A wireless, implantable bioelectronic system for monitoring urinary bladder function following surgical recovery.

Partial cystectomy procedures for urinary bladder-related dysfunction involve long recovery periods, during which urodynamic studies (UDS) intermittently assess lower urinary tract function. However, UDS are not patient-friendly, they exhibit user-to-user variability, and they amount to snapshots in time, limiting the ability to collect continuous, longitudinal data. These procedures also pose the risk of catheter-associated urinary tract infections, which can progress to ascending pyelonephritis due to prolonged lower tract manipulation in high-risk patients. Here, we introduce a fully bladder-implantable platform that allows for continuous, real-time measurements of changes in mechanical strain associated with bladder filling and emptying via wireless telemetry, including a wireless bioresorbable strain gauge validated in a benchtop partial cystectomy model. We demonstrate that this system can reproducibly measure real-time changes in a rodent model up to 30 d postimplantation with minimal foreign body response. Studies in a nonhuman primate partial cystectomy model demonstrate concordance of pressure measurements up to 8 wk compared with traditional UDS. These results suggest that our system can be used as a suitable alternative to UDS for long-term postoperative bladder recovery monitoring.

Dynamics of plosive consonants via imaging, computations, and soft electronics.

A quantitative understanding of the coupled dynamics of flow and particles in aerosol and droplet transmission associated with speech remains elusive. Here, we summarize an effort that integrates insights into flow-particle dynamics induced by the production plosive sounds during speech with skin-integrated electronic systems for monitoring the production of these sounds. In particular, we uncover diffusive and ballistic regimes separated by a threshold particle size and characterize the Lagrangian acceleration and pair dispersion. Lagrangian dynamics of the particles in the diffusive regime exhibit features of isotropic turbulence. These fundamental findings highlight the value in skin-interfaced wireless sensors for continuously measuring critical speech patterns in clinical settings, work environments, and the home, based on unique neck biomechanics associated with the generation of plosive sounds. We introduce a wireless, soft device that captures these motions to enable detection of plosive sounds in multiple languages through a convolutional neural network approach. This work spans fundamental flow-particle physics to soft electronic technology, with implications in monitoring and studying critical speech patterns associated with aerosol and droplet transmissions relevant to the spread of infectious diseases.

Miniaturized wireless, skin-integrated sensor networks for quantifying full-body movement behaviors and vital signs in infants.

Early identification of atypical infant movement behaviors consistent with underlying neuromotor pathologies can expedite timely enrollment in therapeutic interventions that exploit inherent neuroplasticity to promote recovery. Traditional neuromotor assessments rely on qualitative evaluations performed by specially trained personnel, mostly available in tertiary medical centers or specialized facilities. Such approaches are high in cost, require geographic proximity to advanced healthcare resources, and yield mostly qualitative insight. This paper introduces a simple, low-cost alternative in the form of a technology customized for quantitatively capturing continuous, full-body kinematics of infants during free living conditions at home or in clinical settings while simultaneously recording essential vital signs data. The system consists of a wireless network of small, flexible inertial sensors placed at strategic locations across the body and operated in a wide-bandwidth and time-synchronized fashion. The data serve as the basis for reconstructing three-dimensional motions in avatar form without the need for video recordings and associated privacy concerns, for remote visual assessments by experts. These quantitative measurements can also be presented in graphical format and analyzed with machine-learning techniques, with potential to automate and systematize traditional motor assessments. Clinical implementations with infants at low and at elevated risks for atypical neuromotor development illustrates application of this system in quantitative and semiquantitative assessments of patterns of gross motor skills, along with body temperature, heart rate, and respiratory rate, from long-term and follow-up measurements over a 3-mo period following birth. The engineering aspects are compatible for scaled deployment, with the potential to improve health outcomes for children worldwide via early, pragmatic detection methods.

A wireless, skin-interfaced biosensor for cerebral hemodynamic monitoring in pediatric care.

The standard of clinical care in many pediatric and neonatal neurocritical care units involves continuous monitoring of cerebral hemodynamics using hard-wired devices that physically adhere to the skin and connect to base stations that commonly mount on an adjacent wall or stand. Risks of iatrogenic skin injuries associated with adhesives that bond such systems to the skin and entanglements of the patients and/or the healthcare professionals with the wires can impede clinical procedures and natural movements that are critical to the care, development, and recovery of pediatric patients. This paper presents a wireless, miniaturized, and mechanically soft, flexible device that supports measurements quantitatively comparable to existing clinical standards. The system features a multiphotodiode array and pair of light-emitting diodes for simultaneous monitoring of systemic and cerebral hemodynamics, with ability to measure cerebral oxygenation, heart rate, peripheral oxygenation, and potentially cerebral pulse pressure and vascular tone, through the utilization of multiwavelength reflectance-mode photoplethysmography and functional near-infrared spectroscopy. Monte Carlo optical simulations define the tissue-probing depths for source-detector distances and operating wavelengths of these systems using magnetic resonance images of the head of a representative pediatric patient to define the relevant geometries. Clinical studies on pediatric subjects with and without congenital central hypoventilation syndrome validate the feasibility for using this system in operating hospitals and define its advantages relative to established technologies. This platform has the potential to substantially enhance the quality of pediatric care across a wide range of conditions and use scenarios, not only in advanced hospital settings but also in clinics of lower- and middle-income countries.

Soft, skin-interfaced microfluidic systems with integrated immunoassays, fluorometric sensors, and impedance measurement capabilities.

Soft microfluidic systems that capture, store, and perform biomarker analysis of microliter volumes of sweat, in situ, as it emerges from the surface of the skin, represent an emerging class of wearable technology with powerful capabilities that complement those of traditional biophysical sensing devices. Recent work establishes applications in the real-time characterization of sweat dynamics and sweat chemistry in the context of sports performance and healthcare diagnostics. This paper presents a collection of advances in biochemical sensors and microfluidic designs that support multimodal operation in the monitoring of physiological signatures directly correlated to physical and mental stresses. These wireless, battery-free, skin-interfaced devices combine lateral flow immunoassays for cortisol, fluorometric assays for glucose and ascorbic acid (vitamin C), and digital tracking of skin galvanic responses. Systematic benchtop evaluations and field studies on human subjects highlight the key features of this platform for the continuous, noninvasive monitoring of biochemical and biophysical correlates of the stress state.

A Wireless Near-Infrared Spectroscopy Device for Flap Monitoring: Proof of Concept in a Porcine Musculocutaneous Flap Model.

BACKGROUND: Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are highly sensitive for detecting malperfusion. However, the clinical utility and user experience are limited by the wired connection between the sensor and bedside console. This wire leads to instability of the flap-sensor interface and may cause false alarms. METHODS: We present a novel wearable wireless NIRS sensor for continuous fasciocutaneous free flap monitoring. This waterproof silicone-encapsulated Bluetooth-enabled device contains two light-emitting diodes and two photodetectors in addition to a battery sufficient for 5 days of uninterrupted function. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. RESULTS: Devices were tested in four flaps using three animals. Both devices produced very similar tissue oxygen saturation (StO2) tracings throughout the vascular clamping events, with obvious and parallel changes occurring on arterial clamping, arterial release, venous clamping, and venous release. Small interdevice variations in absolute StO2 value readings and magnitude of change were observed. The normalized cross-correlation at zero lag describing correspondence between the novel NIRS and T.Ox devices was >0.99 in each trial. CONCLUSION: The wireless NIRS flap monitor is capable of detecting StO2 changes resultant from arterial vascular occlusive events. In this porcine flap model, the functionality of this novel sensor closely mirrored that of the T.Ox wired platform. This device is waterproof, highly adhesive, skin conforming, and has sufficient battery life to function for 5 days. Clinical testing is necessary to determine if this wireless functionality translates into fewer false-positive alarms and a better user experience.

Kangaroo father care: A pilot feasibility study of physiologic, biologic, and psychosocial measures to capture the effects of father-infant and mother-infant skin-to-skin contact in the Neonatal Intensive Care Unit.

Robust literature supports the positive effects of kangaroo mother care (KMC) on infant physiologic stability and parent-infant bonding in the Neonatal Intensive Care Unit (NICU). Comparatively little is known about kangaroo father care (KFC) in the NICU, and KFC implementation has been limited. Our pilot feasibility study objective was to examine KFC effects on premature infants and fathers as compared to KMC. Parents of preterm NICU infants independently completed a 90-min Kangaroo Care (KC) session on consecutive days. Infant heart rate variability (HRV) and apnea/periodicity measures were compared (pre-KC to KC; KFC to KMC). Additionally, we assessed the feasibility of administering three psychosocial questionnaires to fathers and mothers in the NICU and after discharge. Ten preterm infants completed 20 KC sessions (334/7 -374/7  weeks post-menstrual age). Results demonstrated similar infant physiologic responses between KMC and KFC, including significant differences in measures of HRV (p < .05) between KC and non-KC periods. Eighty-eight percentage of questionnaires administered were completed, supporting the utilization of these instruments in future research of this population. If confirmed, these preliminary results identify an opportunity to objectively assess KFC effects, supporting the development of empirically based KFC programs benefitting NICU families.

Aim high energy conversion efficiency in triboelectric nanogenerators.

Triboelectric nanogenerators (TENGs) that enable the conversion of a given mechanical energy into electrical energy at high efficiency have been very important in practice. Since the given mechanical energy is involuntarily converted to secondary energy sources (light, heat, and sound during triboelectrification), the significant amount of energy being converted is lost. Various studies have thus been continuously carried out to overcome this issue. Since the first TENGs found in 2012, various developments in TENGs have been made: (1) the mechanical-electrical energy conversion characteristics of potential organic/inorganic material groups have been introduced, (2) the integration into the device structure considering the diversity of mechanical energy, and (3) user friendly and industrial application platforms have been aggressively studied. Despite the remarkable progress and improvement of TENGs, their mechanical-electrical conversion efficiency is still quite low. We therefore need to discover and develop materials that can be converted to improve efficiency. Here, we outline the recent progress made in a group of high polarity triboelectric materials that exploit surface charge density and charge transfer properties. We also review the recent boosting powering TENGs. The aim of this work is to provide insight into the future direction and strategies for highly enhanced powering TENGs through material research.

Graphene/h-BN/ZnO van der Waals tunneling heterostructure based ultraviolet photodetector.

We report a novel ultraviolet photodetector based on graphene/h-BN/ZnO van der Waals heterostructure. Graphene/ZnO heterostructure shows poor rectification behavior and almost no photoresponse. In comparison, graphene/h-BN/ZnO structure shows improved electrical rectified behavior and surprising high UV photoresponse (1350AW(-1)), which is two or three orders magnitude larger than reported GaN UV photodetector (0.2~20AW(-1)). Such high photoresponse mainly originates from the introduction of ultrathin two-dimensional (2D) insulating h-BN layer, which behaves as the tunneling layer for holes produced in ZnO and the blocking layer for holes in graphene. The graphene/h-BN/ZnO heterostructure should be a novel and representative 2D heterostructure for improving the performance of 2D materials/Semiconductor heterostructure based optoelectronic devices.

Advancements in Skin-Mediated Drug Delivery: Mechanisms, Techniques, and Applications.

Skin-mediated drug delivery methods currently are receiving significant attention as a promising approach for the enhanced delivery of drugs through the skin. Skin-mediated drug delivery offers the potential to overcome the limitations of traditional drug delivery methods, including oral administration and intravenous injection. The challenges associated with drug permeation through layers of skin, which act as a major barrier, are explored, and strategies to overcome these limitations are discussed in detail. This review categorizes skin-mediated drug delivery methods based on the means of increasing drug permeation, and it provides a comprehensive overview of the mechanisms and techniques associated with these methods. In addition, recent advancements in the application of skin-mediated drug delivery are presented. The review also outlines the limitations of ongoing research and suggests future perspectives of studies regarding the skin-mediated delivery of drugs.

Materials and Device Designs for Wireless Monitoring of Temperature and Thermal Transport Properties of Wound Beds during Healing.

Chronic wounds represent a major health risk for diabetic patients. Regeneration of such wounds requires regular medical treatments over periods that can extend for several months or more. Schemes for monitoring the healing process can provide important feedback to the patient and caregiver. Although qualitative indicators such as malodor or fever can provide some indirect information, quantitative measurements of the wound bed have the potential to yield important insights. The work presented here introduces materials and engineering designs for a wireless system that captures spatio-temporal temperature and thermal transport information across the wound continuously throughout the healing process. Systematic experimental and computational studies establish the materials aspects and basic capabilities of this technology. In vivo studies reveal that both the temperature and the changes in this quantity offer information on wound status, with indications of initial exothermic reactions and mechanisms of scar tissue formation. Bioresorbable materials serve as the foundations for versions of this device that create possibilities for monitoring on and within the wound site, in a way that bypasses the risks of physical removal.

A skin-interfaced, miniaturized platform for triggered induction, capture and colorimetric multicomponent analysis of microliter volumes of sweat.

Eccrine sweat can serve as a source of biomarkers for assessing physiological health and nutritional balance, for tracking loss of essential species from the body and for evaluating exposure to hazardous substances. The growing interest in this relatively underexplored class of biofluid arises in part from its non-invasive ability for capture and analysis. The simplest devices, and the only ones that are commercially available, exploit soft microfluidic constructs and colorimetric assays with purely passive modes of operation. The most sophisticated platforms exploit batteries, electronic components and radio hardware for inducing sweat, for electrochemical evaluation of its content and for wireless transmission of this information. The work reported here introduces a technology that combines the advantages of these two different approaches, in the form of a cost-effective, easy-to-use device that supports on-demand evaluation of multiple biomarkers in sweat. This flexible, skin-interfaced, miniaturized system incorporates a hydrogel that contains an approved drug to activate eccrine sweat glands, electrodes and a simple circuit and battery to delivery this drug by iontophoresis through the surface of the skin, microfluidic channels and microreservoirs to capture the induced sweat, and multiple colorimetric assays to evaluate the concentrations of chloride, zinc, and iron. As demonstrated in healthy human participants monitored before and after a meal, such devices yield results that match those of traditional laboratory analysis techniques. Clinical studies that involve cystic fibrosis pediatric patients illustrate the use of this technology as a simple, painless, and reliable alternative to traditional hospital systems for measurements of sweat chloride.

Responsive materials and mechanisms as thermal safety systems for skin-interfaced electronic devices.

Soft, wireless physiological sensors that gently adhere to the skin are capable of continuous clinical-grade health monitoring in hospital and/or home settings, of particular value to critically ill infants and other vulnerable patients, but they present risks for injury upon thermal failure. This paper introduces an active materials approach that automatically minimizes such risks, to complement traditional schemes that rely on integrated sensors and electronic control circuits. The strategy exploits thin, flexible bladders that contain small volumes of liquid with boiling points a few degrees above body temperature. When the heat exceeds the safe range, vaporization rapidly forms highly effective, thermally insulating structures and delaminates the device from the skin, thereby eliminating any danger to the skin. Experimental and computational thermomechanical studies and demonstrations in a skin-interfaced mechano-acoustic sensor illustrate the effectiveness of this simple thermal safety system and suggest its applicability to nearly any class of skin-integrated device technology.

Synchronized wearables for the detection of haemodynamic states via electrocardiography and multispectral photoplethysmography.

Cardiovascular health is typically monitored by measuring blood pressure. Here we describe a wireless on-skin system consisting of synchronized sensors for chest electrocardiography and peripheral multispectral photoplethysmography for the continuous monitoring of metrics related to vascular resistance, cardiac output and blood-pressure regulation. We used data from the sensors to train a support-vector-machine model for the classification of haemodynamic states (resulting from exposure to heat or cold, physical exercise, breath holding, performing the Valsalva manoeuvre or from vasopressor administration during post-operative hypotension) that independently affect blood pressure, cardiac output and vascular resistance. The model classified the haemodynamic states on the basis of an unseen subset of sensor data for 10 healthy individuals, 20 patients with hypertension undergoing haemodynamic stimuli and 15 patients recovering from cardiac surgery, with an average precision of 0.878 and an overall area under the receiver operating characteristic curve of 0.958. The multinodal sensor system may provide clinically actionable insights into haemodynamic states for use in the management of cardiovascular disease.

Bioresorbable, wireless, and battery-free system for electrotherapy and impedance sensing at wound sites.

Chronic wounds, particularly those associated with diabetes mellitus, represent a growing threat to public health, with additional notable economic impacts. Inflammation associated with these wounds leads to abnormalities in endogenous electrical signals that impede the migration of keratinocytes needed to support the healing process. This observation motivates the treatment of chronic wounds with electrical stimulation therapy, but practical engineering challenges, difficulties in removing stimulation hardware from the wound site, and absence of means to monitor the healing process create barriers to widespread clinical use. Here, we demonstrate a miniaturized wireless, battery-free bioresorbable electrotherapy system that overcomes these challenges. Studies based on a splinted diabetic mouse wound model confirm the efficacy for accelerated wound closure by guiding epithelial migration, modulating inflammation, and promoting vasculogenesis. Changes in the impedance provide means for tracking the healing process. The results demonstrate a simple and effective platform for wound site electrotherapy.

A Skin-Interfaced, Miniaturized Microfluidic Analysis and Delivery System for Colorimetric Measurements of Nutrients in Sweat and Supply of Vitamins Through the Skin.

Nutrients play critical roles in maintaining core physiological functions and in preventing diseases. Technologies for delivering these nutrients and for monitoring their concentrations can help to ensure proper nutritional balance. Eccrine sweat is a potentially attractive class of biofluid for monitoring purposes due to the ability to capture sweat easily and noninvasively from nearly any region of the body using skin-integrated microfluidic technologies. Here, a miniaturized system of this type is presented that allows simple, rapid colorimetric assessments of the concentrations of multiple essential nutrients in sweat, simultaneously and without any supporting electronics - vitamin C, calcium, zinc, and iron. A transdermal patch integrated directly with the microfluidics supports passive, sustained delivery of these species to the body throughout a period of wear. Comparisons of measurement results to those from traditional lab analysis methods demonstrate the accuracy and reliability of this platform. On-body tests with human subjects reveal correlations between the time dynamics of concentrations of these nutrients in sweat and those of the corresponding concentrations in blood. Studies conducted before and after consuming certain foods and beverages highlight practical capabilities in monitoring nutritional balance, with strong potential to serve as a basis for guiding personalized dietary choices.

A bioresorbable peripheral nerve stimulator for electronic pain block.

Local electrical stimulation of peripheral nerves can block the propagation of action potentials, as an attractive alternative to pharmacological agents for the treatment of acute pain. Traditional hardware for such purposes, however, involves interfaces that can damage nerve tissue and, when used for temporary pain relief, that impose costs and risks due to requirements for surgical extraction after a period of need. Here, we introduce a bioresorbable nerve stimulator that enables electrical nerve block and associated pain mitigation without these drawbacks. This platform combines a collection of bioresorbable materials in architectures that support stable blocking with minimal adverse mechanical, electrical, or biochemical effects. Optimized designs ensure that the device disappears harmlessly in the body after a desired period of use. Studies in live animal models illustrate capabilities for complete nerve block and other key features of the technology. In certain clinically relevant scenarios, such approaches may reduce or eliminate the need for use of highly addictive drugs such as opioids.

Biodegradable, three-dimensional colorimetric fliers for environmental monitoring.

Recently reported winged microelectronic systems offer passive flight mechanisms as a dispersal strategy for purposes in environmental monitoring, population surveillance, pathogen tracking, and other applications. Initial studies indicate potential for technologies of this type, but advances in structural and responsive materials and in aerodynamically optimized geometries are necessary to improve the functionality and expand the modes of operation. Here, we introduce environmentally degradable materials as the basis of 3D fliers that allow remote, colorimetric assessments of multiple environmental parameters-pH, heavy metal concentrations, and ultraviolet exposure, along with humidity levels and temperature. Experimental and theoretical investigations of the aerodynamics of these systems reveal design considerations that include not only the geometries of the structures but also their mass distributions across a range of bioinspired designs. Preliminary field studies that rely on drones for deployment and for remote colorimetric analysis by machine learning interpretation of digital images illustrate scenarios for practical use.

A transient, closed-loop network of wireless, body-integrated devices for autonomous electrotherapy.

Temporary postoperative cardiac pacing requires devices with percutaneous leads and external wired power and control systems. This hardware introduces risks for infection, limitations on patient mobility, and requirements for surgical extraction procedures. Bioresorbable pacemakers mitigate some of these disadvantages, but they demand pairing with external, wired systems and secondary mechanisms for control. We present a transient closed-loop system that combines a time-synchronized, wireless network of skin-integrated devices with an advanced bioresorbable pacemaker to control cardiac rhythms, track cardiopulmonary status, provide multihaptic feedback, and enable transient operation with minimal patient burden. The result provides a range of autonomous, rate-adaptive cardiac pacing capabilities, as demonstrated in rat, canine, and human heart studies. This work establishes an engineering framework for closed-loop temporary electrotherapy using wirelessly linked, body-integrated bioelectronic devices.

Bitter Flavored, Soft Composites for Wearables Designed to Reduce Risks of Choking in Infants.

Wireless, skin-integrated devices for continuous, clinical-quality monitoring of vital signs have the potential to greatly improve the care of patients in neonatal and pediatric intensive-care units. These same technologies can also be used in the home, across a broad spectrum of ages, from beginning to end of life. Although miniaturized forms of such devices minimize patient burden and improve compliance, they represent life-threatening choking hazards for infants. A materials strategy is presented here to address this concern. Specifically, composite materials are introduced as soft encapsulating layers and gentle adhesives that release chemical compounds designed to elicit an intense bitter taste when placed in the mouth. Reflexive reactions to this sensation strongly reduce the potential for ingestion, as a safety feature. The materials systems described involve a non-toxic bitterant (denatonium benzoate) as a dopant in an elastomeric (poly(dimethylsiloxane)) or hydrogel matrix. Experimental and computational studies of these composite materials and the kinetics of release of the bitterant define the key properties. Incorporation into various wireless skin-integrated sensors demonstrates their utility in functional systems. This simple strategy offers valuable protective capabilities, with broad practical relevance to the welfare of children monitored with wearable devices.