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Cardiovascular disease is a major public health issue, and smart diagnostic approaches play an important role in the analysis of electrocardiograms. Here, we present three-dimensional, soft electrodes of liquid metals that can be conformably attached to the surfaces of the heart and skin for long-term cardiac analysis. The fine micropillar structures of biocompatible liquid metals enable precise targeting to small tissue areas, allowing for spatiotemporal mapping and modulation of cardiac electrical activity with high resolution. The low mechanical modulus of these liquid-metal electrodes not only helps avoid inflammatory responses triggered by modulus mismatch between the tissue and electrodes, but also minimizes pain when embedded in biological tissues such as the skin and heart. Furthermore, in vivo experiments with animal models and human trials demonstrate long-term and accurate monitoring of electrocardiograms over a period of 30 days.
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Electrodos , Animales , Humanos , Electrocardiografía , Metales/química , Tecnología Inalámbrica , Corazón , RatasRESUMEN
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.
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Potenciales Evocados Somatosensoriales , Percepción del Tacto , Tacto , Transistores Electrónicos , Humanos , Potenciales Evocados Somatosensoriales/fisiología , Masculino , Percepción del Tacto/fisiología , Tacto/fisiología , Femenino , Adulto , Corteza Somatosensorial/fisiología , Presión , Dedos/fisiología , Adulto Joven , Mecanorreceptores/fisiología , Retroalimentación Sensorial/fisiologíaRESUMEN
Auxetic metamaterials are a unique class of materials or structures with a negative Poisson's ratio and a wide array of functionalities. However, their inherent porosity presents challenges in practical applications. Filling the inherent perforations while preserving their unique auxeticity is difficult because it demands the seamless integration of components that have highly distinct mechanical characteristics. Here we introduce a seamless auxetic substrate film capable of achieving a negative Poisson's ratio of -1, the theoretical limit of isotropic materials. This breakthrough is realized by incorporating a highly rigid auxetic structure reinforced by glass-fabric, with surface-flattening soft elastomers. We effectively optimize the mechanical properties of these components by systematic experimental and theoretical investigations into the effects of relative differences in the moduli of the constituents. Using the developed auxetic film we demonstrate an image distortion-free display having 25 PPI resolution of micro-LEDs that is capable of 25% stretching without performance degradation.
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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.
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Microelectrodos , Organoides , Retina , Células Ganglionares de la Retina , Organoides/citología , Animales , Ratones , Humanos , Impresión Tridimensional , Metales/química , Fenómenos ElectrofisiológicosRESUMEN
Various strain isolation strategies that combine rigid and stretchable regions for stretchable electronics were recently proposed, but the vulnerability of inorganic materials to mechanical stress has emerged as a major impediment to their performance. We report a strain-isolation system that combines heteropolymers with different elastic moduli (i.e., hybrid stretchable polymers) and utilize it to construct a rugged island-bridge inorganic electronics system. Two types of prepolymers were simultaneously cross-linked to form an interpenetrating polymer network at the rigid-stretchable interface, resulting in a hybrid stretchable polymer that exhibited efficient strain isolation and mechanical stability. The system, including stretchable micro-LEDs and microheaters, demonstrated consistent operation under external strain, suggesting that the rugged island-bridge inorganic electronics mounted on a locally strain-isolated substrate offer a promising solution for replacing conventional stretchable electronics, enabling devices with a variety of form factors.
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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.
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Lentes de Contacto Hidrofílicos , Diabetes Mellitus , Animales , Humanos , Glucosa/análisis , Glucemia , Lágrimas/química , Diabetes Mellitus/diagnósticoRESUMEN
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.
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Encéfalo , Cabeza , Animales , Ratones , Reproducibilidad de los Resultados , Cráneo , Electrónica , Tecnología InalámbricaRESUMEN
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.
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Células Endoteliales , Células Madre Pluripotentes Inducidas , Humanos , Diferenciación Celular , Miocitos Cardíacos , Ingeniería de Tejidos/métodosRESUMEN
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.
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Glaucoma , Presión Intraocular , Animales , Glaucoma/diagnóstico , Glaucoma/cirugía , Tonometría Ocular , Cámara Anterior/cirugía , RetinaRESUMEN
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.
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Electrónica , Neuronas , Animales , Ratones , Neuronas/fisiología , Encéfalo/fisiología , Cráneo/diagnóstico por imagen , Metales , Impresión TridimensionalRESUMEN
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.
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Microelectrodos , Prótesis Visuales , Prótesis Visuales/química , Animales , Ratones , Células Ganglionares de la Retina/fisiología , Degeneración Retiniana/terapia , Degeneración Retiniana/patología , Retina , Electrodos Implantados , Platino (Metal)/químicaRESUMEN
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.
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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.
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Electrocardiografía , Corazón , Humanos , Electrodos , Monitoreo Fisiológico , Metales , Impedancia EléctricaRESUMEN
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.
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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.
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Células Madre Pluripotentes Inducidas , Organoides , Electrodos , Corazón , Humanos , MetalesRESUMEN
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.
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Arritmias Cardíacas , Corazón , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/terapia , Electrocardiografía , Electrodos , Corazón/diagnóstico por imagen , Humanos , Contracción MiocárdicaRESUMEN
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.
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Técnicas Biosensibles , Lentes de Contacto Hidrofílicos , Animales , Colesterol , Humanos , Conejos , Reproducibilidad de los Resultados , LágrimasRESUMEN
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.
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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.
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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.