RESUMEN
Intracortical probe technology, consisting of arrays of microelectrodes, offers a means of recording the bioelectrical activity from neural tissue. A major limitation of existing intracortical probe technology pertains to limited lifetime of 6 months to a year of recording after implantation. A major contributor to device failure is widely believed to be the interfacial mechanical mismatch of conventional stiff intracortical devices and the surrounding brain tissue. We describe the design, development, and demonstration of a novel functional intracortical probe technology that has a tunable Young's modulus from â¼2 GPa to â¼50 MPa. This technology leverages advances in dynamically softening materials, specifically thiol-ene/acrylate thermoset polymers, which exhibit minimal swelling of < 3% weight upon softening in vitro. We demonstrate that a shape memory polymer-based multichannel intracortical probe can be fabricated, that the mechanical properties are stable for at least 2 months and that the device is capable of single unit recordings for durations up to 77 days in vivo. This novel technology, which is amenable to processes suitable for manufacturing via standard semiconductor fabrication techniques, offers the capability of softening in vivo to reduce the tissue-device modulus mismatch to ultimately improve long term viability of neural recordings. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 159-168, 2017.
Asunto(s)
Ondas Encefálicas , Lóbulo Frontal/fisiología , Animales , Módulo de Elasticidad , Electrodos , RatonesRESUMEN
Thiol-click reactions lead to polymeric materials with a wide range of interesting mechanical, electrical, and optical properties. However, this reaction mechanism typically results in bulk materials with a low glass transition temperature (Tg ) due to rotational flexibility around the thioether linkages found in networks such as thiol-ene, thiol-epoxy, and thiol-acrylate systems. This report explores the thiol-maleimide reaction utilized for the first time as a solvent-free reaction system to synthesize high-Tg thermosetting networks. Through thermomechanical characterization via dynamic mechanical analysis, the homogeneity and Tg s of thiol-maleimide networks are compared to similarly structured thiol-ene and thiol-epoxy networks. While preliminary data show more heterogeneous networks for thiol-maleimide systems, bulk materials exhibit Tg s 80 °C higher than other thiol-click systems explored herein. Finally, hollow tubes are synthesized using each thiol-click reaction mechanism and employed in low- and high-temperature environments, demonstrating the ability to withstand a compressive radial 100 N deformation at 100 °C wherein other thiol-click systems fail mechanically.
Asunto(s)
Química Clic , Maleimidas/química , Polímeros/síntesis química , Compuestos de Sulfhidrilo/química , Temperatura de Transición , Vidrio , Estructura Molecular , Polímeros/químicaRESUMEN
Softening microelectrode arrays, or flexible bioelectronic systems which can dynamically change modulus under the application of an external stimulus such as heat or electromagnetic radiation, have been of significant interest in the literature within the previous decade. Through their ability to actively soften in vivo, these devices have shown the capacity to attenuate the neuronal damage associated with insertion of rigid microelectrode arrays into soft tissue. Thiol-click substrates specifically have shown particularly impressive results for fabricating devices requiring small-scale, high-performance electronics for neural recording. However, previous attempts to engineer increasingly lower-modulus substrates for these devices have failed due to the fundamental chemistries' (the thioether linkage) flexibility. This failure has led to substrates without sufficient mechanical rigidity for penetrating soft tissue at physiological temperatures, or sufficient softening capacity to reduce the mechanical mismatch between soft tissue and implantable device. In this work, a ternary thiol-epoxy/maleimide network is investigated as a potential substrate materials space in which the degree of softening can be modulated without sacrificing the mechanical rigidity at physiological temperatures. Using these networks as platforms for the microfabrication of electrode arrays, example implantable intracortical microelectrode arrays are fabricated on both thiol-epoxy and thiol-epoxy/maleimide networks to demonstrate the insertion capacity of microelectrode arrays on the ternary polymer networks.
RESUMEN
Hydrolytically stable, tunable modulus polymer networks are demonstrated to survive harsh alkaline environments and offer promise for use in long-term implantable bioelectronic medicines known as electroceuticals. Today's polymer networks (such as polyimides or polysiloxanes) succeed in providing either stiff or soft substrates for bioelectronics devices; however, the capability to significantly tune the modulus of such materials is lacking. Within the space of materials with easily modified elastic moduli, thiol-ene copolymers are a subset of materials that offer a promising solution to build next generation flexible bioelectronics but have typically been susceptible to hydrolytic degradation chronically. In this inquiry, we demonstrate a materials space capable of tuning the substrate modulus and explore the mechanical behavior of such networks. Furthermore, we fabricate an array of microelectrodes that can withstand accelerated aging environments shown to destroy conventional flexible bioelectronics.
Asunto(s)
Materiales Biocompatibles/química , Polímeros/química , Siloxanos/química , Compuestos de Sulfhidrilo/química , Módulo de Elasticidad , Electrónica/instrumentación , Hidrólisis , Cinética , MicroelectrodosRESUMEN
Softening neural interfaces are implanted stiff to enable precise insertion, and they soften in physiological conditions to minimize modulus mismatch with tissue. In this work, a high-charge-injection-capacity iridium electrode fabrication process is detailed. For the first time, this process enables integration of iridium electrodes onto softening substrates using photolithography to define all features in the device. Importantly, no electroplated layers are utilized, leading to a highly scalable method for consistent device fabrication. The iridium electrode is metallically bonded to the gold conductor layer, which is covalently bonded to the softening substrate via sulfur-based click chemistry. The resulting shape-memory polymer neural interfaces can deliver more than 2 billion symmetric biphasic pulses (100 µs/phase), with a charge of 200 µC/cm(2) and geometric surface area (GSA) of 300 µm(2). A transfer-by-polymerization method is used in combination with standard semiconductor processing techniques to fabricate functional neural probes onto a thiol-ene-based, thin film substrate. Electrical stability is tested under simulated physiological conditions in an accelerated electrical aging paradigm with periodic measurement of electrochemical impedance spectra (EIS) and charge storage capacity (CSC) at various intervals. Electrochemical characterization and both optical and scanning electron microscopy suggest significant breakdown of the 600 nm-thick parylene-C insulation, although no delamination of the conductors or of the final electrode interface was observed. Minor cracking at the edges of the thin film iridium electrodes was occasionally observed. The resulting devices will provide electrical recording and stimulation of the nervous system to better understand neural wiring and timing, to target treatments for debilitating diseases, and to give neuroscientists spatially selective and specific tools to interact with the body. This approach has uses for cochlear implants, nerve cuff electrodes, penetrating cortical probes, spinal stimulators, blanket electrodes for the gut, stomach, and visceral organs and a host of other custom nerve-interfacing devices.