The development of reliable long-term encapsulation technologies for implantable biomedical devices is of paramount importance for the safe and stable operation of implants in the body over a period of several decades. Conventional technologies based on titanium or ceramic packaging, however, are not suitable for encapsulating microfabricated devices due to their limited scalability, incompatibility with microfabrication processes, and difficulties with miniaturization. A variety of emerging materials have been proposed for encapsulation of microfabricated implants, including thin-film inorganic coatings of Al2O3, HfO2, SiO2, SiC, and diamond, as well as organic polymers of polyimide, parylene, liquid crystal polymer, silicone elastomer, SU-8, and cyclic olefin copolymer. While none of these materials have yet been proven to be as hermetic as conventional metal packages nor widely used in regulatory approved devices for chronic implantation, a number of studies have demonstrated promising outcomes on their long-term encapsulation performance through a multitude of fabrication and testing methodologies. The present review article aims to provide a comprehensive, up-to-date overview of the long-term encapsulation performance of these emerging materials with a specific focus on publications that have quantitatively estimated the lifetime of encapsulation technologies in aqueous environments.
The application of a neural stimulator to small animals is highly desired for the investigation of electrophysiological studies and development of neuroprosthetic devices. For this purpose, it is essential for the device to be implemented with the capabilities of full implantation and wireless control. Here, we present a fully implantable stimulator with remote controllability, compact size, and minimal power consumption. Our stimulator consists of modular units of (1) a surface-type cortical array for inducing directional change of a rat, (2) a depth-type array for providing rewards, and (3) a package for accommodating the stimulating electronics, a battery and ZigBee telemetry, all of which are assembled after independent fabrication and implantation using customized flat cables and connectors. All three modules were packaged using liquid crystal polymer (LCP) to avoid any chemical reaction after implantation. After bench-top evaluation of device functionality, the stimulator was implanted into rats to train the animals to turn to the left (or right) following a directional cue applied to the barrel cortex. Functionality of the device was also demonstrated in a three-dimensional (3D) maze structure, by guiding the rats to better navigate in the maze. The movement of the rat could be wirelessly controlled by a combination of artificial sensation evoked by the surface electrode array and reward stimulation. We could induce rats to turn left or right in free space and help their navigation through the maze. The polymeric packaging and modular design could encapsulate the devices with strict size limitations, which made it possible to fully implant the device into rats. Power consumption was minimized by a dual-mode power-saving scheme with duty cycling. The present study demonstrated feasibility of the proposed neural stimulator to be applied to neuroprosthesis research.
A significant challenge in improving the deep brain stimulation (DBS) system is the miniaturization of the device, aiming to integrate both the stimulator and the electrode into a compact unit with a wireless charging capability to reduce invasiveness. We present a miniaturized, fully implantable, and battery-free DBS system designed for rats, using a liquid crystal polymer (LCP), a biocompatible and long-term reliable material. The system integrates the simulator circuit, the receiver coil, and a 20 mm long depth-type microelectrode array in a dome-shaped LCP package that is 13 mm in diameter and 5 mm in height. Wireless powering and control via an inductive link enable device miniaturization, allowing for full implantation and, thus, the free behavior of untethered animals. The eight-channel stimulation electrode array was microfabricated on an LCP substrate to form a multilayered system substrate, which was monolithically encapsulated by a domed LCP lid using a specialized spot-welding process. The device functionality was validated via an in vivo animal experiment using a neuropathic pain model in rats. This experiment demonstrated an increase in the mechanical withdrawal threshold of the rats with microelectrical stimulation delivered using the fully implanted device, highlighting the effectiveness of the system.