Conductive Polymer-Based Hydrogels for Wearable Electrochemical Biosensors.

Hydrogels are gaining popularity for use in wearable electronics owing to their inherent biomimetic characteristics, flexible physicochemical properties, and excellent biocompatibility. Among various hydrogels, conductive polymer-based hydrogels (CP HGs) have emerged as excellent candidates for future wearable sensor designs. These hydrogels can attain desired properties through various tuning strategies extending from molecular design to microstructural configuration. However, significant challenges remain, such as the limited strain-sensing range, significant hysteresis of sensing signals, dehydration-induced functional failure, and surface/interfacial malfunction during manufacturing/processing. This review summarizes the recent developments in polymer-hydrogel-based wearable electrochemical biosensors over the past five years. Initially serving as carriers for biomolecules, polymer-hydrogel-based sensors have advanced to encompass a wider range of applications, including the development of non-enzymatic sensors facilitated by the integration of nanomaterials such as metals, metal oxides, and carbon-based materials. Beyond the numerous existing reports that primarily focus on biomolecule detection, we extend the scope to include the fabrication of nanocomposite conductive polymer hydrogels and explore their varied conductivity mechanisms in electrochemical sensing applications. This comprehensive evaluation is instrumental in determining the readiness of these polymer hydrogels for point-of-care translation and state-of-the-art applications in wearable electrochemical sensing technology.

Iridium oxide-based non-enzymatic glucose sensor: Superior electro-catalytic performance in biological environmental media.

Nanostructured inorganic materials have potential advantages as glucose-sensing elements in diabetes care, thereby circumventing the need for expensive enzymatic agents. However, many nonenzymatic sensors face challenges related to selectivity and reliability, reducing their efficacy in body fluids. In this study, we introduce an Iridium oxide (IrO2)-based non-enzymatic glucose sensor. This sensor demonstrates exceptional electro-catalytic properties in human serum, characterized by high sensitivity (638 µA µM-1cm2) and a consistent recovery rate (∼104%) across 15 cycles in saline. Furthermore, its impressive performance in human serum, as evidenced by a low relative standard deviation (RSD <1.57%), underscores its applicability in biological matrices such as interstitial fluids. Overall, the IrO2 sensor is a promising, highly reversible, economical, and simple method for detecting glucose in continuous monitoring systems.

Large-scale smart bioreactor with fully integrated wireless multivariate sensors and electronics for long-term in situ monitoring of stem cell culture.

Achieving large-scale, cost-effective, and reproducible manufacturing of stem cells with the existing devices is challenging. Traditional single-use cell-bag bioreactors, limited by their rigid and single-point sensors, struggle with accuracy and scalability for high-quality cell manufacturing. Here, we introduce a smart bioreactor system that enables multi-spatial sensing for real-time, wireless culture monitoring. This scalable system includes a low-profile, label-free thin-film sensor array and electronics integrated with a flexible cell bag, allowing for simultaneous assessment of culture properties such as pH, dissolved oxygen, glucose, and temperature, to receive real-time feedback for up to 30 days. The experimental results show the accurate monitoring of time-dynamic and spatial variations of stem cells and myoblast cells with adjustable carriers from a plastic dish to a 2-liter cell bag. These advances open up the broad applicability of the smart sensing system for large-scale, lower-cost, reproducible, and high-quality engineered cell manufacturing for broad clinical use.

Fully Screen-Printed PI/PEG Blends Enabled Patternable Electrodes for Scalable Manufacturing of Skin-Conformal, Stretchable, Wearable Electronics.

Recent advances in soft materials and nano-microfabrication have enabled the development of flexible wearable electronics. At the same time, printing technologies have been demonstrated to be efficient and compatible with polymeric materials for manufacturing wearable electronics. However, wearable device manufacturing still counts on a costly, complex, multistep, and error-prone cleanroom process. Here, we present fully screen-printable, skin-conformal electrodes for low-cost and scalable manufacturing of wearable electronics. The screen printing of the polyimide (PI) layer enables facile, low-cost, scalable, high-throughput manufacturing. PI mixed with poly(ethylene glycol) exhibits a shear-thinning behavior, significantly improving the printability of PI. The premixed Ag/AgCl ink is then used for conductive layer printing. The serpentine pattern of the screen-printed electrode accommodates natural deformation under stretching (30%) and bending conditions (180°), which are verified by computational and experimental studies. Real-time wireless electrocardiogram monitoring is also successfully demonstrated using the printed electrodes with a flexible printed circuit. The algorithm developed in this study can calculate accurate heart rates, respiratory rates, and heart rate variability metrics for arrhythmia detection.

Tuning the sensing responses towards room-temperature hypersensitive methanol gas sensor using exfoliated graphene-enhanced ZnO quantum dot nanostructures.

A suitable and non-invasive methanol sensor workable in ambient temperature conditions with a high response has gained wide interest to prevent detrimental consequences for industrial workers from its low-level intoxication. In this work, we present a tunable and highly responsive ppb-level methanol gas sensor device working at room temperature via a bottom-up synthetic approach using exfoliated graphene sheet (EGs) and ZnO quantum dots (QDs) on an aluminum anodic oxide (AAO) template. It is verified that EGs-supported AAO with a vertical electrode configuration enabled high and fast-responsive methanol sensing. Moreover, the hydroxyl and carboxyl groups of the high surface area EGs and ZnO QDs with a 3.37 eV bandgap efficiently absorbing UV light led to 56 times high response due to the enhanced polarization on the sensor surface compared to non-UV-radiated EGs/AAO at 800 ppb of methanol. The optimal resonance frequency of methanol is determined to be 100 kHz, which could detect methanol with high response of 2.65% at 100 ppm. The limit of detection (LOD) concentration is obtained at 2 ppb level. This study demonstrates the potential of UV-assisted ZnO, EGs, and AAO-based capacitance sensor material for rapidly detecting hazardous gaseous light organic molecules at ambient conditions, and the overall approach can be easily expanded to a novel non-invasive monitoring strategy for light and hazardous volatile organic exposures.

Fully implantable wireless batteryless vascular electronics with printed soft sensors for multiplex sensing of hemodynamics.

The continuous monitoring of hemodynamics attainable with wireless implantable devices would improve the treatment of vascular diseases. However, demanding requirements of size, wireless operation, and compatibility with endovascular procedures have limited the development of vascular electronics. Here, we report an implantable, wireless vascular electronic system, consisting of a multimaterial inductive stent and printed soft sensors capable of real-time monitoring of arterial pressure, pulse rate, and flow without batteries or circuits. Developments in stent design achieve an enhanced wireless platform while matching conventional stent mechanics. The fully printed pressure sensors demonstrate fast response times, high durability, and sensing at small bending radii. The device is monitored via inductive coupling at communication distances notably larger than prior vascular sensors. The wireless electronic system is validated in artery models, while minimally invasive catheter implantation is demonstrated in an in vivo rabbit study. Overall, the vascular system offers an adaptable framework for comprehensive monitoring of hemodynamics.

Smart bioelectronic pacifier for real-time continuous monitoring of salivary electrolytes.

Monitoring electrolytes is critical for newborns and babies in the intensive care unit. However, the gold standard methods use a blood draw, which is painful and only offers discrete measures. Although salivary-based detection offers promise as an alternative, existing devices are ineffective for real-time, continuous monitoring of electrolytes due to their rigidity, bulky form factors, and lack of salivary accumulation. Here, we introduce a smart, wireless, bioelectronic pacifier for salivary electrolyte monitoring of neonates, which can detect real-time continuous sodium and potassium levels without a blood draw. The miniature system facilitates the seamless integration of the ultralight and low-profile device with a commercial pacifier without additional fixtures or structural modifications. The portable device includes ion-selective sensors, flexible circuits, and microfluidic channels, allowing simplified measurement protocols in non-invasive electrolyte monitoring. The flexible microfluidic channel enables continuous and efficient saliva collection from a mouth. By modifying the surface properties of the channels and the structure of the capillary reservoir, we achieve reliable pumping of the viscous medium for quick calibration and measurement. Embedded sensors in the system show good stability and sensitivity: 52 and 57 mV/decade for the sodium and potassium sensor, respectively. In vivo study with neonates in the intensive care unit captures the device's feasibility and performance in the natural saliva-based detection of the critical electrolytes without induced stimulation.

Fully implantable batteryless soft platforms with printed nanomaterial-based arterial stiffness sensors for wireless continuous monitoring of restenosis in real time.

Atherosclerosis is a common cause of coronary artery disease and a significant factor in broader cardiovascular diseases, the leading cause of death. While implantation of a stent is a prevalent treatment of coronary artery disease, a frequent complication is restenosis, where the stented artery narrows and stiffens. Although early detection of restenosis can be achieved by continuous monitoring, no available device offers such capability without surgeries. Here, we report a fully implantable soft electronic system without batteries and circuits, which still enables continuous wireless monitoring of restenosis in real-time with a set of nanomembrane strain sensors in an electronic stent. The low-profile system requires minimal invasive implantation to deploy the sensors into a blood vessel through catheterization. The entirely printed, nanomaterial-based set of soft membrane strain sensors utilizes a sliding mechanism to offer enhanced sensitivity and detection of low strain while unobtrusively integrating with an inductive stent for passive wireless sensing. The performance of the soft sensor platform is demonstrated by wireless monitoring of restenosis in an artery model and an ex-vivo study in a coronary artery of ovine hearts. The capacitive sensor-based artery implantation system offers unique advantages in wireless, real-time monitoring of stent treatments and arterial health for cardiovascular disease.

Recent Advances in Printing Technologies of Nanomaterials for Implantable Wireless Systems in Health Monitoring and Diagnosis.

The development of wireless implantable sensors and integrated systems, enabled by advances in flexible and stretchable electronics technologies, is emerging to advance human health monitoring, diagnosis, and treatment. Progress in material and fabrication strategies allows for implantable electronics for unobtrusive monitoring via seamlessly interfacing with tissues and wirelessly communicating. Combining new nanomaterials and customizable printing processes offers unique possibilities for high-performance implantable electronics. Here, this report summarizes the recent progress and advances in nanomaterials and printing technologies to develop wireless implantable sensors and electronics. Advances in materials and printing processes are reviewed with a focus on challenges in implantable applications. Demonstrations of wireless implantable electronics and advantages based on these technologies are discussed. Lastly, existing challenges and future directions of nanomaterials and printing are described.

Segregation-controlled self-assembly of silver nanowire networks using a template-free solution-based process.

Metal conductive patterning has been studied as an alternative to the most commonly used indium tin oxide electrodes. Printed electrodes are fabricated by several complicated processes including etching, photolithography, and laser- and template-based techniques. However, these patterning methods have increasingly encountered critical issues of long manufacturing times and high equipment costs that necessitate vacuum and high-temperature conditions. In this study, we present a template-free solution-based patterning method for the fabrication of transparent electronics by inducing segregation-based networks of silver nanowires (SGAgNWs); this is a potential method to fabricate cost effective and scalable optoelectronics. Micro-dimensional fine-patterned segregated networks with conductive cells are created by the self-assembly of one-dimensional nanomaterials under optimal ink conditions wherein different types of solvents and aspect ratios of silver nanowires (AgNWs) are formulated. Photoelectric properties can be controlled by adjusting the size of the cell, which is an empty domain surrounded by the AgNW assembly with microscale cell-to-cell distance dimensions ranging between 4 to 345 µm. The as-obtained AgNW metal grid-formulated on a polyethylene terephthalate film-was identified as a high-performance transparent electrode (TE) device with excellent optoelectronic properties of 87.08% transmittance and 50 Ω â–¡-1 resistance. In addition, the electrical conductivity of the TE film is enhanced with a very low haze of less than 4% because of the intense pulsed light treatment that diminished the sheet resistance to 21.36 Ω â–¡-1, which is attributed to the creation of welded silver networks. The SGAgNW concept for TE technology demonstrates a very promising potential for use in next-generation flexible electronic devices.

Development of Flexible Ion-Selective Electrodes for Saliva Sodium Detection.

Saliva can be used for health monitoring with non-invasive wearable systems. Such devices, including electrochemical sensors, may provide a safe, fast, and cost-efficient way of detecting target ions. Although salivary ions are known to reflect those in blood, no available clinical device can detect essential ions directly from saliva. Here, we introduce an all-solid-state, flexible film sensor that allows highly accurate detection of sodium levels in saliva, comparable to those in blood. The wireless film sensor system can successfully measure sodium ions from a small volume of infants' saliva (<400 µL), demonstrating its potential as a continuous health monitor. This study includes the structural characterization and error analysis of a carbon/elastomer-based ion-selective electrode and a reference electrode to confirm the signal reliability. The sensor, composed of a pair of the electrodes, shows good sensitivity (58.9 mV/decade) and selectivity (log K = -2.68 for potassium), along with a broad detection range of 5 × 10-5 ≈ 1 M with a low detection limit of 4.27 × 10-5 M. The simultaneous comparison between the film sensor and a commercial electrochemical sensor demonstrates the accuracy of the flexible sensor and a positive correlation in saliva-to-blood sodium levels. Collectively, the presented study shows the potential of the wireless ion-selective sensor system for a non-invasive, early disease diagnosis with saliva.

Breathable, large-area epidermal electronic systems for recording electromyographic activity during operant conditioning of H-reflex.

Operant conditioning of Hoffmann's reflex (H-reflex) is a non-invasive and targeted therapeutic intervention for patients with movement disorders following spinal cord injury. The reflex-conditioning protocol uses electromyography (EMG) to measure reflexes from specific muscles elicited using transcutaneous electrical stimulation. Despite recent advances in wearable electronics, existing EMG systems that measure muscle activity for operant conditioning of spinal reflexes still use rigid metal electrodes with conductive gels and aggressive adhesives, while requiring precise positioning to ensure reliability of data across experimental sessions. Here, we present the first large-area epidermal electronic system (L-EES) and demonstrate its use in every step of the reflex-conditioning protocol. The L-EES is a stretchable and breathable composite of nanomembrane electrodes (16 electrodes in a four by four array), elastomer, and fabric. The nanomembrane electrode array enables EMG recording from a large surface area on the skin and the breathable elastomer with fabric is biocompatible and comfortable for patients. We show that L-EES can record direct muscle responses (M-waves) and H-reflexes, both of which are comparable to those recorded using conventional EMG recording systems. In addition, L-EES may improve the reflex-conditioning protocol; it has potential to automatically optimize EMG electrode positioning, which may reduce setup time and error across experimental sessions.

All-printed nanomembrane wireless bioelectronics using a biocompatible solderable graphene for multimodal human-machine interfaces.

Recent advances in nanomaterials and nano-microfabrication have enabled the development of flexible wearable electronics. However, existing manufacturing methods still rely on a multi-step, error-prone complex process that requires a costly cleanroom facility. Here, we report a new class of additive nanomanufacturing of functional materials that enables a wireless, multilayered, seamlessly interconnected, and flexible hybrid electronic system. All-printed electronics, incorporating machine learning, offers multi-class and versatile human-machine interfaces. One of the key technological advancements is the use of a functionalized conductive graphene with enhanced biocompatibility, anti-oxidation, and solderability, which allows a wireless flexible circuit. The high-aspect ratio graphene offers gel-free, high-fidelity recording of muscle activities. The performance of the printed electronics is demonstrated by using real-time control of external systems via electromyograms. Anatomical study with deep learning-embedded electrophysiology mapping allows for an optimal selection of three channels to capture all finger motions with an accuracy of about 99% for seven classes.

Wireless, Flexible, Ion-Selective Electrode System for Selective and Repeatable Detection of Sodium.

Wireless, flexible, ion-selective electrodes (ISEs) are of great interest in the development of wearable health monitors and clinical systems. Existing film-based electrochemical sensors, however, still have practical limitations due to poor electrical contact and material-interfacial leakage. Here, we introduce a wireless, flexible film-based system with a highly selective, stable, and reliable sodium sensor. A flexible and hydrophobic composite with carbon black and soft elastomer serves as an ion-to-electron transducer offering cost efficiency, design simplicity, and long-term stability. The sensor package demonstrates repeatable analysis of selective sodium detection in saliva with good sensitivity (56.1 mV/decade), stability (0.53 mV/h), and selectivity coefficient of sodium against potassium (-3.0). The film ISEs have an additional membrane coating that provides reinforced stability for the sensor upon mechanical bending. Collectively, the comprehensive study of materials, surface chemistry, and sensor design in this work shows the potential of the wireless flexible sensor system for low-profile wearable applications.

Printed, Soft, Nanostructured Strain Sensors for Monitoring of Structural Health and Human Physiology.

Soft strain sensors that are mechanically flexible or stretchable are of significant interest in the fields of structural health monitoring, human physiology, and human-machine interfaces. However, existing deformable strain sensors still suffer from complex fabrication processes, poor reusability, limited adhesion strength, or structural rigidity. In this work, we introduce a versatile, high-throughput fabrication method of nanostructured, soft material-enabled, miniaturized strain sensors for both structural health monitoring and human physiology detection. Aerosol jet printing of polyimide and silver nanowires enables multifunctional strain sensors with tunable resistance and gauge factor. Experimental study of soft material compositions and multilayered structures of the strain sensor demonstrates the capabilities of strong adhesion and conformal lamination on different surfaces without the use of conventional fixtures and/or tapes. A two-axis, printed strain gauge enables the detection of force-induced strain changes on a curved stem valve for structural health management while offering reusability over 10 times without losing the sensing performance. Direct comparison with a commercial film sensor captures the advantages of the printed soft sensor in enhanced gauge factor and sensitivity. Another type of a stretchable strain sensor in skin-wearable applications demonstrates a highly sensitive monitoring of a subject's motion, pulse, and breathing, validated by comparing it with a clinical-grade system. Overall, the presented comprehensive study of materials, mechanics, printing-based fabrication, and interfacial adhesion shows a great potential of the printed soft strain sensor for applications in continuous structural health monitoring, human health detection, machine-interfacing systems, and environmental condition monitoring.

Soft, wireless periocular wearable electronics for real-time detection of eye vergence in a virtual reality toward mobile eye therapies.

Recent advancements in electronic packaging and image processing techniques have opened the possibility for optics-based portable eye tracking approaches, but technical and safety hurdles limit safe implementation toward wearable applications. Here, we introduce a fully wearable, wireless soft electronic system that offers a portable, highly sensitive tracking of eye movements (vergence) via the combination of skin-conformal sensors and a virtual reality system. Advancement of material processing and printing technologies based on aerosol jet printing enables reliable manufacturing of skin-like sensors, while the flexible hybrid circuit based on elastomer and chip integration allows comfortable integration with a user's head. Analytical and computational study of a data classification algorithm provides a highly accurate tool for real-time detection and classification of ocular motions. In vivo demonstration with 14 human subjects captures the potential of the wearable electronics as a portable therapy system, whose minimized form factor facilitates seamless interplay with traditional wearable hardware.

Skin-conformal, soft material-enabled bioelectronic system with minimized motion artifacts for reliable health and performance monitoring of athletes.

Recent advances in biosensors, bioelectronics, and system integration allow the development of wristband-type devices for health and performance monitoring of athletes. Although these devices provide adequate sensing outputs, they suffer from signal loss due to improper contact of a rigid sensor with the skin. In addition, when a rubber band tightly secures the sensor to the skin, the gap between sensor and skin causes inevitable motion artifacts, resulting in corrupted data. Consequently, the rigidity and bulky form factor of the existing devices are not suitable for a practical use since athletes typically go through strenuous activities during training and matches. Here, we introduce a soft, wearable flexible hybrid electronics (WFHE) with integrated flexible sensors and circuits in an ultrathin, low-modulus elastomer. The thin-film bioelectronic system avoids the use of bulky, rigid sensors, while providing negligible mechanical and thermal burdens to the wearer. Enabling conformal contact between sensor and skin minimizes undesired motion artifacts. A set of computational and experimental studies of soft materials, flexible mechanics, and system packaging provides key fundamental design factors for a comfortable, reliable, waterproof bioelectronic system. Skin conformal WFHE with sparse signal reconstruction enables reliable, continuous monitoring of photoplethysmogram, heart rate, and activities of athletes. Development of a quantitative analysis between impact force and impact velocity extracted from motion acceleration provides an objective assessment of an athletic punching force. Collectively, this study shows the first demonstration of a wireless, soft, thin-film electronics for a real-time, reliable assessment of athletic health and performance.

Advanced Soft Materials, Sensor Integrations, and Applications of Wearable Flexible Hybrid Electronics in Healthcare, Energy, and Environment.

Recent advances in soft materials and system integration technologies have provided a unique opportunity to design various types of wearable flexible hybrid electronics (WFHE) for advanced human healthcare and human-machine interfaces. The hybrid integration of soft and biocompatible materials with miniaturized wireless wearable systems is undoubtedly an attractive prospect in the sense that the successful device performance requires high degrees of mechanical flexibility, sensing capability, and user-friendly simplicity. Here, the most up-to-date materials, sensors, and system-packaging technologies to develop advanced WFHE are provided. Details of mechanical, electrical, physicochemical, and biocompatible properties are discussed with integrated sensor applications in healthcare, energy, and environment. In addition, limitations of the current materials are discussed, as well as key challenges and the future direction of WFHE. Collectively, an all-inclusive review of the newly developed WFHE along with a summary of imperative requirements of material properties, sensor capabilities, electronics performance, and skin integrations is provided.

Fully Printed, Wireless, Stretchable Implantable Biosystem toward Batteryless, Real-Time Monitoring of Cerebral Aneurysm Hemodynamics.

This study introduces a high-throughput, large-scale manufacturing method that uses aerosol jet 3D printing for a fully printed stretchable, wireless electronics. A comprehensive study of nanoink preparation and parameter optimization enables a low-profile, multilayer printing of a high-performance, capacitance flow sensor. The core printing process involves direct, microstructured patterning of biocompatible silver nanoparticles and polyimide. The optimized fabrication approach allows for transfer of highly conductive, patterned silver nanoparticle films to a soft elastomeric substrate. Stretchable mechanics modeling and seamless integration with an implantable stent display a highly stretchable and flexible sensor, deployable by a catheter for extremely low-profile, conformal insertion in a blood vessel. Optimization of a transient, wireless inductive coupling method allows for wireless detection of biomimetic cerebral aneurysm hemodynamics with the maximum readout distance of 6 cm through meat. In vitro demonstrations include wireless monitoring of flow rates (0.05-1 m s-1) in highly contoured and narrow human neurovascular models. Collectively, this work shows the potential of the printed biosystem to offer a high throughput, additive manufacturing of stretchable electronics with advances toward batteryless, real-time wireless monitoring of cerebral aneurysm hemodynamics.

Soft Material-Enabled, Active Wireless, Thin-Film Bioelectronics for Quantitative Diagnostics of Cervical Dystonia.

Recent advances in flexible materials, nanomanufacturing, and system integration have provided a great opportunity to develop wearable flexible hybrid electronics for human healthcare, diagnostics, and therapeutics. However, existing medical devices still rely on rigid electronics with many wires and separate components, which hinders wireless, comfortable, continuous monitoring of health-related human motions. Here, we introduce advanced materials and system integration technologies that enable a soft, active wireless, thin-film bioelectronics. The low-modulus, highly flexible wearable electronic system incorporates a nanomembrane wireless circuit and functional chip components, enclosed by a soft elastomeric membrane. The bioelectronic system offers a gentle, seamless mounting on the skin, while offering a comfortable, highly sensitive and accurate detection of head movements. We utilize the wireless wearable hybrid system for quantitative diagnostics of cervical dystonia (CD) that is characterized by involuntary abnormal head postures and repetitive head movements, sometimes with neck muscle pain. A set of analytical and experimental studies shows a soft system packaging, hard-soft materials integration, and quantitative assessment of physiological signals detected by the SKINTRONICS. In vivo demonstration, involving ten human subjects, captures the device feasibility for use in CD measurement.