Chiral Shell Core–Satellite Nanostructures for Ultrasensitive Detection of Mycotoxin

Herein, the design of a DNA‐based chiral biosensor is described utilizing the self‐assembly of shell core–gold (Au) satellite nanostructures for the detection of mycotoxin, ochratoxin A (OTA). The assembly of core–satellite nanostructures based on OTA‐aptamer binding exhibits a strong chiral signal with an intense circular dichroism (CD) peak. The integrity of the assembly of core–satellite nanostructures is limited to some extent in the presence of different levels of OTA. Correspondingly, the chiral intensity of assembly is weakened with increasing OTA concentrations, allowing quantitative determination of the target. The developed chiral sensor shows an excellent linear relationship between the CD signal and concentrations of OTA in the range of 0.1–5 pg mL^?1 with a limit of detection as low as 0.037 pg mL^?1. The effectiveness of the biosensor in a sample of red wine is verified and a good recovery rate is obtained. These results suggest that the strategy has great potential for practical application.     

Single Iron Site Nanozyme for Ultrasensitive Glucose Detection

Nanomaterials with enzyme‐mimicking characteristics have engaged great awareness in various fields owing to their comparative low cost, high stability, and large‐scale preparation. However, the wide application of nanozymes is seriously restricted by the relatively low catalytic activity and poor specificity, primarily because of the inhomogeneous catalytic sites and unclear catalytic mechanisms. Herein, a support‐sacrificed strategy is demonstrated to prepare a single iron site nanozyme (Fe SSN) dispersed on the porous N‐doped carbon. With well‐defined coordination structure and high density of active sites, the Fe SSN performs prominent peroxidase‐like activity by efficiently activating H₂O₂ into hydroxyl radical (?OH) species. Furthermore, the Fe SSN is applied in colorimetric detection of glucose through a multienzyme biocatalytic cascade platform. Moreover, a low‐cost integrated agarose‐based hydrogel colorimetric biosensor is designed and successfully achieves the visualization evaluation and quantitative detection of glucose. This work expands the application of single‐site catalysts in the fields of nanozyme‐based biosensors and personal biomedical diagnosis.     

Hyperboloid‐Drum Microdisk Laser Biosensors for Ultrasensitive Detection of Human IgG

Whispering gallery mode (WGM) microresonators have been used as optical sensors in fundamental research and practical applications. The majority of WGM sensors are passive resonators that require complex systems, thereby limiting their practicality. Active resonators enable the remote excitation and collection of WGM‐modulated fluorescence spectra, without requiring complex systems, and can be used as alternatives to passive microresonators. This paper demonstrates an active microresonator, which is a microdisk laser in a hyperboloid‐drum (HD) shape. The HD microdisk lasers are a combination of a rhodamine B‐doped photoresist and a silica microdisk. These HD microdisk lasers can be utilized for the detection of label‐free biomolecules. The biomolecule concentration can be as low as 1 ag mL^?1, whereas the theoretical detection limit of the biosensor for human IgG in phosphate buffer saline is 9 ag mL^?1 (0.06 a_M). Additionally, the biosensors are able to detect biomolecules in an artificial serum, with a theoretical detection limit of 9 ag mL^?1 (0.06 a_M). These results are approximately four orders of magnitude more sensitive than those for the typical active WGM biosensors. The proposed HD microdisk laser biosensors show enormous detection potential for biomarkers in protein secretions or body fluids.     

A Plasmonic Fluor-Lightened Microneedle Array Enables Ultrasensitive Multitarget Whole Blood Diagnosis of Anemia in A Paper Origami-Based Device

This work reports a portable, origami-type paper device with a plasmonic fluor-labeled microneedle sensing module for the multiplexed quantification of anemia biomarkers in whole blood. Sequential steps, including serum separation, target enrichment, and multiplexed readout by a gel imager, are rapidly accomplished with the flexible and highly integrated device. The microneedle array enabled efficient sampling of trace targets from ng mL⁻¹ to pg mL⁻¹ level. Combined with the plasmonic fluor label, the signal is improved by ≈7.6 folds compared with the flat substrate-based assay. The device is applied to simultaneously quantify hemoglobin (Hb), ferritin, folic acid (FA), and vitamin B₁₂ (VB₁₂), which are four anemia biomarkers distributed in different environments with different concentration ranges. Featured by the small sample volume (150 µL), short assay time (20 min), low cost (2 $), robust stability, and user-friendliness, the device is promising for the rapid and accurate diagnosis of anemia in real practice.     

Au@gap@AuAg Nanorod Side‐by‐Side Assemblies for Ultrasensitive SERS Detection of Mercury and its Transformation

As one of the most toxic heavy metal elements, mercury ion (Hg²⁺) and its methylated product, methylmercury (MeHg) can pose a threat to human health and the environment. Herein, a novel Raman biosensor with cascade sensitivity is developed for Hg²⁺ detection through Au@gap@AuAg nanorod side‐by‐side assemblies. Due to the strong electromagnetic coupling from the assemblies and core–shell structure, the Raman sensor possesses high sensitivity with the limit of detection (LOD) of 0.001 ng mL^‐1, which is about one order lower than traditional atomic fluorescence spectrometer (AFS) methods. Moreover, the fabricated biosensor is used to measure residual mercury levels in tissues and eggs of hens fed high‐mercury diets, and the results show total mercury in collected egg yolks is 20 times higher than whites. Furthermore, the form of mercury in the eggs is also analyzed by high‐performance liquid chromatography coupled with AFS, and, unexpectedly, the methylated product MeHg tends to only be found in egg whites. These interesting differences may indicate a new research direction for the toxicity of mercury in living organisms, and the developed ultrasensitive Surface Enhanced Raman Scattering (SERS) method could pave a broad way for the application of biosensors in Hg detection.     

Polydopamine‐Capped Bimetallic AuPt Hydrogels Enable Robust Biosensor for Organophosphorus Pesticide Detection

Noble metal hydrogels/aerogels with macroscopic nanoassemblies characterized by ultralow density, profuse continuous porosity, and extremely large surface area have gained abundant interest due to not only their tunable physicochemical properties, but also promising applications in catalysis and sensing. Coupling the increased reaction temperature with dopamine‐induced effect, herein, a one‐step synthetic approach with accelerated gelation kinetics is reported for the synthesis of polydopamine‐capped bimetallic AuPt hydrogels. 3D porous nanowire networks with surface functionalization of polydopamine make them a promising biocompatible microenvironment for immobilizing acetylcholinesterase (AChE) and constructing enzyme‐based biosensors for sensitive detection of organophosphorus compounds. Taking advantage of their favorable structure and composition, the optimized product exhibits superior electrochemical activity toward thiocholine produced by AChE‐catalyzed hydrolysis of acetylthiocholine. Based on the inhibition of organophosphorus pesticide on the enzymatic activity of AChE, the inhibition mode for the detection of paraoxon‐ethyl is established, displaying linear regions over the range of 0.5–1000 ng L^?1 with a low detection limit of 0.185 ng L^?1.     

Emerging Prospects of Exosomes for Cancer Treatment: From Conventional Therapy to Immunotherapy

Exosomes are a class of extracellular vesicles of around 100 nm in diameter that are secreted by most cells and contain various bioactive molecules reflecting their cellular origin and mediate intercellular communication. Studies of these exosomal features in tumor pathogenesis have led to the development of therapeutic and diagnostic approaches using exosomes for cancer therapy. Exosomes have many advantages for conveying therapeutic agents such as small interfering RNAs, microRNAs, membrane-associated proteins, and chemotherapeutic compounds; thus, they are considered a prime candidate as a delivery tool for cancer treatment. Since exosomes also provide an optimal microenvironment for the effective function of immunomodulatory factors, exosomes harboring bioactive molecules have been bioengineered as cancer immunotherapies that can effectively activate each stage of the cancer immunity cycle to successfully elicit cancer-specific immunity. This review discusses the advantages of exosomes for treating cancer and the challenges that must be overcome for their successful clinical development.     

一个用于肺癌早期诊断的彩色图像处理系统

介绍了一个用于肺癌早期诊断的彩色图像处理系统，该系统能够识别痰液涂片彩色显微图像中的肺癌细胞。为了提高识别癌细胞的稳定性与有效性，系统采用了一种细胞分割与分类的分层处理结构，首先，在某一特定的归一化彩色空间中利用自适应阈值的方法对细胞核进行分割，利用细胞核的形态学特征检出可疑癌细胞，最后用细胞核区的色度学特征和纹理特征对可疑癌细胞进行分类与识别，从而确定是否存在癌细胞。     

A Novel Biosensor Based on Molybdenum Disulfide (MoS2) Modified Porous Anodic Aluminum Oxide Nanochannels for Ultrasensitive microRNA‐155 Detection

Artificial photoresponsive nanochannels have attracted widespread attention because of their capacity to achieve ion transport through light modulation. Herein, a biosensor for ultrasensitive miRNA‐155 detection is devised based on molybdenum disulfide (MoS₂) modified porous anodic aluminum oxide (AAO) photoresponsive nanochannels by atomic layer deposition (ALD). According to the optimized experimental results, when the cycles of ALD, the wavelength, and the power of the excitation laser are 70 cycles, 450 nm, and 80 mW, respectively, the most supreme photocurrent performance of these photoresponsive nanochannels are obtained. AAO nanochannels modified with MoS₂ can work as a photoelectrochemical (PEC) biosensor by generating photoexcitation current; what is more, the high channel density in AAO can magnify the ion current signal response effectively by aggrandizing the flux of electroactive species. By using AAO photoresponsive nanochannels with an average diameter of 150 nm as PEC biosensor, an ultrasensitive detection record ranging from 0.01 fM to 0.01 nM with a detection limit of 3 aM can be achieved. This work not only proposes a simple method for manufacturing semiconductor photoresponsive nanochannels, but also exhibits great potential in the ultrasensitive detection of biomolecules.     

Construction of Exosome SORL1 Detection Platform Based on 3D Porous Microfluidic Chip and its Application in Early Diagnosis of Colorectal Cancer

Exosomes are promising new biomarkers for colorectal cancer (CRC) diagnosis, due to their rich biological fingerprints and high level of stability. However, the accurate detection of exosomes with specific surface receptors is limited to clinical application. Herein, an exosome enrichment platform on a 3D porous sponge microfluidic chip is constructed and the exosome capture efficiency of this chip is ≈90%. Also, deep mass spectrometry analysis followed by multi-level expression screenings revealed a CRC-specific exosome membrane protein (SORL1). A method of SORL1 detection by specific quantum dot labeling is further designed and the ensemble classification system is established by extracting features from 64-patched fluorescence images. Importantly, the area under the curve (AUC) using this system is 0.99, which is significantly higher (p < 0.001) than that using a conventional biomarker (carcinoembryonic antigen (CEA), AUC of 0.71). The above system showed similar diagnostic performance, dealing with early-stage CRC, young CRC, and CEA-negative CRC patients.     

A Sensitive Aptasensor Based on a Hemin/G‐Quadruplex‐Assisted Signal Amplification Strategy for Electrochemical Detection of Gastric Cancer Exosomes

Emerging evidence indicates that exosomes derived from gastric cancer cells enhance tumor migration and invasion through the modulation of the tumor microenvironment. However, it remains a major problem to detect cancer‐specific exosomes due to technical and biological challenges. Most of the methods reported could not achieve efficient detection of tumor‐derived exosomes in the background of normal exosomes. Herein, a label‐free electrochemical aptasensor is presented for specific detection of gastric cancer exosomes. This platform contains an anti‐CD63 antibody modified gold electrode and a gastric cancer exosome specific aptamer. The aptamer is linked to a primer sequence that is complementary to a G‐quadruplex circular template. The presence of target exosomes could trigger rolling circle amplification and produce multiple G‐quadruplex units. This horseradish peroxidase mimicking DNAzyme could catalyze the reduction of H₂O₂ and generate electrochemical signals. This aptasensor exhibits high selectivity and sensitivity toward gastric cancer exosomes with a detection limit of 9.54 × 10² mL^?1 and a linear response range from 4.8 × 10³ to 4.8 × 10⁶ exosomes per milliliter. Therefore, this electrochemical aptasensor is expected to become a useful tool for the early diagnosis of gastric cancer.     

Digital Detection of Single Virus Particles by Multi-Spot,Label-Free Imaging Biosensor on Anti-Reflective Glass

Rapid detection of whole virus particles in biological or environmental samples represents an unmet need for the containment of infectious diseases. Here, an optical device enabling the enumeration of single virion particles binding on antibody or aptamers immobilized on a surface with anti-reflective coating is described. In this regime, nanoparticles adhering to the sensor surface provide localized contributions to the reflected field that become detectable because of their mixing with the interfering waves in the reflection direction. Thus, these settings are exploited to realize a scan-free, label-free, micro-array-type digital assay on a disposable cartridge, in which the virion counting takes place in wide field-of-view imaging. With this approach we could quantify, by enumeration, different variants of SARS-CoV-2 virions interacting with antibodies and aptamers immobilized on different spots. For all tested variants, the aptamers showed larger affinity but lower specificity relative to the antibodies. It is found that the combination of different probes on the same surface enables increasing specificity of detection and dynamic range.     

海洋工程结构故障的模式识别诊断

本文提出固定式导管架平台结构故障的模式识别诊断.首先介绍模式识别的基本思想,然后讨论统计判别函数方法.对一个二维导管架平台模型,用随机激励进行了正常平台、台面质量增加、横撑斜撑切断以及根部开裂等多种结构状态的振动试验.取频响函数幅值和随机减量函数作为被识别的模式,得到了很好的结果,从而说明这是一种很有希望的导管架平台结构故障的诊断方法.     

机床颤振的早期诊断与在线监控

本文基于大量试验,分析了在切削从平稳走向失稳的过渡过程中,机床振动的加速度信号的特征变化,并引入几个特征量和模式向量平面来描述这些特征变化,以实现颤振的早期诊断.根据所建立的机床颤振的非线性理论及模型,讨论了颤振振幅与切削用量的关系,并制定了颤振的在线控制策略. 根据以上结果,把早期诊断与在线控制有机地联在一起,建立了颤振的在线监控试验系统.大量试验表明,机床颤振的早期诊断与在线监控这一技术思想是切实可行的.     

FluorMango,an RNA-Based Fluorogenic Biosensor for the Direct and Specific Detection of Fluoride

Nucleic acids are not only essential actors of cell life but also extremely appealing molecular objects in the development of synthetic molecules for biotechnological application, such as biosensors to report on the presence and concentration of a target ligand by emission of a measurable signal. In this work, FluorMango, a fluorogenic ribonucleic acid (RNA)-based biosensor specific for fluoride is introduced. The molecule consists of two RNA aptamer modules, a fluoride-specific sensor derived from the crcB riboswitch which changes its structure upon interaction with the target ion, and the light-up RNA Mango-III that emits fluorescence when complexed with a fluorogen. The two modules are connected by an optimized communication module identified by ultrahigh-throughput screening, which results in extremely high fluorescence of FluorMango in the presence of fluoride, and background fluorescence in its absence. The value and efficiency of this biosensor by direct monitoring of defluorinase activity in living bacterial cells is illustrated, and the use of this new tool in future screening campaigns aiming at discovering new defluorinase activities is discussed.     

Upconversion Luminescence Resonance Energy Transfer (LRET)‐Based Biosensor for Rapid and Ultrasensitive Detection of Avian Influenza Virus H7 Subtype

Avian influenza viruses (AIV) with good adaptation and various mutations have threatened both human and animals’ health. The H7 subtypes have the potential to cause pandemic threats to human health due to the highly pathogenic characteristics. Therefore, it is quite urgent to develop a novel biosensor for rapid and sensitive detection of H7 subtypes. In this work, a biosensor based on luminescence resonance energy transfer (LRET) from BaGdF₅:Yb/Er upconversion nanoparticles (UCNPs) to gold nanoparticles (AuNPs) has been developed for rapid and sensitive H7 subtypes detection. The amino modified capture oligonucleotide probes are covalently linked to poly(ethylenimine) (PEI) modified BaGdF₅:Yb/Er UCNPs. The thiol modified oligonucleotides with H7 hemagglutinin gene sequence are conjugated to surfaces of AuNPs. The hybridization process between complementary strands of H7 Hemagglutinin gene and its probe brings the energy donor and acceptor into close proximity, leading to the quenching of fluorescence of UCNPs. A linear response is obtained ranging from 10 pm to 10 nm and the limit of detection (LOD) is around 7 pm with detection time around 2 hours. This biosensor is expected to be a valuable diagnostic tool for rapid and sensitive detection of AIV.     

随机共振技术在齿轮箱故障检测中的应用

讨论了利用SR原理从强背景噪声中提取微弱周期特征信号的方法，给出了SR模型数值求解的新算法。在对齿轮箱故障进行数值仿真的基础上，将此方法用于某型直升机中间减速器齿轮点蚀故障的微弱特征信号提取，结果表明，该方法能有效提取出齿轮发生早期点蚀故障时的微弱特征信号，为直升机减速器齿轮箱的状态监测与早期故障检测提供了一条新途径。