Article

Wireless Instantaneous Neurotransmitter Concentration System-based amperometric detection of dopamine, adenosine, and glutamate for intraoperative neurochemical monitoring: Laboratory investigation

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota 55905, USA.
Journal of Neurosurgery (Impact Factor: 3.15). 06/2009; 111(4):701-11. DOI: 10.3171/2009.3.JNS0990
Source: PubMed

ABSTRACT In a companion study, the authors describe the development of a new instrument named the Wireless Instantaneous Neurotransmitter Concentration System (WINCS), which couples digital telemetry with fast-scan cyclic voltammetry (FSCV) to measure extracellular concentrations of dopamine. In the present study, the authors describe the extended capability of the WINCS to use fixed potential amperometry (FPA) to measure extracellular concentrations of dopamine, as well as glutamate and adenosine. Compared with other electrochemical techniques such as FSCV or high-speed chronoamperometry, FPA offers superior temporal resolution and, in combination with enzyme-linked biosensors, the potential to monitor nonelectroactive analytes in real time.
The WINCS design incorporated a transimpedance amplifier with associated analog circuitry for FPA; a microprocessor; a Bluetooth transceiver; and a single, battery-powered, multilayer, printed circuit board. The WINCS was tested with 3 distinct recording electrodes: 1) a carbon-fiber microelectrode (CFM) to measure dopamine; 2) a glutamate oxidase enzyme-linked electrode to measure glutamate; and 3) a multiple enzyme-linked electrode (adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase) to measure adenosine. Proof-of-principle analyses included noise assessments and in vitro and in vivo measurements that were compared with similar analyses by using a commercial hardwired electrochemical system (EA161 Picostat, eDAQ; Pty Ltd). In urethane-anesthetized rats, dopamine release was monitored in the striatum following deep brain stimulation (DBS) of ascending dopaminergic fibers in the medial forebrain bundle (MFB). In separate rat experiments, DBS-evoked adenosine release was monitored in the ventrolateral thalamus. To test the WINCS in an operating room setting resembling human neurosurgery, cortical glutamate release in response to motor cortex stimulation (MCS) was monitored using a large-mammal animal model, the pig.
The WINCS, which is designed in compliance with FDA-recognized consensus standards for medical electrical device safety, successfully measured dopamine, glutamate, and adenosine, both in vitro and in vivo. The WINCS detected striatal dopamine release at the implanted CFM during DBS of the MFB. The DBS-evoked adenosine release in the rat thalamus and MCS-evoked glutamate release in the pig cortex were also successfully measured. Overall, in vitro and in vivo testing demonstrated signals comparable to a commercial hardwired electrochemical system for FPA.
By incorporating FPA, the chemical repertoire of WINCS-measurable neurotransmitters is expanded to include glutamate and other nonelectroactive species for which the evolving field of enzyme-linked biosensors exists. Because many neurotransmitters are not electrochemically active, FPA in combination with enzyme-linked microelectrodes represents a powerful intraoperative tool for rapid and selective neurochemical sampling in important anatomical targets during functional neurosurgery.

0 Followers
 · 
96 Views
  • Source
    • "The system has been extensively tested using WINCSbased neurochemical recordings in a large animal model (pig) of DBS as a prelude to the studies in humans. It can measure in vivo dopamine and adenosine release with CFMs and glutamate release with an enzyme-linked biosensor during DBS (Agnesi et al. 2009; Bledsoe et al. 2009; Shon et al. 2010a,b). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The brain operates through complex interactions in the flow of information and signal processing within neural networks. The "wiring" of such networks, being neuronal or glial, can physically and/or functionally go rogue in various pathological states. Neuromodulation, as a multidisciplinary venture, attempts to correct such faulty nets. In this review, selected approaches and challenges in neuromoduation are discussed. The use of water-dispersible carbon nanotubes have proven effective in modulation of neurite outgrowth in culture as well as in aiding regeneration after spinal cord injury in vivo. Studying neural circuits using computational biology and analytical engineering approaches brings to light geometrical mapping of dynamics within neural networks, much needed information for stimulation interventions in medical practice. Indeed, sophisticated desynchronization approaches used for brain stimulation have been successful in coaxing "misfiring" neuronal circuits to resume productive firing patterns in various human disorders. Devices have been developed for the real time measurement of various neurotransmitters as well as electrical activity in the human brain during electrical deep brain stimulation. Such devices can establish the dynamics of electrochemical changes in the brain during stimulation. With increasing application of nanomaterials in devices for electrical and chemical recording and stimulating in the brain, the era of cellular, and even intracellular, precision neuromodulation will soon be upon us. © 2012 International Society for Neurochemistry, J. Neurochem. (2012) 10.1111/jnc.12105.
    Journal of Neurochemistry 11/2012; DOI:10.1111/jnc.12105 · 4.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The review is focused on methods and approaches, which are widely used to monitor neurotransmitter release from diverse cells and to explore underlying mechanisms. A variety of methods and technical approaches for ex vivo and in vivo experiments are discussed, including microdialysis, microelectrode voltammetry, and enzymatic biosensors. The method of the cellular biosensor is specifically discussed as an effective approach for assaying neurotransmitter release from single cells. Keywordsneurotransmitters–biosensors–ATP–serotonin
    Biochemistry (Moscow) Supplement Series A Membrane and Cell Biology 03/2011; 5(1):1-10. DOI:10.1134/S1990747810061030
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Wireless Instantaneous Neurotransmitter Concentration Sensing System (WINCS) measures extracellular neurotransmitter concentration in vivo and displays the data graphically in nearly real time. WINCS implements two electroanalytical methods, fast-scan cyclic voltammetry (FSCV) and fixed-potential amperometry (FPA), to measure neurotransmitter concentrations at an electrochemical sensor, typically a carbon-fiber microelectrode. WINCS comprises a battery-powered patient module and a custom software application (WINCSware) running on a nearby personal computer. The patient module impresses upon the electrochemical sensor either a constant potential (for FPA) or a time-varying waveform (for FSCV). A transimpedance amplifier converts the resulting current to a signal that is digitized and transmitted to the base station via a Bluetooth radio link. WINCSware controls the operational parameters for FPA or FSCV, and records the transmitted data stream. Filtered data is displayed in various formats, including a background-subtracted plot of sequential FSCV scans - a representation that enables users to distinguish the signatures of various analytes with considerable specificity. Dopamine, glutamate, adenosine and serotonin were selected as analytes for test trials. Proof-of-principle tests included in vitro flow-injection measurements and in vivo measurements in rat and pig. Further testing demonstrated basic functionality in a 3-Tesla MRI unit. WINCS was designed in compliance with consensus standards for medical electrical device safety, and it is anticipated that its capability for real-time intraoperative monitoring of neurotransmitter release at an implanted sensor will prove useful for advancing functional neurosurgery.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2009; 2009:4856-9. DOI:10.1109/IEMBS.2009.5332773
Show more

Full-text (2 Sources)

Download
38 Downloads
Available from
Jun 1, 2014