In-depth correlation analysis between tear glucose and blood glucose using a wireless smart contact lens.

Tears have emerged as a promising alternative to blood for diagnosing diabetes. Despite increasing attempts to measure tear glucose using smart contact lenses, the controversy surrounding the correlation between tear glucose and blood glucose still limits the clinical usage of tears. Herein, we present an in-depth investigation of the correlation between tear glucose and blood glucose using a wireless and soft smart contact lens for continuous monitoring of tear glucose. This smart contact lens is capable of quantitatively monitoring the tear glucose levels in basal tears excluding the effect of reflex tears which might weaken the relationship with blood glucose. Furthermore, this smart contact lens can provide an unprecedented level of continuous tear glucose data acquisition at sub-minute intervals. These advantages allow the precise estimation of lag time, enabling the establishment of the concept called 'personalized lag time'. This demonstration considers individual differences and is successfully applied to both non-diabetic and diabetic humans, as well as in animal models, resulting in a high correlation.

Power-integrated, wireless neural recording systems on the cranium using a direct printing method for deep-brain analysis.

Conventional power-integrated wireless neural recording devices suffer from bulky, rigid batteries in head-mounted configurations, hindering the precise interpretation of the subject's natural behaviors. These power sources also pose risks of material leakage and overheating. We present the direct printing of a power-integrated wireless neural recording system that seamlessly conforms to the cranium. A quasi-solid-state Zn-ion microbattery was 3D-printed as a built-in power source geometrically synchronized to the shape of a mouse skull. Soft deep-brain neural probes, interconnections, and auxiliary electronics were also printed using liquid metals on the cranium with high resolutions. In vivo studies using mice demonstrated the reliability and biocompatibility of this wireless neural recording system, enabling the monitoring of neural activities across extensive brain regions without notable heat generation. This all-printed neural interface system revolutionizes brain research, providing bio-conformable, customizable configurations for improved data quality and naturalistic experimentation.

Versatile human cardiac tissues engineered with perfusable heart extracellular microenvironment for biomedical applications.

Engineered human cardiac tissues have been utilized for various biomedical applications, including drug testing, disease modeling, and regenerative medicine. However, the applications of cardiac tissues derived from human pluripotent stem cells are often limited due to their immaturity and lack of functionality. Therefore, in this study, we establish a perfusable culture system based on in vivo-like heart microenvironments to improve human cardiac tissue fabrication. The integrated culture platform of a microfluidic chip and a three-dimensional heart extracellular matrix enhances human cardiac tissue development and their structural and functional maturation. These tissues are comprised of cardiovascular lineage cells, including cardiomyocytes and cardiac fibroblasts derived from human induced pluripotent stem cells, as well as vascular endothelial cells. The resultant macroscale human cardiac tissues exhibit improved efficacy in drug testing (small molecules with various levels of arrhythmia risk), disease modeling (Long QT Syndrome and cardiac fibrosis), and regenerative therapy (myocardial infarction treatment). Therefore, our culture system can serve as a highly effective tissue-engineering platform to provide human cardiac tissues for versatile biomedical applications.

In-vivo integration of soft neural probes through high-resolution printing of liquid electronics on the cranium.

Current soft neural probes are still operated by bulky, rigid electronics mounted to a body, which deteriorate the integrity of the device to biological systems and restrict the free behavior of a subject. We report a soft, conformable neural interface system that can monitor the single-unit activities of neurons with long-term stability. The system implements soft neural probes in the brain, and their subsidiary electronics which are directly printed on the cranial surface. The high-resolution printing of liquid metals forms soft neural probes with a cellular-scale diameter and adaptable lengths. Also, the printing of liquid metal-based circuits and interconnections along the curvature of the cranium enables the conformal integration of electronics to the body, and the cranial circuit delivers neural signals to a smartphone wirelessly. In the in-vivo studies using mice, the system demonstrates long-term recording (33 weeks) of neural activities in arbitrary brain regions. In T-maze behavioral tests, the system shows the behavior-induced activation of neurons in multiple brain regions.

Real-time in vivo monitoring of intraocular pressure distribution in the anterior chamber and vitreous chamber for diagnosis of glaucoma.

Glaucoma causes irreversible vision loss due to optic nerve damage and retinal cell degeneration. Since high intraocular pressure (IOP) is a major risk factor for glaucoma development, accurate IOP measurement is crucial, especially intravitreal IOP affecting the optical nerve and cells. However, conventional methods have limits in selectively and directly detecting local retina pressure. Here, we present continuous measurements of local IOP values in the anterior chamber and vitreous chamber of living animals using minimally invasive probes with pressure-sensitive transistors. After inducing glaucoma in animal models, we compared the local IOP distribution between normal and glaucomatous eyes. We also compared IOP values detected in the cornea using tonometry measurements. Our findings revealed that glaucoma induced higher IOP in the vitreous chamber than in the anterior chamber, indicating that measuring IOP in the vitreous chamber is key to the glaucoma model. This progress offers future directions for diagnosis and treatment of glaucoma.

Liquid-metal-based three-dimensional microelectrode arrays integrated with implantable ultrathin retinal prosthesis for vision restoration.

Electronic retinal prostheses for stimulating retinal neurons are promising for vision restoration. However, the rigid electrodes of conventional retinal implants can inflict damage on the soft retina tissue. They also have limited selectivity due to their poor proximity to target cells in the degenerative retina. Here we present a soft artificial retina (thickness, 10 µm) where flexible ultrathin photosensitive transistors are integrated with three-dimensional stimulation electrodes of eutectic gallium-indium alloy. Platinum nanoclusters locally coated only on the tip of these three-dimensional liquid-metal electrodes show advantages in reducing the impedance of the stimulation electrodes. These microelectrodes can enhance the proximity to the target retinal ganglion cells and provide effective charge injections (72.84 mC cm-2) to elicit neural responses in the retina. Their low Young's modulus (234 kPa), owing to their liquid form, can minimize damage to the retina. Furthermore, we used an unsupervised machine learning approach to effectively identify the evoked spikes to grade neural activities within the retinal ganglion cells. Results from in vivo experiments on a retinal degeneration mouse model reveal that the spatiotemporal distribution of neural responses on their retina can be mapped under selective localized illumination areas of light, suggesting the restoration of their vision.

Smart Contact Lenses as Wearable Ophthalmic Devices for Disease Monitoring and Health Management.

The eye contains a complex network of physiological information and biomarkers for monitoring disease and managing health, and ocular devices can be used to effectively perform point-of-care diagnosis and disease management. This comprehensive review describes the target biomarkers and various diseases, including ophthalmic diseases, metabolic diseases, and neurological diseases, based on the physiological and anatomical background of the eye. This review also includes the recent technologies utilized in eye-wearable medical devices and the latest trends in wearable ophthalmic devices, specifically smart contact lenses for the purpose of disease management. After introducing other ocular devices such as the retinal prosthesis, we further discuss the current challenges and potential possibilities of smart contact lenses.

Magnetic Manipulation of Locomotive Liquid Electrodes for Wireless Active Cardiac Monitoring.

For electrocardiogram (ECG) detection, the position of conventional patch-type electrodes based on solid-state metals are difficult to manipulate after attachment and also can lead to poor interface with stretchable, rough skin surfaces. Herein, we present a liquid form of ECG electrodes that can be magnetically reconfigured on human skin by providing its conformal interfacing. These electrodes consist of biocompatible liquid-metal droplets where magnetic particles are homogeneously dispersed, and their conformal contact with skin can yield significantly low impedance as well as high signal-to-noise ratio of ECG peaks. These electrodes are also capable of complex motions such as linear movements, splitting, and merging under external magnetic fields. Furthermore, magnetic manipulation of each electrode position on human skin enables precise monitoring of ECG signals with the change in ECG vectors. The integration of liquid-state electrodes with electronic circuitry demonstrates wireless and continuous ECG monitoring while magnetically moving this entire system on human skin.

Gate-Tunable Electrostatic Friction of Grain Boundary in Chemical-Vapor-Deposited MoS2.

Two-dimensional (2D) semiconducting materials, such as MoS2, are widely studied owing to their great potential in advanced electronic devices. However, MoS2 films grown using chemical vapor deposition (CVD) exhibit lower-than-expected properties owing to numerous defects. Among them, grain boundary (GB) is a critical parameter that determines electrical and mechanical properties of MoS2. Herein, we report the gate-tunable electrostatic friction of GBs in CVD-grown MoS2. Using atomic force microscopy (AFM), we found that electrostatic friction of MoS2 is generated by the Coulomb interaction between tip and carriers of MoS2, which is associated with the local band structure of GBs. Therefore, electrostatic friction is enhanced by localized charge carrier distribution at GB, which is linearly related to the loading force of the tip. Our study shows a strong correlation between electrostatic friction and localized band structure in MoS2 GB, providing a novel method for identifying and characterizing GBs of polycrystalline 2D materials.

Multimodal Characterization of Cardiac Organoids Using Integrations of Pressure-Sensitive Transistor Arrays with Three-Dimensional Liquid Metal Electrodes.

Herein, we present an unconventional method for multimodal characterization of three-dimensional cardiac organoids. This method can monitor and control the mechanophysiological parameters of organoids within a single device. In this method, local pressure distributions of human-induced pluripotent stem-cell-derived cardiac organoids are visualized spatiotemporally by an active-matrix array of pressure-sensitive transistors. This array is integrated with three-dimensional electrodes formed by the high-resolution printing of liquid metal. These liquid-metal electrodes are inserted inside an organoid to form the intraorganoid interface for simultaneous electrophysiological recording and stimulation. The low mechanical modulus and low impedance of the liquid-metal electrodes are compatible with organoids' soft biological tissue, which enables stable electric pacing at low thresholds. In contrast to conventional electrophysiological methods, this measurement of a cardiac organoid's beating pressures enabled simultaneous treatment of electrical therapeutics using a single device without any interference between the pressure signals and electrical pulses from pacing electrodes, even in wet organoid conditions.

In situ diagnosis and simultaneous treatment of cardiac diseases using a single-device platform.

The in situ diagnosis of cardiac activities with simultaneous therapeutic electrical stimulation of the heart is key to preventing cardiac arrhythmia. Here, we present an unconventional single-device platform that enables in situ monitoring even in a wet condition and control of beating heart motions without interferences to the recording signal. This platform consists of the active-matrix array of pressure-sensitive transistors for detecting cardiac beatings, biocompatible, low-impedance electrodes for cardiac stimulations, and an alginate-based hydrogel adhesive for attaching this platform conformally to the epicardium. In contrast to conventional electrophysiological sensing using electrodes, the pressure-sensitive transistors measured mechanophysiological characteristics by monitoring the spatiotemporal distributions of cardiac pressures during heart beating motions. In vivo tests show mechanophysiological readings having good correlation with electrocardiography and negligible interference with the electrical artifacts caused during cardiac stimulations. This platform can therapeutically synchronize the rhythm of abnormal heartbeats through efficient pacing of cardiac arrhythmia.

Wireless Non-Invasive Monitoring of Cholesterol Using a Smart Contact Lens.

Herein, a wireless and soft smart contact lens that enables real-time quantitative recording of cholesterol in tear fluids for the monitoring of patients with hyperlipidemia using a smartphone is reported. This contact lens incorporates an electrochemical biosensor for the continuous detection of cholesterol concentrations, stretchable antenna, and integrated circuits for wireless communication, which makes a smartphone the only device required to operate this lens remotely without obstructing the wearer's vision. The hyperlipidemia rabbit model is utilized to confirm the correlation between cholesterol levels in tear fluid and blood and to confirm the feasibility of this smart contact lens for diagnostic application of cholesterol-related diseases. Further in vivo tests with human subjects demonstrated its good biocompatibility, wearability, and reliability as a non-invasive healthcare device.

High-Resolution 3D Printing for Electronics.

The ability to form arbitrary 3D structures provides the next level of complexity and a greater degree of freedom in the design of electronic devices. Since recent progress in electronics has expanded their applicability in various fields in which structural conformability and dynamic configuration are required, high-resolution 3D printing technologies can offer significant potential for freeform electronics. Here, the recent progress in novel 3D printing methods for freeform electronics is reviewed, with providing a comprehensive study on 3D-printable functional materials and processes for various device components. The latest advances in 3D-printed electronics are also reviewed to explain representative device components, including interconnects, batteries, antennas, and sensors. Furthermore, the key challenges and prospects for next-generation printed electronics are considered, and the future directions are explored based on research that has emerged recently.

3D Heterogeneous Device Arrays for Multiplexed Sensing Platforms Using Transfer of Perovskites.

Despite recent substantial advances in perovskite materials, their 3D integration capability for next-generation electronic devices is limited owing to their inherent vulnerability to heat and moisture with degradation of their remarkable optoelectronic properties during fabrication processing. Herein, a facile method to transfer the patterns of perovskites to planar or nonplanar surfaces using a removable polymer is reported. After fabricating perovskite devices on this removable polymer film, the conformal attachment of this film on target surfaces can place the entire devices on various substrates by removing this sacrificial film. This transfer method enables the formation of a perovskite image sensor array on a soft contact lens, and in vivo tests using rabbits demonstrate its wearability. Furthermore, 3D heterogeneous integration of a perovskite photodetector array with an active-matrix array of pressure-sensitive silicon transistors using this transfer method demonstrates the formation of a multiplexed sensing platform detecting distributions of light and tactile pressure simultaneously.

Multimodal Digital X-ray Scanners with Synchronous Mapping of Tactile Pressure Distributions using Perovskites.

Visual and tactile information are the key intuitive perceptions in sensory systems, and the synchronized detection of these two sensory modalities can enhance accuracy of object recognition by providing complementary information between them. Herein, multimodal integration of flexible, high-resolution X-ray detectors with a synchronous mapping of tactile pressure distributions for visualizing internal structures and morphologies of an object simultaneously is reported. As a visual-inspection method, perovskite materials that convert X-rays into charge carriers directly are synthesized. By incorporating pressure-sensitive air-dielectric transistors in the perovskite components, X-ray detectors with dual modalities (i.e., vision and touch) are attained as an active-matrix platform for digital visuotactile examinations. Also, in vivo X-ray imaging and pressure sensing are demonstrated using a live rat. This multiplexed platform has high spatial resolution and good flexibility, thereby providing highly accurate inspection and diagnoses even for the distorted images of nonplanar objects.

A soft and transparent contact lens for the wireless quantitative monitoring of intraocular pressure.

Continuous detection of raised intraocular pressure (IOP) could benefit the monitoring of patients with glaucoma. Current contact lenses with embedded sensors for measuring IOP are rigid, bulky, partially block vision or are insufficiently sensitive. Here, we report the design and testing in volunteers of a soft and transparent contact lens for the quantitative monitoring of IOP in real time using a smartphone. The contact lens incorporates a strain sensor, a wireless antenna, capacitors, resistors, stretchable metal interconnects and an integrated circuit for wireless communication. In rabbits, the lens provided measurements that match those of a commercial tonometer. In ten human participants, the lens proved to be safe, and reliably provided accurate quantitative measurements of IOP without inducing inflammation.

3D Electrodes for Bioelectronics.

In recent studies related to bioelectronics, significant efforts have been made to form 3D electrodes to increase the effective surface area or to optimize the transfer of signals at tissue-electrode interfaces. Although bioelectronic devices with 2D and flat electrode structures have been used extensively for monitoring biological signals, these 2D planar electrodes have made it difficult to form biocompatible and uniform interfaces with nonplanar and soft biological systems (at the cellular or tissue levels). Especially, recent biomedical applications have been expanding rapidly toward 3D organoids and the deep tissues of living animals, and 3D bioelectrodes are getting significant attention because they can reach the deep regions of various 3D tissues. An overview of recent studies on 3D bioelectronic devices, such as the use of electrical stimulations and the recording of neural signals from biological subjects, is presented. Subsequently, the recent developments in materials and fabrication processing to 3D micro- and nanostructures are introduced, followed by broad applications of these 3D bioelectronic devices at various in vitro and in vivo conditions.

Smart contact lens and transparent heat patch for remote monitoring and therapy of chronic ocular surface inflammation using mobiles.

Wearable electronic devices that can monitor physiological signals of the human body to provide biomedical information have been drawing extensive interests for sustainable personal health management. Here, we report a human pilot trial of a soft, smart contact lens and a skin-attachable therapeutic device for wireless monitoring and therapy of chronic ocular surface inflammation (OSI). As a diagnostic device, this smart contact lens enables real-time measurement of the concentration of matrix metalloproteinase-9, a biomarker for OSI, in tears using a graphene field-effect transistor. As a therapeutic device, we also fabricated a stretchable and transparent heat patch attachable on the human eyelid conformably. Both diagnostic and therapeutic devices can be incorporated using a smartphone for their wireless communications, thereby achieving instantaneous diagnosis of OSI and automated hyperthermia treatments. Furthermore, in vivo tests using live animals and human subjects confirm their good biocompatibility and reliability as a noninvasive, mobile health care solution.

Liquid Metal-Based Soft Electronics for Wearable Healthcare.

Wearable healthcare devices have garnered substantial interest for the realization of personal health management by monitoring the physiological parameters of individuals. Attaining the integrity between the devices and the biological interfaces is one of the greatest challenges to achieving high-quality body information in dynamic conditions. Liquid metals, which exist in the liquid phase at room temperatures, are advanced intensively as conductors for deformable devices because of their excellent stretchability and self-healing ability. The unique surface chemistry of liquid metals allows the development of various sensors and devices in wearable form. Also, the biocompatibility of liquid metals, which is verified through numerous biomedical applications, holds immense potential in uses on the surface and inside of a living body. Here, the recent progress of liquid metal-based wearable electronic devices for healthcare with respect to the featured properties and the processing technologies is discussed. Representative examples of applications such as biosensors, neural interfaces, and a soft interconnection for devices are reviewed. The current challenges and prospects for further development are also discussed, and the future directions of advances in the latest research are explored.

Recent progress on wearable point-of-care devices for ocular systems.

The eye is a complex sensory organ that contains abundant information for specific diseases and pathological responses. It has emerged as a facile biological interface for wearable healthcare platforms because of its excellent accessibility. Recent advances in electronic devices have led to the extensive research of point-of-care (POC) systems for diagnosing and monitoring diseases by detecting the biomarkers within the eye. Among these systems, contact lenses, which make direct contact with the ocular surfaces, have been utilized as one of the promising candidates for non-invasive POC testing of various diseases. The continuous and long-term measurement from the sensor allows the patients to manage their symptoms in an effective and convenient way. Herein, we review the progress of contact lens sensors in terms of the materials, methodologies, device designs, and target biomarkers. The anatomical structure and biological mechanisms of the eye are also discussed to provide a comprehensive understanding of the principles of contact lens sensors. Intraocular pressure and glucose, which are the representative biomarkers found in the eyes, can be measured with the biosensors integrated with contact lenses for the diagnosis of glaucoma and diabetes. Furthermore, contact lens sensors for various general pathologies as well as other ocular diseases are also considered, thereby providing the prospects for further developments of smart contact lenses as a future POC system.