Interfacing Conducting Polymer Nanotubes with the Central Nervous System: Chronic Neural Recording using Poly(3,4-ethylenedioxythiophene) Nanotubes.

2009 WILEY-VCH Verlag Gmb Development of advanced chronic, high-fidelity neural interfaces is accelerating research into brain function [1] and more effective treatments for neurological conditions. The primary functional requirements of these interfaces include recording and/or stimulating from a number of discretely sampled volumes of the brain at requisite spatial resolutions for specific time periods that may extend from hours to years. This translates to a push towards smaller electrodes that are more biologically transparent and biocompatible with a high density of electrode sites that remain functional for long period of time. As electrode size goes to the microscale (higher spatial selectivity), the impedance of electrode site increases, and consequently, the quality of signal recordings decreases (lower sensitivity). Thus, there is a trade off between the size (spatial selectivity) and quality of signal recordings (sensitivity) in neural microelectrodes. Studies have also shown that the response of brain tissue to implanted microelectrodes includes an acute injury and a chronic reactive tissue response. The chronic response is characterized by the presence of both activated microglia and reactive astrocytes, which eventually encapsulate the electrode to some degree. Consequently, in addition to the initial high impedance of microelectrodes, these reactive tissue responses have been associated with a progressive increase in the impedance of the electrode/tissue interface. Therefore, achieving a very low impedance electrode/tissue interface is important for maintaining and improving signal quality. Signal transduction at the electrode/tissue interface is a complex function of electrode properties and tissue characteristics. Transduction between the ionically conducting tissue and the electronically conducting electrode is primarily through capacitive currents and/or Faradaic currents from reversible reduction–oxidation reactions at the electrode surface. However, conventional metal electrodes, including gold, tungsten, platinum, and iridium, create a relatively abrupt materials interface that have well defined electrical characteristics, but have few options for dramatic impedance improvement. Therefore, new materials are required to decrease the electrode impedance, facilitate the ions to electrons signal transduction, and improve the biocompatibility at the electrode/tissue interface. The recent advances in the application of nanoscience in biology have enabled the design of nanomaterials such as carbon nanotubes and silicon nanowires that can be used for neural interfaces. Nanostructured materials may provide a means to significantly alter the structure/function relationship of microelectrode sites to reconcile the sometimes-conflicting requirements for smaller size, favorable electrical characteristics, and biocompatibility. Conducting polymers such as poly(pyrrole) (PPy) and poly(3,4-ethylenedioxythiophene) (PEDOT) have both electronic and ionic conductivity and have been recently considered as bioelectronic interface materials for biomedical applications, especially neuronal cell signaling and neural interfaces. Conducting polymers have favorable reactive tissue responses through attenuation of glial responses and enhanced integration and signaling of neuronal processes. Although PEDOT exhibits higher conductivity and chemical stability than PPy in the oxidized state, both PPy and PEDOT have been reported to decrease electrode impedance and increase charge injection capacity as compared to metal sites of similar geometric area. Here, we report for the first time the use of conducting polymer nanotubes for highly selective, chronic neural recording at the microscale. We demonstrate that PEDOT nanotubes enhance quality of recording signals. We measured in vivo electrochemical impedance spectroscopy (EIS), noise level, quality of unit activity, and analyzed local field potentials (LFPs). We show that electrodes modified with PEDOT nanotubes registered high quality unit activity (signal-to-noise ratio, SNR> 4) on 30% more sites than controls (uncoated), primarily as a result of a reduced noise floor. Moreover, we demonstrate that sites modified with PEDOTnanotubes have significantly less low