Biomedical Micro-/Nanomotors: Design,Imaging, and Disease Treatment

Untethered mobile micro-/nanomotors (MNMs), as newly-emerging attractive and versatile nanotechnologies, are expected to be the next-generation disease treatment tools, for breaking through the limitations of conventional passive drug delivery manner. However, the advances in these fascinating platforms have been hampered by the complexity of the biological environment and the particularity of disease microenvironment. Consequently, specific design strategies and clinical imaging techniques are essential to ensure the high-efficiency of biomedical MNMs on actuation, targeting, localization, and therapy when performing assigned in vivo tasks. This review thus comprehensively addresses three aspects of biomedical MNMs, including design, imaging, and disease treatment, highlighting the intelligent MNMs with biomimetic functionality and chemotactic capability, emphasizing the applicability of different imaging techniques, and focusing on various proof-of-concept studies based on physiological characteristics for the treatment of major diseases. In addition, the key challenges and limitations of current biomedical MNMs are addressed, which may inspire future research and facilitate translation toward clinical treatment.     

Lightweight,Superelastic Boron Nitride/Polydimethylsiloxane Foam as Air Dielectric Substitute for Multifunctional Capacitive Sensor Applications

Porous polymeric foams as dielectric layer for highly sensitive capacitive based pressure sensors have been extensively explored owing to their excellent flexibility and elasticity. Despite intensive efforts, most of previously reported porous polymer foams still suffer from difficulty in further lowering the attainable density limit of ≈0.1 g cm^?3 while retaining high sensitivity and compressibility due to the limitations on existing fabrication techniques and materials. Herein, utilizing 3D interconnected networks of few‐layer hexagonal boron nitride foams (h‐BNFs) as supporting frameworks, lightweight and highly porous BN/polydimethylsiloxane composite foams (BNF@PDMS) with densities reaching as low as 15 mg cm^?3 and permittivity close to that of air are fabricated. This is the lightest PDMS‐based foam reported to date. Owing to the synergistic effects between BN and PDMS, these lightweight composite foams possess excellent mechanical resilience, extremely high compressibility (up to 95% strain), good cyclic performance, and superelasticity. Being electrically nonconductive, the potential application of BNF@PDMS as a dielectric layer for capacitive sensors is further demonstrated. Remarkably, the as‐fabricated device can perform multiple sensing functions such as noncontact touch sensor, environmental monitoring sensor, and high sensitivity pressure sensor that can detect extremely low pressures of below 1 Pa.     

Flexible,Graphene‐Coated Biocomposite for Highly Sensitive,Real‐Time Molecular Detection

Wearable biosensors hold significant potential for healthcare and environmental applications, and the development of flexible and biocompatible sensing platforms for high accuracy detection of physiological biomarkers remains an elusive goal. Herein, an ultrasensitive, flexible sensor is described that is based on a 3D hierarchical biocomposite comprised of hollow, natural pollen microcapsules that are coated with a conductive graphene layer. Modular assembly of the graphene‐coated microcapsules onto an ultrathin polyethylene terephthalate layer enables a highly flexible sensor configuration with tunable selectivity afforded by subsequent covalent immobilization of antibodies against target antigens. In a proof‐of‐concept example, the biosensor demonstrates ultrahigh sensitivity detection of prostate specific antigen (PSA) down to 1.7 × 10^?15m with real‐time feedback and superior performance over conventional 2D graphene‐coated sensors. Importantly, the device performance is consistently high across various bending conditions. Taken together, the results demonstrated in this work highlight the merits of employing lightweight biocomposites as modular building blocks for the design of flexible biosensors with highly responsive and sensitive molecular detection capabilities.     

Direct Optical Fabrication of Fluorescent,Multilevel 3D Nanostructures for Highly Efficient Chemosensing Platforms

Development of fast and intuitive detection techniques for explosive vapors is highly desired for security applications. Among those techniques, fluorescence quenching has advantages in terms of portability and maintenance cost compared to electrically driven platforms. One of the challenging issues is the restricted sensitivity (i.e., low initial quenching and quenching saturation) caused by hindered diffusion of gaseous analytes inside a dense, solid film, and resulting limited surface area, where the target molecules are reacting. Here, multilevel 3D porous nanostructures are introduced, which possess strong fluorescence and enhanced sensing abilities, produced by a rapid and scalable lithographic technique. The cyanostilbene fluorophore with low‐absorption around patterning wavelengths (≈355 nm) is newly designed to be incorporated into transparent photopolymer. The emission color and intensity of the composite films under excitation can be precisely controlled by adjusting the concentration of fluorophore based on intermolecular effects. The patterned, monolithic film with low‐volume fraction (<40%) offers efficient diffusion paths inside a film and a large number of reaction sites for detecting gaseous analytes, enabling fast fluorescence quenching at an early stage (≈7.5 times higher than the solid film at 30 s) and fully suppressed fluorescence without quenching saturation, which cannot be achieved by conventional solid films.     

Distortion analysis of Miller-compensated three-stage amplifiers

This paper proposes a theoretical approach for evaluating distortion in the frequency domain of three-stage amplifiers adopting two commonly used compensation techniques, namely the nested Miller (NM) and the reversed NM. The analysis is based on appropriate amplifier modeling and on the assumption that the nonlinearity generated by each stage is static. Calculations are thus greatly simplified avoiding complex methods based on the Volterra series. Only dominant contributions need to be taken into account, thereby highlighting those mechanisms generating distortion and their features in the frequency domain. Moreover, the adopted approach provides useful design guidelines and explains why the NM compensation technique allows generally better linearity performance at low frequency and why the reversed NM is best suited to high frequencies. Simulation results with Spectre on two transistor-level CMOS circuits are also provided and found to be in very good agreement with expected results.     

A Versatile Photoinduced Electron Transfer‐Based Upconversion Fluorescent Biosensing Platform for the Detection of Disease Biomarkers and Nerve Agent

Upconversion nanoparticles (UCNPs) have emerged to be a new family of fluorescent probes for bioanalytical applications. In a typical design, the UCNPs act as the energy donors in a fluorescence resonance energy transfer (FRET) system, in which the target molecules mediate the energy transfer from the UCNPs to the acceptors, and their quantity information is consequently converted into the “on‐off” upconverting signals for readout. However, each UCNP contains thousands of emitting center ions and most of them are beyond the FRET critical distance, which hinders the fluorescence energy transfer efficiency, resulting in a low signal‐to‐background ratio (SBR). Herein, a new design is presented in which the energy of UCNPs is transferred to the o‐quinones on their surface via the photoinduced electron transfer (PET) mechanism. In this system, the quenching efficiency of UCNPs' fluorescence can be up to 94.73%, providing a high SBR. The performance of the PET‐based design is systematically testified, and the high‐sensitivity detection of disease biomarkers (tyrosinase and alkaline phosphatase) is demonstrated. Moreover, this UCNP‐PET platform is also capable of sensing the simulant of nerve agent sarin. This work will pave new ways to the design of UCNP‐based platforms toward bioanalytical applications.     

Enhancing the Sensitivity of Percolative Graphene Films for Flexible and Transparent Pressure Sensor Arrays

Flexible and transparent pressure sensor arrays can find applications in many places such as touch panels, artificial skin, or human motion detection. However, conventional strain gauges are rigid and opaque and are not suitable for such applications. Graphene‐based percolative strain gauges can overcome these challenges but currently are still in the infancy of their development. In this work, the performance of graphene‐based percolative strain gauges is investigated and guidelines to improve the durability and sensitivity of graphene films as sensing elements are developed. It is found that the gauge factor depends on the initial resistance of the graphene film. For the same film resistance, it is found that graphene flake size and film morphology also play a role in determining the gauge factor. Increasing the flake–flake resistance through assembly of surfactant molecules between graphene flakes provides an additional route to enhance the gauge factor. Furthermore, encapsulating the percolative film in micrometer‐thin Poly(methyl methacrylate) does not disrupt the sensing process but significantly improves the sensor's durability. Finally, thus enhanced graphene strain gauges are integrated into flexible and transparent pressure sensor arrays that exhibit high reproducibility and sensitivity.     

基于解码转发的协作频谱感知技术

频谱感知技术中的单点检测设计复杂度低,采用技术成熟,易于实现,但是由于自身的局限性,面临着隐藏终端,感知灵敏度底等问题,而协作分集技术可以克服这些问题。基于解码转发(DF,DecodeAnd Forward)的协作频谱感知技术,利用了分集增益原理,提高了认知用户的单点检测概率,从而改善了整个无线电系统的性能。在瑞利衰落环境下对该检测方案进行分析,并通过与非协作检测的性能比较,说明了协作检测的优势。     

Two‐Color Emitting Colloidal Nanocrystals as Single‐Particle Ratiometric Probes of Intracellular pH

Intracellular pH is a key parameter in many biological mechanisms and cell metabolism and is used to detect and monitor cancer formation and brain or heart diseases. pH‐sensing is typically performed by fluorescence microscopy using pH‐responsive dyes. Accuracy is limited by the need for quantifying the absolute emission intensity in living biological samples. An alternative with a higher sensitivity and precision uses probes with a ratiometric response arising from the different pH‐sensitivity of two emission channels of a single emitter. Current ratiometric probes are complex constructs suffering from instability and cross‐readout due to their broad emission spectra. Here, we overcome such limitations using a single‐particle ratiometric pH probe based on dot‐in‐bulk CdSe/CdS nanocrystals (NCs). These nanostructures feature two fully‐separated narrow emissions with different pH sensitivity arising from radiative recombination of core‐ and shell‐localized excitons. The core emission is nearly independent of the pH, whereas the shell luminescence increases in the 3–11 pH range, resulting in a cross‐readout‐free ratiometric response as strong as 600%. In vitro microscopy demonstrates that the ratiometric response in biologic media resembles the precalibralation curve obtained through far‐field titration experiments. The NCs show good biocompatibility, enabling us to monitor in real‐time the pH in living cells.     

Laser Direct Writing of Ultrahigh Sensitive SiC‐Based Strain Sensor Arrays on Elastomer toward Electronic Skins

Electronic skins (e‐skins) have been widely investigated as important platforms for healthcare monitoring, human/machine interfaces, and soft robots. However, mask‐free formation of patterned active materials on elastomer substrates without involving high‐cost and complicate processes is still a grand challenge in developing e‐skins. Here, SiC‐based strain sensor arrays are fabricated on elastomer for e‐skins by a laser direct writing (LDW) technique, which is mask‐free, highly efficient, and scalable. The direct synthesis of active material on elastomer is ascribed to the LDW‐induced conversion of siloxanes to SiC. The SiC‐based devices own a highest sensitivity of ≈2.47 × 10⁵ achieved at a laser power of 0.8 W and a scanning velocity of 1.25 mm s^?1. Moreover, the LDW‐developed device provides a minimum strain detection limit of 0.05%, a small temperature drift, and a high mechanical durability for over 10 000 cycles. When it is mounted onto human skins, the SiC‐based device is able to monitor external stimuli and human health conditions, with the capability of wireless data transmission. Its potential application in e‐skins is further proved by an LDW‐fabricated device having 3 × 3 SiC sensor array for tactile sensing.     

Recent Advances in Pen‐Based Writing Electronics and their Emerging Applications

The emerging demand for cost‐effective, easily accessible, and rapid prototyping electronics fabrication calls for novel techniques to design and manufacture electronic components and devices for wearable functional sensing, on‐skin medical monitoring, and body‐worn energy conversion. Inspired by daily hand‐writing, innovative and ubiquitously available pens can be employed to write conductive patterns on multiple substrates; such a low‐cost, fast, and user‐friendly direct writing paradigm has recently aroused remarkable research interest as a promising electronics prototyping strategy. In this review, state‐of‐art advances in techniques for direct writing of electronics are presented, and pros and cons of each fabrication route are discussed. Emerging applications of pen‐based writing electronics are also summarized. Based on these, final conclusions, limitations and challenges, as well as ongoing perspectives are illustrated.     

Electrospun Fibrous Architectures for Drug Delivery,Tissue Engineering and Cancer Therapy

The versatile electrospinning technique is recognized as an efficient strategy to deliver active pharmaceutical ingredients and has gained tremendous progress in drug delivery, tissue engineering, cancer therapy, and disease diagnosis. Numerous drug delivery systems fabricated through electrospinning regarding the carrier compositions, drug incorporation techniques, release kinetics, and the subsequent therapeutic efficacy are presented herein. Targeting for distinct applications, the composition of drug carriers vary from natural/synthetic polymers/blends, inorganic materials, and even hybrids. Various drug incorporation approaches through electrospinning are thoroughly discussed with respect to the principles, benefits, and limitations. To meet the various requirements in actual sophisticated in vivo environments and to overcome the limitations of a single carrier system, feasible combinations of multiple drug‐inclusion processes via electrospinning could be employed to achieve programmed, multi‐staged, or stimuli‐triggered release of multiple drugs. The therapeutic efficacy of the designed electrospun drug‐eluting systems is further verified in multiple biomedical applications and is comprehensively overviewed, demonstrating promising potential to address a variety of clinical challenges.     

Determination of Urinary 1‐Hydroxypyrene for Biomonitoring of Human Exposure to Polycyclic Aromatic Hydrocarbons Carcinogens by a Lanthanide‐functionalized Metal‐Organic Framework Sensor

1‐Hydroxypyrene (1‐HP), which is a biomarker of polycyclic aromatic hydrocarbons (PAHs) carcinogens and represents the internal dose of PAHs exposure in the human body, is detected by a newly designed luminescent Eu‐functionalized metal‐organic framework ( 1a ) sensor. The luminescence of 1a can be effectively quenched by 1‐HP via a fluorescent resonant energy transfer process, thus achieving its recognition of 1‐HP. This is the first use of lanthanide metal‐organic frameworks (Ln‐MOFs) as chemical sensors for 1‐HP. The probe exhibits outstanding performances for sensing 1‐HP, such as high selectivity, excellent sensitivity, fast response, and good reusability. Importantly, the sensing system enables the detection of 1‐HP in real human urine specimens, and a portable 1‐HP urine test paper is also developed. Hence, the reported 1‐HP sensing platform has promising application potential for clinical diagnosis of the intoxication level of PAHs.     

Hybrid Vesicular Drug Delivery Systems for Cancer Therapeutics

Nanoscale vesicles have provided a versatile platform for the transportation of various types of anticancer and diagnostic agents. Vesicular carriers comprised of liposomes, polymersomes, and peptide‐based vesicles have exhibited potential characteristics for nanomedicine developments. However, the represented systems and current therapeutic approaches to cancers are confronted with serious limitations that hinder their clinical translation. The aforementioned limitations could be minimized by implementing combinatorial hybrid systems. With this method, hybrid vesicular systems can integrate the advantages of several carriers into one structure thereby resulting in an increased therapeutic index and better clinical outcome. The current study has reviewed recently introduced types of hybrid vesicles made of polymer–lipids, polymer–peptides, and lipid–peptides, and its main focus is on multiple metallic‐based nanoparticles incorporated into vesicular carriers to provide theranostic platforms and to boost the efficient cytotoxic effects of the delivered agents.     

Recent Advances in Sensing Applications of Graphene Assemblies and Their Composites

Development of next‐generation sensor devices is gaining tremendous attention in both academia and industry because of their broad applications in manufacturing processes, food and environment control, medicine, disease diagnostics, security and defense, aerospace, and so forth. Current challenges include the development of low‐cost, ultrahigh, and user‐friendly sensors, which have high selectivity, fast response and recovery times, and small dimensions. The critical demands of these new sensors are typically associated with advanced nanoscale sensing materials. Among them, graphene and its derivatives have demonstrated the ideal properties to overcome these challenges and have merged as one of the most popular sensing platforms for diverse applications. A broad range of graphene assemblies with different architectures, morphologies, and scales (from nano‐, micro‐, to macrosize) have been explored in recent years for designing new high‐performing sensing devices. Herein, this study presents and discusses recent advances in synthesis strategies of assembled graphene‐based superstructures of 1D, 2D, and 3D macroscopic shapes in the forms of fibers, thin films, and foams/aerogels. The fabricated state‐of‐the‐art applications of these materials in gas and vapor, biomedical, piezoresistive strain and pressure, heavy metal ion, and temperature sensors are also systematically reviewed and discussed, and their sensing performance is compared.     

Fast Spectrum Sensing with Coordinate System in Cognitive Radio Networks

Spectrum sensing is an elementary function in cognitive radio designed to monitor the existence of a primary user (PU). To achieve a high rate of detection, most techniques rely on knowledge of prior spectrum patterns, with a trade‐off between high computational complexity and long sensing time. On the other hand, blind techniques ignore pattern matching processes to reduce processing time, but their accuracy degrades greatly at low signal‐to‐noise ratios. To achieve both a high rate of detection and short sensing time, we propose fast spectrum sensing with coordinate system (FSC) — a novel technique that decomposes a spectrum with high complexity into a new coordinate system of salient features and that uses these features in its PU detection process. Not only is the space of a buffer that is used to store information about a PU reduced, but also the sensing process is fast. The performance of FSC is evaluated according to its accuracy and sensing time against six other well‐known conventional techniques through a wireless microphone signal based on the IEEE 802.22 standard. FSC gives the best performance overall.     

Wafer‐Scale High‐Yield Manufacturing of Degradable Electronics for Environmental Monitoring

Degradable electronics that dissolve or disintegrate in the environment after completing target functions are highly desirable due to great capabilities to eliminate the disposal, retrieval, and recycling of electronic waste worldwide. Constructing electronic systems on water‐soluble substrates via transfer printing technology has emerged as a promising approach toward this goal. However, the current approach suffers from low yields and thus hinders the complexity and scale of the obtained system in practical applications. Here, a wafer‐scale manufacturing process is proposed for degradable systems with high yields. As a demonstration, chips based on carbon nanotube thin films are 100% successfully transferred to water‐soluble substrates with an average device yield of 96.6%. Great uniformity is also obtained in the transferred thin‐film transistors (TFTs) and integrated circuits with a minimum standard deviation of 55 and 60 mV in the threshold voltage of TFTs and switching threshold voltage of inverters, respectively. System‐level demonstration of real‐time environmental monitoring is implemented in a simulated ecosystem together with a degradation demonstration under artificial rain. With its combined great performance, processing robustness, and high yields, this technology provides new opportunities for batch manufacturing of degradable electronics and next‐generation ecofriendly sensing platforms for the coming Internet of Things era.     

A Highly Stretchable ZnO@Fiber‐Based Multifunctional Nanosensor for Strain/Temperature/UV Detection

Stretchable and multifunctional sensors can be applied in multifunctional sensing devices, safety forewarning equipment, and multiparametric sensing platforms. However, a stretchable and multifunctional sensor was hard to fabricate until now. Herein, a scalable and efficient fabrication strategy is adopted to yield a sensor consisting of ZnO nanowires and polyurethane fibers. The device integrates high stretchability (tolerable strain up to 150%) with three different sensing capabilities, i.e., strain, temperature, and UV. Typically achieved specifications for strain detection are a fast response time of 38 ms, a gauge factor of 15.2, and a high stability of >10 000 cyclic loading tests. Temperature is detected with a high temperature sensitivity of 39.3% °C^?1, while UV monitoring features a large ON/OFF ratio of 158.2. With its fiber geometry, mechanical flexibility, and high stretchability, the sensor holds tremendous prospect for multiparametric sensing platforms, including wearable devices.     

Living Cells Directly Growing on a DNA/Mn3(PO4)2‐Immobilized and Vertically Aligned CNT Array as a Free‐Standing Hybrid Film for Highly Sensitive In Situ Detection of Released Superoxide Anions

It is important to detect reactive oxygen species (ROS) in situ for investigation of various critical biological processes, and this is however very challenging because of the limited sensitivity or/and selectivity of existing methods that are mainly based on sensing ROS released by cells with short lifetimes and low concentrations in a culture medium. Here, a new approach is reported to directly grow living cells on DNA/Mn₃(PO₄)₂‐immobilized and vertically aligned carbon nanotube (VACNT) array nanostructure as a smart free‐standing hybrid film, of which the DNA/Mn₃(PO₄)₂ and VACNT provide high electroactivity and excellent electron transport, respectively, while the directly grown cell on the nanostructure offers short diffusion distance to reaction sites, thus constructing a highly sensitive in situ method for detection of cancer‐cell‐released ROS under drug stimulations. Compared to the measured ROS released by cells in a culture medium, the detection sensitivity with this constructed hybrid film increases by more than six times, which implies that ROS molecules (superoxide anions) secreted from living cells are immediately captured by this smart structure without diffusion process or with extremely short diffusion distance. This design considerably reduces the time from release to detection of the target molecules, minimizing the potential molecular decay due to the short lifetime or high reactivity.     

A Battery‐Less Arbitrary Motion Sensing System Using Magnetic Repulsion‐Based Self‐Powered Motion Sensors and Hybrid Nanogenerator

Self‐powered arbitrary motion sensors are in high demand in the field of autonomous controlled systems. In this work, a magnetic repulsion‐assisted self‐powered motion sensor is integrated with a hybrid nanogenerator (MRSMS–HNG) as a battery‐less arbitrary motion sensing system. The proposed device can efficiently detect the motion parameters of a moving object along any arbitrary direction and simultaneously convert low frequency (<5 Hz) vibrations into useful electricity. The MRSMS–HNG consists of a central magnet for the electromagnetic (EMG)–triboelectric (TENG) nanogenerator and four side magnets for motion sensors. Because all the magnets are aligned in the same magnetization direction, the repulsive force owing to the movement of the central magnet actuates the side magnets to achieve self‐powered arbitrary motion sensing. These self‐powered motion sensors exhibit a high sensitivity of 981.33 mV g^?1 under linear motion excitation and have a tilting angle sensitivity of 9.83 mV deg^?1. The proposed device can deliver peak powers of 27 mW and 56 µW from the EMG and TENG, respectively. By integrating the self‐powered motion sensors and hybrid nanogenerator on a single device, real‐time wireless transmission of motion sensor data to a smartphone is successfully demonstrated, thus realizing a battery‐less arbitrary motion‐sensing system for future autonomous control applications.