biosensor performance. Interestingly, protein-based nanocarriers have also emerged as useful drug and gene delivery platforms. This is important since, despite recent advancements, there are still biological barriers and other obstacles limiting gene and drug delivery efficacy. Currently available strategies for gene therapy are not cost-effective, and they do not deliver the genetic cargo effectively to target sites. With rapid advancements in nanotechnology, novel gene delivery systems are introduced as nonviral vectors such as protein, peptide, and amino acid-based nanostructures. These nano-based delivery platforms can be tailored into functional transformation using proteins and peptides ligands based nanocarriers, usually overexpressed in the specified diseases. The purpose of this review is to shed light on traditional and nanotechnology-based methods to detect amino acids, peptides, and proteins. Furthermore, new insights into the potential of amino protein-based nanoassemblies for targeted drug delivery or gene transfer are presented

Advanced Electrochemical Biosensors

With the progress of nanoscience and biotechnology, advanced electrochemical biosensors have been widely investigated for various application fields. Such electrochemical sensors are well suited to miniaturization and integration for portable devices and parallel processing chips. Therefore, advanced electrochemical biosensors can open a new era in health care, drug discovery, and environmental monitoring. This Special Issue serves the need to promote exploratory research and development on emerging electrochemical biosensor technologies while aiming to reflect on the current state of research in this emerging field

Multifunctional Neural Interfaces for Closed-Loop Control of Neural Activity

Microfabrication and nanotechnology have significantly expanded the technological capabilities for monitoring and modulating neural activity with the goal of studying the nervous system and managing neurological disorders. This feature article initially provides a tutorial‐like review of the prominent technologies for enabling this two‐way communication with the nervous system via electrical, chemical, and optical means. Following this overview, the article discusses emerging high‐throughput methods for identifying device attributes that enhance the functionality of interfaces. The discussion then extends into opportunities and challenges in integrating different device functions within a small footprint with the goal of closed‐loop control of neural activity with high spatiotemporal resolution and reduced adverse tissue response. The article concludes with an outline of future directions in the development and applications of multifunctional neural interfaces

A fully integrated CMOS microelectrode system for electrochemistry

Electroanalysis has proven to be one of the most widely used technologies for point-of-care devices. Owing to the direct recording of the intrinsic properties of biochemical functions, the field has been involved in the study of biology since electrochemistry’s conception in the 1800’s. With the advent of microelectronics, humanity has welcomed self-monitoring portable devices such as the glucose sensor in its everyday routine. The sensitivity of amperometry/ voltammetry has been enhanced by the use of microelectrodes. Their arrangement into microelectrode arrays (MEAs) took a step forward into sensing biomarkers, DNA and pathogens on a multitude of sites. Integrating these devices and their operating circuits on CMOS monolithically miniaturised these systems even more, improved the noise response and achieved parallel data collection. Including microfluidics on this type of devices has led to the birth of the Lab-on-a-Chip technology. Despite the technology’s inclusion in many bioanalytical instruments there is still room for enhancing its capabilities and application possibilities. Even though research has been conducted on the selective preparation of microelectrodes with different materials in a CMOS MEA to sense several biomarkers, limited effort has been demonstrated on improving the parallel electroanalytical capabilities of these devices. Living and chemical materials have a tendency to alter their composition over time. Therefore analysing a biochemical sample using as many electroanalytical methods as possible simultaneously could offer a more complete diagnostic snapshot. This thesis describes the development of a CMOS Lab-on-a-Chip device comprised of many electrochemical cells, capable of performing simultaneous amperometric/voltammetric measurements in the same fluidic chamber. The chip is named an electrochemical cell microarray (ECM) and it contains a MEA controlled by independent integrated potentiostats. The key stages in this work were: to investigate techniques for the electrochemical cell isolation through simulations; to design and implement a CMOS ECM ASIC; to prepare the CMOS chip for use in an electrochemical environment and encapsulate it to work with liquids; to test and characterise the CMOS chip housed in an experimental system; and to make parallel measurements by applying different simultaneous electroanalytical methods. It is envisaged that results from the system could be combined with multivariate analysis to describe a molecular profile rather than only concentration levels. Simulations to determine the microelectrode structure and the potentiostat design, capable of constructing isolated electrochemical cells, were made using the Cadence CAD software package. The electrochemical environment and the microelectrode structure were modelled using a netlist of resistors and capacitors. The netlist was introduced in Cadence and it was simulated with potentiostat designs to produce 3-D potential distribution and electric field intensity maps of the chemical volume. The combination of a coaxial microelectrode structure and a fully differential potentiostat was found to result in independent electrochemical cells isolated from each other. A 4 x 4 integrated ECM controlled by on-chip fully differential potentiostats and made up by a 16 × 16 working electrode MEA (laid out with the coaxial structure) was designed in an unmodified 0.35 μm CMOS process. The working electrodes were connected to a circuit capable of multiplexing them along a voltammetric measurement, maintaining their diffusion layers during stand-by time. Two readout methods were integrated, a simple resistor for an analogue readout and a discrete time digital current-to-frequency charge-sensitive amplifier. Working electrodes were designed with a 20 μm side length while the counter and reference electrodes had an 11 μm width. The microelectrodes were designed using the aluminium top metal layer of the CMOS process. The chips were received from the foundry unmodified and passivated, thus they were post-process fabricated with photolithographic processes. The passivation layer had to be thinned over the MEA and completely removed on top of the microelectrodes. The openings were made 25 % smaller than the top metal layer electrode size to ensure a full coverage of the easily corroded Al metal. Two batches of chips were prepared, one with biocompatible Au on all the microelectrodes and one altered with Pd on the counter and Ag on the reference electrode. The chips were packaged on ceramic pin grid array packages and encapsulated using chemically resistant materials. Electroplating was verified to deposit Au with increased roughness on the microelectrodes and a cleaning step was performed prior to electrochemical experiments. An experimental setup containing a PCB, a PXIe system by National Instruments, and software programs coded for use with the ECM was prepared. The programs were prepared to conduct various voltammetric and amperometric methods as well as to analyse the results. The first batch of post-processed encapsulated chips was used for characterisation and experimental measurements. The on-chip potentiostat was verified to perform alike a commercial potentiostat, tested with microelectrode samples prepared to mimic the coaxial structure of the ECM. The on-chip potentiostat’s fully differential design achieved a high 5.2 V potential window range for a CMOS device. An experiment was also devised and a 12.3 % cell-to-cell electrochemical cross-talk was found. The system was characterised with a 150 kHz bandwidth enabling fast-scan cyclic voltammetry(CV) experiments to be performed. A relatively high 1.39 nA limit-of-detection was recorded compared to other CMOS MEAs, which is however adequate for possible applications of the ECM. Due to lack of a current polarity output the digital current readout was only eligible for amperometric measurements, thus the analogue readout was used for the rest of the measurements. The capability of the ECM system to perform independent parallel electroanalytical measurements was demonstrated with 3 different experimental techniques. The first one was a new voltammetric technique made possible by the ECM’s unique characteristics. The technique was named multiplexed cyclic voltammetry and it increased the acquisition speed of a voltammogram by a parallel potential scan on all the electrochemical cells. The second technique measured a chemical solution with 5 mM of ferrocene with constant potential amperometry, staircase cyclic voltammetry, normal pulse voltammetry, and differential pulse voltammetry simultaneously on different electrochemical cells. Lastly, a chemical solution with 2 analytes (ferrocene and decamethylferrocene) was prepared and they were sensed separately with constant potential amperometry and staircase cyclic voltammetry on different cells. The potential settings of each electrochemical cell were adjusted to detect its respective analyte

Carbon-Based Nanomaterials for (Bio)Sensors Development

Carbon-based nanomaterials have been increasingly used in sensors and biosensors design due to their advantageous intrinsic properties, which include, but are not limited to, high electrical and thermal conductivity, chemical stability, optical properties, large specific surface, biocompatibility, and easy functionalization. The most commonly applied carbonaceous nanomaterials are carbon nanotubes (single- or multi-walled nanotubes) and graphene, but promising data have been also reported for (bio)sensors based on carbon quantum dots and nanocomposites, among others. The incorporation of carbon-based nanomaterials, independent of the detection scheme and developed platform type (optical, chemical, and biological, etc.), has a major beneficial effect on the (bio)sensor sensitivity, specificity, and overall performance. As a consequence, carbon-based nanomaterials have been promoting a revolution in the field of (bio)sensors with the development of increasingly sensitive devices. This Special Issue presents original research data and review articles that focus on (experimental or theoretical) advances, challenges, and outlooks concerning the preparation, characterization, and application of carbon-based nanomaterials for (bio)sensor development

Ultra-sensitive bioelectronic transducers for extracellular electrophysiological studies

Extracellular electrical activity of cells is commonly recorded using microelectrode arrays (MEA) with planar electrodes. MEA technology has been optimized to record signals generated by excitable cells such as neurons. These cells produce spikes referred to as action potentials. However, all cells produce membrane potentials. In contrast to action potentials, electrical signals produced by non-excitable or non-electrogenic cells, do not exhibit spikes, rather smooth potentials that can change over periods of several minutes with amplitudes of only a few microvolts. These bioelectric signals serve functional roles in signalling pathways that control cell proliferation, differentiation and migration. Measuring and understanding these signals is of high priority in developmental biology, regenerative medicine and cancer research. The objective of this thesis is to fabricate and characterise bioelectronic transducers to measure in vitro the bioelectrical activity of non-electrogenic cells. Since these signals are in the order of few microvolts the electrodes must have an unrivaled low detection limit in the order of hundreds of nanovolts. To meet this challenge a methodology to analyze how bioelectrical signals are coupled into sensing surfaces was developed. The methodology relies on a description of the sensing interface by an equivalent circuit. Procedures for circuit parameter extraction are presented. Relation between circuit parameters, material properties and geometrical design was established. This knowledge was used to establish guidelines for device optimization. The methodology was first used to interpret recordings using gold electrodes, later it as extended to conducting polymers surfaces (PEDOT:PSS ) and finally to graphene electrolyte-gated transistors. The results of this thesis have contributed to the advance of the knowledge in bioelectronic transducers in the following aspects: (i) Detection of signals produced by an important class of neural cells, astrocyte and glioma that thus far had remained inaccessible using conventional extracellular electrodes. (ii) Development of an electrophysiological quantitative method for in vitro monitoring of cancer cell migration and cell-to-cell connections. (iii)An understanding of the limitations of electrolyte-gated transistors to record high frequency signals.A atividade elétrica extracelular das células é geralmente medida usando matrizes de micro-elétrodos (MEA) planares. A tecnologia MEA foi otimizada para medir sinais gerados por células excitáveis, como os neurónios. Essas células produzem sinais conhecidos como potenciais de ação. No entanto, todas as células produzem potenciais de membrana. Em contraste com os potenciais de ação, os sinais elétricos gerados por células não excitáveis ou não eletrogénicas, não são “spikes”, mas sinais que variam lentamente e que podem mudar ao longo de períodos de vários minutos com amplitudes de apenas alguns microvolts. Estes sinais desempenham funções importantes nos mecanismos de sinalização que controlam a proliferação, a diferenciação e a migração celular. Medir e entender esses sinais é importante na biologia do desenvolvimento, na medicina regenerativa e no desenvolvimento de novas terapias para combater células cancerosas. O objetivo desta tese é fabricar e caracterizar transdutores para medir in vitro a atividade de células não eletrogénicas. Como esses sinais são da ordem de alguns microvolts, os elétrodos devem ter um limite de detecção na ordem de centenas de nanovolts. Para enfrentar este desafio, foi desenvolvida uma metodologia para analisar a forma como os sinais se acoplam à superfície do sensor. A metodologia baseia-se na descrição da interface de detecção por um circuito eléctrico equivalente. Procedimentos para extração dos parâmetros de circuito e a relação com as propriedades do material e o desenho geométrico foi estabelecida. Este conhecimento foi usado para estabelecer diretrizes para otimização dos transdutores. Em primeiro lugar a metodologia foi usada para interpretar as medidas de sinais usando elétrodos de ouro, posteriormente estendida para analisar superfícies de polímeros condutores (PEDOT: PSS) e, finalmente, para compreender o funcionamento de transístores. Os resultados desta tese contribuíram para o avanço do conhecimento em transdutores bioeletrónicos nos seguintes aspectos: (i) Detecção de sinais produzidos por uma importante classe de células neurais, astrócitos e gliomas, que tem permanecido inacessíveis usando elétrodos extracelulares. (ii) Desenvolvimento de um método eletrofisiológico para medir a migração de células cancerosas e o estabelecimento de conexões entre células. (ii) Estudo das limitações dos transístores para medir sinais eletrofisiológicos rápidos.The work developed in this thesis was carried out within the framework of the project entitled: “Implantable Organic Devices for Advanced Therapies (INNOVATE)”, ref. PTDC/EEI-AUT/5442/2014, financed by Fundação para a Ciência e Tecnologia (FCT).This project was carried out at the laboratories of the “ Instituto de Telecomunicações (IT) UID/Multi/04326/2013” at the University of the Algarve. The PhD study period received full scholarship under European EM program, “Erasmus Mundus Action 2 (EMA2)” coordinated by University of Warsaw

Electronic Devices for the Combination of Electrically Controlled Drug Release, Electrostimulation, and Optogenetic Stimulation for Nerve Tissue Regeneration

[ES] La capacidad de las células madre para proliferar formando distintas células especializadas les otorga la potencialidad de servir de base para terapias efectivas para patologías cuyo tratamiento era inimaginable hasta hace apenas dos décadas. Sin embargo, esta capacidad se encuentra mediada por estímulos fisiológicos, químicos, y eléctricos, específicos y complejos, que dificultan su traslación a la rutina clínica. Por ello, las células madre representan un campo de estudio en el que se invierten amplios esfuerzos por parte de la comunidad científica. En el ámbito de la regeneración nerviosa, para modular su desarrollo y diferenciación el tratamiento farmacológico, la electroestimulación, y la estimulación optogenética son técnicas que están consiguiendo prometedores resultados. Es por ello por lo que en la presente tesis se ha desarrollado un conjunto de sistemas electrónicos para permitir la aplicación combinada de estas técnicas in vitro, con perspectiva a su aplicación in vivo. Hemos diseñado una novedosa tecnología para la liberación eléctricamente controlada de fármacos. Esta tecnología está basada en nanopartículas de sílice mesoporosa y puertas moleculares de bipiridina-heparina. Las puertas moleculares son electroquímicamente reactivas, y encierran los fármacos en el interior de las nanopartículas, liberándolos ante un estímulo eléctrico. Hemos caracterizado esta tecnología, y la hemos validado mediante la liberación controlada de rodamina en cultivos celulares de HeLa. Para la combinación de liberación controlada de fármacos y electroestimulación hemos desarrollado dispositivos que permiten aplicar los estímulos eléctricos de forma configurable desde una interfaz gráfica de usuario. Además, hemos diseñado un módulo de expansión que permite multiplexar las señales eléctricas a diferentes cultivos celulares. Además, hemos diseñado un dispositivo de estimulación optogenética. Este tipo de estimulación consiste en la modificación genética de las células para que sean sensibles a la radiación lumínica de determinada longitud de onda. En el ámbito de la regeneración de tejido mediante células precursoras neurales, es de interés poder inducir ondas de calcio, favoreciendo su diferenciación en neuronas y la formación de circuitos sinápticos. El dispositivo diseñado permite obtener imágenes en tiempo real mediante microscopía confocal de las respuestas transitorias de las células al ser irradiadas. El dispositivo se ha validado irradiando neuronas modificadas con luz pulsada de 100 ms. También hemos diseñado un dispositivo electrónico complementario de medida de irradiancia con el doble fin de permitir la calibración del equipo de irradiancia y medir la irradiancia en tiempo real durante los experimentos in vitro. Los resultados del uso de los bioactuadores en procesos complejos y dinámicos, como la regeneración de tejido nervioso, son limitados en lazo abierto. Uno de los principales aspectos analizados es el desarrollo de biosensores que permitiesen la cuantización de ciertas biomoléculas para ajustar la estimulación suministrada en tiempo real. Por ejemplo, la segregación de serotonina es una respuesta identificada en la elongación de células precursoras neurales, pero hay otras biomoléculas de interés para la implementación de un control en lazo cerrado. Entre las tecnologías en el estado del arte, los biosensores basados en transistores de efecto de campo (FET) funcionalizados con aptámeros son realmente prometedores para esta aplicación. Sin embargo, esta tecnología no permitía la medición simultánea de más de una biomolécula objetivo en un volumen reducido debido a las interferencias entre los distintos FETs, cuyos terminales se encuentran inmersos en la solución. Por ello, hemos desarrollado instrumentación electrónica capaz de medir simultáneamente varios de estos biosensores, y la hemos validado mediante la medición simultánea de pH y la detección preliminar de serotonina y glutamato.[CA] La capacitat de les cèl·lules mare per a proliferar formant diferents cèl·lules especialitzades els atorga la potencialitat de servir de base per a teràpies efectives per a patologies el tractament de les quals era inimaginable fins fa a penes dues dècades. No obstant això, aquesta capacitat es troba mediada per estímuls fisiològics, químics, i elèctrics, específics i complexos, que dificulten la seua translació a la rutina clínica. Per això, les cèl·lules mare representen un camp d'estudi en el qual s'inverteixen amplis esforços per part de la comunitat científica. En l'àmbit de la regeneració nerviosa, per a modular el seu desenvolupament i diferenciació el tractament farmacològic, l'electroestimulació, i l'estimulació optogenética són tècniques que estan aconseguint prometedors resultats. És per això que en la present tesi s'ha desenvolupat un conjunt de sistemes electrònics per a permetre l'aplicació combinada d'aquestes tècniques in vitro, amb perspectiva a la seua aplicació in vivo. Hem dissenyat una nova tecnologia per a l'alliberament elèctricament controlat de fàrmacs. Aquesta tecnologia està basada en nanopartícules de sílice mesoporosa i portes moleculars de bipiridina-heparina. Les portes moleculars són electroquímicament reactives, i tanquen els fàrmacs a l'interior de les nanopartícules, alliberant-los davant un estímul elèctric. Hem caracteritzat aquesta tecnologia, i l'hem validada mitjançant l'alliberament controlat de rodamina en cultius cel·lulars de HeLa. Per a la combinació d'alliberament controlat de fàrmacs i electroestimulació hem desenvolupat dispositius que permeten aplicar els estímuls elèctrics de manera configurable des d'una interfície gràfica d'usuari. A més, hem dissenyat un mòdul d'expansió que permet multiplexar els senyals elèctrics a diferents cultius cel·lulars. A més, hem dissenyat un dispositiu d'estimulació optogenètica. Aquest tipus d'estimulació consisteix en la modificació genètica de les cèl·lules perquè siguen sensibles a la radiació lumínica de determinada longitud d'ona. En l'àmbit de la regeneració de teixit mitjançant cèl·lules precursores neurals, és d'interés poder induir ones de calci, afavorint la seua diferenciació en neurones i la formació de circuits sinàptics. El dispositiu dissenyat permet obtindré imatges en temps real mitjançant microscòpia confocal de les respostes transitòries de les cèl·lules en ser irradiades. El dispositiu s'ha validat irradiant neurones modificades amb llum polsada de 100 ms. També hem dissenyat un dispositiu electrònic complementari de mesura d'irradiància amb el doble fi de permetre el calibratge de l'equip d'irradiància i mesurar la irradiància en temps real durant els experiments in vitro. Els resultats de l'ús dels bioactuadors en processos complexos i dinàmics, com la regeneració de teixit nerviós, són limitats en llaç obert. Un dels principals aspectes analitzats és el desenvolupament de biosensors que permeteren la quantització de certes biomolècules per a ajustar l'estimulació subministrada en temps real. Per exemple, la segregació de serotonina és una resposta identificada amb l'elongació de les cèl·lules precursores neurals, però hi ha altres biomolècules d'interés per a la implementació d'un control en llaç tancat. Entre les tecnologies en l'estat de l'art, els biosensors basats en transistors d'efecte de camp (FET) funcionalitzats amb aptàmers són realment prometedors per a aquesta aplicació. No obstant això, aquesta tecnologia no permetia el mesurament simultani de més d'una biomolècula objectiu en un volum reduït a causa de les interferències entre els diferents FETs, els terminals dels quals es troben immersos en la solució. Per això, hem desenvolupat instrumentació electrònica capaç de mesurar simultàniament diversos d'aquests biosensors i els hem validat amb mesurament simultani del pH i la detecció preliminar de serotonina i glutamat.[EN] The stem cells' ability to proliferate to form different specialized cells gives them the potential to serve as the basis for effective therapies for pathologies whose treatment was unimaginable until just two decades ago. However, this capacity is mediated by specific and complex physiological, chemical, and electrical stimuli that complicate their translation to clinical routine. For this reason, stem cells represent a field of study in which the scientific community is investing a great deal of effort. In the field of nerve regeneration, to modulate their development and differentiation, pharmacological treatment, electrostimulation, and optogenetic stimulation are techniques that are achieving promising results. For this reason, we have developed a set of electronic systems to allow the combined application of these techniques in vitro, with a view to their application in vivo. We have designed a novel technology for the electrically controlled release of drugs. This technology is based on mesoporous silica nanoparticles and bipyridine-heparin molecular gates. The molecular gates are electrochemically reactive and entrap the drugs inside the nanoparticles, releasing them upon electrical stimulus. We have characterized this technology and validated it by controlled release of rhodamine in HeLa cell cultures. For combining electrostimulation and controlled drug release we have developed devices that allow applying the different electrical stimuli in a configurable way from a graphical user interface. In addition, we have designed an expansion module that allows multiplexing electrical signals to different cell cultures. In addition, we have designed an optogenetic stimulation device. This type of stimulation consists of genetically modifying cells to make them sensitive to light radiation of a specific wavelength. In tissue regeneration using neural precursor cells, it is interesting to be able to induce calcium waves, favoring the cell differentiation into neurons and the formation of synaptic circuits. The designed device enable the obtention of real-time images through confocal microscopy of the transient responses of cells upon irradiation. The device has been validated by irradiating modified neurons with 100 ms pulsed light stimulation. We have also designed a complementary electronic irradiance measurement device to allow calibration of the irradiator equipment and measuring irradiance in real time during in vitro experiments. The results of using bioactuators in complex and dynamic processes, such as nerve tissue regeneration, are limited in an open loop. One of the main aspects analyzed is the development of biosensors that would allow quantifying of specific biomolecules to adjust the stimulation provided in real time. For instance, serotonin secretion is an identified response of neural precursor cells elongation, among other biomolecules of interest for the implementation of a closed-loop control. Among the state-of-the-art technologies, biosensors based on field effect transistors (FETs) functionalized with aptamers are promising for this application. However, this technology did not allow the simultaneous measurement of more than one target biomolecule in a small volume due to interferences between the different FETs, whose terminals are immersed in the solution. This is why we have developed electronic instrumentation capable of simultaneously measuring several of these biosensors, and we have validated it with the simultaneous pH measurement and the preliminary detection of serotonin and glutamate.Monreal Trigo, J. (2023). Electronic Devices for the Combination of Electrically Controlled Drug Release, Electrostimulation, and Optogenetic Stimulation for Nerve Tissue Regeneration [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/19384

Multimodal Investigation of the Efficiency and Stability of Microstimulation using Electrodes Coated with PEDOT/CNT and Iridium Oxide

Electrical microstimulation is an invaluable tool in neuroscience research to dissect neural circuits, relate brain areas, and identify relationships between brain structure and behavior. In the clinic, electrical microstimulation has enabled partial restoration of vision, movement, sensation and autonomic functions. Recently, novel materials and new fabrication techniques of traditional metals have emerged such as iridium oxide and the conducting polymer PEDOT/CNT. These materials have demonstrated particular promise in the improvement in electrical efficiency. However, the in vivo stimulation efficiency and the in vivo stability of these materials have not been thoroughly characterized. In this dissertation, we use a multimodal approach to study the efficiency and stability of electrode-tissue interface using novel materials in microstimulation

Biomimetic Based Applications

The interaction between cells, tissues and biomaterial surfaces are the highlights of the book "Biomimetic Based Applications". In this regard the effect of nanostructures and nanotopographies and their effect on the development of a new generation of biomaterials including advanced multifunctional scaffolds for tissue engineering are discussed. The 2 volumes contain articles that cover a wide spectrum of subject matter such as different aspects of the development of scaffolds and coatings with enhanced performance and bioactivity, including investigations of material surface-cell interactions