CHARACTERIZATION AND OPTIMIZATION OF MICROELECTRODE ARRAYS FOR GLUTAMATE MEASUREMENTS IN THE RAT HIPPOCAMPUS

An overarching goal of the Gerhardt laboratory is the development of an implantable neural device that allows for long-term glutamate recordings in the hippocampus. Proper L-glutamate regulation is essential for hippocampal function, while glutamate dysregulation is implicated in many neurodegenerative diseases. Direct evidence for subregional glutamate regulation is lacking in previous in vivo studies because of limitations in the spatio-temporal resolution of conventional experimental techniques. We used novel enzyme-coated microelectrode arrays (MEAs) for rapid measurements (2Hz) of extracellular glutamate in urethane-anesthetized rats. Potassium-evoked glutamate release was highest in the cornu ammonis 1 (CA1) subregion and lowest in the cornu ammonis 3 (CA3). In the dentate gyrus (DG), evoked-glutamate release was diminished at a higher potassium concentration but demonstrated faster release kinetics. These studies are the first to show subregion specific regulation of glutamate release in the hippocampus. To allow for in vivo glutamate measurements in awake rats, we have adapted our MEAs for chronic use. Resting glutamate measurements were obtained up to six days post-implantation but recordings were unreliable at later time points. To determine the cause(s) for recording failure, a detailed investigation of MEA surface characteristics was conducted. Scanning electron microscopy and atomic force microscopy showed that PT sites have unique surface chemistry, a microwell geometry and nanometer-sized features, all of which appear to be favorable for high sensitivity recordings. Accordingly, studies were initiated to improve enzyme coatings using a computer-controlled microprinting system (Microfab Technologies, Plano, TX). Preliminary testing showed that microprinting allowed greater control over the coating process and produced MEAs that met our performance criteria. Our final studies investigated the effects of chronic MEA implantation. Immunohistochemical analysis showed that the MEA produced minimal damage in the hippocampus at all time points from 1 day to 6 months. Additionally, tissue attachment to the MEA surface was minimal. Taken together with previous electrophysiology data supporting that MEAs are functional up to six months, these studies established that our chronic MEAs technology is capable of maintaining a brain-device interface that is both functional and biocompatible for extended periods of time

Microfabricated Probes for Studying Brain Chemistry: A Review

Probe techniques for monitoring in vivo chemistry (e.g., electrochemical sensors and microdialysis sampling probes) have significantly contributed to a better understanding of neurotransmission in correlation to behaviors and neurological disorders. Microfabrication allows construction of neural probes with high reproducibility, scalability, design flexibility, and multiplexed features. This technology has translated well into fabricating miniaturized neurochemical probes for electrochemical detection and sampling. Microfabricated electrochemical probes provide a better control of spatial resolution with multisite detection on a single compact platform. This development allows the observation of heterogeneity of neurochemical activity precisely within the brain region. Microfabricated sampling probes are starting to emerge that enable chemical measurements at high spatial resolution and potential for reducing tissue damage. Recent advancement in analytical methods also facilitates neurochemical monitoring at high temporal resolution. Furthermore, a positive feature of microfabricated probes is that they can be feasibly built with other sensing and stimulating platforms including optogenetics. Such integrated probes will empower researchers to precisely elucidate brain function and develop novel treatments for neurological disorders.Microfabricated neurochemical probes: Microfabrication technology emerges as an important tool for developing miniature, high precision probes for electrochemical detection and sampling from live brain tissues. This review describes advances and perspectives in adapting microfabrication to create the next generation of neurochemical probes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144231/1/cphc201701180_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144231/2/cphc201701180.pd

Design and Analysis of Multi-Level Active Queue Management Mechanisms for Emergency Traffic

Active Queue Management (AQM) is proposed as a solution for providing available and dependable service to traffic from emergency users after disasters. MAMT is a simple but effective approach that can be applied at strategic network locations where heavy congestion is anticipated. It can provide low loss to emergency packets while dropping non-emergency packets only as much as necessary. Fluid flow analysis and simulation is conducted to provide guidelines for proper MAMT design, especially regarding the queue size and averaging parameters that are most important. This work considers non-responsive traffic exclusively, since non-responsive traffic types are currently getting the most attention from emergency management organizations. Plus, very little work has been performed regarding AQM and non-responsive traffic. It demonstrates queue oscillation problems that previously may have been attributed to the interactions between TCP and AQM, but which are actually inherent to AQM and can be greatly reduced with proper parameter settings. MAMT is shown to perform well over a range of loads and can effectively protect emergency traffic from surges in non-emergency traffic. Keywords—System design, simulations, active queue management, emergency services, quality of service. I

Removal of the Noise Source Inherent to AQM

implementations drop packets randomly as a function of the average queue fill. Over a short window of time, all packets are dropped with virtually equal probability. This causes the actual number of dropped packets to vary according to a binomial distribution, and can result in a significant difference between the actual numbers of dropped packets and the expected. As a result, this introduces unnecessary noise to the system which substantially affects variations in queue fill. A new approach to calculating dropping probabilities is proposed here that adapts the dropping probability over a window of packets and ensures that the number of packets that are actually dropped is virtually equal to the number that are expected to be dropped. It is shown here that this substantially reduces unnecessary variance in queue fill. Index Terms—Active queue management, random early dropping. I

Modelling of Impulsional pH Variations Using ChemFET-Based Microdevices: Application to Hydrogen Peroxide Detection

International audienceThis work presents the modelling of impulsional pH variations in microvolume related to water-based electrolysis and hydrogen peroxide electrochemical oxidation using an ElecFET (Electrochemical Field Effect Transistor) microdevice. This ElecFET device consists of a pH-ChemFET (pH-Chemical FET) with an integrated microelectrode around the dielectric gate area in order to trigger electrochemical reactions. Combining oxidation/reduction reactions on the microelectrode, water self-ionization and diffusion properties of associated chemical species, the model shows that the sensor response depends on the main influential parameters as: (i) polarization parameters on the microelectrode, i.e. voltage (V p) and time (t p), (ii) distance between the gate sensitive area and the microelectrode (d), and (iii) hydrogen peroxide concentration ([H 2 O 2 ]). The model developed can predict the ElecFET response behaviour and creates new opportunities for H 2 O 2 –based enzymatic detection of biomolecules