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.

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.

Motion Detection Using Tactile Sensors Based on Pressure-Sensitive Transistor Arrays.

In recent years, to develop more spontaneous and instant interfaces between a system and users, technology has evolved toward designing efficient and simple gesture recognition (GR) techniques. As a tool for acquiring human motion, a tactile sensor system, which converts the human touch signal into a single datum and executes a command by translating a bundle of data into a text language or triggering a preset sequence as a haptic motion, has been developed. The tactile sensor aims to collect comprehensive data on various motions, from the touch of a fingertip to large body movements. The sensor devices have different characteristics that are important for target applications. Furthermore, devices can be fabricated using various principles, and include piezoelectric, capacitive, piezoresistive, and field-effect transistor types, depending on the parameters to be achieved. Here, we introduce tactile sensors consisting of field-effect transistors (FETs). GR requires a process involving the acquisition of a large amount of data in an array rather than a single sensor, suggesting the importance of fabricating a tactile sensor as an array. In this case, an FET-type pressure sensor can exploit the advantages of active-matrix sensor arrays that allow high-array uniformity, high spatial contrast, and facile integration with electrical circuitry. We envision that tactile sensors based on FETs will be beneficial for GR as well as future applications, and these sensors will provide substantial opportunities for next-generation motion sensing systems.

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.

Electrophysiological Analysis of Retinal Organoid Development Using 3D Microelectrodes of Liquid Metals.

Despite of the substantial potential of human-derived retinal organoids, the degeneration of retinal ganglion cells (RGCs) during maturation limits their utility in assessing the functionality of later-born retinal cell subtypes. Additionally, conventional analyses primarily rely on fluorescent emissions, which limits the detection of actual cell functionality while risking damage to the 3D cytoarchitecture of organoids. Here, an electrophysiological analysis is presented to monitor RGC development in early to mid-stage retinal organoids, and compare distinct features with fully-mature mouse retina. This approach utilizes high-resolution 3D printing of liquid-metal microelectrodes, enabling precise targeting of specific inner retinal layers within organoids. The adaptable distribution and softness of these microelectrodes facilitate the spatiotemporal recording of inner retinal signals. This study not only demonstrates the functional properties of RGCs in retinal organoid development but also provides insights into their synaptic connectivity, reminiscent of fetal native retinas. Further comparison with fully-mature mouse retina in vivo verifies the organoid features, highlighting the potential of early-stage retinal organoids in biomedical research.

Interference haptic stimulation and consistent quantitative tactility in transparent electrotactile screen with pressure-sensitive transistors.

Integrating tactile feedback through haptic interfaces enhances experiences in virtual and augmented reality. However, electrotactile systems, which stimulate mechanoreceptors directly, often yield inconsistent tactile results due to variations in pressure between the device and the finger. In this study, we present the integration of a transparent electrotactile screen with pressure-sensitive transistors, ensuring highly consistent quantitative haptic sensations. These transistors effectively calibrate tactile variations caused by touch pressure. Additionally, we explore remote-distance tactile stimulations achieved through the interference of electromagnetic waves. We validated tactile perception using somatosensory evoked potentials, monitoring the somatosensory cortex response. Our haptic screen can stimulate diverse electrotactile sensations and demonstrate various tactile patterns, including Morse code and Braille, when integrated with portable smart devices, delivering a more immersive experience. Furthermore, interference of electric fields allows haptic stimulation to facilitate diverse stimulus positioning at lower current densities, extending the reach beyond direct contact with electrodes of our screen.

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.

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.

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.

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.

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.