insertion-flexible-neural-probes-using-rigid-stiffeners-attached-with

Insertion of Flexible Neural Probes Using Rigid Stiffeners Attached with Biodissolvable Adhesive

Microelectrode  arrays for neural interface devices that are made of biocompatible thin-film  polymer are expected to have extended functional lifetime ...

Lawrence Livermore National Laboratory

Using Micro-Electro-Mechanical-Systems (MEMS) technologies, we have developed silicon wafer-based platinum microelectrode arrays (MEAs) modified with glutamate oxidase (GluOx) for electroenzymatic detection of glutamate in vivo. These MEAs were designed to have optimal spatial resolution for in vivo recordings. Selective detection of glutamate in the presence of the electroactive interferents, dopamine and ascorbic acid, was attained by deposition of polypyrrole and Nafion. The sensors responded to glutamate with a limit of detection under 1muM and a sub-1-second response time in solution. In addition to extensive in vitro characterization, the utility of these MEA glutamate biosensors was also established in vivo. In the anesthetized rat, these MEA glutamate biosensors were used for detection of cortically-evoked glutamate release in the ventral striatum. The MEA biosensors also were applied to the detection of stress-induced glutamate release in the dorsal striatum of the freely-moving rat.

Silicon Wafer-Based Platinum Microelectrode Array Biosensor for Near Real-Time Measurement of Glutamate in Vivo.

The ability to make rapid, informed decisions about whether or not to engage in a sequence of actions to earn reward is essential for survival. Modeling in rodents has demonstrated a critical role for the basolateral amygdala (BLA) in such reward-seeking actions, but the precise neurochemical underpinnings are not well understood. Taking advantage of recent advancements in biosensor technologies, we made spatially discrete near-real-time extracellular recordings of the major excitatory transmitter, glutamate, in the BLA of rats performing a self-paced lever-pressing sequence task for sucrose reward. This allowed us to detect rapid transient fluctuations in extracellular BLA glutamate time-locked to action performance. These glutamate transients tended to precede lever-pressing actions and were markedly increased in frequency when rats were engaged in such reward-seeking actions. Based on muscimol and tetrodotoxin microinfusions, these glutamate transients appeared to originate from the terminals of neurons with cell bodies in the orbital frontal cortex. Importantly, glutamate transient amplitude and frequency fluctuated with the value of the earned reward and positively predicted lever-pressing rate. Such novel rapid glutamate recordings during instrumental performance identify a role for glutamatergic signaling within the BLA in instrumental reward-seeking actions.

Transient extracellular glutamate events in the basolateral amygdala track reward-seeking actions.

An implantable micromachined multi-electrode array (MEA) microprobe modified for utilization as a complete electrochemical biosensor for rapid glutamate detection is described. A post-fabrication method for electrochemical deposition of an iridium oxide (IrOx) film onto a designated microelectrode enabled incorporation of an IrOx reference electrode (RE) on the microprobe. The on-probe IrOx RE provides an alternative to the commonly utilized Ag/AgCl wire RE, which has been shown to be unstable and to cause an inflammatory response in living tissue. The IrOx film electrodeposited onto a platinum site was tested as part of a complete chemical sensing system that included a platinum counter electrode and enzymatic glutamate sensing electrodes all on a single silicon-based MEA platform. The thin film IrOx was mechanically robust enough to endure conditions of repeated heating and wetting during the MEA fabrication process. The pH dependence of the IrOx open circuit potential (OCP) was measured at -77Â±0.4 mV/pH and remained stable over a two-week period. The on-probe IrOx RE was tested in a two- and three-electrode system with glutamate biosensors. The biosensors were shown to detect a physiologically relevant range of glutamate concentrations and to reject the interferents, dopamine and ascorbic acid. By incorporating all of the electrodes onto a single device, baseline noise was reduced by an average of âˆ¼61% in vitro and âˆ¼71% in vivo with reduced tissue damage, since only a single probe needed to be implanted.

Electrochemically deposited iridium oxide reference electrode integrated with an electroenzymatic glutamate sensor on a multi-electrode array microprobe.

Article	Year
Silicon Wafer-Based Platinum Microelectrode Array Biosensor for Near Real-Time Measurement of Glutamate in Vivo. Sensors (Basel, Switzerland)\| PubMed ID: 19543440	2008
Transient extracellular glutamate events in the basolateral amygdala track reward-seeking actions. The Journal of neuroscience : the official journal of the Society for Neuroscience\| PubMed ID: 22357857	2012
Electrochemically deposited iridium oxide reference electrode integrated with an electroenzymatic glutamate sensor on a multi-electrode array microprobe. Biosensors & bioelectronics\| PubMed ID: 23208095	2013

Vanessa M. Tolosa

Biography

JoVE Journal Publications

Other Publications