Wireless Battery-free and Fully Implantable Organ Interfaces.

Advances in soft materials, miniaturized electronics, sensors, stimulators, radios, and battery-free power supplies are resulting in a new generation of fully implantable organ interfaces that leverage volumetric reduction and soft mechanics by eliminating electrochemical power storage. This device class offers the ability to provide high-fidelity readouts of physiological processes, enables stimulation, and allows control over organs to realize new therapeutic and diagnostic paradigms. Driven by seamless integration with connected infrastructure, these devices enable personalized digital medicine. Key to advances are carefully designed material, electrophysical, electrochemical, and electromagnetic systems that form implantables with mechanical properties closely matched to the target organ to deliver functionality that supports high-fidelity sensors and stimulators. The elimination of electrochemical power supplies enables control over device operation, anywhere from acute, to lifetimes matching the target subject with physical dimensions that supports imperceptible operation. This review provides a comprehensive overview of the basic building blocks of battery-free organ interfaces and related topics such as implantation, delivery, sterilization, and user acceptance. State of the art examples categorized by organ system and an outlook of interconnection and advanced strategies for computation leveraging the consistent power influx to elevate functionality of this device class over current battery-powered strategies is highlighted.

Biosymbiotic platform for chronic long-range monitoring of biosignals in limited resource settings.

Remote patient monitoring is a critical component of digital medicine, and the COVID-19 pandemic has further highlighted its importance. Wearable sensors aimed at noninvasive extraction and transmission of high-fidelity physiological data provide an avenue toward at-home diagnostics and therapeutics; however, the infrastructure requirements for such devices limit their use to areas with well-established connectivity. This accentuates the socioeconomic and geopolitical gap in digital health technology and points toward a need to provide access in areas that have limited resources. Low-power wide area network (LPWAN) protocols, such as LoRa, may provide an avenue toward connectivity in these settings; however, there has been limited work on realizing wearable devices with this functionality because of power and electromagnetic constraints. In this work, we introduce wearables with electromagnetic, electronic, and mechanical features provided by a biosymbiotic platform to realize high-fidelity biosignals transmission of 15 miles without the need for satellite infrastructure. The platform implements wireless power transfer for interaction-free recharging, enabling long-term and uninterrupted use over weeks without the need for the user to interact with the devices. This work presents demonstration of a continuously wearable device with this long-range capability that has the potential to serve resource-constrained and remote areas, providing equitable access to digital health.

Wireless, battery-free subdermally implantable photometry systems for chronic recording of neural dynamics.

Recording cell-specific neuronal activity while monitoring behaviors of freely moving subjects can provide some of the most significant insights into brain function. Current means for monitoring calcium dynamics in genetically targeted populations of neurons rely on delivery of light and recording of fluorescent signals through optical fibers that can reduce subject mobility, induce motion artifacts, and limit experimental paradigms to isolated subjects in open, two-dimensional (2D) spaces. Wireless alternatives eliminate constraints associated with optical fibers, but their use of head stages with batteries adds bulk and weight that can affect behaviors, with limited operational lifetimes. The systems introduced here avoid drawbacks of both types of technologies, by combining highly miniaturized electronics and energy harvesters with injectable photometric modules in a class of fully wireless, battery-free photometer that is fully implantable subdermally to allow for the interrogation of neural dynamics in freely behaving subjects, without limitations set by fiber optic tethers or operational lifetimes constrained by traditional power supplies. The unique capabilities of these systems, their compatibility with magnetic resonant imaging and computed tomography and the ability to manufacture them with techniques in widespread use for consumer electronics, suggest a potential for broad adoption in neuroscience research.

Context-aware electromagnetic design for continuously wearable biosymbiotic devices.

Imperceptible wireless wearable devices are critical to advance digital medicine with the goal to capture clinical-grade biosignals continuously. Design of these systems is complex because of unique interdependent electromagnetic, mechanic and system level considerations that directly influence performance. Typically, approaches consider body location, related mechanical loads, and desired sensing capabilities, however, design for real world application context is not formulated. Wireless power casting eliminates user interaction and the need to recharge batteries, however, implementation is challenging because the use case influences performance. To facilitate a data-driven approach to design, we demonstrate a method for personalized, context-aware antenna, rectifier and wireless electronics design that considers human behavioral patterns and physiology to optimize electromagnetic and mechanical features for best performance across an average day of the target user group. Implementation of these methods result in devices that enable continuous recording of high-fidelity biosignals over weeks without the need for human interaction.

Wireless, Battery-Free Implants for Electrochemical Catecholamine Sensing and Optogenetic Stimulation.

Neurotransmitters and neuromodulators mediate communication between neurons and other cell types; knowledge of release dynamics is critical to understanding their physiological role in normal and pathological brain function. Investigation into transient neurotransmitter dynamics has largely been hindered due to electrical and material requirements for electrochemical stimulation and recording. Current systems require complex electronics for biasing and amplification and rely on materials that offer limited sensor selectivity and sensitivity. These restrictions result in bulky, tethered, or battery-powered systems impacting behavior and that require constant care of subjects. To overcome these challenges, we demonstrate a fully implantable, wireless, and battery-free platform that enables optogenetic stimulation and electrochemical recording of catecholamine dynamics in real time. The device is nearly 1/10th the size of previously reported examples and includes a probe that relies on a multilayer electrode architecture featuring a microscale light emitting diode (µ-LED) and a carbon nanotube (CNT)-based sensor with sensitivities among the highest recorded in the literature (1264.1 nA µM-1 cm-2). High sensitivity of the probe combined with a center tapped antenna design enables the realization of miniaturized, low power circuits suitable for subdermal implantation even in small animal models such as mice. A series of in vitro and in vivo experiments highlight the sensitivity and selectivity of the platform and demonstrate its capabilities in freely moving, untethered subjects. Specifically, a demonstration of changes in dopamine concentration after optogenetic stimulation of the nucleus accumbens and real-time readout of dopamine levels after opioid and naloxone exposure in freely behaving subjects highlight the experimental paradigms enabled by the platform.

Wearable devices for continuous monitoring of biosignals: Challenges and opportunities.

The ability for wearable devices to collect high-fidelity biosignals continuously over weeks and months at a time has become an increasingly sought-after characteristic to provide advanced diagnostic and therapeutic capabilities. Wearable devices for this purpose face a multitude of challenges such as formfactors with long-term user acceptance and power supplies that enable continuous operation without requiring extensive user interaction. This review summarizes design considerations associated with these attributes and summarizes recent advances toward continuous operation with high-fidelity biosignal recording abilities. The review also provides insight into systematic barriers for these device archetypes and outlines most promising technological approaches to expand capabilities. We conclude with a summary of current developments of hardware and approaches for embedded artificial intelligence in this wearable device class, which is pivotal for next generation autonomous diagnostic, therapeutic, and assistive health tools.

Wireless and battery-free platforms for collection of biosignals.

Recent progress in biosensors have quantitively expanded current capabilities in exploratory research tools, diagnostics and therapeutics. This rapid pace in sensor development has been accentuated by vast improvements in data analysis methods in the form of machine learning and artificial intelligence that, together, promise fantastic opportunities in chronic sensing of biosignals to enable preventative screening, automated diagnosis, and tools for personalized treatment strategies. At the same time, the importance of widely accessible personal monitoring has become evident by recent events such as the COVID-19 pandemic. Progress in fully integrated and chronic sensing solutions is therefore increasingly important. Chronic operation, however, is not truly possible with tethered approaches or bulky, battery-powered systems that require frequent user interaction. A solution for this integration challenge is offered by wireless and battery-free platforms that enable continuous collection of biosignals. This review summarizes current approaches to realize such device architectures and discusses their building blocks. Specifically, power supplies, wireless communication methods and compatible sensing modalities in the context of most prevalent implementations in target organ systems. Additionally, we highlight examples of current embodiments that quantitively expand sensing capabilities because of their use of wireless and battery-free architectures.

Biosymbiotic, personalized, and digitally manufactured wireless devices for indefinite collection of high-fidelity biosignals.

Digital medicine, the ability to stream continuous information from the body to gain insight into health status, manage disease, and predict onset health problems, is only gradually developing. Key technological hurdles that slow the proliferation of this approach are means by which clinical grade biosignals are continuously obtained without frequent user interaction. To overcome these hurdles, solutions in power supply and interface strategies that maintain high-fidelity readouts chronically are critical. This work introduces a previously unexplored class of devices that overcomes the limitations using digital manufacturing to tailor geometry, mechanics, electromagnetics, electronics, and fluidics to create unique personalized devices optimized to the wearer. These elastomeric, three-dimensional printed, and laser-structured constructs, called biosymbiotic devices, enable adhesive-free interfaces and the inclusion of high-performance, far-field energy harvesting to facilitate continuous wireless and battery-free operation of multimodal and multidevice, high-fidelity biosensing in an at-home setting without user interaction.

Wireless, battery-free, and fully implantable electrical neurostimulation in freely moving rodents.

Implantable deep brain stimulation (DBS) systems are utilized for clinical treatment of diseases such as Parkinson's disease and chronic pain. However, long-term efficacy of DBS is limited, and chronic neuroplastic changes and associated therapeutic mechanisms are not well understood. Fundamental and mechanistic investigation, typically accomplished in small animal models, is difficult because of the need for chronic stimulators that currently require either frequent handling of test subjects to charge battery-powered systems or specialized setups to manage tethers that restrict experimental paradigms and compromise insight. To overcome these challenges, we demonstrate a fully implantable, wireless, battery-free platform that allows for chronic DBS in rodents with the capability to control stimulation parameters digitally in real time. The devices are able to provide stimulation over a wide range of frequencies with biphasic pulses and constant voltage control via low-impedance, surface-engineered platinum electrodes. The devices utilize off-the-shelf components and feature the ability to customize electrodes to enable broad utility and rapid dissemination. Efficacy of the system is demonstrated with a readout of stimulation-evoked neural activity in vivo and chronic stimulation of the medial forebrain bundle in freely moving rats to evoke characteristic head motion for over 36 days.