Wireless, intraoral hybrid electronics for real-time quantification of sodium intake toward hypertension management.

Recent wearable devices offer portable monitoring of biopotentials, heart rate, or physical activity, allowing for active management of human health and wellness. Such systems can be inserted in the oral cavity for measuring food intake in regard to controlling eating behavior, directly related to diseases such as hypertension, diabetes, and obesity. However, existing devices using plastic circuit boards and rigid sensors are not ideal for oral insertion. A user-comfortable system for the oral cavity requires an ultrathin, low-profile, and soft electronic platform along with miniaturized sensors. Here, we introduce a stretchable hybrid electronic system that has an exceptionally small form factor, enabling a long-range wireless monitoring of sodium intake. Computational study of flexible mechanics and soft materials provides fundamental aspects of key design factors for a tissue-friendly configuration, incorporating a stretchable circuit and sensor. Analytical calculation and experimental study enables reliable wireless circuitry that accommodates dynamic mechanical stress. Systematic in vitro modeling characterizes the functionality of a sodium sensor in the electronics. In vivo demonstration with human subjects captures the device feasibility for real-time quantification of sodium intake, which can be used to manage hypertension.

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.

Synthesis of shape-programmable elastomer for a bioresorbable, wireless nerve stimulator.

Materials that have the ability to manipulate shapes in response to stimuli such as heat, light, humidity and magnetism offer a means for versatile, sophisticated functions in soft robotics or biomedical implants, while such a reactive transformation has certain drawbacks including high operating temperatures, inherent rigidity and biological hazard. Herein, we introduce biodegradable, self-adhesive, shape-transformable poly (L-lactide-co-ε-caprolactone) (BSS-PLCL) that can be triggered via thermal stimulation near physiological temperature (∼38 °C). Chemical inspections confirm the fundamental properties of the synthetic materials in diverse aspects, and study on mechanical and biochemical characteristics validates exceptional stretchability up to 800 % and tunable dissolution behaviors under biological conditions. The integration of the functional polymer with a bioresorbable electronic system highlights potential for a wide range of biomedical applications.

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.

Advances in Materials, Sensors, and Integrated Systems for Monitoring Eye Movements.

Eye movements show primary responses that reflect humans' voluntary intention and conscious selection. Because visual perception is one of the fundamental sensory interactions in the brain, eye movements contain critical information regarding physical/psychological health, perception, intention, and preference. With the advancement of wearable device technologies, the performance of monitoring eye tracking has been significantly improved. It also has led to myriad applications for assisting and augmenting human activities. Among them, electrooculograms, measured by skin-mounted electrodes, have been widely used to track eye motions accurately. In addition, eye trackers that detect reflected optical signals offer alternative ways without using wearable sensors. This paper outlines a systematic summary of the latest research on various materials, sensors, and integrated systems for monitoring eye movements and enabling human-machine interfaces. Specifically, we summarize recent developments in soft materials, biocompatible materials, manufacturing methods, sensor functions, systems' performances, and their applications in eye tracking. Finally, we discuss the remaining challenges and suggest research directions for future studies.

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.

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

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

Size-selective immunofluorescence of Mycobacterium tuberculosis cells by capillary- and viscous forces.

Rapid, low cost screening of tuberculosis requires an effective enrichment method of Mycobacterium tuberculosis (MTB) cells. Currently, microfiltration and centrifugation steps are frequently used for sample preparation, which are cumbersome and time-consuming. In this study, the size-selective capturing mechanism of a microtip-sensor is presented to directly enrich MTB cells from a sample mixture. When a microtip is withdrawn from a spherical suspension in the radial direction, the cells that are concentrated by AC electroosmosis are selectively enriched to the tip due to capillary- and viscous forces. The size-selectivity is characterized by using polystyrene microspheres, which is then applied to size-selective capture of MTB from a sample mixture. Our approach yields a detection limit of 800 cells mL(-1), one of the highest-sensitivity immunosensors to date.

Recent Advances in Portable Biosensors for Biomarker Detection in Body Fluids.

A recent development in portable biosensors allows rapid, accurate, and on-site detection of biomarkers, which helps to prevent disease spread by the control of sources. Less invasive sample collection is necessary to use portable biosensors in remote environments for accurate on-site diagnostics and testing. For non- or minimally invasive sampling, easily accessible body fluids, such as saliva, sweat, blood, or urine, have been utilized. It is also imperative to find accurate biomarkers to provide better clinical intervention and treatment at the onset of disease. At the same time, these reliable biomarkers can be utilized to monitor the progress of the disease. In this review, we summarize the most recent development of portable biosensors to detect various biomarkers accurately. In addition, we discuss ongoing issues and limitations of the existing systems and methods. Lastly, we present the key requirements of portable biosensors and discuss ideas for functional enhancements.

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.

Use of Superelastic Nitinol and Highly-Stretchable Latex to Develop a Tongue Prosthetic Assist Device and Facilitate Swallowing for Dysphagia Patients.

We introduce a new tongue prosthetic assist device (TPAD), which shows the first prosthetic application for potential treatment of swallowing difficulty in dysphagia patients. The native tongue has a number of complex movements that are not feasible to mimic using a single mechanical prosthetic device. In order to overcome this challenge, our device has three key features, including (1) a superelastic nitinol structure that transfers the force produced by the jaws during chewing towards the palate, (2) angled composite tubes for guiding the nitinol strips smoothly during the motion, and (3) highly stretchable thin polymeric membrane as a covering sheet in order to secure the food and fluids on top of the TPAD for easy swallowing. A set of mechanical experiments has optimized the size and angle of the guiding tubes for the TPAD. The low-profile TPAD was successfully placed in a cadaver model and its mobility effectively provided a simplistic mimic of the native tongue elevation function by applying vertical chewing motions. This is the first demonstration of a new oral device powered by the jaw motions in order to create a bulge in the middle of the mouth mimicking native tongue behavior.

Soft Electronics Enabled Ergonomic Human-Computer Interaction for Swallowing Training.

We introduce a skin-friendly electronic system that enables human-computer interaction (HCI) for swallowing training in dysphagia rehabilitation. For an ergonomic HCI, we utilize a soft, highly compliant ("skin-like") electrode, which addresses critical issues of an existing rigid and planar electrode combined with a problematic conductive electrolyte and adhesive pad. The skin-like electrode offers a highly conformal, user-comfortable interaction with the skin for long-term wearable, high-fidelity recording of swallowing electromyograms on the chin. Mechanics modeling and experimental quantification captures the ultra-elastic mechanical characteristics of an open mesh microstructured sensor, conjugated with an elastomeric membrane. Systematic in vivo studies investigate the functionality of the soft electronics for HCI-enabled swallowing training, which includes the application of a biofeedback system to detect swallowing behavior. The collection of results demonstrates clinical feasibility of the ergonomic electronics in HCI-driven rehabilitation for patients with swallowing disorders.

Recent advances in salivary cancer diagnostics enabled by biosensors and bioelectronics.

There is a high demand for a non-invasive, rapid, and highly accurate tool for disease diagnostics. Recently, saliva based diagnostics for the detection of specific biomarkers has drawn significant attention since the sample extraction is simple, cost-effective, and precise. Compared to blood, saliva contains a similar variety of DNA, RNA, proteins, metabolites, and microbiota that can be compiled into a multiplex of cancer detection markers. The salivary diagnostic method holds great potential for early-stage cancer diagnostics without any complicated and expensive procedures. Here, we review various cancer biomarkers in saliva and compare the biomarkers efficacy with traditional diagnostics and state-of-the-art bioelectronics. We summarize biomarkers in four major groups: genomics, transcriptomics, proteomics, and metabolomics/microbiota. Representative bioelectronic systems for each group are summarized based on various stages of a cancer. Systematic study of oxidative stress establishes the relationship between macromolecules and cancer biomarkers in saliva. We also introduce the most recent examples of salivary diagnostic electronics based on nanotechnologies that can offer rapid, yet highly accurate detection of biomarkers. A concluding section highlights areas of opportunity in the further development and applications of these technologies.

Microstructured Thin Film Nitinol for a Neurovascular Flow-Diverter.

A cerebral aneurysm occurs as a result of a weakened blood vessel, which allows blood to flow into a sac or a ballooned section. Recent advancement shows that a new device, 'flow-diverter', can divert blood flow away from the aneurysm sac. People found that a flow-diverter based on thin film nitinol (TFN), works very effectively, however there are no studies proving the mechanical safety in irregular, curved blood vessels. Here, we study the mechanical behaviors and structural safety of a novel microstructured TFN membrane through the computational and experimental studies, which establish the fundamental aspects of stretching and bending mechanics of the structure. The result shows a hyper-elastic behavior of the TFN with a negligible strain change up to 180° in bending and over 500% in radial stretching, which is ideal in the use in neurovascular curved arteries. The simulation determines the optimal joint locations between the TFN and stent frame. In vitro experimental test qualitatively demonstrates the mechanical flexibility of the flow-diverter with multi-modal bending. In vivo micro X-ray and histopathology study demonstrate that the TFN can be conformally deployed in the curved blood vessel of a swine model without any significant complications or abnormalities.

Immunologic and tissue biocompatibility of flexible/stretchable electronics and optoelectronics.

Recent development of flexible/stretchable integrated electronic sensors and stimulation systems has the potential to establish an important paradigm for implantable electronic devices, where shapes and mechanical properties are matched to those of biological tissues and organs. Demonstrations of tissue and immune biocompatibility are fundamental requirements for application of such kinds of electronics for long-term use in the body. Here, a comprehensive set of experiments studies biocompatibility on four representative flexible/stretchable device platforms, selected on the basis of their versatility and relevance in clinical usage. The devices include flexible silicon field effect transistors (FETs) on polyimide and stretchable silicon FETs, InGaN light-emitting diodes (LEDs), and AlInGaPAs LEDs, each on low modulus silicone substrates. Direct cytotoxicity measured by exposure of a surrogate fibroblast line and leachable toxicity by minimum essential medium extraction testing reveal that all of these devices are non-cytotoxic. In vivo immunologic and tissue biocompatibility testing in mice indicate no local inflammation or systemic immunologic responses after four weeks of subcutaneous implantation. The results show that these new classes of flexible implantable devices are suitable for introduction into clinical studies as long-term implantable electronics.

Multifunctional skin-like electronics for quantitative, clinical monitoring of cutaneous wound healing.

Non-invasive, biomedical devices have the potential to provide important, quantitative data for the assessment of skin diseases and wound healing. Traditional methods either rely on qualitative visual and tactile judgments of a professional and/or data obtained using instrumentation with forms that do not readily allow intimate integration with sensitive skin near a wound site. Here, an electronic sensor platform that can softly and reversibly laminate perilesionally at wounds to provide highly accurate, quantitative data of relevance to the management of surgical wound healing is reported. Clinical studies on patients using thermal sensors and actuators in fractal layouts provide precise time-dependent mapping of temperature and thermal conductivity of the skin near the wounds. Analytical and simulation results establish the fundamentals of the sensing modalities, the mechanics of the system, and strategies for optimized design. The use of this type of "epidermal" electronics system in a realistic clinical setting with human subjects establishes a set of practical procedures in disinfection, reuse, and protocols for quantitative measurement. The results have the potential to address important unmet needs in chronic wound management.

Rugged and breathable forms of stretchable electronics with adherent composite substrates for transcutaneous monitoring.

Research in stretchable electronics involves fundamental scientific topics relevant to applications with importance in human healthcare. Despite significant progress in active components, routes to mechanically robust construction are lacking. Here, we introduce materials and composite designs for thin, breathable, soft electronics that can adhere strongly to the skin, with the ability to be applied and removed hundreds of times without damaging the devices or the skin, even in regions with substantial topography and coverage of hair. The approach combines thin, ultralow modulus, cellular silicone materials with elastic, strain-limiting fabrics, to yield a compliant but rugged platform for stretchable electronics. Theoretical and experimental studies highlight the mechanics of adhesion and elastic deformation. Demonstrations include cutaneous optical, electrical and radio frequency sensors for measuring hydration state, electrophysiological activity, pulse and cerebral oximetry. Multipoint monitoring of a subject in an advanced driving simulator provides a practical example.

Multifunctional epidermal electronics printed directly onto the skin.

Materials and designs are presented for electronics and sensors that can be conformally and robustly integrated onto the surface of the skin. A multifunctional device of this type can record various physiological signals relevant to health and wellness. This class of technology offers capabilities in biocompatible, non-invasive measurement that lie beyond those available with conventional, point-contact electrode interfaces to the skin.