Fully bioresorbable hybrid opto-electronic neural implant system for simultaneous electrophysiological recording and optogenetic stimulation.

Bioresorbable neural implants based on emerging classes of biodegradable materials offer a promising solution to the challenges of secondary surgeries for removal of implanted devices required for existing neural implants. In this study, we introduce a fully bioresorbable flexible hybrid opto-electronic system for simultaneous electrophysiological recording and optogenetic stimulation. The flexible and soft device, composed of biodegradable materials, has a direct optical and electrical interface with the curved cerebral cortex surface while exhibiting excellent biocompatibility. Optimized to minimize light transmission losses and photoelectric artifact interference, the device was chronically implanted in the brain of transgenic mice and performed to photo-stimulate the somatosensory area while recording local field potentials. Thus, the presented hybrid neural implant system, comprising biodegradable materials, promises to provide monitoring and therapy modalities for versatile applications in biomedicine.

Integration of in vivo electrophysiology and optogenetics in rodents with PEDOT:PSS neural electrode array.

Here, we present a protocol for the fabrication of transparent implantable electrode arrays for integrating optogenetics and electrophysiology. We describe steps for fabricating microelectrodes using the conductive polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate). We then detail procedures for analyzing performance of the electrodes and recording light-evoked neural activities from the transgenic mouse. This protocol utilizes photolithography rather than conventional electrodeposition. For complete details on the use and execution of this protocol, please refer to Cho et al. (2022).1.

Optimal bilayer composites for temperature-tracking wireless electronics.

Modern silicone-based epidermal electronics engineered for body temperature sensing represent a pivotal development in the quest for advancing preventive medicine and enhancing post-surgical monitoring. While these compact and highly flexible electronics empower real-time monitoring in dynamic environments, a noteworthy limitation is the challenge in regulating the infiltration or obstruction of heat from the external environment into the surface layers of these electronics. The study presents a cost-effective temperature sensing solution by embedding wireless electronics in a multi-layered elastomeric composite to meet the dual needs of enhanced thermal insulation for encapsulation in contact with air and improved thermal conductivity for the substrate in contact with the skin. The encapsulating composite benefits from the inclusion of hollow silica microspheres, which reduce the thermal conductivity by 40%, while non-spherical aluminum nitride enhances the thermal conductivity of the substrate by 370%. The addition of particles to the respective composites inevitably leads to an increase in modulus. Two composite elements are engineered to coexist while maintaining a matching low modulus of 3.4 MPa and a stretchability exceeding 30%, all without compromising the optimized thermal properties. Consecutive thermal, electrical, and mechanical characterization confirms the sensor's capacity for precise body temperature monitoring during a single day's lifespan, while also assessing the influence of behavioral factors on body temperature.

Bionic artificial skin with a fully implantable wireless tactile sensory system for wound healing and restoring skin tactile function.

Tactile function is essential for human life as it enables us to recognize texture and respond to external stimuli, including potential threats with sharp objects that may result in punctures or lacerations. Severe skin damage caused by severe burns, skin cancer, chemical accidents, and industrial accidents damage the structure of the skin tissue as well as the nerve system, resulting in permanent tactile sensory dysfunction, which significantly impacts an individual's daily life. Here, we introduce a fully-implantable wireless powered tactile sensory system embedded artificial skin (WTSA), with stable operation, to restore permanently damaged tactile function and promote wound healing for regenerating severely damaged skin. The fabricated WTSA facilitates (i) replacement of severely damaged tactile sensory with broad biocompatibility, (ii) promoting of skin wound healing and regeneration through collagen and fibrin-based artificial skin (CFAS), and (iii) minimization of foreign body reaction via hydrogel coating on neural interface electrodes. Furthermore, the WTSA shows a stable operation as a sensory system as evidenced by the quantitative analysis of leg movement angle and electromyogram (EMG) signals in response to varying intensities of applied pressures.

A wireless, solar-powered, optoelectronic system for spatial restriction-free long-term optogenetic neuromodulations.

Numerous wireless optogenetic systems have been reported for practical tether-free optogenetics in freely moving animals. However, most devices rely on battery-powered or coil-powered systems requiring periodic battery replacement or bulky, high-cost charging equipment with delicate antenna design. This leads to spatiotemporal constraints, such as limited experimental duration due to battery life or animals' restricted movement within specific areas to maintain wireless power transmission. In this study, we present a wireless, solar-powered, flexible optoelectronic device for neuromodulation of the complete freely behaving subject. This device provides chronic operation without battery replacement or other external settings including impedance matching technique and radio frequency generators. Our device uses high-efficiency, thin InGaP/GaAs tandem flexible photovoltaics to harvest energy from various light sources, which powers Bluetooth system to facilitate long-term, on-demand use. Observation of sustained locomotion behaviors for a month in mice via secondary motor cortex area stimulation demonstrates the notable capabilities of our device, highlighting its potential for space-free neuromodulating applications.

Fluorescent-based biodegradable microneedle sensor array for tether-free continuous glucose monitoring with smartphone application.

Continuous glucose monitoring (CGM) allows patients with diabetes to manage critical disease effectively and autonomously and prevent exacerbation. A painless, wireless, compact, and minimally invasive device that can provide CGM is essential for monitoring the health conditions of freely moving patients with diabetes. Here, we propose a glucose-responsive fluorescence-based highly sensitive biodegradable microneedle CGM system. These ultrathin and ultralight microneedle sensor arrays continuously and precisely monitored glucose concentration in the interstitial fluid with minimally invasive, pain-free, wound-free, and skin inflammation-free outcomes at various locations and thicknesses of the skin. Bioresorbability in the body without a need for device removal after use was a key characteristic of the microneedle glucose sensor. We demonstrated the potential long-term use of the bioresorbable device by applying the tether-free CGM system, thus confirming the successful detection of glucose levels based on changes in fluorescence intensity. In addition, this microneedle glucose sensor with a user-friendly designed home diagnosis system using mobile applications and portable accessories offers an advance in CGM and its applicability to other bioresorbable, wearable, and implantable monitoring device technology.

Ultrathin Crystalline Silicon Nano and Micro Membranes with High Areal Density for Low-Cost Flexible Electronics.

Ultrathin crystalline silicon is widely used as an active material for high-performance, flexible, and stretchable electronics, from simple passive and active components to complex integrated circuits, due to its excellent electrical and mechanical properties. However, in contrast to conventional silicon wafer-based devices, ultrathin crystalline silicon-based electronics require an expensive and rather complicated fabrication process. Although silicon-on-insulator (SOI) wafers are commonly used to obtain a single layer of crystalline silicon, they are costly and difficult to process. Therefore, as an alternative to SOI wafers-based thin layers, here, a simple transfer method is proposed for printing ultrathin multiple crystalline silicon sheets with thicknesses between 300 nm to 13 µm and high areal density (>90%) from a single mother wafer. Theoretically, the silicon nano/micro membrane can be generated until the mother wafer is completely consumed. In addition, the electronic applications of silicon membranes are successfully demonstrated through the fabrication of a flexible solar cell and flexible NMOS transistor arrays.

Vertical full-colour micro-LEDs via 2D materials-based layer transfer.

Micro-LEDs (µLEDs) have been explored for augmented and virtual reality display applications that require extremely high pixels per inch and luminance1,2. However, conventional manufacturing processes based on the lateral assembly of red, green and blue (RGB) µLEDs have limitations in enhancing pixel density3-6. Recent demonstrations of vertical µLED displays have attempted to address this issue by stacking freestanding RGB LED membranes and fabricating top-down7-14, but minimization of the lateral dimensions of stacked µLEDs has been difficult. Here we report full-colour, vertically stacked µLEDs that achieve, to our knowledge, the highest array density (5,100 pixels per inch) and the smallest size (4 µm) reported to date. This is enabled by a two-dimensional materials-based layer transfer technique15-18 that allows the growth of RGB LEDs of near-submicron thickness on two-dimensional material-coated substrates via remote or van der Waals epitaxy, mechanical release and stacking of LEDs, followed by top-down fabrication. The smallest-ever stack height of around 9 µm is the key enabler for record high µLED array density. We also demonstrate vertical integration of blue µLEDs with silicon membrane transistors for active matrix operation. These results establish routes to creating full-colour µLED displays for augmented and virtual reality, while also offering a generalizable platform for broader classes of three-dimensional integrated devices.

Fabrication of gold-doped crystalline-silicon nanomembrane-based wearable temperature sensor.

Wearable temperature sensors with high thermal sensitivity are required for precise and continuous body temperature monitoring. Here, we present a protocol for fabricating a thin, stretchable, and ultrahigh thermal-sensitive wearable sensor based on gold-doped crystalline-silicon nanomembrane (SiNM). We provide detailed steps of gold doping technique to SiNM and fabrication processes for gold-doped crystalline-SiNM based wearable temperature sensor. For complete details on the use and execution of this protocol, please refer to Sang et al. (2022).1.

Ultrathin crystalline-silicon-based strain gauges with deep learning algorithms for silent speech interfaces.

A wearable silent speech interface (SSI) is a promising platform that enables verbal communication without vocalization. The most widely studied methodology for SSI focuses on surface electromyography (sEMG). However, sEMG suffers from low scalability because of signal quality-related issues, including signal-to-noise ratio and interelectrode interference. Hence, here, we present a novel SSI by utilizing crystalline-silicon-based strain sensors combined with a 3D convolutional deep learning algorithm. Two perpendicularly placed strain gauges with minimized cell dimension (<0.1 mm2) could effectively capture the biaxial strain information with high reliability. We attached four strain sensors near the subject's mouths and collected strain data of unprecedently large wordsets (100 words), which our SSI can classify at a high accuracy rate (87.53%). Several analysis methods were demonstrated to verify the system's reliability, as well as the performance comparison with another SSI using sEMG electrodes with the same dimension, which exhibited a relatively low accuracy rate (42.60%).

Ultra-Thin Flexible Encapsulating Materials for Soft Bio-Integrated Electronics.

Recently, bioelectronic devices extensively researched and developed through the convergence of flexible biocompatible materials and electronics design that enables  more precise diagnostics and therapeutics in human health care and opens up the potential to expand into various fields, such as clinical medicine and biomedical research. To establish an accurate and stable bidirectional bio-interface, protection against the external environment and high mechanical deformation is essential for wearable bioelectronic devices. In the case of implantable bioelectronics, special encapsulation materials and optimized mechanical designs and configurations that provide electronic stability and functionality are required for accommodating various organ properties, lifespans, and functions in the biofluid environment. Here, this study introduces recent developments of ultra-thin encapsulations with novel materials that can preserve or even improve the electrical performance of wearable and implantable bio-integrated electronics by supporting safety and stability for protection from destruction and contamination as well as optimizing the use of bioelectronic systems in physiological environments. In addition, a summary of the materials, methods, and characteristics of the most widely used encapsulation technologies is introduced, thereby providing a strategic selection of appropriate choices of recently developed flexible bioelectronics.

VR-enabled portable brain-computer interfaces via wireless soft bioelectronics.

Noninvasive, wearable brain-computer interfaces (BCI) find limited use due to their obtrusive nature and low information. Currently available portable BCI systems are limited by device rigidity, bulky form factors, and gel-based skin-contact electrodes - and therefore more prone to noise and motion artifacts. Here, we introduce virtual reality (VR)-enabled split-eye asynchronous stimulus (SEAS) allowing a target to present different stimuli to either eye. This results in unique asynchronous stimulus patterns measurable with as few as four EEG electrodes, as demonstrated with improved wireless soft electronics for portable BCI. This VR-embedded SEAS paradigm demonstrates potential for improved throughput with a greater number of unique stimuli. A wearable soft platform featuring dry needle electrodes and shielded stretchable interconnects enables high throughput decoding of steady-state visually evoked potentials (SSVEP) for a text spelling interface. A combination of skin-conformal electrodes and soft materials offers high-quality recordings of SSVEP with minimal motion artifacts, validated by comparing the performance with a conventional wearable system. A deep-learning algorithm provides real-time classification, with an accuracy of 78.93% for 0.8 s and 91.73% for 2 s with 33 classes from nine human subjects, allowing for a successful demonstration of VR text spelling and navigation of a real-world environment. With as few as only four data recording channels, the system demonstrates a highly competitive information transfer rate (243.6 bit/min). Collectively, the VR-enabled soft system offers unique advantages in wireless, real-time monitoring of brain signals for portable BCI, neurological rehabilitation, and disease diagnosis.

Stretchable Surface Electrode Arrays Using an Alginate/PEDOT:PSS-Based Conductive Hydrogel for Conformal Brain Interfacing.

An electrocorticogram (ECoG) is the electrical activity obtainable from the cerebral cortex and an informative source with considerable potential for future advanced applications in various brain-interfacing technologies. Considerable effort has been devoted to developing biocompatible, conformal, soft, and conductive interfacial materials for bridging devices and brain tissue; however, the implementation of brain-adaptive materials with optimized electrical and mechanical characteristics remains challenging. Herein, we present surface electrode arrays using the soft tough ionic conductive hydrogel (STICH). The newly proposed STICH features brain-adaptive softness with Young's modulus of ~9.46 kPa, which is sufficient to form a conformal interface with the cortex. Additionally, the STICH has high toughness of ~36.85 kJ/mm3, highlighting its robustness for maintaining the solid structure during interfacing with wet brain tissue. The stretchable metal electrodes with a wavy pattern printed on the elastomer were coated with the STICH as an interfacial layer, resulting in an improvement of the impedance from 60 kΩ to 10 kΩ at 1 kHz after coating. Acute in vivo experiments for ECoG monitoring were performed in anesthetized rodents, thereby successfully realizing conformal interfacing to the animal's cortex and the sensitive recording of electrical activity using the STICH-coated electrodes, which exhibited a higher visual-evoked potential (VEP) amplitude than that of the control device.

Ultrahigh Sensitive Au-Doped Silicon Nanomembrane Based Wearable Sensor Arrays for Continuous Skin Temperature Monitoring with High Precision.

Monitoring the body temperature with high accuracy provides a fast, facile, yet powerful route about the human body in a wide range of health information standards. Here, the first ever ultrasensitive and stretchable gold-doped silicon nanomembrane (Au-doped SiNM) epidermal temperature sensor array is introduced. The ultrasensitivity is achieved by shifting freeze-out region to intrinsic region in carrier density and modulation of fermi energy level of p-type SiNM through the development of a novel gold-doping strategy. The Au-doped SiNM is readily transferred onto an ultrathin polymer layer with a well-designed serpentine mesh structure, capable of being utilized as an epidermal temperature sensor array. Measurements in vivo and in vitro show temperature coefficient of resistance as high as -37270.72 ppm °C-1 , 22 times higher than existing metal-based temperature sensors with similar structures, and one of the highest thermal sensitivity among the inorganic material based temperature sensors. Applications in the continuous monitoring of body temperature and respiration rate during exercising are demonstrated with a successful capture of information. This work lays a foundation for monitoring body temperature, potentially useful for precision diagnosis (e.g., continuous monitoring body temperature in coronavirus disease 2019 cases) and management of disease relevance to body temperature in healthcare.

Wireless Soft Scalp Electronics and Virtual Reality System for Motor Imagery-Based Brain-Machine Interfaces.

Motor imagery offers an excellent opportunity as a stimulus-free paradigm for brain-machine interfaces. Conventional electroencephalography (EEG) for motor imagery requires a hair cap with multiple wired electrodes and messy gels, causing motion artifacts. Here, a wireless scalp electronic system with virtual reality for real-time, continuous classification of motor imagery brain signals is introduced. This low-profile, portable system integrates imperceptible microneedle electrodes and soft wireless circuits. Virtual reality addresses subject variance in detectable EEG response to motor imagery by providing clear, consistent visuals and instant biofeedback. The wearable soft system offers advantageous contact surface area and reduced electrode impedance density, resulting in significantly enhanced EEG signals and classification accuracy. The combination with convolutional neural network-machine learning provides a real-time, continuous motor imagery-based brain-machine interface. With four human subjects, the scalp electronic system offers a high classification accuracy (93.22 ± 1.33% for four classes), allowing wireless, real-time control of a virtual reality game.

Emerging Materials and Technologies with Applications in Flexible Neural Implants: A Comprehensive Review of Current Issues with Neural Devices.

Neuroscience is an essential field of investigation that reveals the identity of human beings, with a comprehensive understanding of advanced mental activities, through the study of neurobiological structures and functions. Fully understanding the neurotransmission system that allows for connectivity among neuronal circuits has paved the way for the development of treatments for neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and depression. The field of flexible implants has attracted increasing interest mainly to overcome the mechanical mismatch between rigid electrode materials and soft neural tissues, enabling precise measurements of neural signals from conformal contact. Here, the current issues of flexible neural implants (chronic device failure, non-bioresorbable electronics, low-density electrode arrays, among others are summarized) by presenting material candidates and designs to address each challenge. Furthermore, the latest investigations associated with the aforementioned issues are also introduced, including suggestions for ideal neural implants. In terms of the future direction of these advances, designing flexible devices would provide new opportunities for the study of brain-machine interfaces or brain-computer interfaces as part of locomotion through brain signals, and for the treatment of neurodegenerative diseases.

Ultra-Lightweight, Flexible InGaP/GaAs Tandem Solar Cells with a Dual-Function Encapsulation Layer.

Lightweight, flexible solar cells from III-V semiconductors offer new application opportunities for devices that require a power supply, such as cars, drones, satellites, or wearable devices, due to their outstanding efficiency and power-to-weight ratio (specific power). However, the specific power and stability of flexible photovoltaic (PV) devices need to be enhanced for use in such applications because current flexible PV devices are vulnerable to moisture and heat. Here, we develop ultra-lightweight, flexible InGaP/GaAs tandem solar cells with a dual-function encapsulation layer that serves as both a moisture barrier and an antireflection coating for the active device layer. Using a thin polymer film as a substrate and an ultrathin metal as a bonding layer, the total weight of the device is dramatically reduced. Therefore, the specific power of our solar cells is remarkably high with a value of over 5000 W/kg under the AM 1.5G solar spectrum. Additionally, there is no degradation even if the solar cells are exposed to harsh environmental conditions.

Flexible GaAs photodetector arrays hetero-epitaxially grown on GaP/Si for a low-cost III-V wearable photonics platform.

We demonstrate flexible GaAs photodetector arrays that were hetero-epitaxially grown on a Si wafer for a new cost-effective and reliable wearable optoelectronics platform. A high crystalline quality GaAs layer was transferred onto a flexible foreign substrate and excellent retention of device performance was demonstrated by measuring the optical responsivities and dark currents. Optical simulation proves that the metal stacks used for wafer bonding serve as a back-reflector and enhance GaAs photodetector responsivity via a resonant-cavity effect. Device durability was also tested by bending 1000 times and no performance degradation was observed. This work paves a way for a cost-effective and flexible III-V optoelectronics technology with high durability.

Adaptive self-healing electronic epineurium for chronic bidirectional neural interfaces.

Realizing a clinical-grade electronic medicine for peripheral nerve disorders is challenging owing to the lack of rational material design that mimics the dynamic mechanical nature of peripheral nerves. Electronic medicine should be soft and stretchable, to feasibly allow autonomous mechanical nerve adaptation. Herein, we report a new type of neural interface platform, an adaptive self-healing electronic epineurium (A-SEE), which can form compressive stress-free and strain-insensitive electronics-nerve interfaces and enable facile biofluid-resistant self-locking owing to dynamic stress relaxation and water-proof self-bonding properties of intrinsically stretchable and self-healable insulating/conducting materials, respectively. Specifically, the A-SEE does not need to be sutured or glued when implanted, thereby significantly reducing complexity and the operation time of microneurosurgery. In addition, the autonomous mechanical adaptability of the A-SEE to peripheral nerves can significantly reduce the mechanical mismatch at electronics-nerve interfaces, which minimizes nerve compression-induced immune responses and device failure. Though a small amount of Ag leaked from the A-SEE is observed in vivo (17.03 ppm after 32 weeks of implantation), we successfully achieved a bidirectional neural signal recording and stimulation in a rat sciatic nerve model for 14 weeks. In view of our materials strategy and in vivo feasibility, the mechanically adaptive self-healing neural interface would be considered a new implantable platform for a wide range application of electronic medicine for neurological disorders in the human nervous system.

Development of a neural interface for high-definition, long-term recording in rodents and nonhuman primates.

Long-lasting, high-resolution neural interfaces that are ultrathin and flexible are essential for precise brain mapping and high-performance neuroprosthetic systems. Scaling to sample thousands of sites across large brain regions requires integrating powered electronics to multiplex many electrodes to a few external wires. However, existing multiplexed electrode arrays rely on encapsulation strategies that have limited implant lifetimes. Here, we developed a flexible, multiplexed electrode array, called "Neural Matrix," that provides stable in vivo neural recordings in rodents and nonhuman primates. Neural Matrix lasts over a year and samples a centimeter-scale brain region using over a thousand channels. The long-lasting encapsulation (projected to last at least 6 years), scalable device design, and iterative in vivo optimization described here are essential components to overcoming current hurdles facing next-generation neural technologies.