Objective. Brain?computer interfaces (BCIs) using chronically implanted intracortical microelectrode arrays (MEAs) have the potential to restore lost function to people with disabilities if they work reliably for years. Current sensors fail to provide reliably useful signals over extended periods of time for reasons that are not clear. This study reports a comprehensive retrospective analysis from a large set of implants of a single type of intracortical MEA in a single species, with a common set of measures in order to evaluate failure modes. Approach. Since 1996, 78 silicon MEAs were implanted in 27 monkeys (Macaca mulatta). We used two approaches to find reasons for sensor failure. First, we classified the time course leading up to complete recording failure as acute (abrupt) or chronic (progressive). Second, we evaluated the quality of electrode recordings over time based on signal features and electrode impedance. Failure modes were divided into four categories: biological, material, mechanical, and unknown. Main results. Recording duration ranged from 0 to 2104?days (5.75?years), with a mean of 387?days and a median of 182?days (n = 78). Sixty-two arrays failed completely with a mean time to failure of 332?days (median = 133?days) while nine array experiments were electively terminated for experimental reasons (mean = 486?days). Seven remained active at the close of this study (mean = 753?days). Most failures (56%) occurred within a year of implantation, with acute mechanical failures the most common class (48%), largely because of connector issues (83%). Among grossly observable biological failures (24%), a progressive meningeal reaction that separated the array from the parenchyma was most prevalent (14.5%). In the absence of acute interruptions, electrode recordings showed a slow progressive decline in spike amplitude, noise amplitude, and number of viable channels that predicts complete signal loss by about eight years. Impedance measurements showed systematic early increases, which did not appear to affect recording quality, followed by a slow decline over years. The combination of slowly falling impedance and signal quality in these arrays indicates that insulating material failure is the most significant factor. Significance. This is the first long-term failure mode analysis of an emerging BCI technology in a large series of non-human primates. The classification system introduced here may be used to standardize how neuroprosthetic failure modes are evaluated. The results demonstrate the potential for these arrays to record for many years, but achieving reliable sensors will require replacing connectors with implantable wireless systems, controlling the meningeal reaction, and improving insulation materials. These results will focus future research in order to create clinical neuroprosthetic sensors, as well as valuable research tools, that are able to safely provide reliable neural signals for over a decade.

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Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates

In this review article, we focus on the various types of materials used in biomedical implantable devices, including the polymeric materials used as substrates and for the packaging of such devices. Polymeric materials are used because of the ease of fabrication, flexibility, and their biocompatible nature as well as their wide range of mechanical, electrical, chemical, and thermal behaviors when combined with different materials as composites. Biocompatible and biostable polymers are extensively used to package implanted devices, with the main criteria that include gas permeability and water permeability of the packaging polymer to protect the electronic circuit of the device from moisture and ions inside the human body. Polymeric materials must also have considerable tensile strength and should be able to contain the device over the envisioned lifetime of the implant. For substrates, structural properties and, at times, electrical properties would be of greater concern. Section 1 gives an introduction o...

Polymeric Biomaterials for Medical Implants and Devices

At the convergence of organic electronics and biology, organic bioelectronics attracts great scientific interest. The potential applications of organic semiconductors to reversibly transmit biological signals or stimulate biological tissues inspires many research groups to explore the use of organic electronics in biological systems. Considering the surfaces of movable living tissues being arbitrarily curved at physiological environments, the flexibility of organic bioelectronic devices is of paramount importance in enabling stable and reliable performances by improving the contact and interaction of the devices with biological systems. Significant advances in flexible organic bio-electronics have been achieved in the areas of flexible organic thin film transistors (OTFTs), polymer electrodes, smart textiles, organic electrochemical ion pumps (OEIPs), ion bipolar junction transistors (IBJTs) and chemiresistors. This review will firstly discuss the materials used in flexible organic bioelectronics, which is followed by an overview on various types of flexible organic bioelectronic devices. The versatility of flexible organic bioelectronics promises a bright future for this emerging area.

Flexible Organic Electronics in Biology: Materials and Devices

Advancement in neurotechnologies for electrophysiology, neurochemical sensing, neuromodulation, and optogenetics are revolutionizing scientific understanding of the brain while enabling treatments, cures, and preventative measures for a variety of neurological disorders. The grand challenge in neural interface engineering is to seamlessly integrate the interface between neurobiology and engineered technology, to record from and modulate neurons over chronic timescales. However, the biological inflammatory response to implants, neural degeneration, and long-term material stability diminish the quality of interface overtime. Recent advances in functional materials have been aimed at engineering solutions for chronic neural interfaces. Yet, the development and deployment of neural interfaces designed from novel materials have introduced new challenges that have largely avoided being addressed. Many engineering efforts that solely focus on optimizing individual probe design parameters, such as softness or flexibility, downplay critical multi-dimensional interactions between different physical properties of the device that contribute to overall performance and biocompatibility. Moreover, the use of these new materials present substantial new difficulties that must be addressed before regulatory approval for use in human patients will be achievable. In this review, the interdependence of different electrode components are highlighted to demonstrate the current materials-based challenges facing the field of neural interface engineering.

A Materials Roadmap to Functional Neural Interface Design

Mechanical failure modes of chronically implanted planar silicon-based neural probes for laminar recording

The applicability of parylene C as an encapsulation material for implanted neural prostheses was characterized and optimized. The adhesion of parylene C was tested on different substrate materials, which were commonly used in neural prostheses and the efficiency of different adhesion promotion methods was investigated. On Si(3)N(4), platinum, and on a first film of parylene C, a satisfactory adhesion was achieved with Silane A-174, which even withstood standard steam sterilization. The adhesion to gold and polyimide could not be improved sufficiently with the tested methods. Furthermore, tensile tests and measurements of the degree of crystallinity were performed on untreated, on steam sterilized, and on annealed parylene C layers to investigate the influence of thermal treatment. This led to more brittle and stiffer films due to an increase in the crystalline portion in the parylene layers. Finally, an electrochemical impedance spectroscopy was used to test if a parylene C layer was able to protect a metallic structure against corrosion on a Si(3)N(4) substrate. The results indicated that this could be only possible by treating the substrate with Silane A-174. To receive parylene C layers with a good encapsulation performance, it is important to consider the materials, which are used in the neural prosthesis, to find the best suited process parameters.

Characterization of parylene C as an encapsulation material for implanted neural prostheses

Parylene C is one of the established encapsulation polymers for chronic implants We investigated the influence of annealing Parylene C on its mechanical properties, chemical structure, and on the stability of Parylene C – platinum – Parylene C sandwich structures as a model of flexible neural interfaces in 09 % saline solution Films of Parylene C were annealed at 200 °C, 300 °C, 350 °C, and 400 °C in nitrogen atmosphere Temperatures of 350 °C and higher as well as annealing in air destroyed the Parylene C layers; films annealed at lower temperatures showed identical infrared spectra Higher anneal temperatures produced increased values of elongation at break, tensile and yield strength, and yield strain while at the same time Young’s modulus was shown to decrease Crystallinity increased with annealing temperature The structural stability of sandwich structures benefitted remarkably from annealing Sandwich structures annealed at 300 °C maintained their structural integrity during 320 days in saline solution at 37 °C and the insulation capability stayed consistently high

The effects of annealing on mechanical, chemical, and physical properties and structural stability of Parylene C

This paper reports on a novel interconnection technology for silicon-based neural devices used in extracellular recording. It is based on a flip-chip bonding process establishing the electrical connection of the silicon specimen and a highly flexible polymer cable via electroplated contact structures. This process makes possible the parallel connection of multiple bonding pads with high integration density. By the integration of a structurable fluoropolymer on the cables as an adhesion layer the mechanical connection is improved simultaneously. Further, the adhesion layer inherently encapsulates the bonding sites and allows omitting the application of an additional underfill. Test structures were characterized with respect to the electrical and mechanical reliability of this interconnection approach. The storage in Ringer’s solution for 12 days minimally affected the cable connection and its inherent encapsulation capability. Furthermore, a neural device was assembled with this technology and its capability for intracortical neural recording was demonstrated.

A Novel Assembly Method for Silicon-Based Neural Devices

Diffusion-limited deposition (DLD) allows the deposition of parylene C layers of two different thicknesses in one step with smooth transitions in between. Needlelike microelectrode structures for implantation in the brain were successfully coated with a taper along the needles' shafts. Diffusion limitation was obtained in the parylene coater by containers with perforated cover lids through which the needles were placed. The polymer layer condensing on the shafts is remarkably thinner than that on the regions outside the container. In this paper, we characterized the parameters influencing the DLD of parylene C. Systematic depositions were made using nine screens with different aperture sizes and screen thicknesses. The parylene thickness declined from approximately 9 to 1 μm and less due to the DLD. The geometric parameters affected the transitions' lengths (180 to 630 μm), shapes, slopes, and symmetries. The process was established to obtain uncovered electrode sites, a mandatory property to assure a direct metal-tissue contact to record bioelectric signals.

Diffusion-Limited Deposition of Parylene C

The structural and electrical stability of Parylene C - platinum - Parylene C sandwich structures is severely reduced by the sterilization methods autoclav- ing, gamma irradiation and ethylene oxide The re- sistance of platinum interdigitated electrodes embedded in Parylene C stored in saline solution at 37°C after steri- lization declined within several days, and optical analysis revealed delamination of Parylene and corrugation of platinum thin films Neither mechanical properties nor the FT-IR spectra of Parylene C were changed A control group of not sterilized samples was stable for more than 300 days under same conditions

Rene P. von Metzen

Papers

Characterization of parylene C as an encapsulation material for implanted neural prostheses

The effects of annealing on mechanical, chemical, and physical properties and structural stability of Parylene C

A Novel Assembly Method for Silicon-Based Neural Devices

Diffusion-Limited Deposition of Parylene C

Impact of Sterilization Procedures on the Stability of Parylene Based Flexible Multilayer Structures