Battery-free, wireless soft sensors for continuous multi-site measurements of pressure and temperature from patients at risk for pressure injuries.

Capabilities for continuous monitoring of pressures and temperatures at critical skin interfaces can help to guide care strategies that minimize the potential for pressure injuries in hospitalized patients or in individuals confined to the bed. This paper introduces a soft, skin-mountable class of sensor system for this purpose. The design includes a pressure-responsive element based on membrane deflection and a battery-free, wireless mode of operation capable of multi-site measurements at strategic locations across the body. Such devices yield continuous, simultaneous readings of pressure and temperature in a sequential readout scheme from a pair of primary antennas mounted under the bedding and connected to a wireless reader and a multiplexer located at the bedside. Experimental evaluation of the sensor and the complete system includes benchtop measurements and numerical simulations of the key features. Clinical trials involving two hemiplegic patients and a tetraplegic patient demonstrate the feasibility, functionality and long-term stability of this technology in operating hospital settings.

Skin-interfaced soft microfluidic systems with modular and reusable electronics for in situ capacitive sensing of sweat loss, rate and conductivity.

Important insights into human health can be obtained through the non-invasive collection and detailed analysis of sweat, a biofluid that contains a wide range of essential biomarkers. Skin-interfaced microfluidic platforms, characterized by soft materials and thin geometries, offer a collection of capabilities for in situ capture, storage, and analysis of sweat and its constituents. In ambulatory uses cases, the ability to provide real-time feedback on sweat loss, rate and content, without visual inspection of the device, can be important. This paper introduces a low-profile skin-interfaced system that couples disposable microfluidic sampling devices with reusable 'stick-on' electrodes and wireless readout electronics that remain isolated from the sweat. An ultra-thin capping layer on the microfluidic platform permits high-sensitivity, contactless capacitive measurements of both sweat loss and sweat conductivity. This architecture avoids the potential for corrosion of the sensing components and eliminates the need for cleaning/sterilizing the electronics, thereby resulting in a cost-effective platform that is simple to use. Optimized electrode designs follow from a combination of extensive benchtop testing, analytical calculations and FEA simulations for two sensing configurations: (1) sweat rate and loss, and (2) sweat conductivity, which contains information about electrolyte content. Both configurations couple to a flexible, wireless electronics platform that digitizes and transmits information to Bluetooth-enabled devices. On-body field testing during physical exercise validates the performance of the system in scenarios of practical relevance to human health and performance.

Wirelessly controlled, bioresorbable drug delivery device with active valves that exploit electrochemically triggered crevice corrosion.

Implantable drug release platforms that offer wirelessly programmable control over pharmacokinetics have potential in advanced treatment protocols for hormone imbalances, malignant cancers, diabetic conditions, and others. We present a system with this type of functionality in which the constituent materials undergo complete bioresorption to eliminate device load from the patient after completing the final stage of the release process. Here, bioresorbable polyanhydride reservoirs store drugs in defined reservoirs without leakage until wirelessly triggered valve structures open to allow release. These valves operate through an electrochemical mechanism of geometrically accelerated corrosion induced by passage of electrical current from a wireless, bioresorbable power-harvesting unit. Evaluations in cell cultures demonstrate the efficacy of this technology for the treatment of cancerous tissues by release of the drug doxorubicin. Complete in vivo studies of platforms with multiple, independently controlled release events in live-animal models illustrate capabilities for control of blood glucose levels by timed delivery of insulin.

Development of a neural interface for high-definition, long-term recording in rodents and nonhuman primates.

Long-lasting, high-resolution neural interfaces that are ultrathin and flexible are essential for precise brain mapping and high-performance neuroprosthetic systems. Scaling to sample thousands of sites across large brain regions requires integrating powered electronics to multiplex many electrodes to a few external wires. However, existing multiplexed electrode arrays rely on encapsulation strategies that have limited implant lifetimes. Here, we developed a flexible, multiplexed electrode array, called "Neural Matrix," that provides stable in vivo neural recordings in rodents and nonhuman primates. Neural Matrix lasts over a year and samples a centimeter-scale brain region using over a thousand channels. The long-lasting encapsulation (projected to last at least 6 years), scalable device design, and iterative in vivo optimization described here are essential components to overcoming current hurdles facing next-generation neural technologies.

Soft, skin-interfaced microfluidic systems with integrated enzymatic assays for measuring the concentration of ammonia and ethanol in sweat.

Eccrine sweat is a rich and largely unexplored biofluid that contains a range of important biomarkers, from electrolytes, metabolites, micronutrients and hormones to exogenous agents, each of which can change in concentration with diet, stress level, hydration status and physiologic or metabolic state. Traditionally, clinicians and researchers have used absorbent pads and benchtop analyzers to collect and analyze the biochemical constituents of sweat in controlled, laboratory settings. Recently reported wearable microfluidic and electrochemical sensing devices represent significant advances in this context, with capabilities for rapid, in situ evaluations, in many cases with improved repeatability and accuracy. A limitation is that assays performed in these platforms offer limited control of reaction kinetics and mixing of different reagents and samples. Here, we present a multi-layered microfluidic device platform with designs that eliminate these constraints, to enable integrated enzymatic assays with demonstrations of in situ analysis of the concentrations of ammonia and ethanol in microliter volumes of sweat. Careful characterization of the reaction kinetics and their optimization using statistical techniques yield robust analysis protocols. Human subject studies with sweat initiated by warm-water bathing highlight the operational features of these systems.

Mechano-acoustic sensing of physiological processes and body motions via a soft wireless device placed at the suprasternal notch.

Skin-mounted soft electronics that incorporate high-bandwidth triaxial accelerometers can capture broad classes of physiologically relevant information, including mechano-acoustic signatures of underlying body processes (such as those measured by a stethoscope) and precision kinematics of core-body motions. Here, we describe a wireless device designed to be conformally placed on the suprasternal notch for the continuous measurement of mechano-acoustic signals, from subtle vibrations of the skin at accelerations of around 10-3 m s-2 to large motions of the entire body at about 10 m s-2, and at frequencies up to around 800 Hz. Because the measurements are a complex superposition of signals that arise from locomotion, body orientation, swallowing, respiration, cardiac activity, vocal-fold vibrations and other sources, we exploited frequency-domain analysis and machine learning to obtain-from human subjects during natural daily activities and exercise-real-time recordings of heart rate, respiration rate, energy intensity and other essential vital signs, as well as talking time and cadence, swallow counts and patterns, and other unconventional biomarkers. We also used the device in sleep laboratories and validated the measurements using polysomnography.

Multimodal Sensing with a Three-Dimensional Piezoresistive Structure.

Sensors that reproduce the complex characteristics of cutaneous receptors in the skin have important potential in the context of artificial systems for controlled interactions with the physical environment. Multimodal responses with high sensitivity and wide dynamic range are essential for many such applications. This report introduces a simple, three-dimensional type of microelectromechanical sensor that incorporates monocrystalline silicon nanomembranes as piezoresistive elements in a configuration that enables separate, simultaneous measurements of multiple mechanical stimuli, such as normal force, shear force, and bending, along with temperature. The technology provides high sensitivity measurements with millisecond response times, as supported by quantitative simulations. The fabrication and assembly processes allow scalable production of interconnected arrays of such devices with capabilities in spatiotemporal mapping. Integration with wireless data recording and transmission electronics allows operation with standard consumer devices.

Passive sweat collection and colorimetric analysis of biomarkers relevant to kidney disorders using a soft microfluidic system.

The rich range of biomarkers in sweat and the ability to collect sweat in a non-invasive manner create interest in the use of this biofluid for assessments of health and physiological status, with potential applications that range from sports and fitness to clinical medicine. This paper introduces two important advances in recently reported classes of soft, skin-interfaced microfluidic systems for sweat capture and analysis: (1) a simple, broadly applicable means for collection of sweat that bypasses requirements for physical/mental exertion or pharmacological stimulation and (2) a set of enzymatic chemistries and colorimetric readout approaches for determining the concentrations of creatinine and urea in sweat, throughout ranges that are physiologically relevant. The results allow for routine, non-pharmacological capture of sweat for patient populations, such as infants and the elderly, that cannot be expected to sweat through exercise, and they create potential opportunities in the use of sweat for kidney disease screening/monitoring. Studies on human subjects demonstrate these essential capabilities, with quantitative comparisons to standard methods. The results expand the range of options available in microfluidic sampling and sensing of sweat for disease diagnostics and health monitoring.

Soft, Skin-Integrated Multifunctional Microfluidic Systems for Accurate Colorimetric Analysis of Sweat Biomarkers and Temperature.

Real-time measurements of the total loss of sweat, the rate of sweating, the temperature of sweat, and the concentrations of electrolytes and metabolites in sweat can provide important insights into human physiology. Conventional methods use manual collection processes (e.g., absorbent pads) to determine sweat loss and lab-based instrumentation to analyze its chemical composition. Although such schemes can yield accurate data, they cannot be used outside of laboratories or clinics. Recently reported wearable electrochemical devices for sweat sensing bypass these limitations, but they typically involve on-board electronics, electrodes, and/or batteries for measurement, signal processing, and wireless transmission, without direct means for measuring sweat loss or capturing and storing small volumes of sweat. Alternative approaches exploit soft, skin-integrated microfluidic systems for collection and colorimetric chemical techniques for analysis. Here, we present the most advanced platforms of this type, in which optimized chemistries, microfluidic designs, and device layouts enable accurate assessments not only of total loss of sweat and sweat rate but also of quantitatively accurate values of the pH and temperature of sweat, and of the concentrations of chloride, glucose, and lactate across physiologically relevant ranges. Color calibration markings integrated into a graphics overlayer allow precise readout by digital image analysis, applicable in various lighting conditions. Field studies conducted on healthy volunteers demonstrate the full capabilities in measuring sweat loss/rate and analyzing multiple sweat biomarkers and temperature, with performance that quantitatively matches that of conventional lab-based measurement systems.

Solution processes for ultrabroadband and omnidirectional graded-index glass lenses with near-zero reflectivity in high concentration photovoltaics.

Concentrator photovoltaic (CPV) systems, where incident direct solar radiation is tightly concentrated onto high-efficiency multi-junction solar cells by geometric optical elements, exhibit the highest efficiencies in converting the sun's energy into electric power. Their energy conversion efficiencies are greatly limited, however, due to Fresnel reflection losses occurring at three air/optics interfaces in the most sophisticated dual-stage CPV platforms. This paper describes a facile one-step wet-etching process to create a nanoporous surface with a graded-index profile on both flat and curved glasses, with capabilities of achieving ~99% average transmission efficiency in a wide wavelength range from 380 nm to 1.3 µm and for a wide range of incident angles up to ±40° regardless of the polarization state of incident sunlight. The simplicity of the etching process remarkably increases their versatility in various optical elements that require unconventional form factors such as Fresnel lenses and microlens arrays, and/or demanding curvatures along with much reduced dimensions such as ball lenses. Etched glass surfaces on two-stage optical concentrating systems yield enhancements in total optical transmission efficiencies by 13.8% and in the photocurrent by 14.3%, as experimentally determined by measurements on microscale triple-junction solar cells. The presented strategy can be widely adapted in a variety of applications such as image sensors, display systems, and other optoelectronic devices.

Wireless bioresorbable electronic system enables sustained nonpharmacological neuroregenerative therapy.

Peripheral nerve injuries represent a significant problem in public health, constituting 2-5% of all trauma cases1. For severe nerve injuries, even advanced forms of clinical intervention often lead to incomplete and unsatisfactory motor and/or sensory function2. Numerous studies report the potential of pharmacological approaches (for example, growth factors, immunosuppressants) to accelerate and enhance nerve regeneration in rodent models3-10. Unfortunately, few have had a positive impact in clinical practice. Direct intraoperative electrical stimulation of injured nerve tissue proximal to the site of repair has been demonstrated to enhance and accelerate functional recovery11,12, suggesting a novel nonpharmacological, bioelectric form of therapy that could complement existing surgical approaches. A significant limitation of this technique is that existing protocols are constrained to intraoperative use and limited therapeutic benefits13. Herein we introduce (i) a platform for wireless, programmable electrical peripheral nerve stimulation, built with a collection of circuit elements and substrates that are entirely bioresorbable and biocompatible, and (ii) the first reported demonstration of enhanced neuroregeneration and functional recovery in rodent models as a result of multiple episodes of electrical stimulation of injured nervous tissue.

Soft, Skin-Interfaced Microfluidic Systems with Wireless, Battery-Free Electronics for Digital, Real-Time Tracking of Sweat Loss and Electrolyte Composition.

Sweat excretion is a dynamic physiological process that varies with body position, activity level, environmental factors, and health status. Conventional means for measuring the properties of sweat yield accurate results but their requirements for sampling and analytics do not allow for use in the field. Emerging wearable devices offer significant advantages over existing approaches, but each has significant drawbacks associated with bulk and weight, inability to quantify volumetric sweat rate and loss, robustness, and/or inadequate accuracy in biochemical analysis. This paper presents a thin, miniaturized, skin-interfaced microfluidic technology that includes a reusable, battery-free electronics module for measuring sweat conductivity and rate in real-time using wireless power from and data communication to electronic devices with capabilities in near field communications (NFC), including most smartphones. The platform exploits ultrathin electrodes integrated within a collection of microchannels as interfaces to circuits that leverage NFC protocols. The resulting capabilities are complementary to those of previously reported colorimetric strategies. Systematic studies of these combined microfluidic/electronic systems, accurate correlations of measurements performed with them to those of laboratory standard instrumentation, and field tests on human subjects exercising and at rest establish the key operational features and their utility in sweat analytics.

A fluorometric skin-interfaced microfluidic device and smartphone imaging module for in situ quantitative analysis of sweat chemistry.

The rich composition of solutes and metabolites in sweat and its relative ease of collection upon excretion from skin pores make this class of biofluid an attractive candidate for point of care analysis. Wearable technologies that combine electrochemical sensors with conventional or emerging semiconductor device technologies offer valuable capabilities in sweat sensing, but they are limited to assays that support amperometric, potentiometric, and colorimetric analyses. Here, we present a complementary approach that exploits fluorometric sensing modalities integrated into a soft, skin-interfaced microfluidic system which, when paired with a simple smartphone-based imaging module, allows for in situ measurement of important biomarkers in sweat. A network array of microchannels and a collection of microreservoirs pre-filled with fluorescent probes that selectively react with target analytes in sweat (e.g. probes), enable quantitative, rapid analysis. Field studies on human subjects demonstrate the ability to measure the concentrations of chloride, sodium and zinc in sweat, with accuracy that matches that of conventional laboratory techniques. The results highlight the versatility of advanced fluorescent-based imaging modalities in body-worn sweat microfluidics platforms, and they suggest some practical potential for these ideas.

Super-Absorbent Polymer Valves and Colorimetric Chemistries for Time-Sequenced Discrete Sampling and Chloride Analysis of Sweat via Skin-Mounted Soft Microfluidics.

This paper introduces super absorbent polymer valves and colorimetric sensing reagents as enabling components of soft, skin-mounted microfluidic devices designed to capture, store, and chemically analyze sweat released from eccrine glands. The valving technology enables robust means for guiding the flow of sweat from an inlet location into a collection of isolated reservoirs, in a well-defined sequence. Analysis in these reservoirs involves a color responsive indicator of chloride concentration with a formulation tailored to offer stable operation with sensitivity optimized for the relevant physiological range. Evaluations on human subjects with comparisons against ex situ analysis illustrate the practical utility of these advances.

Thin, Soft, Skin-Mounted Microfluidic Networks with Capillary Bursting Valves for Chrono-Sampling of Sweat.

Systems for time sequential capture of microliter volumes of sweat released from targeted regions of the skin offer the potential to enable analysis of temporal variations in electrolyte balance and biomarker concentration throughout a period of interest. Current methods that rely on absorbent pads taped to the skin do not offer the ease of use in sweat capture needed for quantitative tracking; emerging classes of electronic wearable sweat analysis systems do not directly manage sweat-induced fluid flows for sample isolation. Here, a thin, soft, "skin-like" microfluidic platform is introduced that bonds to the skin to allow for collection and storage of sweat in an interconnected set of microreservoirs. Pressure induced by the sweat glands drives flow through a network of microchannels that incorporates capillary bursting valves designed to open at different pressures, for the purpose of passively guiding sweat through the system in sequential fashion. A representative device recovers 1.8 µL volumes of sweat each from 0.8 min of sweating into a set of separate microreservoirs, collected from 0.03 cm2 area of skin with approximately five glands, corresponding to a sweat rate of 0.60 µL min-1 per gland. Human studies demonstrate applications in the accurate chemical analysis of lactate, sodium, and potassium concentrations and their temporal variations.

Utilization of hydrolysate from lignocellulosic biomass pretreatment to generate electricity by enzymatic fuel cell system.

The waste hydrolysate after dilute acid pretreatment (DAP) of lignocellulosic biomass was utilized to generate electricity using an enzymatic fuel cell (EFC) system. During DAP, the components of biomass containing hemicellulose and other compounds are hydrolyzed, and glucose is solubilized into the dilute acid solution, called as the hydrolysate liquid. Glucose oxidase (GOD) and laccase (Lac) were assembled on the electrode of the anode and cathode, respectively. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were measured, and the maximum power density was found to be 1.254×10(3) µW/cm(2). The results indicate that the hydrolysate from DAP is a reliable electrolyte containing the fuel of EFC. Moreover, the impurities in the hydrolysate such as phenols and furans slightly affected the charge transfer on the surface of the electrode, but did not affect the power generation of the EFC system in principal.

Phenolic compounds: Strong inhibitors derived from lignocellulosic hydrolysate for 2,3-butanediol production by Enterobacter aerogenes.

Lignocellulosic biomass are attractive feedstocks for 2,3-butanediol production due to their abundant supply and low price. During the hydrolysis of lignocellulosic biomass, various byproducts are formed and their effects on 2,3-butanediol production were not sufficiently studied compared to ethanol production. Therefore, the effects of compounds derived from lignocellulosic biomass (weak acids, furan derivatives and phenolics) on the cell growth, the 2,3-butanediol production and the enzymes activity involved in 2,3-butanediol production were evaluated using Enterobacter aerogenes ATCC 29007. The phenolic compounds showed the most toxic effects on cell growth, 2,3-butanediol production and enzyme activity, followed by furan derivatives and weak acids. The significant effects were not observed in the presence of acetic acid and formic acid. Also, feasibility of 2,3-butanediol production from lignocellulosic biomass was evaluated using Miscanthus as a feedstock. In the fermentation of Miscanthus hydrolysate, 11.00 g/L of 2,3-butanediol was obtained from 34.62 g/L of reducing sugar. However, 2,3-butanediol was not produced when the concentration of total phenolic compounds in the hydrolysate increased to more than 1.5 g/L. The present study provides useful information to develop strategies for biological production of 2,3-butanediol and to establish biorefinery for biochemicals from lignocellulosic biomass.

Process design and evaluation of production of bioethanol and ß-lactam antibiotic from lignocellulosic biomass.

To design biorefinery processes producing bioethanol from lignocellulosic biomass with dilute acid pretreatment, biorefinery processes were simulated using the SuperPro Designer program. To improve the efficiency of biomass use and the economics of biorefinery, additional pretreatment processes were designed and evaluated, in which a combined process of dilute acid and aqueous ammonia pretreatments, and a process of waste media containing xylose were used, for the production of 7-aminocephalosporanic acid. Finally, the productivity and economics of the designed processes were compared.

Co-fermentation of carbon sources by Enterobacter aerogenes ATCC 29007 to enhance the production of bioethanol.

We investigated the enhancement of bioethanol production in Enterobacter aerogenes ATCC 29007 by co-fermentation of carbon sources such as glycerol, glucose, galactose, sucrose, fructose, xylose, starch, mannitol and citric acid. Biofuel production increases with increasing growth rate of microorganisms; that is why we investigated the optimal growth rate of E. aerogenes ATCC 29007, using mixtures of different carbon sources with glycerol. E. aerogenes ATCC 29007 was incubated in media containing each carbon source and glycerol; growth rate and bioethanol production improved in all cases compared to those in medium containing glycerol alone. The growth rate and bioethanol production were highest with mannitol. Fermentation was carried out at 37 °C for 18 h, pH 7, using 50 mL defined production medium in 100 mL serum bottles at 200 rpm. Bioethanol production under optimized conditions in medium containing 16 g/L mannitol and 20 g/L glycerol increased sixfold (32.10 g/L) than that containing glycerol alone (5.23 g/L) as the carbon source in anaerobic conditions. Similarly, bioethanol production using free cells in continuous co-fermentation also improved (27.28 g/L) when 90.37 % of 16 g/L mannitol and 67.15 % of 20 g/L glycerol were used. Although naturally existing or engineered microorganisms can ferment mixed sugars sequentially, the preferential utilization of glucose to non-glucose sugars often results in lower overall yield and productivity of ethanol. Here, we present new findings in E. aerogenes ATCC 29007 that can be used to improve bioethanol production by simultaneous co-fermentation of glycerol and mannitol.