From Passive Inorganic Oxides to Active Matters of Micro/Nanomotors

Controllable actuation and coordinating motion of artificial self‐propelled micro/nanomotors to mimic the motile natural microorganism systems are of great significance for constructing intelligent nanoscale machines. In particular, inorganic oxide particles have shown considerable promise in implementation of synthetic micro/nanomotors, due to their unique features and active response to environmental stimuli. This work critically reviews the recent progress in inorganic oxide‐based micro/nanomotors and focuses on their propulsion response to chemical and physical stimuli, especially emphasizing and discussing operating principles in the single engine, adaptive navigation under composite‐driven powers, and intriguing collective behaviors. The impact of oxide structure, multiple fields in motion controllability, and interaction between grouped micro/nanomotors are explored. Practical applications of individual and assembled micro/nanomotors in environmental and biomedical fields are demonstrated, including the removal of pollutants, drug delivery, cancer therapy, and in vivo imaging. Finally, current challenges for the development of novel micro/nanomotors and possible constraints toward the defined structure and accumulated toxicity are discussed along with future opportunities and directions. Owing to their facile synthesis, impressive physicochemical performances, high biocompatibility, and versatile actuations, it is expected that the association of inorganic oxides with micro/nanomotors will bring new and unique capabilities to the field of active matter.     

Synthesis and Applications of Stimuli‐Responsive DNA‐Based Nano‐ and Micro‐Sized Capsules

Stimuli‐responsive, drug‐loaded, DNA‐based nano‐ and micro‐capsules attract scientific interest as signal‐triggered carriers for controlled drug release. The methods to construct the nano‐/micro‐capsules involve i) the layer‐by‐layer deposition of signal‐reconfigurable DNA shells on drug‐loaded microparticles acting as templates, followed by dissolution of the core templates; ii) the assembly of three‐dimensional capsules composed of reconfigurable DNA origami units; and iii) the synthesis of stimuli‐responsive drug‐loaded capsules stabilized by DNA?polymer hydrogels. Triggers to unlock the nano‐/micro‐capsules include enzymes, pH, light, aptamer?ligand complexes, and redox agents. The capsules are loaded with fluorescent polymers, metal nanoparticles, proteins or semiconductor quantum dots as drug models, with anti‐cancer drugs, e.g., doxorubicin, or with antibodies inhibiting cellular networks or enzymes over‐expressed in cancer cells. The mechanisms for unlocking the nano‐/micro‐capsules and releasing the drugs are discussed, and the applications of the stimuli‐responsive nano‐/micro‐capsules as sense‐and‐treat systems are addressed. The scientific challenges and future perspectives of nano‐capsules and micro‐capsules in nanomedicine are highlighted.     

Hierarchical Spiky Microstraws‐Integrated Microfluidic Device for Efficient Capture and In Situ Manipulation of Cancer Cells

Techniques for capturing circulating tumor cells (CTCs) play an important role in cancer diagnosis. Recently, various 3D micro/nanostructures have been applied for effective CTC detection, yet in situ manipulation of the captured cancer cells on micro/nano‐structural substrates is rarely achieved. In this work, a hierarchical spiky microstraw array (HS‐MSA)‐integrated microfluidic device is demonstrated that possessed dual functions of cancer cell capture and in situ chemical manipulations of the captured cells. The 3D micro/nanostructure of HS‐MSA could capture cancer cells with high efficiency (≈84%) and strong specificity. Based on the HS‐MSA‐integrated microfluidic device, extracellular drug delivery to the captured cancer cells is achieved in situ with excellent spatial, dose, and temporal controls. In addition, a drug‐screening assay on the captured cancer cells is implemented to investigate the cell apoptosis behavior under the microstraw‐mediated delivery of staurosporine (STS). This microfluidic system not only presents tremendous potential for CTCs detection technology, but also opens up new opportunities for high‐throughput drug screening on cancer cells and understanding the cellular activity.     

Engineering a Therapy‐Induced “Immunogenic Cancer Cell Death” Amplifier to Boost Systemic Tumor Elimination

Immunogenic cancer cell death (ICD) is drawing worldwide attention as it allows dying cancer cells to regulate the host's anti‐tumor immune system and awaken immunosurveillance. Thus, effectively activating therapy‐induced ICD is of great clinical significance to raise systemic anti‐tumor immunity and eradicate post‐treatment/abscopal cancer tissues. Enhanced cytotoxic reactive oxygen species (ROS) generation in cancer therapy has been positively correlated to ICD induction, which inspires design of a therapy‐induced ICD amplifier. The nanohybrid amplifier (FeOOH@STA/Cu‐LDH) is devised based on Cu‐containing layered double hydroxide (Cu‐LDH), incorporating ROS inducer (FeOOH nanodots), ROS generation booster (Cu‐LDH for photothermal therapy), and heat shock protein inhibitor (STA). Treating 4T1 tumor cells with this amplifier translocates calreticulins (CRT, one of main ICD signals) on the surface of dying cancer cells, which achieves the maximum at fever‐type temperature (40–42 °C). To demonstrate immunotherapeutic efficacy of this nanohybrid, 4T1 tumor‐bearing mouse model is established with primary and abscopal tumors. Significantly, only one treatment with the ICD amplifier eradicates the primary tumor and inhibits the abscopal tumor growth upon fever‐type heating and induces more cytotoxic T lymphocytes in abscopal tumors and spleens after treatment for 1 week. This research thus provides a new insight into nanomaterial‐mediated tumor immunotherapy.     

Light Management with Patterned Micro‐ and Nanostructure Arrays for Photocatalysis,Photovoltaics, and Optoelectronic and Optical Devices

The design and fabrication of patterned micro‐ and nanostructure arrays have been demonstrated to be a powerful strategy toward efficient light management, which is of vital importance to a variety of photon‐related applications such as photocatalysis, photovoltaics, optoelectronic devices, and optical devices. Tunable optical reflectance, scattering, transmittance, and absorption can be readily achieved by adjusting the characteristics of the primary units in the micro‐/nanoarrays and the spatial patterns of the aligned units, thus realizing controllable light–matter interactions. This review describes various light management strategies based on patterned micro‐/nanoarrays, such as scattering enhancement, antireflection, resonances, photonic crystals, and plasmonic structures. Furthermore, recent advances in the applications of patterned micro‐/nanoarrays in photoelectrochemical water splitting, solar cells, photodetectors, light emitting diodes, lasers, color display, microlens arrays, and photonic crystal sensors are summarized, with particular attention paid to the light management mechanisms and the relationship between the structure and device performance. Lastly, the prospects and existing challenges facing the development of the photon‐related applications based on patterned micro‐/nanoarrays are discussed.     

A Patterned Graphene/ZnO UV Sensor Driven by Integrated Asymmetric Micro‐Supercapacitors on a Liquid Metal Patterned Foldable Paper

A foldable array of patterned graphene/ZnO nanoparticle UV sensor and asymmetric micro‐supercapacitors (AMSCs) integrated on a paper substrate with patterned liquid metal interconnections is reported. The resistor type UV sensor based on graphene/ZnO nanoparticles is patterned to be driven by the stored energy of the integrated AMSCs. The AMSC consists of MnO₂ nanoball deposited multiwalled carbon nanotubes (MWNTs) and V₂O₅ wrapped MWNTs as positive and negative electrodes, respectively. As an electrolyte, propylene carbonate‐poly(methyl methacrylate)‐LiClO₄, an organic solvent‐based gel, is used. The UV sensor and AMSCs can be easily integrated on a liquid metal, Galinstan, patterned, waterproof mineral paper and show a mechanically stable UV sensing, regardless of repetitive folding cycles. This work demonstrates a novel foldable nanomaterial based sensor system driven by integrated energy storage devices, applicable to future wearable and portable electronics.     

Fully Integrated Microscale Quasi‐2D Crystalline Molecular Field‐Effect Transistors

Monolithic integration of microscale organic field‐effect transistors (micro‐OFETs) is the only and inevitable path toward low‐cost large‐area electronics and displays. However, to date, such an ultimate technology has not yet evolved due to challenges in positioning and patterning highly crystalline microscale molecular layers as well as in developing micrometer scale integration schemes. In this work, by mastering the local growth of molecular semiconductors on pre‐defined terraces, single‐crystal quasi‐2D molecular layers tens of square micrometers in size are created in dense periodic arrays on a Si substrate. Nondestructive photolithographic processes are developed to pattern micro‐OFETs with mobilities up to 34.6 cm² V^?1 s^?1. This work demonstrates the feasibility to integrate arrays of short‐channel micro‐OFETs into electronic circuitry by highly parallel and size scalable fabrication technologies.     

Luminescent Silicon Diatom Replicas: Self‐Reporting and Degradable Drug Carriers with Biologically Derived Shape for Sustained Delivery of Therapeutics

Current development of drug microcarriers is mainly based on spherical shapes, which are not biologically favorable geometries for complex interactions with biological systems. Scalable synthesis of drug carriers with nonspherical and anisotropic shapes featuring sustained drug‐releasing performances, biocompatibility, degradability, and sensing capabilities is challenging. These challenges are addressed in this work by employing Nature's optimized designs obtained from low‐cost diatomaceous earth mineral derived from single‐cell algae diatoms. Silica diatoms with unique shapes and 3D microcapsule morphology are converted into silicon diatom replicas with identical structure by a magnesiothermic reduction process. The results reveal that prepared silicon diatoms have a set of unique properties including favorable microcapsule structure with high surface area and micro/mesoporosity providing high drug loading, fast biodegradability, and intrinsic luminescence, which make them highly suitable for low‐cost production of advanced drug microcarriers. Their sustained drug release >30 days combined with self‐reporting function based on silicon luminescence properties using nonluminescent and luminescent drugs for intravitreal drug therapy is successfully demonstrated. These silicon diatoms offer promising potential toward scalable production of low‐cost and advanced microcarriers for broad medical therapies, including theranostics and microrobotic guided drug delivery devices.     

Hierarchical Ordered Dual‐Mesoporous Polypyrrole/Graphene Nanosheets as Bi‐Functional Active Materials for High‐Performance Planar Integrated System of Micro‐Supercapacitor and Gas Sensor

Planar integrated systems of micro‐supercapacitors (MSCs) and sensors are of profound importance for 3C electronics, but usually appear poor in compatibility due to the complex connections of device units with multiple mono‐functional materials. Herein, 2D hierarchical ordered dual‐mesoporous polypyrrole/graphene (DM‐PG) nanosheets are developed as bi‐functional active materials for a novel prototype planar integrated system of MSC and NH₃ sensor. Owing to effective coupling of conductive graphene and high‐sensitive pseudocapacitive polypyrrole, well‐defined dual‐mesopores of ≈7 and ≈18 nm, hierarchical mesoporous network, and large surface area of 112 m² g^?1, the resultant DM‐PG nanosheets exhibit extraordinary sensing response to NH₃ as low as 200 ppb, exceptional selectivity toward NH₃ that is much higher than other volatile organic compounds, and outstanding capacitance of 376 F g^?1 at 1 mV s^?1 for supercapacitors, simultaneously surpassing single‐mesoporous and non‐mesoporous counterparts. Importantly, the bi‐functional DM‐PG‐based MSC‐sensor integrated system represents rapid and stable response exposed to 10–40 ppm of NH₃ after only charging for 100 s, remarkable sensitivity of NH₃ detection that is close to DM‐PG‐based MSC‐free sensor, impressive flexibility with ≈82% of initial response value even at 180°, and enhanced overall compatibility, thereby holding great promise for ultrathin, miniaturized, body‐attachable, and portable detection of NH₃.     

High‐Resolution Monolithic Integrated Tribotronic InGaZnO Thin‐Film Transistor Array for Tactile Detection

Tactile detection is a crucial technology in many fields, such as electronic skin, touch screen control, human prostheses, and screen fingerprint identification. Tribotronics has demonstrated active mechanosensation from external mechanical stimuli, which greatly enriches the sensing mechanisms of tactile detection. In this work, a monolithic integrated indium‐gallium‐zinc‐oxide (InGaZnO or IGZO) thin‐film transistor (TFT) array is developed for high‐resolution tactile detection. By using the conventional semiconductor fabrication processes, each IGZO TFT cell in the array shows uniform electrical performance. In addition, the drain–source current can be individually tuned by the electrostatic potential generated by the contact electrification between a movable gate and the gate dielectric. The monolithic integrated array displays a relatively high resolution of 12 pixels per inch and can realize a millimeter‐level tactile perception and motion tracking. This work presents a facile and viable strategy toward micro/nano‐scale tribotronics, which can realize high‐resolution and large‐scale tactile detection.     

“To Catch or Not to Catch”: Microcapsule‐Based Sandwich Assay for Detection of Proteins and Nucleic Acids

The development of new assays that specifically detect intermediate or final products of biotechnological processes or multiple analytes in biomedical research is important for diagnostics and biotechnology. This study presents a microcapsule‐based sandwich assay for detection of proteins and nucleic acids using flow cytometry as an optical readout. The main component of the assay are robust chemically cross‐linked microcapsules that are coated with adaptor proteins such as protein A or streptavidin. In the first approach, the ability of detecting the blood cancer biomarker beta‐2 microglobulin in the fM to pM concentration range with the help of protein A‐coated capsules is demonstrated. In the second approach, streptavidin‐coated capsules are used for detection of nucleic acids in the nM concentration range. The developed assay allows rapid quantitative analyte measurement, while providing high sensitivity and selectivity at very small sample quantities. In the future, protein A‐ and streptavidin‐coated microcapsules can be used as universal tools for detection of a broad range of analytes.     

A Conductive Nanowire‐Mesh Biosensor for Ultrasensitive Detection of Serum C‐Reactive Protein in Melanoma

Detection of extracutaneous melanoma is still challenging and is of importance in improving survival rate. In this report, an ultrasensitive biosensor is constructed where a C‐reactive protein (CRP) aptamers based molecular recognition core and a conductive polypyrrole (PPy) nanowire mesh based signal amplifier are developed. The conductive PPy nanowire (less than 10 nm in diameter) mesh architecture is uniformly dispersed within polymeric matrix via template‐free in situ synthesis. Serum CRP levels are quantitatively analyzed through monitoring the conductance change caused by polymeric network shrinkage upon the aptamer‐CRP binding. The limit of detection (LOD) of the polymeric sensor for human CRP sample can reach 7.85 × 10^?19m . This CRP‐specific biosensor and a commercial CRP enzyme‐linked immunosorbent assay (ELISA) kit are used to perform side‐by‐side measurement of serum CRP in melanoma patients. The results indicate that this conductive polymeric senor is highly sensitive and selective in accurately discriminating melanoma patients from healthy controls using serum CRP as a biomarker, which is further validated by a commercial human CRP ELISA kit. Collectively, this novel ultrasensitive nanowire‐based polymeric biosensor may hold promise in biomarker detection and diagnosis of cancer.     

Enhanced Specificity in Capturing and Restraining Circulating Tumor Cells with Dual Antibody–Dendrimer Conjugates

Specifically capturing and restraining residual circulating tumor cells (CTCs) in cancer patients are the sine qua non for safely and effectively preventing cancer metastasis, to which the current chemotherapy has been limited due to its toxicity. Moreover, because of CTCs’ rarity and low activity, the current technology for capturing CTCs based solely on a single surface biomarker has limited capacity and is used mainly for in vitro diagnosis. Here, it is possible to sequentially conjugate two CTCs antibodies (aEpCAM and aSlex) to the functionalized dendrimers to specifically capture human hepatocellular CTCs in both artificial and clinical patient blood samples, and restrain their activities. The molecular entities of the conjugates are demonstrated by various means. The dual antibody conjugate captured CTCs threefold more than the single counterparts from the high concentrations of interfering red blood cells or leukocytes, as well as from the blood of liver cancer patients, and exhibits the superiority to their single counterparts in down‐regulating the captured CTCs. These results collectively provide the strong evidence that two antibodies can be compatibly conjugated to a nanomaterial, resulting in an enhanced specificity in restraining CTCs in blood.     

Advanced Functional Structure‐Based Sensing and Imaging Strategies for Cancer Detection: Possibilities,Opportunities, Challenges,and Prospects

Cancer is the second most common cause of death in the world. The principal limitations thus far encountered in the clinical practice of probing cancer are diverse and include low sensitivity, time consumption, bulkiness, and cost. In this respect, nanomaterial (NM)‐based sensing techniques are recognized as a superior alternative to efficiently resolve such limitations. A better understanding of NM‐based sensing platforms is thus important so that these novel avenues can easily be explored for clinical applications. These platforms have the merits of high sensitivity, high specificity, rapid response, and easy‐to‐read signals. This review offers a comprehensive survey of NM‐based advanced cancer‐sensing techniques and will help the scientific community establish optimum sensing strategies based on an accurate assessment of the interactions between cancer biomarkers and NM‐based platforms.     

M13 Bacteriophage as Materials for Amplified Surface Enhanced Raman Scattering Protein Sensing

Because of their unique properties, nanomaterials have been actively investigated in recent years for biosensing applications. A typical approach for biomarker detection is to attach capture or detection antibodies to nanomaterials, allow the analyte to bind, and measure the resulting change in signal. While antibodies or aptamers possess at most one binding site each for the nanomaterial and analyte, it is shown that the high surface area filamentous M13 bacteriophage can be utilized as a scaffold for generating an amplified signal. Since only a few proteins at the tip of the micrometer‐long virus are involved in antigen binding, the rest of the bacteriophage can be augmented with hundreds of functional groups, each of which can bind to a specific nanomaterial. It is demonstrated that the combination of DNA‐modified M13 bacteriophage and surface enhanced Raman spectroscopy (SERS) active nanoparticles can be used to produce exponential gains in Raman signal compared to that of antibodies at the same antigen concentration. Because of these high sensitivities, Raman measurements can be made directly from individual silica microparticles, potentially enabling future single step identification and analysis of different proteins in complex mixtures, while avoiding additional processing steps or prepatterned microarrays.     

Elastically and Plastically Foldable Electrothermal Micro‐Origami for Controllable and Rapid Shape Morphing

Integrating origami principles within traditional microfabrication methods can produce shape morphing microscale metamaterials and 3D systems with complex geometries and programmable mechanical properties. However, available micro‐origami systems usually have slow folding speeds, provide few active degrees of freedom, rely on environmental stimuli for actuation, and allow for either elastic or plastic folding but not both. This work introduces an integrated fabrication–design–actuation methodology of an electrothermal micro‐origami system that addresses the above‐mentioned challenges. Controllable and localized Joule heating from electrothermal actuator arrays enables rapid, large‐angle, and reversible elastic folding, while overheating can achieve plastic folding to reprogram the static 3D geometry. Because the proposed micro‐origami do not rely on an environmental stimulus for actuation, they can function in different atmospheric environments and perform controllable multi‐degrees‐of‐freedom shape morphing, allowing them to achieve complex motions and advanced functions. Combining the elastic and plastic folding enables these micro‐origami to first fold plastically into a desired geometry and then fold elastically to perform a function or for enhanced shape morphing. The proposed origami systems are suitable for creating medical devices, metamaterials, and microrobots, where rapid folding and enhanced control are desired.     

Head‐Mounted Devices for Noninvasive Cancer Imaging and Intraoperative Image‐Guided Surgery

Medical imaging methods have improved the detection of human diseases with increasing accuracy. The ability to probe molecular processes noninvasively or using tissue‐selective imaging agents and nanoparticles has made it possible to localize, identify the stage, and determine the functional status of pathological lesions. The challenges in detecting cancer particularly have driven the development of diverse imaging technologies. While earlier cancer imaging methods enabled preoperative evaluation, the need to track and visualize cancer location in the operating room itself has ushered in new systems capable of providing concurrent images of cancer during surgery. Intraoperative use of conventional clinical imaging modalities is often limited by bulky hardware design, prohibitive cost, lack of real‐time image display, and compatibility with conventional hardware interfaces. For these reasons, focus on fluorescence‐guided surgery (FGS) devices has increased to take advantage of real‐time, high‐resolution, functional imaging with hardware that has become increasingly amenable to miniaturization. In particular, the adaptation of wearable devices for FGS presents hands‐free capability for optimal navigation during cancer surgery. The evolution of head‐mounted devices in the operating room and adaptation for FGS is highlighted. Key challenges to wide clinical adoption of this imaging platform are identified and potential future directions are suggested.     

Statistical fingerprint‐based intrusion detection system (SF‐IDS)

Intrusion detection systems (IDS) are systems aimed at analyzing and detecting security problems. The IDS may be structured into misuse and anomaly detection. The former are often signature/rule IDS that detect malicious software by inspecting the content of packets or files looking for a “signature” labeling malware. They are often very efficient, but their drawback stands in the weakness of the information to check (eg, the signature), which may be quickly dated, and in the computation time because each packet or file needs to be inspected. The IDS based on anomaly detection and, in particular, on statistical analysis have been originated to bypass the mentioned problems. Instead of inspecting packets, each traffic flow is observed so getting a statistical characterization, which represents the fingerprint of the flow. This paper introduces a statistical analysis based intrusion detection system, which, after extracting the statistical fingerprint, uses machine learning classifiers to decide whether a flow is affected by malware or not. A large set of tests is presented. The obtained results allow selecting the best classifiers and show the performance of a decision maker that exploits the decisions of a bank of classifiers acting in parallel.     

Ultrahigh‐Working‐Frequency Embedded Supercapacitors with 1T Phase MoSe2 Nanosheets for System‐in‐Package Application

Commercial aluminium electrolyte capacitors (AECs) are too large for integration in future highly integrated electronic systems. Supercapacitors, in comparison, possess a much higher capacitance per unit volume and can be embedded as passive capacitors to address such challenges in electronics scaling. However, the slow frequency response (<10¹ Hz) typical of supercapacitors is a major hurdle to their practical application. Here, it is demonstrated that 1T‐phase MoSe₂ nanosheets obtained by laser‐induced phase transformation can be used as an electrode material in embedded micro‐supercapacitors. The metallic nature of MoSe₂ nanosheet‐based electrodes provides excellent electron‐ and ion‐transport properties, which leads to an unprecedented high‐frequency response (up to 10⁴ Hz) and cycle stability (up to 10⁶ cycles) when integrated in supercapacitors, and their power density can be ten times higher than that of commercial AECs. Furthermore, fabrication processes of the present device are fully compatible with system‐in‐package device manufacturing to meet stringent specifications for the size of embedded components. The present research represents a critical step forward in in‐package and on‐chip applications of electrolytic capacitors.     

Programmable Arrays of “Micro‐Bubble” Constructs via Self‐Encapsulation

The fabrication of ordered arrays of self‐encapsulated “micro‐bubble” material constructs based on the capillary‐driven collapse of flexible silk fibroin sheets during propagation of the diffusion front of the encapsulated material is demonstrated. The individual micro‐bubbles of different shapes are composed of a sacrificial material encapsulated within the ultrathin silk coating, which covers and seals the inner material during dissolution of supporting layer. The array of microscopic rectangular multi‐layer silk sheets on supporting polymer layers can be selectively dissolved along the edges to initiate their self‐encapsulation. The resulting micro‐bubble morphology, shape, and arrangements can be readily pre‐programmed by controlling the geometry of the silk sheets, such as thickness, dimension, and aspect ratio. These micro‐bubble constructs can be utilized for encapsulation of various materials as well as nanoparticles in a single or multi compartmental manner. These biocompatible and biodegradable micro‐bubble constructs present a promising platform for one‐shot spatial and controllable loading and locking material arrays with addressable abilities.