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Wireless battery free and fully implantable tools for the interrogation of the central and peripheral nervous system have quantitatively expanded the capabilities to study mechanistic and circuit level behavior in freely moving rodents. The light weight and small footprint of such devices enables full subdermal implantation that results in the capability to perform studies with minimal impact on subject behavior and yields broad application in a range of experimental paradigms. While these advantages have been successfully proven in rodents that move predominantly in 2D, the full potential of a wireless and battery free device can be harnessed with flying species, where interrogation with tethered devices is very difficult or impossible. Here we report on a wireless, battery free and multimodal platform that enables optogenetic stimulation and physiological temperature recording in a highly miniaturized form factor for use in songbirds. The systems are enabled by behavior guided primary antenna design and advanced energy management to ensure stable optogenetic stimulation and thermography throughout 3D experimental arenas. Collectively, these design approaches quantitatively expand the use of wireless subdermally implantable neuromodulation and sensing tools to species previously excluded from in vivo real time experiments. Studies requiring neural modulation in species that fly are difficult because of the need for wired connections to record experimental data. Here, Ausra et al. present a wireless and battery free device that achieves this in songbirds, model organisms used to study vocal learning and maintenance.

Bioelectronic interfaces have been extensively investigated in recent years and advances in technology derived from these tools, such as soft and ultrathin sensors, now offer the opportunity to interface with parts of the body that were largely unexplored due to the lack of suitable tools. The musculoskeletal system is an understudied area where these new technologies can result in advanced capabilities. Bones as a sensor and stimulation location offer tremendous advantages for chronic biointerfaces because devices can be permanently bonded and provide stable optical, electromagnetic, and mechanical impedance over the course of years. Here we introduce a new class of wireless battery-free devices, named osseosurface electronics, which feature soft mechanics, ultra-thin form factor and miniaturized multimodal biointerfaces comprised of sensors and optoelectronics directly adhered to the surface of the bone. Potential of this fully implanted device class is demonstrated via real-time recording of bone strain, millikelvin resolution thermography and delivery of optical stimulation in freely-moving small animal models. Battery-free device architecture, direct growth to the bone via surface engineered calcium phosphate ceramic particles, demonstration of operation in deep tissue in large animal models and readout with a smartphone highlight suitable characteristics for exploratory research and utility as a diagnostic and therapeutic platform. The development of high-performance implantable soft electronics as diagnostic platforms is key to realizing improved health monitoring. Here, the authors design wireless, battery-free, implantable bioelectronics that interface with the osseosurface for chronic musculoskeletal system monitoring.

The digitally connected body with clinical grade multimodal and multisite biosignal acquisition is a key goal of the wearable device communities, which will enable advanced diagnostics and therapeutics. Recent advances in sensor and biointerfaces have enabled insight into biomarkers and physiological states that far exceed the commercially available technologies. However, they often require intimate contact with the target organ, which is possible acutely or over days but may not translate to continuous monitoring without substantial user engagement. Holistic device ecosystems or standards are therefore required to enable a digitally connected body. Here, we discuss current barriers and highlight potential avenues to enable a seamless, almost imperceptible network, of wearable sensors to capture health comprehensively and chronically.Wearable electronics provide opportunities for personalized health monitoring and treatment. This Perspective addresses challenges in the field, including material selection for devices, device integration strategies, and public adoption factors.

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.

The positive or negative value (valence) of past experiences is normally integrated into neuronal circuits that encode episodic memories and plays an important role in guiding behavior. Here, we show, using mouse behavioral models, that glutamatergic afferents from the ventral tegmental area to the dorsal hippocampus (VTA→DH) signal negative valence to memory circuits, leading to the formation of fear-inducing context memories and to context-specific reinstatement of fear. To a lesser extent, these projections also contributed to opioid-induced place preference, suggesting a role in signaling positive valence as well, and thus a lack of dedicated polarity. Manipulations of VTA terminal activity were more effective in females and paralleled by sex differences in glutamatergic signaling. By prioritizing retrieval of negative and positive over neutral memories, the VTA→DH circuit can facilitate the selection of adaptive behaviors when current and past experiences are valence congruent. The neuronal pathway that signals the positive or negative value of memories is not well understood. Here, the authors report that an excitatory projection from the ventral tegmental area to the dorsal hippocampus carries the valence information, contributing, especially in females, to the recurrence of fear and to drug seeking behavior.

Biophysical signals such as motion and optically acquired hemodynamics represent foundational sensing modalities for wearables. Expansion of this toolset is vital for the progression of digital medicine. Current efforts utilize biofluids such as sweat and interstitial fluid with primarily adhesively mounted sensors that are fundamentally limited by epidermal turnover. A class of potential biomarkers that is largely unexplored are gaseous emissions from the body. In this work, we introduce an approach to capture emission of gas from the skin with a leaky cavity designed to allow for diffusion-based ambient gas exchange with the environment. This approach, coupled with differential measurement of ambient and in-cavity gas concentrations, allows for the real-time analysis of sweat rate, VOCs, and CO 2 while performing everyday tasks. The resulting biosignals are recorded with temporal resolutions that exceed current methodology, providing unparalleled insight into physiological processes without requiring sensor replacement over weeks at a time. Acquiring biomarkers from blood or sweat is limited by invasiveness or biofouling. Skin gas emissions bypass these issues, offering rich biosignals. Authors present passive sensing strategies capturing water vapor (Sweat rate), CO2, and VOCs, enabling real-time tracking of physiological changes.

Traditional technologies for virtual reality (VR) and augmented reality (AR) create human experiences through visual and auditory stimuli that replicate sensations associated with the physical world. The most widespread VR and AR systems use head-mounted displays, accelerometers and loudspeakers as the basis for three-dimensional, computer-generated environments that can exist in isolation or as overlays on actual scenery. In comparison to the eyes and the ears, the skin is a relatively underexplored sensory interface for VR and AR technology that could, nevertheless, greatly enhance experiences at a qualitative level, with direct relevance in areas such as communications, entertainment and medicine 1 , 2 . Here we present a wireless, battery-free platform of electronic systems and haptic (that is, touch-based) interfaces capable of softly laminating onto the curved surfaces of the skin to communicate information via spatio-temporally programmable patterns of localized mechanical vibrations. We describe the materials, device structures, power delivery strategies and communication schemes that serve as the foundations for such platforms. The resulting technology creates many opportunities for use where the skin provides an electronically programmable communication and sensory input channel to the body, as demonstrated through applications in social media and personal engagement, prosthetic control and feedback, and gaming and entertainment. Interfaces for epidermal virtual reality technology are demonstrated that can communicate by programmable patterns of localized mechanical vibrations.

Continuously operating wearables offer detailed insight into chronic health conditions and have the potential to reshape diagnostic and screening tools. However, the energy demands and large datasets created by constant monitoring over weeks to months are difficult or impossible to integrate into existing clinical practice, limiting the utility of this device class. Machine learning offers the opportunity to condense these large datasets into streamlined, digestible trends with the potential for significant clinical impact, although off-device inference requires advanced network infrastructure and substantial power availability for radios. Here, we introduce a device framework that integrates artificial intelligence with clinical grade biosignal acquisition at the edge, performing on-device inference with clinical grade fidelity over extended durations with no interaction required by the wearer. We utilize this framework to perform gait-based frailty assessment during in vivo trials (N 1  = 16) with results that match gold standard diagnostic tools. Clinical utility, model stability, and on-device inference are validated through in vivo trials (N 2  = 14) and ten-day-long extended wear experiments, demonstrating continuous operation without wearer intervention and autonomous longitudinal analysis of high sampling rate biosignals. Energy demand and intensive computation limit the use of machine learning on-device for wearables. Here, the authors deploy edge AI in a wearable form factor to provide clinical-grade gait-based frailty assessment over weeks with no interaction required from the wearer at any point.

Wireless, battery-free, and fully subdermally implantable optogenetic tools are poised to transform neurobiological research in freely moving animals. Current-generation wireless devices are sufficiently small, thin, and light for subdermal implantation, offering some advantages over tethered methods for naturalistic behavior. Yet current devices using wireless power delivery require invasive stimulus delivery, penetrating the skull and disrupting the blood–brain barrier. This can cause tissue displacement, neuronal damage, and scarring. Power delivery constraints also sharply curtail operational arena size. Here, we implement highly miniaturized, capacitive power storage on the platform of wireless subdermal implants. With approaches to digitally manage power delivery to optoelectronic components, we enable two classes of applications: transcranial optogenetic activation millimeters into the brain (validated using motor cortex stimulation to induce turning behaviors) and wireless optogenetics in arenas of more than 1 m² in size. This methodology allows for previously impossible behavioral experiments leveraging the modern optogenetic toolkit.

Small animals support a wide range of pathological phenotypes and genotypes as versatile, affordable models for pathogenesis of cardiovascular diseases and for exploration of strategies in electrotherapy, gene therapy, and optogenetics. Pacing tools in such contexts are currently limited to tethered embodiments that constrain animal behaviors and experimental designs. Here, we introduce a highly miniaturized wireless energy-harvesting and digital communication electronics for thin, miniaturized pacing platforms weighing 110 mg with capabilities for subdermal implantation and tolerance to over 200,000 multiaxial cycles of strain without degradation in electrical or optical performance. Multimodal and multisite pacing in ex vivo and in vivo studies over many days demonstrate chronic stability and excellent biocompatibility. Optogenetic stimulation of cardiac cycles with in-animal control and induction of heart failure through chronic pacing serve as examples of modes of operation relevant to fundamental and applied cardiovascular research and biomedical technology. Pacing tools that support small animals and can serve as models for pathogenesis of cardiovascular diseases are currently not available. Here, the authors report a miniaturized wireless battery-free implantable multimodal and multisite pacemaker that provides unlimited stimulation to test subjects.