A flexible and highly sensitive organic electrochemical transistor-based biosensor for continuous and wireless nitric oxide detection.

As nitric oxide (NO) plays significant roles in a variety of physiological processes, the capability for real-time and accurate detection of NO in live organisms is in great demand. Traditional assessments of NO rely on indirect colorimetric techniques or electrochemical sensors that often comprise rigid constituent materials and can hardly satisfy sensitivity and spatial resolution simultaneously. Here, we report a flexible and highly sensitive biosensor based on organic electrochemical transistors (OECTs) capable of continuous and wireless detection of NO in biological systems. By modifying the geometry of the active channel and the gate electrodes of OECTs, devices achieve optimum signal amplification of NO. The sensor exhibits a low response limit, a wide linear range, high sensitivity, and excellent selectivity, with a miniaturized active sensing region compared with a conventional electrochemical sensor. The device demonstrates continuous detection of the nanomolar range of NO in cultured cells for hours without significant signal drift. Real-time and wireless measurement of NO is accomplished for 8 d in the articular cavity of New Zealand White rabbits with anterior cruciate ligament (ACL) rupture injuries. The observed high level of NO is associated with the onset of osteoarthritis (OA) at the later stage. The proposed device platform could provide critical information for the early diagnosis of chronic diseases and timely medical intervention to optimize therapeutic efficacy.

Recent progress in multifunctional, reconfigurable, integrated liquid metal-based stretchable sensors and standalone systems.

Possessing a unique combination of properties that are traditionally contradictory in other natural or synthetical materials, Ga-based liquid metals (LMs) exhibit low mechanical stiffness and flowability like a liquid, with good electrical and thermal conductivity like metal, as well as good biocompatibility and room-temperature phase transformation. These remarkable properties have paved the way for the development of novel reconfigurable or stretchable electronics and devices. Despite these outstanding properties, the easy oxidation, high surface tension, and low rheological viscosity of LMs have presented formidable challenges in high-resolution patterning. To address this challenge, various surface modifications or additives have been employed to tailor the oxidation state, viscosity, and patterning capability of LMs. One effective approach for LM patterning is breaking down LMs into microparticles known as liquid metal particles (LMPs). This facilitates LM patterning using conventional techniques such as stencil, screening, or inkjet printing. Judiciously formulated photo-curable LMP inks or the introduction of an adhesive seed layer combined with a modified lift-off process further provide the micrometer-level LM patterns. Incorporating porous and adhesive substrates in LM-based electronics allows direct interfacing with the skin for robust and long-term monitoring of physiological signals. Combined with self-healing polymers in the form of substrates or composites, LM-based electronics can provide mechanical-robust devices to heal after damage for working in harsh environments. This review provides the latest advances in LM-based composites, fabrication methods, and their novel and unique applications in stretchable or reconfigurable sensors and resulting integrated systems. It is believed that the advancements in LM-based material preparation and high-resolution techniques have opened up opportunities for customized designs of LM-based stretchable sensors, as well as multifunctional, reconfigurable, highly integrated, and even standalone systems.

Highly Sensitive Wearable Sensor Based on (001)-Orientated TiO2 for Real-Time Electrochemical Detection of Dopamine, Tyrosine, and Paracetamol.

The concentration of dopamine (DA) and tyrosine (Tyr) reflects the condition of patients with Parkinson's disease, whereas moderate paracetamol (PA) can help relieve their pain. Therefore, real-time measurements of these bioanalytes have important clinical implications for patients with Parkinson's disease. However, previous sensors suffer from either limited sensitivity or complex fabrication and integration processes. This work introduces a simple and cost-effective method to prepare high-quality, flexible titanium dioxide (TiO2) thin films with highly reactive (001)-facets. The as-fabricated TiO2 film supported by a carbon cloth electrode (i.e., TiO2-CC) allows excellent electrochemical specificity and sensitivity to DA (1.390 µA µM-1 cm-2), Tyr (0.126 µA µM-1 cm-2), and PA (0.0841 µA µM-1 cm-2). More importantly, accurate DA concentration in varied pH conditions can be obtained by decoupling them within a single differential pulse voltammetry measurement without additional sensing units. The TiO2-CC electrochemical sensor can be integrated into a smart diaper to detect the trace amount of DA or an integrated skin-interfaced patch with microfluidic sampling and wireless transmission units for real-time detection of the sweat Try and PA concentration. The wearable sensor based on TiO2-CC prepared by facile manufacturing methods holds great potential in the daily health monitoring and care of patients with neurological disorders.

Laser Processing of Crumpled Porous Graphene/MXene Nanocomposites for a Standalone Gas Sensing System.

Integrating wearable gas sensors with energy harvesting and storage devices can create self-powered systems for continuous monitoring of gaseous molecules. However, the development is still limited by complex fabrication processes, poor stretchability, and sensitivity. Herein, we report the low-cost and scalable laser scribing of crumpled graphene/MXenes nanocomposite foams to combine stretchable self-charging power units with gas sensors for a fully integrated standalone gas sensing system. The crumpled nanocomposite designed in island-bridge device architecture allows the integrated self-charging unit to efficiently harvest kinetic energy from body movements into stable power with adjustable voltage/current outputs. Meanwhile, given the stretchable gas sensor with a large response of ∼1% ppm-1 and an ultralow detection limit of ∼5 ppb to NO2/NH3, the integrated system provides real-time monitoring of the exhaled human breath and the local air quality. The innovations in materials and structural designs pave the way for the future development of wearable electronics.

Pencil-on-Paper Humidity Sensor Treated with NaCl Solution for Health Monitoring and Skin Characterization.

Although flexible humidity sensors are essential for human health monitoring, it is still challenging to achieve high sensitivity and easy disposal with simple, low-cost fabrication processes. This study presents the design and fabrication of highly reliable hand-drawn interdigital electrodes from pencil-on-paper treated with NaCl solution for highly sensitive hydration sensors working over a wide range of relative humidity (RH) levels from 5.6% to 90%. The applications of the resulting flexible humidity sensor go beyond the monitoring of respiratory rate and proximity to characterizations of human skin types and evaluations of skin barrier functions through insensible sweat measurements. The sensor array can also be integrated with a diaper to result in smart diapers to alert for an early diaper change. The design and fabrication strategies presented in this work could also be leveraged for the development of wearable, self-powered, and recyclable sensors and actuators in the future.

A highly sensitive and long-term stable wearable patch for continuous analysis of biomarkers in sweat.

Although increasing efforts have been devoted to the development of non-invasive wearable or stretchable electrochemical sweat sensors for monitoring physiological and metabolic information, most of them still suffer from poor stability and specificity over time and fluctuating temperatures. This study reports the design and fabrication of a long-term stable and highly sensitive flexible electrochemical sensor based on nanocomposite-modified porous graphene by simple and facile laser treatment for detecting biomarkers such as glucose in sweat. The laser-reduced and patterned stable conductive nanocomposite on the porous graphene electrode provides the resulting glucose sensor with an excellent sensitivity of 1317.69 µAmM-1cm-2 with an ultra-low limit of detection (LOD) of 0.079 µM. The sensor can also detect pH and exhibit extraordinary stability to maintain more than 91% sensitivity over 21 days in ambient conditions. Taken together with a temperature sensor based on the same material system, the dual glucose and pH sensor integrated with a flexible microfluidic sweat sampling network further results in accurate continuous on-body glucose detection calibrated by the simultaneously measured pH and temperature. The low-cost, highly sensitive, and long-term stable platform could facilitate and pave the way for the early identification and continuous monitoring of different biomarkers for non-invasive disease diagnosis and treatment evaluation.

Ultrathin Crystalline Silicon Nano and Micro Membranes with High Areal Density for Low-Cost Flexible Electronics.

Ultrathin crystalline silicon is widely used as an active material for high-performance, flexible, and stretchable electronics, from simple passive and active components to complex integrated circuits, due to its excellent electrical and mechanical properties. However, in contrast to conventional silicon wafer-based devices, ultrathin crystalline silicon-based electronics require an expensive and rather complicated fabrication process. Although silicon-on-insulator (SOI) wafers are commonly used to obtain a single layer of crystalline silicon, they are costly and difficult to process. Therefore, as an alternative to SOI wafers-based thin layers, here, a simple transfer method is proposed for printing ultrathin multiple crystalline silicon sheets with thicknesses between 300 nm to 13 µm and high areal density (>90%) from a single mother wafer. Theoretically, the silicon nano/micro membrane can be generated until the mother wafer is completely consumed. In addition, the electronic applications of silicon membranes are successfully demonstrated through the fabrication of a flexible solar cell and flexible NMOS transistor arrays.

Role of an FNIP Repeat Domain-Containing Protein Encoded by Megavirus Baoshan during Viral Infection.

FNIP repeat domain-containing protein (FNIP protein) is a little-studied atypical leucine-rich repeat domain-containing protein found in social amoebae and mimiviruses. Here, a recently reported mimivirus of lineage C, Megavirus baoshan, was analyzed for FNIP protein genes. A total of 82 FNIP protein genes were identified, each containing up to 26 copies of the FNIP repeat, and mostly having an F-box domain at the N terminus. Both nucleotide and amino acid sequences of FNIP repeat were highly conserved. Most of the FNIP protein genes clustered together tandemly in groups of two to 14 genes. Nearly all FNIP protein genes shared similar expression patterns and were expressed 4 to 9 h postinfection. A typical viral FNIP protein, Mb0983, was selected for functional analysis. Protein interactome analysis identified two small GTPases, Rap1B and Rab7A, that interacted with Mb0983 in cytoplasm. The overexpression of Mb0983 in Acanthamoeba castellanii accelerated the degradation of Rap1B and Rab7A during viral infection. Mb0983 also interacted with host SKP1 and cullin-1, which were conserved components of the SKP1-cullin-1-F-box protein (SCF)-type ubiquitin E3 ligase complex. Deletion of the F-box domain of Mb0983 not only abolished its interaction with SKP1 and cullin-1 but also returned the speed of Rap1B and Rab7A degradation to normal in infected A. castellanii. These results suggested that Mb0983 is a part of the SCF-type ubiquitin E3 ligase complex and plays a role in the degradation of Rap1B and Rab7A. They also implied that other viral F-box-containing FNIP proteins might have similar effects on various host proteins. IMPORTANCE Megavirus baoshan encodes 82 FNIP proteins, more than any other reported mimiviruses. Their genetic and transcriptional features suggest that they are important for virus infection and adaption. Since most mimiviral FNIP proteins have the F-box domain, they were predicted to be involved in protein ubiquitylation. FNIP protein Mb0983 interacted with host SKP1 and cullin-1 through the F-box domain, supporting the idea that it is a part of the SCF-type ubiquitin E3 ligase complex. The substrates of Mb0983 for degradation were identified as the host small GTPases Rap1B and Rab7A. Combining the facts of the presence of a large number of FNIP genes in megavirus genomes, the extremely high expression level of the viral ubiquitin gene, and the reported observation that 35% of megavirus-infected amoeba cells died without productive infection, it is likely that megavirus actively explores the host ubiquitin-proteasome pathway in infection and that viral FNIP proteins play roles in the process.

In situ laser-assisted synthesis and patterning of graphene foam composites as a flexible gas sensing platform.

Gas-sensitive semiconducting nanomaterials (e.g., metal oxides, graphene oxides, and transition metal dichalcogenides) and their heterojunctions hold great promise in chemiresistive gas sensors. However, they often require a separate synthesis method (e.g., hydrothermal, so-gel, and co-precipitation) and their integration on interdigitated electrodes (IDE) via casting is also associated with weak interfacial properties. This work demonstrates in situ laser-assisted synthesis and patterning of various sensing nanomaterials and their heterojunctions on laser-induced graphene (LIG) foam to form LIG composites as a flexible and stretchable gas sensing platform. The porous LIG line or pattern with nanomaterial precursors dispensed on top is scribed by laser to allow for in situ growth of corresponding nanomaterials. The versatility of the proposed method is highlighted through the creation of different types of gas-sensitive materials, including transition metal dichalcogenide (e.g., MoS2), metal oxide (e.g., CuO), noble metal-doped metal oxide (e.g., Ag/ZnO) and composite metal oxides (e.g., In2O3/Cr2O3). By eliminating the IDE and separate heaters, the LIG gas sensing platform with self-heating also decreases the device complexity. The limit of detection (LOD) of the LIG gas sensor with in situ synthesized MoS2, CuO, and Ag/ZnO to NO2, H2S, and trimethylamine (TMA) is 2.7, 9.8, and 5.6 ppb, respectively. Taken together with the high sensitivity, good selectivity, rapid response/recovery, and tunable operating temperature, the integrated LIG gas sensor array can identify multiple gas species in the environment or exhaled breath.

Superhydrophobic, stretchable kirigami pencil-on-paper multifunctional device platform.

Wearable electronics with applications in healthcare, human-machine interfaces, and robotics often explore complex manufacturing procedures and are not disposable. Although the use of conductive pencil patterns on cellulose paper provides inexpensive, disposable sensors, they have limited stretchability and are easily affected by variations in the ambient environment. This work presents the combination of pencil-on-paper with the hydrophobic fumed SiO2 (Hf-SiO2) coating and stretchable kirigami structures from laser cutting to prepare a superhydrophobic, stretchable pencil-on-paper multifunctional sensing platform. The resulting sensor exhibits a large response to NO2 gas at elevated temperature from self-heating, which is minimally affected by the variations in the ambient temperature and relative humidity, as well as mechanical deformations such as bending and stretching states. The integrated temperature sensor and electrodes with the sensing platform can accurately detect temperature and electrophysiological signals to alert for adverse thermal effects and cardiopulmonary diseases. The thermal therapy and electrical stimulation provided by the platform can also deliver effective means to battle against inflammation/infection and treat chronic wounds. The superhydrophobic pencil-onpaper multifunctional device platform provides a low-cost, disposable solution to disease diagnostic confirmation and early treatment for personal and population health.

Surface Wettability for Skin-Interfaced Sensors and Devices.

The practical applications of skin-interfaced sensors and devices in daily life hinge on the rational design of surface wettability to maintain device integrity and achieve improved sensing performance under complex hydrated conditions. Various bio-inspired strategies have been implemented to engineer desired surface wettability for varying hydrated conditions. Although the bodily fluids can negatively affect the device performance, they also provide a rich reservoir of health-relevant information and sustained energy for next-generation stretchable self-powered devices. As a result, the design and manipulation of the surface wettability are critical to effectively control the liquid behavior on the device surface for enhanced performance. The sensors and devices with engineered surface wettability can collect and analyze health biomarkers while being minimally affected by bodily fluids or ambient humid environments. The energy harvesters also benefit from surface wettability design to achieve enhanced performance for powering on-body electronics. In this review, we first summarize the commonly used approaches to tune the surface wettability for target applications toward stretchable self-powered devices. By considering the existing challenges, we also discuss the opportunities as a small fraction of potential future developments, which can lead to a new class of skin-interfaced devices for use in digital health and personalized medicine.

Bioresorbable silicon electronic sensors for the brain.

Many procedures in modern clinical medicine rely on the use of electronic implants in treating conditions that range from acute coronary events to traumatic injury. However, standard permanent electronic hardware acts as a nidus for infection: bacteria form biofilms along percutaneous wires, or seed haematogenously, with the potential to migrate within the body and to provoke immune-mediated pathological tissue reactions. The associated surgical retrieval procedures, meanwhile, subject patients to the distress associated with re-operation and expose them to additional complications. Here, we report materials, device architectures, integration strategies, and in vivo demonstrations in rats of implantable, multifunctional silicon sensors for the brain, for which all of the constituent materials naturally resorb via hydrolysis and/or metabolic action, eliminating the need for extraction. Continuous monitoring of intracranial pressure and temperature illustrates functionality essential to the treatment of traumatic brain injury; the measurement performance of our resorbable devices compares favourably with that of non-resorbable clinical standards. In our experiments, insulated percutaneous wires connect to an externally mounted, miniaturized wireless potentiostat for data transmission. In a separate set-up, we connect a sensor to an implanted (but only partially resorbable) data-communication system, proving the principle that there is no need for any percutaneous wiring. The devices can be adapted to sense fluid flow, motion, pH or thermal characteristics, in formats that are compatible with the body's abdomen and extremities, as well as the deep brain, suggesting that the sensors might meet many needs in clinical medicine.

Moisture-resistant MXene-sodium alginate sponges with sustained superhydrophobicity for monitoring human activities.

Wearable mechanical sensors are easily influenced by moisture resulting in inaccuracy for monitoring human health and body motions. Though the superhydrophobic barrier has been extensively explored as passive water repel strategy on the sensor surface, the dense superhydrophobic surface not only limits the sensor working under large deformations but also inevitable degradation in high humidity or saturation water vapor environments. This work reports a superhydrophobic MXene-sodium alginate sponge (SMSS) pressure sensor with a low voltage Joule heating effect to provide sustain moisture-insensitive property for both sensing performance and superhydrophobicity by heating-driven water molecules away. Because of the positive temperature coefficient under pressure applied, the Joule heating can provides a stable temperature to the moisture-insensitivity property during the whole dynamic pressure cycled. Therefore, the pressure sensor with a simple spray-coating superhydrophobic coating on the outer layer demonstrates key capabilities even in extreme use scenarios with high humidity or water vapor and also provides stable and reliable bio-signal monitoring.

Fabricating functional circuits on 3D freeform surfaces via intense pulsed light-induced zinc mass transfer.

Deployment of functional circuits on a 3D freeform surface is of significant interest to wearable devices on curvilinear skin/tissue surfaces or smart Internet-of-Things with sensors on 3D objects. Here we present a new fabrication strategy that can directly print functional circuits either transient or long-lasting onto freeform surfaces by intense pulsed light-induced mass transfer of zinc nanoparticles (Zn NPs). The intense pulsed light can locally raise the temperature of Zn NPs to cause evaporation. Lamination of a kirigami-patterned soft semi-transparent polymer film with Zn NPs conforming to a 3D surface results in condensation of Zn NPs to form conductive yet degradable Zn patterns onto a 3D freeform surface for constructing transient electronics. Immersing the Zn patterns into a copper sulfate or silver nitrate solution can further convert the transient device to a long-lasting device with copper or silver. Functional circuits with integrated sensors and a wireless communication component on 3D glass beakers and seashells with complex surface geometries demonstrate the viability of this manufacturing strategy.

Stretchable gas sensors for detecting biomarkers from humans and exposed environments.

The recent advent of stretchable gas sensors demonstrates their capabilities to detect not only gaseous biomarkers from the human body but also toxic gas species from the exposed environment. To ensure accurate gas detection without device breakdown from the mechanical deformations, the stretchable gas sensors often rely on the direct integration of gas-sensitive nanomaterials on the stretchable substrate or fibrous network, as well as being configured into stretchable structures. The nanomaterials in the forms of nanoparticles, nanowires, or thin-films with nanometer thickness are explored for a variety of sensing materials. The commonly used stretchable structures in the stretchable gas sensors include wrinkled structures from a pre-strain strategy, island-bridge layouts or serpentine interconnects, strain isolation approaches, and their combinations. This review aims to summarize the recent advancement in novel nanomaterials, sensor design innovations, and new fabrication approaches of stretchable gas sensors.

Soft, curved electrode systems capable of integration on the auricle as a persistent brain-computer interface.

Recent advances in electrodes for noninvasive recording of electroencephalograms expand opportunities collecting such data for diagnosis of neurological disorders and brain-computer interfaces. Existing technologies, however, cannot be used effectively in continuous, uninterrupted modes for more than a few days due to irritation and irreversible degradation in the electrical and mechanical properties of the skin interface. Here we introduce a soft, foldable collection of electrodes in open, fractal mesh geometries that can mount directly and chronically on the complex surface topology of the auricle and the mastoid, to provide high-fidelity and long-term capture of electroencephalograms in ways that avoid any significant thermal, electrical, or mechanical loading of the skin. Experimental and computational studies establish the fundamental aspects of the bending and stretching mechanics that enable this type of intimate integration on the highly irregular and textured surfaces of the auricle. Cell level tests and thermal imaging studies establish the biocompatibility and wearability of such systems, with examples of high-quality measurements over periods of 2 wk with devices that remain mounted throughout daily activities including vigorous exercise, swimming, sleeping, and bathing. Demonstrations include a text speller with a steady-state visually evoked potential-based brain-computer interface and elicitation of an event-related potential (P300 wave).

Recent Development of Flexible and Stretchable Antennas for Bio-Integrated Electronics.

Wireless technology plays an important role in data communication and power transmission, which has greatly boosted the development of flexible and stretchable electronics for biomedical applications and beyond. As a key component in wireless technology, flexible and stretchable antennas need to be flexible and stretchable, enabled by the efforts with new materials or novel integration approaches with structural designs. Besides replacing the conventional rigid substrates with textile or elastomeric ones, flexible and stretchable conductive materials also need to be used for the radiation parts, including conductive textiles, liquid metals, elastomeric composites embedding conductive fillers, and stretchable structures from conventional metals. As the microwave performance of the antenna (e.g., resonance frequency, radiation pattern, and radiation efficiency) strongly depend on the mechanical deformations, the new materials and novel structures need to be carefully designed. Despite the rapid progress in the burgeoning field of flexible and stretchable antennas, plenty of challenges, as well as opportunities, still exist to achieve miniaturized antennas with a stable or tunable performance at a low cost for bio-integrated electronics.

Bioresorbable silicon electronics for transient spatiotemporal mapping of electrical activity from the cerebral cortex.

Bioresorbable silicon electronics technology offers unprecedented opportunities to deploy advanced implantable monitoring systems that eliminate risks, cost and discomfort associated with surgical extraction. Applications include postoperative monitoring and transient physiologic recording after percutaneous or minimally invasive placement of vascular, cardiac, orthopaedic, neural or other devices. We present an embodiment of these materials in both passive and actively addressed arrays of bioresorbable silicon electrodes with multiplexing capabilities, which record in vivo electrophysiological signals from the cortical surface and the subgaleal space. The devices detect normal physiologic and epileptiform activity, both in acute and chronic recordings. Comparative studies show sensor performance comparable to standard clinical systems and reduced tissue reactivity relative to conventional clinical electrocorticography (ECoG) electrodes. This technology offers general applicability in neural interfaces, with additional potential utility in treatment of disorders where transient monitoring and modulation of physiologic function, implant integrity and tissue recovery or regeneration are required.

Real Time Analysis of Bioanalytes in Healthcare, Food, Zoology and Botany.

The growing demand for real time analysis of bioanalytes has spurred development in the field of wearable technology to offer non-invasive data collection at a low cost. The manufacturing processes for creating these sensing systems vary significantly by the material used, the type of sensors needed and the subject of study as well. The methods predominantly involve stretchable electronic sensors to monitor targets and transmit data mainly through flexible wires or short-range wireless communication devices. Capable of conformal contact, the application of wearable technology goes beyond the healthcare to fields of food, zoology and botany. With a brief review of wearable technology and its applications to various fields, we believe this mini review would be of interest to the reader in broad fields of materials, sensor development and areas where wearable sensors can provide data that are not available elsewhere.

A nonlinear mechanics model of bio-inspired hierarchical lattice materials consisting of horseshoe microstructures.

Development of advanced synthetic materials that can mimic the mechanical properties of non-mineralized soft biological materials has important implications in a wide range of technologies. Hierarchical lattice materials constructed with horseshoe microstructures belong to this class of bio-inspired synthetic materials, where the mechanical responses can be tailored to match the nonlinear J-shaped stress-strain curves of human skins. The underlying relations between the J-shaped stress-strain curves and their microstructure geometry are essential in designing such systems for targeted applications. Here, a theoretical model of this type of hierarchical lattice material is developed by combining a finite deformation constitutive relation of the building block (i.e., horseshoe microstructure), with the analyses of equilibrium and deformation compatibility in the periodical lattices. The nonlinear J-shaped stress-strain curves and Poisson ratios predicted by this model agree very well with results of finite element analyses (FEA) and experiment. Based on this model, analytic solutions were obtained for some key mechanical quantities, e.g., elastic modulus, Poisson ratio, peak modulus, and critical strain around which the tangent modulus increases rapidly. A negative Poisson effect is revealed in the hierarchical lattice with triangular topology, as opposed to a positive Poisson effect in hierarchical lattices with Kagome and honeycomb topologies. The lattice topology is also found to have a strong influence on the stress-strain curve. For the three isotropic lattice topologies (triangular, Kagome and honeycomb), the hierarchical triangular lattice material renders the sharpest transition in the stress-strain curve and relative high stretchability, given the same porosity and arc angle of horseshoe microstructure. Furthermore, a demonstrative example illustrates the utility of the developed model in the rapid optimization of hierarchical lattice materials for reproducing the desired stress-strain curves of human skins. This study provides theoretical guidelines for future designs of soft bio-mimetic materials with hierarchical lattice constructions.