Personalized Machine Learning-Coupled Nanopillar Triboelectric Pulse Sensor for Cuffless Blood Pressure Continuous Monitoring.

A wearable system that can continuously track the fluctuation of blood pressure (BP) based on pulse signals is highly desirable for the treatments of cardiovascular diseases, yet the sensitivity, reliability, and accuracy remain challenging. Since the correlations of pulse waveforms to BP are highly individualized due to the diversity of the patients' physiological characteristics, wearable sensors based on universal designs and algorithms often fail to derive BP accurately when applied on individual patients. Herein, a wearable triboelectric pulse sensor based on a biomimetic nanopillar layer was developed and coupled with Personalized Machine Learning (ML) to provide accurate and continuous monitoring of BP. Flexible conductive nanopillars as the triboelectric layer were fabricated through soft lithography replication of a cicada wing, which could effectively enhance the sensor's output performance to detect weak signal characteristics of pulse waveform for BP derivation. The sensors were coupled with a personalized Partial Least-Squares Regression (PLSR) ML to derive unknown BP based on individual pulse characteristics with reasonable accuracy, avoiding the issue of individual variability that was encountered by General PLSR ML or formula algorithms. The cuffless and intelligent design endow this ML-sensor as a highly promising platform for the care and treatments of hypertensive patients.

A 3D-printed microneedle extraction system integrated with patterned electrodes for minimally invasive transdermal detection.

Point-of-Care-Testing (POCT) is a convenient and timely clinical analysis method, leading the development trend of advanced biosensors. The development of POCT equipment that can achieve minimally invasive percutaneous monitoring can avoid the pain felt by the subjects and achieve in vivo and efficient measurement. Here, we reported the development of a microneedle (MN) extraction system based on patterned electrodes, which could provide convenient and minimally invasive detection of bio-analytes (including glucose, pH, and H2O2). The 3D-printed hollow MN array was used as a painless transdermal tool, while the interstitial fluid was extracted under negative-pressure conditions. The patterned electrodes could improve the electrochemical performance of the sensor, with the synergistic effect of the micropillar structure to increase the enzyme coating surface area and the nanomaterial electron layer. The patterned electrodes were placed on the back of the MN arrays for electrochemical detection. In vitro and in vivo studies showed that the MN-extraction system could detect the corresponding bio-analytes in a minimally invasive manner and it did not cause significant tissue damage. The system developed in this work will provide promising technology to expand the application of POCT for minimal tests on interstitial fluids.

Capacitive-piezoresistive hybrid flexible pressure sensor based on conductive micropillar arrays with high sensitivity over a wide dynamic range.

Flexible pressure sensors are the foundation of wearable/implantable biosensing and human-machine interfaces, and mainly comprise piezoresistive-, capacitive-, piezoelectric-, and triboelectric-type sensors. As each type of sensor exhibits different electro-mechanical behaviors, it is challenging to detect various physiological mechanical signals that cover a large pressure range using a given sensor configuration, or even a single type of sensor. Here, we report a capacitive-piezoresistive hybrid flexible pressure sensor based on face-to-face-mounted conductive micropillar arrays as a solution to this challenge. The sensor exhibited high sensitivity over a wide dynamic range of five orders of magnitude, which covers almost the full range of physiological mechanical signals. A process for fabricating large-scale and morphologically homogeneous conductive micropillar arrays was first developed and refined. This track-etched-membrane-based process provides a facile, cost-effective, and highly flexible way to precisely adjust the morphology, modulus, and conductivity of the micropillars according to the application requirements. Subsequently, conductive-micropillar-array-based pressure sensors (MAPS) were developed and optimized to attain all-round sensing performance. The pillar contact behaviors generated significant variations in both the capacitance and resistance of the MAPS in the low-pressure regime (10-4-0.2 kPa), providing high sensitivity in both the capacitive and piezoresistive working modes. The vertical contact, bending and thickening of the pillars under medium pressure (0.2-16 kPa) led to a continuous linear response in both modes. Configuration and optimization enabled the MAPS to detect acoustic pressure (<1 Pa), milligram weights, soft touch (<1 kPa), arterial pulses (1-16 kPa preload), joint motions and plantar pressure (∼100 kPa), and the hybrid sensing mode allowed the MAPS to work in a desirable way. In this work, the piezoresistive mode was mainly employed for a higher accuracy and sampling rate, and can apparently simplify IC design for wearable applications. The circuit converts the resistive variations into electrical signals via the voltage division method and directly reads out the signals after further amplification, filtering and transmission. The improved facile and highly adjustable fabrication process, as well as the flexible hybrid sensing strategy, will benefit the unified design, batch production, quantifiable optimization, and functional diversity of wearable/implantable bioelectronics.

Wireless-Powered Electrical Bandage Contact Lens for Facilitating Corneal Wound Healing.

Corneal injury can lead to severe vision impairment or even blindness. Although numerous methods are developed to accelerate corneal wound healing, most of them are passive treatments that rarely participate in controlling endogenous cell behaviors or are incompatible with nontransparent bandage. In this work, a wireless-powered electrical bandage contact lens (EBCL) is developed to generate a localized external electric field to accelerate corneal wound healing and vision recovery. The wireless electrical stimulation circuit employed a flower-shaped layout design that can be compactly integrated on bandage contact lens without blocking the vision. The role of the external electric field in promoting corneal wound healing is examined in vitro, where the responses of directional migration and corneal cells alignment to the electric field are observed. The RNA sequencing (RNA-seq) analysis indicates that the electrical stimulation can participate in controlling cell division, proliferation, and migration. Furthermore, the wireless EBCL is demonstrated to accelerate the completed recovery of corneal wounds on rabbits' eyes by electrical stimulation, while the control group exhibits delayed recovery and obvious corneal defects. As a new generation of intelligent device, the wireless and patient-friendly EBCL can provide a promising therapeutic strategy for ocular diseases.

Nanoporous Gold Ring-Integrated Photothermal Intraocular Lens for Active Prevention of Posterior Capsular Opacification.

Posterior capsular opacification (PCO) is the leading complication after cataract surgery, and is mainly induced by the proliferation and migration of residual lens epithelial cells (LECs). Although numerous attempts have been made to reduce the incidence of PCO, this complication remains a critical challenge in postoperative visual recovery. This study aims to report a functionalized intraocular lens (R-IOL) with a region-confined photothermal effect for the active prevention of PCO after implantation. The outer rim of R-IOL (non-optical area) is decorated with a nanoporous gold (NPG) ring, which can effectively eliminate the LECs around R-IOL, ultimately inhibiting the migration of LECs from the periphery to the visual axis center in the initial stage, and preventing the subsequent PCO. Furthermore, the mechanism of LECs elimination can be attributed to apoptosis induced by mild photothermal therapy. After in vivo implantation for 30 days, PCO is rarely observed in the R-IOL group, whereas the considerably higher incidence of PCO (75%) is found in the pristine IOL (P-IOL) group. The region-confined photothermal effect based on NPG not only provides an active strategy to effectively prevent PCO, but also introduces new opportunities for the treatment of undesirable hyperplasia.

Semi-Implantable Bioelectronics.

Developing techniques to effectively and real-time monitor and regulate the interior environment of biological objects is significantly important for many biomedical engineering and scientific applications, including drug delivery, electrophysiological recording and regulation of intracellular activities. Semi-implantable bioelectronics is currently a hot spot in biomedical engineering research area, because it not only meets the increasing technical demands for precise detection or regulation of biological activities, but also provides a desirable platform for externally incorporating complex functionalities and electronic integration. Although there is less definition and summary to distinguish it from the well-reviewed non-invasive bioelectronics and fully implantable bioelectronics, semi-implantable bioelectronics have emerged as highly unique technology to boost the development of biochips and smart wearable device. Here, we reviewed the recent progress in this field and raised the concept of "Semi-implantable bioelectronics", summarizing the principle and strategies of semi-implantable device for cell applications and in vivo applications, discussing the typical methodologies to access to intracellular environment or in vivo environment, biosafety aspects and typical applications. This review is meaningful for understanding in-depth the design principles, materials fabrication techniques, device integration processes, cell/tissue penetration methodologies, biosafety aspects, and applications strategies that are essential to the development of future minimally invasive bioelectronics.

Progress of flexible strain sensors for physiological signal monitoring.

Flexible strain sensors, as a key component of the cutting-edge wearable and implantable electronics, have facilitated applications pertaining to human health monitoring and diagnosis. To fulfill the increasing requirements of sensing performance and broadening the application scope, novel materials and device design strategies have been continuously developed over the past decade. Herein, the recent progresses of flexible strain sensors developed for monitoring the physiological signals are selectively reviewed, from the perspective of the possible correlation between the device microstructure and their corresponding applications. Firstly, representative strain sensors developed based on four fundamental working mechanisms: piezoresistance, capacitance, piezoelectricity and triboelectricity are respectively introduced, subclassified by the type of active material or the similarity in microstructure. Next, a number of biomedical applications of flexible strain sensors are highlighted, including the detections of different types of physiological signals using specific microstructured strain sensors. Lastly, the role of the transduction mechanism and the device microstructure in the sensing characteristic are comprehensively discussed, and prospective forms of flexible strain sensors to meet the existing and future challenges in wearable/implantable electronics are summarized.

Determination of Transdermal Rate of Metallic Microneedle Array through an Impedance Measurements-Based Numerical Check Screening Algorithm.

Microneedle systems have been widely used in health monitoring, painless drug delivery, and medical cosmetology. Although many studies on microneedle materials, structures, and applications have been conducted, the applications of microneedles often suffered from issues of inconsistent penetration rates due to the complication of skin-microneedle interface. In this study, we demonstrated a methodology of determination of transdermal rate of metallic microneedle array through impedance measurements-based numerical check screening algorithm. Metallic sheet microneedle array sensors with different sizes were fabricated to evaluate different transdermal rates. In vitro sensing of hydrogen peroxide confirmed the effect of transdermal rate on the sensing outcomes. An FEM simulation model of a microneedle array revealed the monotonous relation between the transdermal state and test current. Accordingly, two methods were primely derived to calculate the transdermal rate from the test current. First, an exact logic method provided the number of unpenetrated tips per sheet, but it required more rigorous testing results. Second, a fuzzy logic method provided an approximate transdermal rate on adjacent areas, being more applicable and robust to errors. Real-time transdermal rate estimation may be essential for improving the performance of microneedle systems, and this study provides various fundaments toward that goal.

Flexible Tongue Electrode Array System for In Vivo Mapping of Electrical Signals of Taste Sensation.

Tongue is a unique organ that senses tastes, and the scientific puzzle about whether electricity can evoke taste sensations and how the sensations have been distributed on the tongue has not been solved. Investigations on tongue stimulation by electricity might benefit the developments of techniques for clinical neuromodulation, tissue activation, and a brain-tongue-machine interface. To solve the scientific puzzle of whether electrical stimulation induces taste-related sensations, a portable flexible tongue electrode array system (FTEAS) was developed, which can synchronously provide electrical stimulation and signal mapping at each zone of the tongue. Utilizing the FTEAS to perform tests on the rat tongue in vivo, specific electrical signals were observed to be evoked by chemical and electrical stimulations. The features and distributions of the electric signals evoked during the rat tongue tests were systematically studied and comprehensively analyzed. The results show that an appropriate electrical stimulation can induce multiple sensations simultaneously, while the distribution of each sensation was not significantly distinguished among different zones of the tongue, and at the same time, this taste-related electrical signal can be recorded by the FTEAS. This work establishes a promising platform to solve the scientific puzzle of how sensations are activated chemically and electrically on the tongue and may provide advanced noninvasive oral-electrotherapy and a brain-tongue-machine interface.

Tumor-on-a-chip: from bioinspired design to biomedical application.

Cancer is one of the leading causes of human death, despite enormous efforts to explore cancer biology and develop anticancer therapies. The main challenges in cancer research are establishing an efficient tumor microenvironment in vitro and exploring efficient means for screening anticancer drugs to reveal the nature of cancer and develop treatments. The tumor microenvironment possesses human-specific biophysical and biochemical factors that are difficult to recapitulate in conventional in vitro planar cell models and in vivo animal models. Therefore, model limitations have hindered the translation of basic research findings to clinical applications. In this review, we introduce the recent progress in tumor-on-a-chip devices for cancer biology research, medicine assessment, and biomedical applications in detail. The emerging tumor-on-a-chip platforms integrating 3D cell culture, microfluidic technology, and tissue engineering have successfully mimicked the pivotal structural and functional characteristics of the in vivo tumor microenvironment. The recent advances in tumor-on-a-chip platforms for cancer biology studies and biomedical applications are detailed and analyzed in this review. This review should be valuable for further understanding the mechanisms of the tumor evolution process, screening anticancer drugs, and developing cancer therapies, and it addresses the challenges and potential opportunities in predicting drug screening and cancer treatment.

Lacidipine Ameliorates the Endothelial Senescence and Inflammatory Injury Through CXCR7/P38/C/EBP-ß Signaling Pathway.

Background: Lacidipine, a third-generation calcium channel blocker, exerts beneficial effects on the endothelium of hypertensive patients in addition to blood pressure lowering. However, the detailed mechanism underlying Lacidipine-related endothelial protection is still elusive. Methods: Sixteen spontaneous hypertensive rats (SHRs) were randomly divided into two groups: Lacidipine-treated SHR group and saline-treated control group. Tail systolic blood pressure was monitored for four consecutive weeks. Endothelial cells (ECs) were pretreated with Lacidipine prior to being stimulated with H2O2, bleomycin, or Lipopolysaccharides (LPS) in vitro. Then, cell activity, migration, and senescence were measured by Cell Counting Kit-8 assay, transwell assay, and ß-galactosidase staining, respectively. The fluorescent probe 2', 7'-dichlorofluorescein diacetate (DCFH-DA) was used to assess the intracellular reactive oxygen species (ROS). Related protein expression was detected by Western blotting and immunofluorescence. Results: Our data showed that Lacidipine treatment lowered the blood pressure of SHRs accompanied by the elevation of CXCR7 expression and suppression of P38 and CCAAT/enhancer-binding protein beta (C/EBP-ß) compared with the control group. In vitro experiments further demonstrated that Lacidipine increased the cell viability and function of ECs under oxidative stress, cell senescence, and inflammatory activation via the CXCR7/P38/signaling pathway. Conclusions: Our results suggested that Lacidipine plays a protective role in EC senescence, oxidative stress, and inflammatory injury through the regulation of CXCR7/P38/C/EBP-ß signaling pathway.

A Fully Integrated Closed-Loop System Based on Mesoporous Microneedles-Iontophoresis for Diabetes Treatment.

A closed-loop system that can mini-invasively track blood glucose and intelligently treat diabetes is in great demand for modern medicine, yet it remains challenging to realize. Microneedles technologies have recently emerged as powerful tools for transdermal applications with inherent painlessness and biosafety. In this work, for the first time to the authors' knowledge, a fully integrated wearable closed-loop system (IWCS) based on mini-invasive microneedle platform is developed for in situ diabetic sensing and treatment. The IWCS consists of three connected modules: 1) a mesoporous microneedle-reverse iontophoretic glucose sensor; 2) a flexible printed circuit board as integrated and control; and 3) a microneedle-iontophoretic insulin delivery component. As the key component, mesoporous microneedles enable the painless penetration of stratum corneum, implementing subcutaneous substance exchange. The coupling with iontophoresis significantly enhances glucose extraction and insulin delivery and enables electrical control. This IWCS is demonstrated to accurately monitor glucose fluctuations, and responsively deliver insulin to regulate hyperglycemia in diabetic rat model. The painless microneedles and wearable design endows this IWCS as a highly promising platform to improve the therapies of diabetic patients.

GPR4 signaling is essential for the promotion of acid-mediated angiogenic capacity of endothelial progenitor cells by activating STAT3/VEGFA pathway in patients with coronary artery disease.

BACKGROUND: Patients with coronary artery disease (CAD) are characterized by a decline in vascular regeneration, which is related to the dysfunction of endothelial progenitor cells (EPCs). G-protein-coupled receptor 4 (GPR4) is a proton-sensing G-protein-coupled receptor (GPCR) that contributes to neovascularization in acidic microenvironments. However, the role of GPR4 in regulating the angiogenic capacity of EPCs from CAD patients in response to acidity generated in ischemic tissue remains completely unclear. METHODS: The angiogenic capacity of EPCs collected from CAD patients and healthy subjects was evaluated in different pH environments. The GPR4 function of regulating EPC-mediated angiogenesis was analyzed both in vitro and in vivo. The downstream mechanisms were further investigated by genetic overexpression and inhibition. RESULTS: Acidic environment prestimulation significantly enhanced the angiogenic capacity of EPCs from the non-CAD group both in vivo and in vitro, while the same treatment yielded the opposite result in the CAD group. Among the four canonical proton-sensing GPCRs, GPR4 displays the highest expression in EPCs. The expression of GRP4 was markedly lower in EPCs from CAD patients than in EPCs from non-CAD individuals independent of acid stimulation. The siRNA-mediated knockdown of GPR4 with subsequent decreased phosphorylation of STAT3 mimicked the impaired function of EPCs from CAD patients at pH 6.4 but not at pH 7.4. Elevating GPR4 expression restored the neovessel formation mediated by EPCs from CAD patients in an acidic environment by activating STAT3/VEGFA signaling. Moreover, the beneficial impact of GPR4 upregulation on EPC-mediated angiogenic capacity was abrogated by blockade of the STAT3/VEGFA signaling pathway. CONCLUSIONS: Our present study demonstrated for the first time that loss of GPR4 is responsible for the decline in proton sensing and angiogenic capacity of EPCs from CAD patients. Augmentation of GPR4 expression promotes the neovessel formation of EPCs by activating STAT3/VEGF signaling. This finding implicates GPR4 as a potential therapeutic target for CAD characterized by impaired neovascularization in ischemic tissues.

Vertical nanowire array-based biosensors: device design strategies and biomedical applications.

Biosensors have been extensively studied in the areas of biology, electronics, chemistry, biotechnology, medicine, and various engineering fields. The interdisciplinarity creates an ideal platform for scientists to analyze biological species and chemical materials in a direct, efficient, and sensitive manner; this is expected to revolutionize the life sciences, basic medicine, and the healthcare industry. To carry out high-performance biosensing, nanoprobes - with specific nanoscale properties - have been proposed for ultrasensitive and in situ monitoring/detection of tracer biomolecules, cellular behavior, cellular microenvironments, and electrophysiological activity. Here, we review the development of vertical nanowire (VNW) array-based devices for the effective collection of biomedical information at the molecular level, extracellular level, and intracellular level. In particular, we summarize VNW-based technologies in the aspects of detecting biochemical information, cellular information, and bioelectrical information, all of which facilitate the understanding of fundamental biology and development of therapeutic techniques. Finally, we present a conclusion and prospects for the development of VNW platforms in practical biomedical applications, and we identify the challenges and opportunities for VNW-based biosensor systems in future biological research.

Specific recognition of ion channel blocker by high-content cardiomyocyte electromechanical integrated correlation.

Cardiac arrhythmia and drug-induced cardiotoxicity seriously threaten the human life. To develop antiarrhythmic agents and prevent the drug-induced cardiotoxicity, it is demanded to explore the high-specificity and high-efficiency drug screening platforms for preclinical investigations. Here, a specific electromechanical integrated correlation (EMIC) model was established based on the synchronized signal recording of cardiomyocyte-based biosensing system. The cardiomyocyte-based biosensing system consists of an integrated electromechanical device and a synchronized recording instrument. By extracting the feature points and correlation information of both electrical and mechanical signals, the multi-parameters of EMIC are applied for the drug recognition, showing the good specificity to analyze the typical Na+, K+, Ca2+ channel blockers. Further, visualized analysis of EMIC parameters was performed using the extracted parameters of synchronized recording signals to present the drug specific recognition functions. By heat map, radar map, and principal component analysis (PCA), the specific features and patterns were intuitively displayed to achieve the drug recognition. We believe this high-content and high-specific drug recognition strategy will be a promising and alternative method for the preclinical screening of cardiac safety and drug development in biomedical fields.

Biodegradable Therapeutic Microneedle Patch for Rapid Antihypertensive Treatment.

A hypertensive emergency causes severe cardiovascular diseases accompanied by acute target organ damage, requiring rapid and smooth blood pressure (BP) reduction. Current medicines for treating hypertensive emergencies, such as sodium nitroprusside (SNP), require careful dose control to avoid side effects (e.g., cyanide poisoning). The clinical administration of SNP using intravenous injection or drip further restrict its usage for first aid or self-aid in emergencies. Here, we developed an antihypertensive microneedle (aH-MN) technique to transdermally deliver SNP in combination with sodium thiosulfate (ST) as a cyanide antidote in a painless way. Dissolvable microneedles loaded with SNP and ST were fabricated via the centrifugation casting method, where the SNPs were stably packaged in microneedles and would be immediately released into the systemic circulation via subcutaneous capillaries when aH-MNs penetrated the skin. The antihypertensive effects were demonstrated on spontaneously hypertensive rat models. Rapid and potent BP reduction was achieved via aH-MN treatment, fulfilling clinical BP-control requirements for hypertensive emergencies. The side effects including skin irritation and target organ damage of aH-MN therapies were evaluated; the combinative delivery of ST effectively suppressed these side effects induced by the consecutive intake of SNP. This study introduces an efficient and patient-friendly antihypertensive therapy with a favorable side-effect profile, particularly a controllable and self-administrable approach to treat hypertensive emergencies.

Injectable Slippery Lubricant-Coated Spiky Microparticles with Persistent and Exceptional Biofouling-Resistance.

Injectable micron-sized particles have historically achieved promising applications, but they continued to suffer from long-term biofouling caused by the adhesions of biomolecules, cells, and bacteria. Recently, a slippery lubricant infusion porous substrate (SLIPS) exhibited robust antiadhesiveness against many liquids; however, they were constructed using a 2D substrate, and they were not suitable for in vivo applications, such as injectable biomaterials. Inspired by SLIPS, here, we report the first case of injectable solid microparticles coated with a lubricating liquid surface to continuously resist biofouling. In our design, microparticles were attached with nanospikes and fluorinated to entrap the lubricant. The nanospikes enabled the lubricant-coated spiky microparticles (LCSMPs) to anomalously disperse in water despite the attraction between the surfaces of the microparticles. This result indicated that the LCSMPs exhibited persistent anomalous dispersity in water while maintaining a robust lubricating surface layer. LCSMPs prevented the adhesion of proteins, mammalian cells, and bacteria, including Escherichia coli and Staphylococcus aureus. LCSMPs also reduced in vivo fibrosis while conventional microparticles were heavily biofouled. This technology introduced a new class of injectable anti-biofouling microparticles with reduced risks of inflammation and infections.

Protection of Nanostructures-Integrated Microneedle Biosensor Using Dissolvable Polymer Coating.

Real-time transdermal biosensing provides a direct route to quantify biomarkers or physiological signals of local tissues. Although microneedles (MNs) present a mini-invasive transdermal technique, integration of MNs with advanced nanostructures to enhance sensing functionalities has rarely been achieved. This is largely due to the fact that nanostructures present on MNs surface could be easily destructed due to friction during skin insertion. In this work, we reported a dissolvable polymer-coating technique to protect nanostructures-integrated MNs from mechanical destruction during MNs insertion. After penetration into the skin, the polymer could readily dissolve by interstitial fluids so that the superficial nanostructures on MNs could be re-exposed for sensing purpose. To demonstrate this technique, metallic and resin MNs decorated with vertical ZnO nanowires (vNWs) were employed as an example. Dissolvable poly(vinyl pyrrolidone) was spray-coated on the vNW-MNs surface as a protective layer, which effectively protected the superficial ZnO NWs when MNs penetrated the skin. Transdermal biosensing of H2O2 biomarker in skin tissue using the polymer-protecting MNs sensor was demonstrated both ex vivo and in vivo. The results indicated that polymer coating successfully preserved the sensing functionalities of the MNs sensor after inserting into the skin, whereas the sensitivity of the MN sensor without a coating protection was significantly compromised by 3-folds. This work provided unique opportunities of protecting functional nanomodulus on MNs surface for minimally invasive transdermal biosensing.

Reduced Graphene Oxide Nanohybrid-Assembled Microneedles as Mini-Invasive Electrodes for Real-Time Transdermal Biosensing.

A variety of nanomaterial-based biosensors have been developed to sensitively detect biomolecules in vitro, yet limited success has been achieved in real-time sensing in vivo. The application of microneedles (MN) may offer a solution for painless and minimally-invasive transdermal biosensing. However, integration of nanostructural materials on microneedle surface as transdermal electrodes remains challenging in applications. Here, a transdermal H2 O2 electrochemical biosensor based on MNs integrated with nanohybrid consisting of reduced graphene oxide and Pt nanoparticles (Pt/rGO) is developed. The Pt/rGO significantly improves the detection sensitivity of the MN electrode, while the MNs are utilized as a painless transdermal tool to access the in vivo environment. The Pt/rGO nanostructures are protected by a water-soluble polymer layer to avoid mechanical destruction during the MN skin insertion process. The polymer layer can readily be dissolved by the interstitial fluid and exposes the Pt/rGO on MNs for biosensing in vivo. The applications of the Pt/rGO-integrated MNs for in situ and real-time sensing of H2 O2 in vivo are demonstrated both on pigskin and living mice. This work offers a unique real-time transdermal biosensing system, which is a promising tool for sensing in vivo with high sensitivity but in a minimally-invasive manner.

Stretchable Strain Vector Sensor Based on Parallelly Aligned Vertical Graphene.

The development of wearable strain sensors for the human-machine interface has attracted considerable research interest. Most existing wearable strain sensors were incapable of simultaneously detecting strain amplitudes and directions, and they failed to fully record stretching vectors that occurred on the body. Graphene and graphene-derived materials have been utilized to construct wearable strain sensors with excellent electrical sensitivities. Although the growth techniques of planar graphene and vertical graphene (VG) have been established, the fabrication of VG aligned in parallel within a larger area has not been previously achieved. Here, parallelly aligned VG (PAVG) in a large area was successfully fabricated and constructed as a wearable strain vector sensor. The PAVG was fabricated via inductively coupled plasma chemical vapor deposition assisted by metal inducers. The as-fabricated sensor was electrically anisotropic because of the profiles of the VG nanosheets aligned in parallel. Therefore, the sensor could simultaneously and sensitively detect the direction and the amplitude of the strain vectors with excellent accuracy. Application of this strain vector sensor for the human-sensor interface to identify the stretching directions and amplitudes of finger joints was also demonstrated. This work established the fabrication methodology of graphene with unique vertical and parallel alignment morphology. This study introduced a new opportunity of developing wearable sensors that could fully detect multidirectional human actions.