Ceramic Microelectrode Research Articles

Carbon ceramic microelectrodes modified with buckyballs for simultaneous determination of redox-active biomolecules

In this report, simultaneous electrochemical determination of ascorbic acid (AA), dopamine (DA), uric acid (UA) and tryptophan (Trp) was achieved using buckyball-modified carbon ceramic microelectrodes (CCMEs). A concentration-dependent increase in anodic peak current signals was observed in comparison with those obtained at bare CCMEs. The optimal pH for simultaneous determination of a quaternary mixture of AA–DA–UA–Trp was determined to be pH 4. The peak separations for the mixture containing AA–DA–UA–Trp were well-defined at the scan rate of 50 mV s−1. The catalytic peak current obtained was linearly dependent on the AA, DA, UA and Trp concentrations in the range of 6.0–600, 6.0–600, 6.0–600 and 4.0–440 μM, respectively. The detection limits for AA, DA, UA and Trp were also determined to be 1.64, 0.82, 0.36 and 1.22 μM, respectively. The analytical performance of this sensor has also been challenged for simultaneous electrochemical detection of AA, DA, UA and Trp in real samples.

Riluzole rescues alterations in rapid glutamate transients in the hippocampus of rTg4510 mice.

Those at risk for Alzheimer's disease (AD) often exhibit hippocampal hyperexcitability in the years preceding diagnosis. Our previous work with the rTg(TauP301L)4510 tau mouse model of AD suggests that this increase in hyperexcitability is likely mediated by an increase in depolarization-evoked glutamate release and a decrease in glutamate uptake, alterations of which correlate with learning and memory deficits. Treatment with riluzole restored glutamate regulation and rescued memory deficits in the TauP301L model. Here, we used enzyme-based ceramic microelectrode array technology to measure real-time phasic glutamate release and uptake events in the hippocampal subregions of TauP301L mice. For the first time, we demonstrate that perturbations in glutamate transients (rapid, spontaneous bursts of glutamate) exist in a tau mouse model of AD mouse model and that riluzole mitigates these alterations. These results help to inform our understanding of how glutamate signaling is altered in the disease process and also suggest that riluzole may serve as a clinically applicable therapeutic approach in AD.

Tonic glutamate in CA1 of aging rats correlates with phasic glutamate dysregulation during seizure.

Characterize glutamate neurotransmission in the hippocampus of awake-behaving rodents during focal seizures in a model of aging. We used enzyme-based ceramic microelectrode array technology to measure in vivo extracellular tonic glutamate levels and real-time phasic glutamate release and clearance events in the hippocampus of awake Fischer 344 rats. Local application of 4-aminopyridine (4-AP) into the CA1 region was used to induce focal motor seizures in different animal age groups representing young, late-middle aged and elderly humans. Rats with the highest preseizure tonic glutamate levels (all in late-middle aged or elderly groups) experienced the most persistent 4-AP-induced focal seizure motor activity (wet dog shakes) and greatest degree of acute seizure-associated disruption of glutamate neurotransmission measured as rapid transient changes in extracellular glutamate levels. Increased seizure susceptibility was demonstrated in the rats with the highest baseline hippocampal extracellular glutamate levels, all of which were late-middle aged or aged animals. The manifestation of seizures behaviorally was associated with dynamic changes in glutamate neurotransmission. To our knowledge, this is the first report of a relationship between seizure susceptibility and alterations in both baseline tonic and phasic glutamate neurotransmission.

Cutaneous and electrically evoked glutamate signaling in the adult rat somatosensory system

Glutamate neurotransmission plays critical roles in normal central nervous system (CNS) function, neurodegenerative diseases, and neurotrauma. We determined whether glutamate signaling could be evoked within the anesthetized normal adult rat CNS with clinically relevant peripheral stimulation and recorded (at >1Hz) with glutamate-sensitive, ceramic microelectrode arrays (MEAs). Basal glutamate levels and both forelimb cutaneous and electrical stimulation-evoked glutamate release were measured within the cuneate nucleus, a relay of the mammalian dorsal columns somatosensory system. The MEAs with triangular, sharp-point tips were more effective at tissue penetration than the flat, blunt tips. Basal glutamate levels of 2.1±4.4μM (mean±SD, n=10 animals) were detected from 150μm to 1200μm below the brainstem dorsal surface. Cutaneous evoked glutamate signals showed an amplitude of 1.1±1.1μM and a duration of 7.3±6.5s (26 signals, n=6). Electrically evoked signals, like cutaneous ones, were both rapid and slowly rising. Electrically evoked signals, especially those evoked by stimulation trains, were more reproducible and had an amplitude of 1.2±1.4μM, duration of 19.4±17.3s, and latency from stimulus onset of 21.3±21.5s (25 signals, n=4). In contrast to cutaneous stimulation, glutamate signals evoked by electrical stimulation had longer durations and were recorded primarily in the middle and ventral cuneate nuclei. Importantly, both cutaneous and electrical stimulation of the contralateral forelimb and hindlimbs did not evoke glutamate signaling. With the use of MEAs, these results show, for the first time, somatosensory-pathway specific changes in glutamate levels during peripheral cutaneous and electrical stimulation.

Histological studies of the effects of chronic implantation of ceramic-based microelectrode arrays and microdialysis probes in rat prefrontal cortex

Chronic implantation of neurotransmitter measuring devices is essential for awake, behavioral studies occurring over multiple days. Little is known regarding the effects of long term implantation on surrounding brain parenchyma and the resulting alterations in the functional properties of this tissue. We examined the extent of tissue damage produced by chronic implantation of either ceramic microelectrode arrays (MEAs) or microdialysis probes. Histological studies were carried out on fixed tissues using stains for neurons (cresyl violet), astrocytes (GFAP), microglia (Iba1), glutamatergic nerve fibers (VGLUT1), and the blood–brain barrier (SMI-71). Nissl staining showed pronounced tissue body loss with microdialysis implants compared to MEAs. The MEAs produced mild gliosis extending 50–100 μm from the tracks, with a significant change in the affected areas starting at 3 days. By contrast, the microdialysis probes produced gliosis extending 200–300 μm from the track, which was significant at 3 and 7 days. Markers for microglia and glutamatergic fibers supported that the MEAs produce minimal damage with significant changes occurring only at 3 and 7 days that return to control levels by 1 month. SMI-71 staining supported the integrity of the blood–brain barrier out to 1 week for both the microdialysis probes and the MEAs. This data support that the ceramic MEA's small size and biocompatibility are necessary to accurately measure neurotransmitter levels in the intact brain. The minimal invasiveness of the MEAs reduce tissue loss, allowing for long term (> 6 month) electrochemical and electrophysiological monitoring of brain activity.

Extruded Ceramic Microelectrodes for Biomedical Applications

A new process, based on the micro-co-extrusion of preceramic precursors, has been studied for manufacturing ceramic microelectrodes to be used in biomedical applications. Commercially available silicon polymers were applied and proper doping resulted in electrically conductive ceramic filaments. Chemical reticulation and high-temperature pyrolysis were applied to convert the polymeric resins into Si-O-C ceramic materials. Circular microelectrodes were manufactured with diameters between 100 microm and 5 mm with a different number of inner conductive lines (from 1 to 80). The flexural strength of the filaments depended on the outer diameter size; doping with carbon black produced filaments with an average conductivity of approximately 0.4 S/cm for a 50% weight carbon black load. The results achieved by in vitro studies confirmed a good biological performance of Si-O-C ceramic structures with both hard and soft tissue cell models.

A Novel Process for the Manufacture of Ceramic Microelectrodes for Biomedical Applications

A novel process, based on microextrusion of preceramic polymers, was developed for manufacturing ceramic microelectrodes, mainly for biomedical applications. A coextrusion approach was used to obtain filaments with inner conductive lines after proper doping. Chemical reticulation and high‐temperature pyrolysis were applied to convert the meltable preceramic, polymeric resins into SiOC ceramic materials. Different cross‐sectional geometries were produced. The flexural strength of filaments depended on the outer diameter size; doping produced filaments with an average conductivity of ∼0.4 1/Ω cm for a 50 wt% carbon black load. The results on L929 and MG63 cell line models indicated good biological performance of Si–O–C ceramics and confirmed citocompatibility.

Mixed conduction and electrode properties of doped cobaltites and chromites

A series of perovskite oxides have been investigated with regard to their electronic conductivity and oxygen transport properties as well as electrode properties. The experiments were carried out on pressed samples with ceramic microelectrodes made of zirconia (20 mol% Y) or ceria (20 mol% Gd) vs. a large area Pt counter electrode and in the temperature range 600–750 °C. Here, we present results on the cobaltites Gd 1− x Sr x CoO 3, Gd 1− x Sr x Co 1− y Mg y O 3, and the chromites La 1− x Ca x CrO 3 and Gd 1− x Sr x CrO 3. Gd 1− x Sr x CoO 3 doped with 20 and 40 mol% Sr showed good oxygen ion conductivities of up to 6.0×10 −4 S/cm (Gd 0.6Sr 0.4CoO 3 at 700 °C in air). This system also yielded a remarkable enhancement of the oxygen electrode reaction in contact with zirconia. The investigated chromites gave rather low oxygen ion conductivities, but a clear catalytic effect for the reduction of oxygen.