Post Doctoral Associate, University of Pittsburgh
Our technology is the first in vivo electrochemical method for directly measuring resting dopamine
Dopamine (DA) signaling throughout the brain regulates a variety of vital life functions, such as motor control, reward, learning and memory. As such, disruption of healthy mechanisms of DA release and uptake is implicated in onset of many devastating neurological disorders, such as Parkinson's disease, Schizophrenia and substance abuse. DA signaling occurs at presynaptic- and postsynaptic neurons through a process of action potential meditated vesicular release at presynaptic neuron terminals and postsynaptic binding to selective DA receptors. The time scale of vesicular DA release is variable. Phasic DA signaling consists of fast, ~100 Hz action potential signaling and produces sub-second transient increases in extracellular DA, whereas tonic DA signaling consists of slow, ~15 Hz action potential signaling and induces changes in DA concentration over long time periods of minutes to hours. The maintenance of proper tonic and phasic DA signaling is entirely paramount to maintaining healthy neurological function. For decades, an electrochemical detection technique called fast scan cyclic voltammetry (FSCV) was performed at bare carbon fiber microelectrodes (CFEs) to measure sub-second phasic DA release in the brain in response a wide variety and experimental and environmental stimuli. This technique is highly effective for measuring phasic events, but technical limitations relating to both FSCV and bare CFEs prevent the measurement of resting, tonic DA concentrations in the brain. We have developed a novel conductive nanocomposite coating consisting of poly 3,4 ethylenedioxythiophene (PEDOT) doped with acid functionalized carbon nanotubes (CNT). We have shown that this PEDOT/CNT coating is highly sensitive and selective for the electrochemical detection of DA using a novel in vivo technique called square wave voltammetry (SWV). In fact, PEDOT/CNT coated CFEs (bare CFEs were previously used for in vivo FSCV detection) are capable of selectively measuring resting DA with a lower limit of detection of <50 nM. Furthermore, we have successfully implanted PEDOT/CNT coated CFEs into the DA rich dorsal striatum of anesthetized rats, recorded the first ever direct electrochemical measurement of in vivo tonic resting DA concentration (400 nM) and shown the ability to measure both increases and decreases in tonic DA resulting from pharmacological treatment. This technology is highly innovative and could serve to revolutionize neurochemical sensing as a whole.
Abstract: Subcellular-sized chronically implanted recording electrodes have demonstrated significant improvement in single unit (SU) yield over larger recording probes. Additional work expands on this initial success by combining the subcellular fiber-like lattice structures with the design space versatility of silicon microfabrication to further improve the signal-to-noise ratio, density of electrodes, and stability of recorded units over months to years. However, ultrasmall microelectrodes present very high impedance, which must be lowered for SU recordings. While poly(3,4-ethylenedioxythiophene) (PEDOT) doped with polystyrene sulfonate (PSS) coating have demonstrated great success in acute to early-chronic studies for lowering the electrode impedance, concern exists over long-term stability. Here, we demonstrate a new blend of PEDOT doped with carboxyl functionalized multiwalled carbon nanotubes (CNTs), which shows dramatic improvement over the traditional PEDOT/PSS formula.Lattice style subcellular electrode arrays were fabricated using previously established method. PEDOT was polymerized with carboxylic acid functionalized carbon nanotubes onto high-impedance (8.0 ± 0.1 MΩ: M ± S.E.) 250-μm(2) gold recording sites.PEDOT/CNT-coated subcellular electrodes demonstrated significant improvement in chronic spike recording stability over four months compared to PEDOT/PSS recording sites.These results demonstrate great promise for subcellular-sized recording and stimulation electrodes and long-term stability.This project uses leading-edge biomaterials to develop chronic neural probes that are small (subcellular) with excellent electrical properties for stable long-term recordings. High-density ultrasmall electrodes combined with advanced electrode surface modification are likely to make significant contributions to the development of long-term (permanent), high quality, and selective neural interfaces.
Pub.: 19 Jun '15, Pinned: 28 Jun '17
Abstract: The function and longevity of implantable microelectrodes for chronic neural stimulation depends heavily on the electrode materials, which need to present high charge injection capability and high stability. While conducting polymers have been coated on neural microelectrodes and shown promising properties for chronic stimulation, their practical applications have been limited due to unsatisfying stability. Here, poly(3,4-ethylenedioxythiophene) (PEDOT) doped with pure carbon nanotubes (CNTs) was electrochemically deposited on Pt microelectrodes to evaluate its properties for chronic stimulation. The PEDOT/CNT coated microelectrodes demonstrated much lower impedance than the bare Pt, and the PEDOT/CNT film exhibited excellent stability. For both acute and chronic stimulation tests, there is no significant increase in the impedance of the PEDOT/CNT coated microelectrodes, and none of the PEDOT/CNT films show any cracks or delamination, which have been the limitation for many conducting polymer coatings on neural electrodes. The charge injection limit of the Pt microelectrode was significantly increased to 2.5 mC/cm(2) with the PEDOT/CNT coating. Further in vitro experiments also showed that the PEDOT/CNT coatings are non-toxic and support the growth of neurons. It is expected that this highly stable PEDOT/CNT composite may serve as excellent new material for neural electrodes.
Pub.: 24 May '11, Pinned: 28 Jun '17
Abstract: Dopamine (DA) is a monoamine neurotransmitter responsible for regulating a variety of vital life functions. In vivo detection of DA poses a challenge due to the low concentration and high speed of physiological signaling. Fast scan cyclic voltammetry at carbon fiber microelectrodes (CFEs) is an effective method to monitor real-time in vivo DA signaling, however the sensitivity is somewhat limited. Electrodeposition of poly(3,4-ethylene dioxythiophene) (PEDOT)/graphene oxide (GO) onto the CFE surface is shown to increase the sensitivity and lower the limit of detection for DA compared to bare CFEs. Thicker PEDOT/GO coatings demonstrate higher sensitivities for DA, but display the negative drawback of slow adsorption and electron transfer kinetics. The moderate thickness resulting from 25 s electrodeposition of PEDOT/GO produces the optimal electrode, exhibiting an 880% increase in sensitivity, a 50% decrease in limit of detection and minimally altered electrode kinetics. PEDOT/GO coated electrodes rapidly and robustly detect DA, both in solution and in the rat dorsal striatum. This increase in DA sensitivity is likely due to increasing the electrode surface area with a PEDOT/GO coating and improved adsorption of DA's oxidation product (DA-o-quinone). Increasing DA sensitivity without compromising electrode kinetics is expected to significantly improve our understanding of the DA function in vivo.
Pub.: 27 May '16, Pinned: 28 Jun '17