Fabrication of Nanoelectrode Arrays for Dopamine Detection

Recent advancements in the semiconductor fabrication technologies have greatly helped in advancing the understanding of electrochemistry at nano scale (10-9 m). Electrodes are being produced at micro (10-6 m) and nano scale with varied materials, designs and for diverse applications. Better electrochemical sensing and detecting capabilities are achieved with nanoelectrodes in comparison with regular macroelectrodes. Lot of theoretical studies of electrochemistry at these nanoelectrodes have been proposed and developed. Despite the theoretical advancements, little has been done in experimental studies of nanoelectrodes. The progress is majorly impeded by lack of reliable fabrication procedures to produce such nanoelectrodes and test them experimentally.;The main goal of this thesis is to develop a new procedure to fabricate nanoelectrode arrays (NEA) for enhanced electrochemical detection. A large area gold NEA is fabricated using nanosphere lithography. The electrochemical advantages of the nanoelectrodes over macro electrodes such as better mass transport of analytes, independent diffusional domains, and faster chemical reaction rates are studied. The dimensions of the electrode are optimized to get the best possible electrochemical sensing capabilities. The optimized NEA is used as a biological sensor for detecting dopamine, a neurotransmitter, in presence of biological levels of ascorbic acid.;The optimized NEA geometry has shown an excellent ability to differentiate and detect the dopamine in presence of high levels of ascorbic acid. This is attributed to the enhanced mass transport of analytes and faster chemical reaction rates at the surface of the nanoelectrodes. Bare gold macroelectrode of similar exposed area has failed to differentiate the dopamine and ascorbic acid signals

Doctor of Philosophy

dissertationParalysis due to spinal cord injury or stroke can leave a person with intact peripheral nerves and muscles, but deficient volitional motor control, thereby reducing their health and quality of life. Functional neuromuscular stimulation (FNS) has been widely studied and employed in clinical devices to aid and restore lost or deficient motor function. Strong, selective, and fatigue-resistant muscle forces can be evoked by asynchronously stimulating small independent groups of motor neurons via multiple intrafascicular electrodes on an implanted Utah slanted electrode array (USEA). Determining the parameters of asynchronous intrafascicular multi-electrode stimulation (aIFMS), i.e., the per-electrode stimulus intensities and the interelectrode stimulus phasing, to evoke precise muscle force or joint motion presents unique challenges because this system has multiple-inputs, the n independently stimulated electrodes, but only one measurable output, the evoked endpoint isometric force or joint position. This dissertation presents three studies towards developing robust real-time control of aIFMS. The first study developed an adaptive feedforward algorithm for selecting aIFMS per-electrode stimulus intensities and interelectrode stimulus phasing to evoke a variety of isometric ankle plantar-flexion force trajectories. In simulation and experiments, desired step, sinusoidal, and more-complex time-varying isometric forces were successfully evoked. The second study developed a closed-loop feedback control method for determining aIFMS per-electrode stimulus intensities to evoke precise single-muscle isometric ankle plantar-flexion force trajectories, in real-time. Using a proportional closed-loop force-feedback controller, desired step, sinusoid, and more complex time-varying forces were evoked with good response characteristics, even in the presence of nonlinear system dynamics, such as muscle fatigue. The third study adapted and extended the closed-loop feedback controller to the more demanding task of controlling joint position in the presence of opposing joint torques. A proportional-plus-velocity-plus-integral (PIV) joint-angle feedback controller evoked and held desired steps in position with responses th a t were stable, consistent, and robust to disturbances. The controller evoked smooth ramp-up (concentric) and ramp-down (eccentric) motion, as well as precise slow moving sinusoidal motion. The control methods developed in this dissertation provide a foundation for new lower-limb FNS-based neuroprostheses that can generate sustained and coordinated muscle forces and joint motions that will be desired by paralyzed individuals on a daily basis. proportional-plus-velocity-plus-integral (PIV) joint-angle feedback controller evoked and held desired steps in position with responses th a t were stable, consistent, and robust to disturbances. The controller evoked smooth ramp-up (concentric) and ramp-down (eccentric) motion, as well as precise slow moving sinusoidal motion. The control methods developed in this dissertation provide a foundation for new lower-limb FNS-based neuroprostheses that can generate sustained and coordinated muscle forces and joint motions that will be desired by paralyzed individuals on a daily basis

Mass transport phenomena at hot microelectrodes

Hot microelectrodes are very small electrodes (usually 1 – 100 µm in diameter), which have a surface temperature much higher than the temperature in the bulk solution. In this work, the heating is achieved by applying an alternating potential of very high frequency (100 MHz – 2 GHz) and of high amplitude (up to 2.8 Vrms) to the microelectrode. As a result, very fast (on the order of milliseconds) changes in the temperature of the electrolyte solution surrounding the electrode can be achieved. Due to the size of the heated microelectrodes, the hot zone in solution is small. Therefore, the solution can be easily overheated and temperatures above the boiling point can be reached. The purpose of this research was to investigate and understand the phenomena occurring at ac polarized microelectrodes and to propose new applications of these electrodes. Using both steady-state and fast-scan (10 V/s) cyclic voltammetry measurements, mass transport of redox species has been studied at ac heated microelectrodes. It has been established that the convection at hot-disk microelectrodes is driven primarily by the electrothermal flow of an electrolyte solution. In addition, other effects such as ac dielectrophoresis and Soret (nonisothermal) diffusion are also observed. Numerical simulations have been employed to predict the distribution of temperature in the hot zone, the direction and magnitude of the electrothermal force and the solution flow rate, as well as the voltammetric response of hot-disk microelectrodes. The results of the simulations agree well with the experimental observations. Theoretical findings of this PhD work are very important for the understanding of the fundamentals of high temperature electrochemistry, particularly mass transport. The proposed explanation of the convection mechanism is most likely applicable not only to ac polarized microelectrodes, but also to the microwave heated microelectrodes, since the only difference between these two heating methods is in the way of delivering electrical energy (wired vs. wireless). The results of the studies of Soret diffusion indicate that it contributes significantly to mass transfer of redox species at hot microelectrodes. Taking into account that the magnitude of the Soret effect has been considered negligible by other electrochemists, the results obtained in this work prove the opposite and show that Soret diffusion affects both the faradaic current and the half-wave potential of the redox reaction. Therefore, the Soret effect can not be ignored if working with hot microelectrodes. Hot microelectrodes can have a number of interesting applications. The results of the initial investigations indicate that these electrodes can be successfully used in the arrangement for Scanning Electrochemical Microscopy (such a novel technique is termed Hot-Tip SECM). In addition, the observed dielectrophoretic and electrothermal convection effects can enhance the performance of the electrochemical sensors based on hot microelectrodes. This can lead to the improvement of the detection limits of many biologically important analytes, such as proteins, bacteria and viruses

Nonlinear Dynamic Modeling, Simulation And Characterization Of The Mesoscale Neuron-electrode Interface

Extracellular neuroelectronic interfacing has important applications in the fields of neural prosthetics, biological computation and whole-cell biosensing for drug screening and toxin detection. While the field of neuroelectronic interfacing holds great promise, the recording of high-fidelity signals from extracellular devices has long suffered from the problem of low signal-to-noise ratios and changes in signal shapes due to the presence of highly dispersive dielectric medium in the neuron-microelectrode cleft. This has made it difficult to correlate the extracellularly recorded signals with the intracellular signals recorded using conventional patch-clamp electrophysiology. For bringing about an improvement in the signalto-noise ratio of the signals recorded on the extracellular microelectrodes and to explore strategies for engineering the neuron-electrode interface there exists a need to model, simulate and characterize the cell-sensor interface to better understand the mechanism of signal transduction across the interface. Efforts to date for modeling the neuron-electrode interface have primarily focused on the use of point or area contact linear equivalent circuit models for a description of the interface with an assumption of passive linearity for the dynamics of the interfacial medium in the cell-electrode cleft. In this dissertation, results are presented from a nonlinear dynamic characterization of the neuroelectronic junction based on Volterra-Wiener modeling which showed that the process of signal transduction at the interface may have nonlinear contributions from the interfacial medium. An optimization based study of linear equivalent circuit models for representing signals recorded at the neuron-electrode interface subsequently iv proved conclusively that the process of signal transduction across the interface is indeed nonlinear. Following this a theoretical framework for the extraction of the complex nonlinear material parameters of the interfacial medium like the dielectric permittivity, conductivity and diffusivity tensors based on dynamic nonlinear Volterra-Wiener modeling was developed. Within this framework, the use of Gaussian bandlimited white noise for nonlinear impedance spectroscopy was shown to offer considerable advantages over the use of sinusoidal inputs for nonlinear harmonic analysis currently employed in impedance characterization of nonlinear electrochemical systems. Signal transduction at the neuron-microelectrode interface is mediated by the interfacial medium confined to a thin cleft with thickness on the scale of 20-110 nm giving rise to Knudsen numbers (ratio of mean free path to characteristic system length) in the range of 0.015 and 0.003 for ionic electrodiffusion. At these Knudsen numbers, the continuum assumptions made in the use of Poisson-Nernst-Planck system of equations for modeling ionic electrodiffusion are not valid. Therefore, a lattice Boltzmann method (LBM) based multiphysics solver suitable for modeling ionic electrodiffusion at the mesoscale neuron-microelectrode interface was developed. Additionally, a molecular speed dependent relaxation time was proposed for use in the lattice Boltzmann equation. Such a relaxation time holds promise for enhancing the numerical stability of lattice Boltzmann algorithms as it helped recover a physically correct description of microscopic phenomena related to particle collisions governed by their local density on the lattice. Next, using this multiphysics solver simulations were carried out for the charge relaxation dynamics of an electrolytic nanocapacitor with the intention of ultimately employing it for a simulation of the capacitive coupling between the neuron and the v planar microelectrode on a microelectrode array (MEA). Simulations of the charge relaxation dynamics for a step potential applied at t = 0 to the capacitor electrodes were carried out for varying conditions of electric double layer (EDL) overlap, solvent viscosity, electrode spacing and ratio of cation to anion diffusivity. For a large EDL overlap, an anomalous plasma-like collective behavior of oscillating ions at a frequency much lower than the plasma frequency of the electrolyte was observed and as such it appears to be purely an effect of nanoscale confinement. Results from these simulations are then discussed in the context of the dynamics of the interfacial medium in the neuron-microelectrode cleft. In conclusion, a synergistic approach to engineering the neuron-microelectrode interface is outlined through a use of the nonlinear dynamic modeling, simulation and characterization tools developed as part of this dissertation research

Dielectrophoretic characterisation and manipulation of sub-micron particles following surface modification

The aim of this thesis is to dielectrophoretically characterise sub-micron particles on the basis of their surface properties and to devise a DEP technique suitable for the fractionation and manipulation of particles on this scale. Polystyrene particles are modified by the attachment of biological ligands using various established localisation techniques and their DEP response observed using micro-electrodes with well defined high and low field regions, corresponding to a previously utilised design and modified in the course of this project for multiple sample handling. The results of these observations are modelled for the first time using a charge relaxation mechanism pertaining to a structured interfacial charge distribution and, through fitting the data to this model, fundamental parameters of the system - the surface conductance and electrokinetic charge - are predicted. The model viability is assessed with reference to both comparisons with alternative measurements and the technical limitations of the data fitting procedure, and corresponding surface charge transport mechanisms are discussed in the light of the DEP response following surface modification. Investigations are made into the possibility of a DEP based device suitable for the transport/fractionation of sub-micron particles. Given the essentially dissipative nature of sub-micro particle ensembles, a Brownian ratchet principle is chosen. A Brownian ratchet is a generic system wherein a net directional drive is effected by biasing Brownian diffusion on a periodically activated anisotropic structure. Without need of thermal gradients or net macroscopic forces Brownian ratchet pumps could be an interesting alternative in many microfluidic applications. Simulated fields and corresponding particle transport rates are compared for two basic electrode structures in order to assess their viability for use as DEP Brownian ratchets and a new design proposed, based on the simultaneous juxtaposition of positive and negative DEP forces. This device is built on the necessary scale using multi-layer fabrication techniques with a silicon elastomer moulded channel. The existence of stochastic transport on the device is investigated experimentally by means of processed video sequences and resulting possibilities for particle separation on the basis of size and surface properties inferred

MICRO AND NANO-PATTERNING OF GRAPHENE AND GRAPHENE OXIDE FOR BIOSENSING APPLICATIONS

Ph.DDOCTOR OF PHILOSOPH