Contact pressure-guided wearable dual-channel bioimpedance device for continuous hemodynamic monitoring.

Wearable devices for continuous monitoring of arterial pulse waves have the potential to improve the diagnosis, prognosis, and management of cardiovascular diseases. These pulse wave signals are often affected by the contact pressure between the wearable device and the skin, limiting the accuracy and reliability of hemodynamic parameter quantification. Here, we report a continuous hemodynamic monitoring device that enables the simultaneous recording of dual-channel bioimpedance and quantification of pulse wave velocity (PWV) used to calculate blood pressure (BP). Our investigations demonstrate the effect of contact pressure on bioimpedance and PWV. The pulsatile bioimpedance magnitude reached its maximum when the contact pressure approximated the mean arterial pressure of the subject. We employed PWV to continuously quantify BP while maintaining comfortable contact pressure for prolonged wear. The mean absolute error and standard deviation of the error compared to the reference value were determined to be 0.1 ± 3.3 mmHg for systolic BP, 1.3 ± 3.7 mmHg for diastolic BP, and -0.4 ± 3.0 mmHg for mean arterial pressure when measurements were conducted in the lying down position. This research demonstrates the potential of wearable dual-bioimpedance sensors with contact pressure guidance for reliable and continuous hemodynamic monitoring.

Molecularly Imprinted Wearable Sensor with Paper Microfluidics for Real-Time Sweat Biomarker Analysis.

The urgent need for real-time and noninvasive monitoring of health-associated biochemical parameters has motivated the development of wearable sweat sensors. Existing electrochemical sensors show promise in real-time analysis of various chemical biomarkers. These sensors often rely on labels and redox probes to generate and amplify the signals for the detection and quantification of analytes with limited sensitivity. In this study, we introduce a molecularly imprinted polymer (MIP)-based biochemical sensor to quantify a molecular biomarker in sweat using electrochemical impedance spectroscopy, which eliminates the need for labels or redox probes. The molecularly imprinted biosensor can achieve sensitive and specific detection of cortisol at concentrations as low as 1 pM, 1000-fold lower than previously reported MIP cortisol sensors. We integrated multimodal electrochemical sensors with an iontophoresis sweat extraction module and paper microfluidics for real-time sweat analysis. Several parameters can be simultaneously quantified, including sweat volume, secretion rate, sodium ion, and cortisol concentration. Paper microfluidic modules not only quantify sweat volume and secretion rate but also facilitate continuous sweat analysis without user intervention. While we focus on cortisol sensing as a proof-of-concept, the molecularly imprinted wearable sensors can be extended to real-time detection of other biochemicals, such as protein biomarkers and therapeutic drugs.

Polymorphic Self-Assembly with Procedural Flexibility for Monodisperse Quaternary Protein Structures of DegQ Enzymes.

As large molecular tertiary structures, some proteins can act as small robots that find, bind, and chaperone target protein clients, showing the potential to serve as smart building blocks in self-assembly fields. Instead of using such intrinsic functions, most self-assembly methodologies for proteins aim for de novo-designed structures with accurate geometric assemblies, which can limit procedural flexibility. Here, a strategy enabling polymorphic clustering of quaternary proteins, exhibiting simplicity and flexibility of self-assembling paths for proteins in forming monodisperse quaternary cage particles is presented. It is proposed that the enzyme protomer DegQ, previously solved at low resolution, may potentially be usable as a threefold symmetric building block, which can form polyhedral cages incorporated by the chaperone action of DegQ in the presence of protein clients. To obtain highly monodisperse cage particles, soft, and hence, less resistive client proteins, which can program the inherent chaperone activity of DegQ to efficient formations of polymorphic cages, depending on the size of clients are utilized. By reconstructing the atomic resolution cryogenic electron microscopy DegQ structures using obtained 12- and 24-meric clusters, the polymorphic clustering of DegQ enzymes is validated in terms of soft and rigid domains, which will provide effective routes for protein self-assemblies with procedural flexibility.

Add-on soft electronic interfaces for continuous cuffless blood pressure monitoring.

Continuous monitoring of arterial blood pressure is clinically important for the diagnosis and management of cardiovascular diseases. Soft electronic devices with skin-like properties show promise in a wide range of applications, including the human-machine interface, the Internet of things, and health monitoring. Here, we report the use of add-on soft electronic interfaces to address the connection challenges between soft electrodes and rigid data acquisition circuitry for bioimpedance monitoring of cardiac signals, including heart rate and cuffless blood pressure. Nanocomposite films in add-on electrodes provide robust electrical and mechanical contact with the skin and the rigid circuitry. We demonstrate bioimpedance sensors composed of add-on electrodes for continuous blood pressure monitoring with high accuracy. Specifically, the bioimpedance collected with add-on nanocomposite electrodes shows a signal-to-noise ratio of 37.0 dB, higher than the ratio of 25.9 dB obtained with standard silver/silver chloride (Ag/AgCl gel) electrodes. Although the sample set is low, the continuously measured systolic and diastolic blood pressure offer accuracy of -2.0 ± 6.3 mmHg and -4.3 ± 3.9 mmHg, respectively, confirming the grade A performance based on the IEEE standard. These results show promise in bioimpedance measurements with add-on soft electrodes for cuffless blood pressure monitoring.

Moldable and Transferrable Conductive Nanocomposites for Epidermal Electronics.

Skin-inspired soft and stretchable electronic devices based on functional nanomaterials have broad applications such as health monitoring, human-machine interface, and the Internet of things. Solution-processed conductive nanocomposites have shown great promise as a building block of soft and stretchable electronic devices. However, realizing conductive nanocomposites with high conductivity, electromechanical stability, and low modulus over a large area at sub-100 µm resolution remains challenging. Here, we report a moldable, transferrable, high-performance conductive nanocomposite comprised of an interpenetrating network of silver nanowires and poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate). The stacked structure of the nanocomposite synergistically integrates the complementary electrical and mechanical properties of the individual components. We patterned the nanocomposite via a simple, low-cost micromolding process and then transferred the patterned large-area electrodes onto various substrates to realize soft, skin-interfaced electrophysiological sensors. Electrophysiological signals measured using the nanocomposite electrodes exhibit a higher signal-to-noise ratio than standard gel electrodes. The nanocomposite design and fabrication approach presented here can be broadly employed for soft and stretchable electronic devices.

Wearable plasmonic paper-based microfluidics for continuous sweat analysis.

Wearable sweat sensors have the potential to provide clinically meaningful information associated with the health and disease states of individuals. Current sensors mainly rely on enzymes and antibodies as biorecognition elements to achieve specific quantification of metabolite and stress biomarkers in sweat. However, enzymes and antibodies are prone to degrade over time, compromising the sensor performance. Here, we introduce a wearable plasmonic paper-based microfluidic system for continuous and simultaneous quantitative analysis of sweat loss, sweat rate, and metabolites in sweat. Plasmonic sensors based on label-free surface-enhanced Raman spectroscopy (SERS) can provide chemical "fingerprint" information for analyte identification. We demonstrate the sensitive detection and quantification of uric acid in sweat at physiological and pathological concentrations. The well-defined flow characteristics of paper microfluidic devices enable accurate quantification of sweat loss and sweat rate. The wearable plasmonic device is soft, flexible, and stretchable, which can robustly interface with the skin without inducing chemical or physical irritation.

Printed Ultrastable Bioplasmonic Microarrays for Point-of-Need Biosensing.

Paper-based point-of-need (PON) biosensors are attractive for various applications, including food safety, agriculture, disease diagnosis, and drug screening, owing to their low cost and ease of use. However, existing paper-based biosensors mainly rely on biolabels, colorimetric reagents, and biorecognition elements and exhibit limited stability under harsh environments. Here, we report a label-free paper-based biosensor composed of bioplasmonic microarrays for sensitive detection and quantification of protein targets in small volumes of biofluids. Bioplasmonic microarrays were printed using an ultrastable bioplasmonic ink, rendering the PON sensors excellent thermal, chemical, and biological stability for their reliable performance in resource-limited settings. We fabricated silicone hydrophobic barriers and bioplasmonic microarrays with direct writing and droplet jetting approaches on a three-dimensional (3D) nanoporous paper. Direct writing hydrophobic barriers can define hydrophilic channels less than 100 µm wide. High-resolution patterning of hydrophilic test domains enables the handling and analysis of small fluid volumes. We show that the plasmonic sensors based on a vertical flow assay provide similar sensitivity and low limit of detection with a 60 µL sample volume compared to those with 500 µL samples based on an immersion approach and can shorten assay time from 90 to 20 min.

Nanoengineered Ink for Designing 3D Printable Flexible Bioelectronics.

Flexible electronics require elastomeric and conductive biointerfaces with native tissue-like mechanical properties. The conventional approaches to engineer such a biointerface often utilize conductive nanomaterials in combination with polymeric hydrogels that are cross-linked using toxic photoinitiators. Moreover, these systems frequently demonstrate poor biocompatibility and face trade-offs between conductivity and mechanical stiffness under physiological conditions. To address these challenges, we developed a class of shear-thinning hydrogels as biomaterial inks for 3D printing flexible bioelectronics. These hydrogels are engineered through a facile vacancy-driven gelation of MoS2 nanoassemblies with naturally derived polymer-thiolated gelatin. Due to shear-thinning properties, these nanoengineered hydrogels can be printed into complex shapes that can respond to mechanical deformation. The chemically cross-linked nanoengineered hydrogels demonstrate a 20-fold rise in compressive moduli and can withstand up to 80% strain without permanent deformation, meeting human anatomical flexibility. The nanoengineered network exhibits high conductivity, compressive modulus, pseudocapacitance, and biocompatibility. The 3D-printed cross-linked structure demonstrates excellent strain sensitivity and can be used as wearable electronics to detect various motion dynamics. Overall, the results suggest that these nanoengineered hydrogels offer improved mechanical, electronic, and biological characteristics for various emerging biomedical applications including 3D-printed flexible biosensors, actuators, optoelectronics, and therapeutic delivery devices.

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.

Wireless sensors for continuous, multimodal measurements at the skin interface with lower limb prostheses.

Precise form-fitting of prosthetic sockets is important for the comfort and well-being of persons with limb amputations. Capabilities for continuous monitoring of pressure and temperature at the skin-prosthesis interface can be valuable in the fitting process and in monitoring for the development of dangerous regions of increased pressure and temperature as limb volume changes during daily activities. Conventional pressure transducers and temperature sensors cannot provide comfortable, irritation-free measurements because of their relatively rigid construction and requirements for wired interfaces to external data acquisition hardware. Here, we introduce a millimeter-scale pressure sensor that adopts a soft, three-dimensional design that integrates into a thin, flexible battery-free, wireless platform with a built-in temperature sensor to allow operation in a noninvasive, imperceptible fashion directly at the skin-prosthesis interface. The sensor system mounts on the surface of the skin of the residual limb, in single or multiple locations of interest. A wireless reader module attached to the outside of the prosthetic socket wirelessly provides power to the sensor and wirelessly receives data from it, for continuous long-range transmission to a standard consumer electronic device such as a smartphone or tablet computer. Characterization of both the sensor and the system, together with theoretical analysis of the key responses, illustrates linear, accurate responses and the ability to address the entire range of relevant pressures and to capture skin temperature accurately, both in a continuous mode. Clinical application in two prosthesis users demonstrates the functionality and feasibility of this soft, wireless system.

Skin-interfaced biosensors for advanced wireless physiological monitoring in neonatal and pediatric intensive-care units.

Standard clinical care in neonatal and pediatric intensive-care units (NICUs and PICUs, respectively) involves continuous monitoring of vital signs with hard-wired devices that adhere to the skin and, in certain instances, can involve catheter-based pressure sensors inserted into the arteries. These systems entail risks of causing iatrogenic skin injuries, complicating clinical care and impeding skin-to-skin contact between parent and child. Here we present a wireless, non-invasive technology that not only offers measurement equivalency to existing clinical standards for heart rate, respiration rate, temperature and blood oxygenation, but also provides a range of important additional features, as supported by data from pilot clinical studies in both the NICU and PICU. These new modalities include tracking movements and body orientation, quantifying the physiological benefits of skin-to-skin care, capturing acoustic signatures of cardiac activity, recording vocal biomarkers associated with tonality and temporal characteristics of crying and monitoring a reliable surrogate for systolic blood pressure. These platforms have the potential to substantially enhance the quality of neonatal and pediatric critical care.

Binodal, wireless epidermal electronic systems with in-sensor analytics for neonatal intensive care.

Existing vital sign monitoring systems in the neonatal intensive care unit (NICU) require multiple wires connected to rigid sensors with strongly adherent interfaces to the skin. We introduce a pair of ultrathin, soft, skin-like electronic devices whose coordinated, wireless operation reproduces the functionality of these traditional technologies but bypasses their intrinsic limitations. The enabling advances in engineering science include designs that support wireless, battery-free operation; real-time, in-sensor data analytics; time-synchronized, continuous data streaming; soft mechanics and gentle adhesive interfaces to the skin; and compatibility with visual inspection and with medical imaging techniques used in the NICU. Preliminary studies on neonates admitted to operating NICUs demonstrate performance comparable to the most advanced clinical-standard monitoring 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.