Biocompatible PEDOT:Nafion composite electrode coatings for selective detection of neurotransmitters in vivo.

A Nafion and poly(3,4-ethylenedioxythiophene) (PEDOT) containing composite polymer has been electropolymerized on carbon-fiber microelectrodes with the goal of creating a mechanically stable, robust, and controllable electrode coating that increases the selectivity and sensitivity of in vivo electrochemical measurements. The coating is deposited on carbon-fiber microelectrodes by applying a triangle waveform from +1.5 V to -0.8 V and back in a dilute solution of ethylenedioxythiophene (EDOT) and Nafion in acetonitrile. Scanning electron microscopy demonstrated that the coating is uniform and ∼100 nm thick. Energy-dispersive X-ray spectroscopy demonstrated that both sulfur and fluorine are present in the coating, indicating the incorporation of PEDOT (poly(3,4-ethylenedioxythiophene) and Nafion. Two types of PEDOT:Nafion coated electrodes were then analyzed electrochemically. PEDOT:Nafion-coated electrodes made using 200 μM EDOT exhibit a 10-90 response time of 0.46 ± 0.09 s versus 0.45 ± 0.11 s for an uncoated fiber in response to a 1.0 μM bolus of dopamine. The electrodes coated using a higher EDOT concentration (400 μM) are slower with a 10-90 response time of 0.84 ± 0.19 s, but display increased sensitivity to dopamine, at 46 ± 13 nA/μM, compared to 26 ± 6 nA/μM for the electrodes coated in 200 μM EDOT and 13 ± 2 nA/μM for an uncoated fiber. PEDOT:Nafion-coated electrodes were lowered into the nucleus accumbens of a rat, and both spontaneous and electrically evoked dopamine release were measured. In addition to improvements in sensitivity and selectivity, the coating dramatically reduces acute in vivo biofouling.

[1]  Pavel Takmakov,et al.  Carbon microelectrodes with a renewable surface. , 2010, Analytical chemistry.

[2]  H von Holst,et al.  Toxicity evaluation of PEDOT/biomolecular composites intended for neural communication electrodes , 2009, Biomedical materials.

[3]  L H Parsons,et al.  Extracellular Concentration and In Vivo Recovery of Dopamine in the Nucleus Accumbens Using Microdialysis , 1992, Journal of neurochemistry.

[4]  D. O'Hare,et al.  Comparative study of poly(styrene-sulfonate)/poly(L-lysine) and fibronectin as biofouling-preventing layers in dissolved oxygen electrochemical measurements. , 2009, The Analyst.

[5]  B. J. Venton,et al.  Nafion-CNT coated carbon-fiber microelectrodes for enhanced detection of adenosine. , 2012, The Analyst.

[6]  Allen J. Bard,et al.  Electrochemical Methods: Fundamentals and Applications , 1980 .

[7]  M. Low,et al.  Locomotor Activity in D2 Dopamine Receptor-Deficient Mice Is Determined by Gene Dosage, Genetic Background, and Developmental Adaptations , 1998, The Journal of Neuroscience.

[8]  J. Bacsa,et al.  Synthesis and characterization of monomeric and polymeric Pd(II) and Pt(II) complexes of 3,4-ethylenedioxythiophene-functionalized phosphine ligands , 2009 .

[9]  Ralph N. Adams,et al.  Nafion-coated electrodes with high selectivity for CNS electrochemistry , 1984, Brain Research.

[10]  G. Rebec,et al.  Interference by DOPAC and ascorbate during attempts to measure drug-induced changes in neostriatal dopamine with Nafion-coated, carbon-fiber electrodes , 1990, Journal of Neuroscience Methods.

[11]  Michael L Heien,et al.  Characterization of poly(3,4-ethylenedioxythiophene):tosylate conductive polymer microelectrodes for transmitter detection. , 2012, The Analyst.

[12]  R. Wightman,et al.  Subsecond adsorption and desorption of dopamine at carbon-fiber microelectrodes. , 2000, Analytical chemistry.

[13]  Long Yang,et al.  An acetylcholinesterase biosensor based on platinum nanoparticles-carboxylic graphene-nafion-modified electrode for detection of pesticides. , 2013, Analytical biochemistry.

[14]  T. Otero,et al.  Electrochemical control of the morphology, adherence, appearance and growth of polypyrrole films , 1988 .

[15]  R. Wightman,et al.  Characterization of local pH changes in brain using fast-scan cyclic voltammetry with carbon microelectrodes. , 2010, Analytical chemistry.

[16]  R. N. Adams,et al.  Electrocoating carbon fiber microelectrodes with Nafion improves selectivity for electroactive neurotransmitters , 1987, Journal of Neuroscience Methods.

[17]  I. Kim,et al.  Bacterial Adhesion, Cell Adhesion and Biocompatibility of Nafion Films , 2009, Journal of biomaterials science. Polymer edition.

[18]  J. Marty,et al.  Amperometric biosensors based on nafion coated screen-printed electrodes for the determination of cholinesterase inhibitors. , 2000, Talanta.

[19]  Parastoo Hashemi,et al.  Chronically Implanted, Nafion-Coated Ag/AgCl Reference Electrodes for Neurochemical Applications. , 2011, ACS chemical neuroscience.

[20]  T. F. Otero,et al.  Synthesis, electropolymerization and oxidation kinetics of an anthraquinone-functionalized poly(3,4-ethylenedioxythiophene) , 2010 .

[21]  Nico Bunzeck,et al.  Dopamine Modulates Episodic Memory Persistence in Old Age , 2012, The Journal of Neuroscience.

[22]  W. Schultz Predictive reward signal of dopamine neurons. , 1998, Journal of neurophysiology.

[23]  S. T. Larsen,et al.  All polymer chip for amperometric studies of transmitter release from large groups of neuronal cells. , 2012, The Analyst.

[24]  A. Andrews,et al.  Head-to-head comparisons of carbon fiber microelectrode coatings for sensitive and selective neurotransmitter detection by voltammetry. , 2011, Analytical chemistry.

[25]  Michael L Heien,et al.  Fast-scan controlled-adsorption voltammetry for the quantification of absolute concentrations and adsorption dynamics. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[26]  D R Kipke,et al.  Reduction of neurovascular damage resulting from microelectrode insertion into the cerebral cortex using in vivo two-photon mapping , 2010, Journal of neural engineering.

[27]  K. Kreuer On the development of proton conducting polymer membranes for hydrogen and methanol fuel cells , 2001 .

[28]  M. Heien,et al.  Rethinking data collection and signal processing. 2. Preserving the temporal fidelity of electrochemical measurements. , 2013, Analytical chemistry.

[29]  Daniele Lecca,et al.  Dopamine and drug addiction: the nucleus accumbens shell connection , 2004, Neuropharmacology.

[30]  Y. Mai,et al.  Electro-synthesis of novel nanostructured PEDOT films and their application as catalyst support , 2011, Nanoscale research letters.

[31]  W. R. Salaneck,et al.  Electrochemical and XPS studies toward the role of monomeric and polymeric sulfonate counterions in the synthesis, composition, and properties of poly(3,4-ethylenedioxythiophene) , 2003 .

[32]  R. Wightman,et al.  Pharmacologically induced, subsecond dopamine transients in the caudate–putamen of the anesthetized rat , 2007, Synapse.

[33]  R. Wightman,et al.  Detecting subsecond dopamine release with fast-scan cyclic voltammetry in vivo. , 2003, Clinical chemistry.

[34]  L. Drzal,et al.  Simple Fabrication of a Highly Sensitive Glucose Biosensor Using Enzymes Immobilized in Exfoliated Graphite Nanoplatelets Nafion Membrane , 2007 .

[35]  R. Wightman,et al.  Subsecond dopamine release promotes cocaine seeking , 2003, Nature.

[36]  Chung-Chih Lin,et al.  Manipulating location, polarity, and outgrowth length of neuron-like pheochromocytoma (PC-12) cells on patterned organic electrode arrays. , 2011, Lab on a chip.

[37]  Robert B. Moore,et al.  State of understanding of nafion. , 2004, Chemical reviews.

[38]  Peng Wang,et al.  PEDOT/Nafion composite thin films supported on Pt electrodes: Facile fabrication and electrochemical activities , 2010 .

[39]  R. Adams,et al.  Nafion‐coated carbon fiber electrodes for neurochemical studies in brain tissue , 1990 .

[40]  David C. Martin,et al.  Electrochemical deposition and characterization of poly(3,4-ethylenedioxythiophene) on neural microelectrode arrays , 2003 .

[41]  J. Ying,et al.  Poly(3,4-ethylenedioxythiophene) (PEDOT) nanobiointerfaces: thin, ultrasmooth, and functionalized PEDOT films with in vitro and in vivo biocompatibility. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[42]  R. Wightman,et al.  Voltammetric detection of 5-hydroxytryptamine release in the rat brain. , 2009, Analytical chemistry.

[43]  W. Lövenich,et al.  PEDOT: Principles and Applications of an Intrinsically Conductive Polymer , 2010 .

[44]  A. Saiardi,et al.  Parkinsonian-like locomotor impairment in mice lacking dopamine D2 receptors , 1995, Nature.

[45]  Keld West,et al.  Vapor-Phase Polymerization of 3,4-Ethylenedioxythiophene: A Route to Highly Conducting Polymer Surface Layers , 2004 .

[46]  P. Goldman-Rakic,et al.  D1 dopamine receptors in prefrontal cortex: involvement in working memory , 1991, Science.

[47]  D. Shohamy,et al.  Dopamine and adaptive memory , 2010, Trends in Cognitive Sciences.