Alexander R. Harris

Conducting polymer coated neural recording electrodes

OBJECTIVE Neural recording electrodes suffer from poor signal to noise ratio, charge density, biostability and biocompatibility. This paper investigates the ability of conducting polymer coated electrodes to record acute neural response in a systematic manner, allowing in depth comparison of electrochemical and electrophysiological response. APPROACH Polypyrrole (Ppy) and poly-3,4-ethylenedioxythiophene (PEDOT) doped with sulphate (SO4) or para-toluene sulfonate (pTS) were used to coat iridium neural recording electrodes. Detailed electrochemical and electrophysiological investigations were undertaken to compare the effect of these materials on acute in vivo recording. MAIN RESULTS A range of charge density and impedance responses were seen with each respectively doped conducting polymer. All coatings produced greater charge density than uncoated electrodes, while PEDOT-pTS, PEDOT-SO4 and Ppy-SO4 possessed lower impedance values at 1 kHz than uncoated electrodes. Charge density increased with PEDOT-pTS thickness and impedance at 1 kHz was reduced with deposition times up to 45 s. Stable electrochemical response after acute implantation inferred biostability of PEDOT-pTS coated electrodes while other electrode materials had variable impedance and/or charge density after implantation indicative of a protein fouling layer forming on the electrode surface. Recording of neural response to white noise bursts after implantation of conducting polymer-coated electrodes into a rat model inferior colliculus showed a general decrease in background noise and increase in signal to noise ratio and spike count with reduced impedance at 1 kHz, regardless of the specific electrode coating, compared to uncoated electrodes. A 45 s PEDOT-pTS deposition time yielded the highest signal to noise ratio and spike count. SIGNIFICANCE A method for comparing recording electrode materials has been demonstrated with doped conducting polymers. PEDOT-pTS showed remarkable low fouling during acute implantation, inferring good biostability. Electrode impedance at 1 kHz was correlated with background noise and inversely correlated with signal to noise ratio and spike count, regardless of coating. These results collectively confirm a potential for improvement of neural electrode systems by coating with conducting polymers.

Voltammetric, EQCM, Spectroscopic, and Microscopic Studies on the Electrocrystallization of Semiconducting, Phase I, CuTCNQ on Carbon, Gold, and Platinum Electrodes by a Nucleation-Growth Process

Cu 7,7,8,8-tetracyanoquinodimethane (CuTCNQ) may be chemically synthesized in two phases, one of which is significantly more conductive (phase I) than the other (phase II). Because CuTCNQ is sparingly soluble in acetonitrile, reduction of TCNQ to TCNQ- in the presence of CU(MeCN)+ under conditions where the solubility is exceeded in this solvent allows CuTCNQ nucleation-growth processes to occur at defect sites on carbon, gold, and platinum macro- and microdisk electrode surfaces. Rapid growth of large branched needle-shaped phase I crystals occurs on the time scale of cyclic voltammetry at semiconducting CuTCNQ nucleation sites. Infrared spectra and the crystal morphology detected by electron microscopy of electrocrystallized solid, are all consistent with growth of purely phase I CuTCNQ solid. The smaller crystals formed on the electrode surface, but not larger ones, may be stripped from the electrode surface by application of positive potentials. Mechanistic aspects of the electrocrystallization and stripping processes are considered.

Voltammetric ion-selective electrodes for the selective determination of cations and anions.

A general theory has been developed for voltammetric ion sensing of cations and anions based on the use of an electrode coated with a membrane containing an electroactive species, an ionophore, and a supporting electrolyte dissolved in a plasticizer. In experimental studies, a membrane coated electrode is fabricated by the drop coating method. In one configuration, a glassy carbon electrode is coated with a poly(vinyl chloride) based membrane, which contains the electroactive species, ionophore, plasticizer and supporting electrolyte. In the case of a cation sensor, ionophore facilitated transfer of the target cation from the aqueous solution to the membrane phase occurs during the course of the reduction of the electroactive species present in the membrane in order to maintain charge neutrality. The formal potential is calculated from the cyclic voltammogram as the average of the reduction and oxidation peak potentials and depends on the identity and concentration of the ion present in the aqueous solution phase. A plot of the formal potential versus the logarithm of the concentration exhibits a close to Nernstian slope of RT/F millivolts per decade change in concentration when the concentration of K(+) and Na(+) is varied over the concentration range of 0.1 mM to 1 M when K(+) or Na(+) ionophores are used in the membrane. The slope is close to RT/2F millivolts for a Ca(2+) voltammetric ion-selective electrode fabricated using a Ca(2+) ionophore. The sensor measurement time is only a few seconds. Voltammetric sensors for K(+), Na(+), and Ca(2+) constructed in this manner exhibit the sensitivity and selectivity required for determination of these ions in environmentally and biologically important matrixes. Analogous principles apply to the fabrication of anion voltammetric sensors.

Controlling brain cells with light: ethical considerations for optogenetic clinical trials

Optogenetics is being optimistically presented in contemporary media for its unprecedented capacity to control cell behavior through the application of light to genetically modified target cells. As such, optogenetics holds obvious potential for application in a new generation of invasive medical devices by which to potentially provide treatment for neurological and psychiatric conditions such as Parkinsons disease, addiction, schizophrenia, autism and depression. Design of a first-in-human optogenetics experimental trial has already begun for the treatment of blindness. Optogenetics trials involve a combination of highly invasive genetic and electronic interventions that results in irreversible and permanent modifications of an individuals nervous system. Given its novelty, its uncertain benefit to patients, and its unique risk profile of irreversible physiological alteration, optogenetics requires a reassessment of the ethical challenges for protecting human participants in clinical trials, particularly at formative stages of clinical evaluation. This study explores the evolving ethical issues surrounding optogenetics’ potential harm to participants within trial design, especially focusing on whether Phase 1 trials should incorporate efficacy as well as safety endpoints in ways that are fair and respectful to research trial participants.

Characterisation of two distinctly different processes associated with the electrocrystallization of microcrystals of phase I CuTCNQ (TCNQ = 7,7,8,8-tetracyanoquinodimethane)

Semi-conducting phase I CuTCNQ (TCNQ = 7,7,8,8-tetracyanoquinodimethane), which is of considerable interest as a switching device for memory storage materials, can be electrocrystallized from CH3CN via two distinctly different pathways when TCNQ is reduced to TCNQ˙− in the presence of [Cu(MeCN)4]+. The first pathway, identified in earlier studies, occurs at potentials where TCNQ is reduced to TCNQ˙− and involves a nucleation–growth mechanism at preferred sites on the electrode to produce arrays of well separated large branched needle-shaped phase I CuTCNQ crystals. The second pathway, now identified at more negative potentials, generates much smaller needle-shaped phase I CuTCNQ crystals. These electrocrystallize on parts of the surface not occupied in the initial process and give rise to film-like characteristics. This process is attributed to the reduction of Cu+[(TCNQ˙−)(TCNQ)] or a stabilised film of TCNQ via a solid–solid conversion process, which also involves ingress of Cu+via a nucleation–growth mechanism. The CuTCNQ surface area coverage is extensive since it occurs at all areas of the electrode and not just at defect sites that dominate the crystal formation sites for the first pathway. Infrared spectra, X-ray diffraction, surface plasmon resonance, quartz crystal microbalance, scanning electron microscopy and optical image data all confirm that two distinctly different pathways are available to produce the kinetically-favoured and more highly conducting phase I CuTCNQ solid, rather than the phase II material.

Structural and Magnetic Properties of the Coordination Polymer Mn(dca)2(H2O)2·2Me4pyz, dca = Dicyanamide (N(CN)2-), Me4pyz = Tetramethylpyrazine

The structure of Mn(dca)2(H2O)2·2Me4pyz (dca = dicyanamide, N(CN)2-; Me4pyz = tetramethylpyrazine) contains one-dimensional polymeric chains of Mn(dca)2(H2O)2. The Me4pyz molecules hydrogen-bond to the water ligands, and form ···Me4pyz···H2O···Me4pyz···H2O··· chains which flank either side of the coordination polymer chains. Magnetic susceptibility studies show that very weak intra-chain antiferromagnetic-coupling occurs.

Structure and magnetism of the ladder-like coordination polymer Co3(dca)2(nic)4(H2O)8·2H2O [dca = dicyanamide anion, N(CN)2−; nic = nicotinate anion]

The structure of the title complex has ladder-like 1D nets containing bridging μ-dca anions and both bridging and terminal nic anions; no long-range magnetic ordering is observed.

Optical and electrochemical methods for determining the effective area and charge density of conducting polymer modified electrodes for neural stimulation.

Neural stimulation is used in the cochlear implant, bionic eye, and deep brain stimulation, which involves implantation of an array of electrodes into a patients brain. The current passed through the electrodes is used to provide sensory queues or reduce symptoms associated with movement disorders and increasingly for psychological and pain therapies. Poor control of electrode properties can lead to suboptimal performance; however, there are currently no standard methods to assess them, including the electrode area and charge density. Here we demonstrate optical and electrochemical methods for measuring these electrode properties and show the charge density is dependent on electrode geometry. This technique highlights that materials can have widely different charge densities but also large variation in performance. Measurement of charge density from an electroactive area may result in new materials and electrode geometries that improve patient outcomes and reduce side effects.

Applications of voltammetric ion selective electrodes to complex matrices

The practical application of two different voltammetric ion selective electrodes (VISE) to measure ion activity in complex solutions has been explored. 7,7,8,8-tetracyanoquinodimethane (TCNQ) and tetrathiafulvalene (TTF) microcrystals adhered to an electrode surface act as a low selectivity voltammetric ion sensor. Resistance drop effects and pH artifacts were minimised by the addition of an “innocent” supporting electrolyte (buffer) to the analyte solution. In this format, addition of an ionophore to improve selectivity resulted in a reduction in current magnitude, due to competition for the ion. In contrast, voltammetry of a thin film containing a redox active species, electrolyte, ionophore and membrane solvent provides a highly selective ion sensor. Choice of ionophore was shown to affect the upper concentration detection limit. Use of ionic liquids as a combined membrane solvent and electrolyte was demonstrated. Methods to attach both VISE types to low-cost screen-printed electrodes have been explored. Various potential referencing techniques were also investigated. Both the microcrystal and thin film VISEs could be used to determine ion activity in complex solutions, as demonstrated in seawater, beverages, plasma and whole blood. Dissolved oxygen does not need to be removed, as it does not affect the response. However calibration methods are important for sensor accuracy and issues relating to electrode fouling must be addressed.

Efficacy Testing as a Primary Purpose of Phase 1 Clinical Trials: Is it Applicable to First-in-Human Bionics and Optogenetics Trials?

In her article, Pascale Hess raises the issue of whether her proposed model may be extrapolated and applied to clinical research fields other than stem-cell based interventions in the brain (SCBI-B)(Hess 2012)