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Title: Monolithically Defined Wireless Fully Implantable Nervous System Interfaces.
Author: Gutruf P.
Journal: Acc Chem Res; 2024 May 07; 57(9):1275-1286. PubMed ID: 38608256.
Abstract:
Evolution of implantable neural interfaces is critical in addressing the challenges in understanding the fundamental working principles and therapeutic applications for central and peripheral nervous systems. Traditional approaches utilizing hermetically sealed, rigid electronics and detached electrodes face challenges in power supply, encapsulation, channel count, dispersed application location, and modality. Employing thin-film, wirelessly powered devices is promising to expand capabilities. Devices that forego bulky power supplies, favoring a configuration where electronics are integrated directly onto thin films, reduce displacement volumes for seamless, fully implantable interfaces with high energy availability and soft mechanics to conform to the neuronal target. We discuss 3 device architectures: (1) Highly miniaturized devices that merge electronics and neural interfaces into a single, injectable format; (2) Interfaces that consolidate power, computation, and neural connectivity on a thin sheet applied directly to the target area; (3) A spatially dislocated approach where power and computation are situated subdermally, connected via a thin interconnect to the neural interface.Each has advantages and constraints in terms of implantation invasiveness, power capturing efficiency, and directional sensitivity of power delivery. In powering these devices, near-field power delivery emerges as the most implemented technique. Key parameters are size and volume of primary and secondary antennas, which determine coupling efficiency and power delivery. Based on application requirements, ranging from small to large animal models, subjects require system level designs. Material strategies play a crucial role; monolithic designs, with materials like polyimide substrates, enable scalability with high performance. This contrasts with established hermetic encapsulation approaches that use a stainless steel or titanium box with passthroughs that result in large tissue displacements and prohibit intimate integration with target organ systems. Encapsulation, particularly with parylene, enables longevity and effectiveness; more research is needed to enable human lifetime operation. Implant-to-ambient device communication, focusing on strategies compatible with well-established standards and off-the-shelf electronics, is discussed with the goal of enabling seamless system integration, reliability, and scalability. The interface with the central nervous system is explored through various wireless, battery-free devices capable of both stimulation (electrical and optogenetic) and recording (photometric and electrochemical). These devices show advanced capabilities for chronic studies and insights into neural dynamics. In the peripheral nervous system, stimulation devices for applications, such as spinal and muscle stimulation, are discussed. The challenges lie in the mechanical and electrochemical durability. Examples that successfully navigate these challenges offer solutions for chronic studies in this domain. The potential of wireless, fully implantable nervous system interfaces using near field resonant power transfer is characterized by monolithically defined device architecture, providing a significant leap toward seamless access to the central and peripheral nervous systems. New avenues for research and therapeutic applications supporting a multimodal and multisite approach to neuromodulation with a high degree of connectivity and a holistic approach toward deciphering and supplementing the nervous system may enable recovery and treatment of injury and chronic disease.

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