title: Rapid evaluation of the durability of cortical neural implants using accelerated aging with reactive oxygen species.
abstract: OBJECTIVE
  A challenge for implementing high bandwidth cortical brain-machine interface devices in patients is the limited functional lifespan of implanted recording electrodes. Development of implant technology currently requires extensive non-clinical testing to demonstrate device performance. However, testing the durability of the implants in vivo is time-consuming and expensive. Validated in vitro methodologies may reduce the need for extensive testing in animal models.
  
  
  METHODS
  Here we describe an in vitro platform for rapid evaluation of implant stability. We designed a reactive accelerated aging (RAA) protocol that employs elevated temperature and reactive oxygen species (ROS) to create a harsh aging environment. Commercially available microelectrode arrays (MEAs) were placed in a solution of hydrogen peroxide at 87 °C for a period of 7 days. We monitored changes to the implants with scanning electron microscopy and broad spectrum electrochemical impedance spectroscopy (1 Hz-1 MHz) and correlated the physical changes with impedance data to identify markers associated with implant failure.
  
  
  RESULTS
  RAA produced a diverse range of effects on the structural integrity and electrochemical properties of electrodes. Temperature and ROS appeared to have different effects on structural elements, with increased temperature causing insulation loss from the electrode microwires, and ROS concentration correlating with tungsten metal dissolution. All array types experienced impedance declines, consistent with published literature showing chronic (>30 days) declines in array impedance in vivo. Impedance change was greatest at frequencies <10 Hz, and smallest at frequencies 1 kHz and above. Though electrode performance is traditionally characterized by impedance at 1 kHz, our results indicate that an impedance change at 1 kHz is not a reliable predictive marker of implant degradation or failure.
  
  
  CONCLUSIONS
  ROS, which are known to be present in vivo, can create structural damage and change electrical properties of MEAs. Broad-spectrum electrical impedance spectroscopy demonstrates increased sensitivity to electrode damage compared with single-frequency measurements. RAA can be a useful tool to simulate worst-case in vivo damage resulting from chronic electrode implantation, simplifying the device development lifecycle.
authors: Division of Biology, Chemistry and Material Science, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, US Food and Drug Administration, White Oak Federal Research Center, Silver Spring, MD, USA.
authors: Pavel
authors: P
authors: Takmakov
authors: Kiersten
authors: K
authors: Ruda
authors: K
authors: K
authors: Scott Phillips
authors: Irada S
authors: IS
authors: Isayeva
authors: Victor
authors: V
authors: Krauthamer
authors: Cristin G
authors: CG
authors: Welle
mesh_terms: D001921:Brain / Q000502:physiology*; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D004567:Electrodes, Implanted; D004867:Equipment Design; D019544:Equipment Failure Analysis / Q000379:methods; D006801:Humans; D008422:Materials Testing / Q000379:methods; D008839:Microelectrodes; D017382:Reactive Oxygen Species / Q000737:chemistry*; D012117:Resins, Synthetic / Q000737:chemistry*; D013997:Time Factors; D014414:Tungsten / Q000737:chemistry*
chemical_list: D020099:Coated Materials, Biocompatible; D017382:Reactive Oxygen Species; D012117:Resins, Synthetic; C029945:polyimide resin; D014414:Tungsten
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