The 100 most-cited articles in Analytical Chemistry, 2023

A novel metal–organic framework (MOF)-on-MOF dual enzyme-mimic nanozyme was designed as enhanced cascade signal amplification for the colorimetric and chemiluminescent (CL) dual-mode aptasensing. The MOF-on-MOF hybrid is composed of MOF-818 with catechol oxidase-like activity and iron porphyrin MOF [PMOF(Fe)] with peroxidase-like activity, called MOF-818@PMOF(Fe). MOF-818 can catalyze the 3,5-di- tert -butylcatechol substrate and produce H 2 O 2 in situ. Subsequently, PMOF(Fe) catalyzes H 2 O 2 to produce reactive oxygen species, which oxidize 3,3′,5,5′-tetramethylbenzidine or luminol to produce color or luminescence. Thanks to the nano-proximity effect and the confinement effect, the efficiency of the biomimetic cascade catalysis is greatly improved, which in turn generates enhanced colorimetric and CL signals. Taking the detection of chlopyrifos as an example, the prepared dual enzyme-mimic MOF nanozyme is combined with the aptamer with specific recognition ability to develop a colorimetric/CL dual-mode aptasensor for highly sensitive and selective detection of chlorpyrifos. The…

Most organophosphorus pesticide (OP) sensors reported in the literature rely on the inhibition effect of OPs on the activity of acetylcholinesterase (AChE), which suffer from the drawbacks of lack of selective recognition of OPs, high cost, and poor stability. Herein, we proposed a novel chemiluminescence (CL) strategy for the direct detection of glyphosate (an organophosphorus herbicide) with high sensitivity and specificity, which is based on the porous hydroxy zirconium oxide nanozyme (ZrO X -OH) obtained via a facile alkali solution treatment of UIO-66. ZrO X -OH displayed excellent phosphatase-like activity, which could catalyze the dephosphorylation of 3-(2′-spiroadamantyl)-4-methoxy-4-(3′-phosphoryloxyphenyl)-1,2-dioxetane (AMPPD) to generate strong CL. The experimental results showed that the phosphatase-like activity of ZrO X -OH is closely related to the content of hydroxyl groups on their surface. Interestingly, ZrO X -OH with phosphatase-like properties exhibited a unique response to glyphosate because of the consumption of the surface hydroxyl group by the unique…

Accurate identification of acutely toxic and low-fatality mycotoxins on a large scale in a quick and cheap manner is critical for reducing population mortality. Herein, a portable photothermal immunosensing platform supported by a microelectromechanical microsystem (MEMS) without enzyme involvement was reported for point-of-care testing of mycotoxins (in the case of aflatoxin B 1, AFB 1 ) in food based on the precise satellite structure of Au nanoparticles. The synthesized Au nanoparticles with a well-defined, graded satellite structure exhibited a significantly enhanced photothermal response and were coupled by AFB 1 antibodies to form signal conversion probes by physisorption for further target-promoted competitive responses in microplates. In addition, a coin-sized miniature NIR camera device was constructed for temperature acquisition during target testing based on advanced MEMS fabrication technology to address the limitation of expensive signal acquisition components of current photothermal sensors. The proposed MEMS readout-based microphotothermal test method provides…

Cation exchange (CE) is a burgeoning method for controlled crystal synthesis; however, its applications in bioanalysis are still in their infancy. Herein, we explored the transformation of ZnIn 2 S 4 in properties after the CE reaction with Cu 2+ ions; furthermore, the discrepancy was employed to design a dual-readout detection system of photothermal and polarity-switchable photoelectrochemical (PEC) immunoassays to realize reliable detection of carcinoembryonic antigen (CEA). In the presence of CEA, the CuO nanoparticles (CuO NPs) employed as dual-signal response probes would bond to the microplates and be acidolyzed by HCl to release Cu 2+, which could replace Zn 2+ and In 3+ via the CE reaction. After the CE reaction is completed, the photocurrent would switch from a weak anodic photocurrent to a cathode one by using a 635 nm laser as a signal amplifier, while the photothermal signal would be enhanced with 808 nm laser illumination. On the basis of the polarity-switchable PEC strategy, CEA could be accurately detected from 0.1 to 50 ng mL –1 with a limit of detection (LOD) of 48…

The growing trend toward high-throughput proteomics demands rapid liquid chromatography-mass spectrometry (LC-MS) cycles that limit the available time to gather the large numbers of MS/MS fragmentation spectra required for identification. Orbitrap analyzers scale performance with acquisition time and necessarily sacrifice sensitivity and resolving power to deliver higher acquisition rates. We developed a new mass spectrometer that combines a mass-resolving quadrupole, the Orbitrap, and the novel Asymmetric Track Lossless (Astral) analyzer. The new hybrid instrument enables faster acquisition of high-resolution accurate mass (HRAM) MS/MS spectra compared with state-of-the-art mass spectrometers. Accordingly, new proteomics methods were developed that leverage the strengths of each HRAM analyzer, whereby the Orbitrap analyzer performs full scans with a high dynamic range and resolution, synchronized with the Astral analyzer's acquisition of fast and sensitive HRAM MS/MS scans. Substantial improvements are demonstrated over previous methods using current state-of-the-art mass…

Photoelectrochemical (PEC) sensing has been rapidly evolving in recent years, while the introduction of small molecules with specific recognition functions into the sensing interface remains a nascent area of study. In this work, we reported a PEC biosensor for formaldehyde (FA) detection based on photoinduced electron transfer (PET)-gated electron injection between organic small molecules and inorganic semiconducting substrates. Specifically, an FA-responsive probe (NA-FA-COOH) and TiO 2 nanoarrays were integrated to construct a PEC platform (NFC/TiO 2 ) via a coordination bond. NFC served simultaneously as a target-specific recognition element and a modulator of photoinduced electron injection. Treatment of NFC/TiO 2 by FA would suppress the intramolecular PET process, with the quenched photocurrent signal due to the changed carrier transfer pathway, thus establishing the PEC platform for FA based on effective PET modulation. The proposed PEC system exhibited high selectivity and sensitivity, with a low detection limit of 0.071 μM. This study presents a novel perspective on the…

Noble-metal nanozymes have demonstrated great potential in various fields. However, aggregation of single-particle nanoparticles severely affects their exposed catalytically active sites to the extent of exhibiting weak enzyme-like activity. Here, we present an organic block surfactant (polyvinylpyrrolidone, PVP) to construct monodisperse water-stable Pt nanoclusters (Pt NCs) for an enhanced immunoassay of cardiac troponin I (cTnI). The PVP-modified Pt NC nanozyme exhibited up to 16.3 U mg –1 peroxidase-mimicking activity, which was mainly attributed to the ligand modification on the surface and the electron-absorbing effect of the ligand on the Pt NCs. The PVP-modified Pt NCs have a lower OH-transition potential, as determined by density functional theory. Under optimized experimental conditions, the enhanced nanozyme immunoassay strategy exhibited an ultrawide dynamic response range of 0.005–50 ng mL –1 for cTnI targets with a detection limit of 1.3 pg mL –1, far superior to some reported test protocols. This work provides a designable pathway for the design of artificial enzymes…

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTLatest Improvements and Expanding Applications of Solid-Phase MicroextractionJuan ZhengJuan ZhengMinistry of Education (MOE) Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry/School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510006, ChinaMore by Juan ZhengView Biography, Yixin KuangYixin KuangMinistry of Education (MOE) Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry/School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510006, ChinaMore by Yixin KuangView Biography, Suxin ZhouSuxin ZhouMinistry of Education (MOE) Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry/School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510006, ChinaMore by Suxin ZhouView Biography, Xinying GongXinying GongMinistry of Education (MOE) Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry/School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510006,…

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTRecent Advances in Separation and Analysis of Chiral CompoundsHai-Long QianHai-Long QianState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaInternational Joint Laboratory on Food Safety, Jiangnan University, Wuxi 214122, ChinaInstitute of Analytical Food Safety, School of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaMore by Hai-Long QianView Biographyhttps://orcid.org/0000-0001-7554-4115, Shu-Ting XuShu-Ting XuState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaInternational Joint Laboratory on Food Safety, Jiangnan University, Wuxi 214122, ChinaInstitute of Analytical Food Safety, School of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaMore by Shu-Ting XuView Biography, and Xiu-Ping Yan*Xiu-Ping YanState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaInternational Joint Laboratory on Food Safety, Jiangnan University, Wuxi 214122, ChinaInstitute of Analytical Food Safety, School…

Functional Basics of Cas12 and Cas13 208 Nuclease Activity of Cas12a 208 Nuclease Activity of Cas13a 208 Quantitative Determination of trans-Cleavage Kinetics of Cas Enzymes 209 trans-Cleavage Kinetics of Cas12 and Cas13 212 trans-Cleavage Kinetics of Cas12 and Its Contributing Factors 212 trans-Cleavage Kinetics of Cas13 and Its Contributing Factors 212 Nucleic Acid Detection Sensitivity Achieved by trans-Cleavage Activity of Cas Enzymes 213 Relations between the trans-Cleavage Kinetics and the Limit of Detection 213 Prediction of Performance Aided by Machine Learning 214 Challenges of trans-Cleavage and Signal Amplification in Live Cells 214

Fully integrated wearable sensors are capable of dynamically, directly, and independently tracking biomarkers in raw noninvasive biofluids without any other equipment or accessories by integrating the unique on-body monitoring feature with the special complete functional implementation attribute. Sweat, saliva, and urine are three important noninvasive biofluids, and changes in their biomarkers hold great potential for revealing physiological conditions. However, it is still a challenge to design single fully integrated wearable sensor arrays (FIWSAs) that are universally able to concurrently measure electrolytes and metabolites in three of the most common noninvasive biofluids including sweat, saliva, and urine. Here, we propose the first single universal FIWSAs for wirelessly, noninvasively, and simultaneously measuring various metabolites (i.e., uric acid) and electrolytes (i.e., Na + and H + ) in raw sweat, saliva, or urine under subjects’ exercise by integrating the specifically designed microfluidic, sensing, and electronic modules in a seamless manner. We evaluate its utility…

A lanthanide-based three-dimensional metal–organic framework with excellent water, acid/base, and solvent stability, namely {[(CH 3 ) 2 NH 2 ] 0.7 [Eu 2 (BTDBA) 1.5 (lac) 0.7 (H 2 O) 2 ]·2H 2 O·2DMF·2CH 3 CN} n ( JXUST-29, H 4 BTDBA = 4′,4‴-(benzo[ c ][1,2,5]thiadiazole-4,7-diyl)bis([1,1′-biphenyl]-3,5-dicarboxylic acid), Hlac = lactic acid), has been synthesized and characterized. Since the N atoms of the thiadiazole group will not coordinate with lanthanide ions, JXUST-29 has a free basic N-site accessible to small H + ions, which allows it to be used as a promising pH fluorescence sensor. Interestingly, the luminescence signal was significantly enhanced, with an approximately 54-fold enhancement in the emission intensity when the pH value was increased from 2 to 5, which is the typical behavior of pH probes. In addition, JXUST-29 can also be used as a luminescence sensor to detect l -arginine (Arg) and l -lysine (Lys) in an aqueous solution through fluorescence enhancement and the blue-shift effect. The detection limits were 0.023 and 0.077 μM, respectively. In addition, JXUST-29…

Precise and sensitive analysis of exosomal microRNA (miRNA) is of great importance for noninvasive early disease diagnosis, but it remains a great challenge to detect exosomal miRNA in human blood samples because of their small size, high sequence homology, and low abundance. Herein, we integrated reliable Pt-S bond-mediated three-dimensional (3D) DNA nanomachine and magnetic separation in a homogeneous electrochemical strategy for the detection of exosomal miRNA with low background and high sensitivity. The 3D DNA nanomachine was easily prepared via a facile and rapid freezing method, and it was capable of resisting the influence of biothiols, thus endowing it with high stability. Notably, the as-developed magnetic 3D DNA nanomachine not only enabled the detection system to have a low background but also coupled with liposome nanocarriers to synergistically amplify the current signal. Consequently, by ingeniously combining the low background and multiple signal-amplification strategies in homogeneous electrochemical biosensing, highly sensitive detection of exosomal miRNA was…

Exosomes are a class of extracellular vesicles secreted by cells, which can be used as promising noninvasive biomarkers for the early diagnosis and treatment of diseases, especially cancer. However, due to the heterogeneity of exosomes, it remains a grand challenge to distinguish accurately and reliably exosomes from clinical samples. Herein, we achieve accurate fuzzy discrimination of exosomes from human serum samples for accurate diagnosis of breast cancer and cervical cancer through machine learning-based label-free surface-enhanced Raman spectroscopy (SERS), by using "hot spot" rich 3D plasmonic AuNPs nanomembranes as substrates. Due to the existence of some weak distinguishable SERS fingerprint signals and the high sensitivity of the method, the machine learning-based SERS analysis can precisely identify three (normal and cancerous) cell lines, two of which are different types of cancer cells, without specific labeling of biomarkers. The prediction accuracy based on the machine learning algorithm was up to 91.1% for the discrimination of different cell lines (H8, HeLa, and…

A new lateral flow immunoassay strip (LFIA) combining sensitive detection and identification of multiple bacteria remains a huge challenge. In this study, we first developed multifunctional urchin-shaped Au–Ag@Pt nanoparticles (UAA@P NPs) with a unique combination of colorimetric-SERS-photothermal-catalytic (CM/SERS/PT/CL) properties and integrated them with LFIA for multiplexed detection and specific discrimination of pathogenic bacteria in blood samples. Unlike the conventional LFIA that relied on antibody (Ab), this novel LFIA introduced 4-mercaptophenylboronic acid (4-MPBA) as an ideal Ab replacer that was functionalized on UAA@P NPs (UAA@P/M NPs) with outstanding binding and enrichment capacities toward bacteria. Taking Staphylococcus aureus ( S. aureus ) as model bacteria, the limit of detection (LOD) was 3 CFU/mL for SERS-LFIA, 27 CFU/mL for PT-LFIA, and 18 CFU/mL for CL-LFIA, three of which were over 330-fold, 37-fold, and 55-fold more sensitive than ordinary visual CM-LFIA, respectively. Besides, this SERS-LFIA is capable of identifying three types of bacterial spiked blood…

biosensor arrays interfaced with biogenic cells.

Natural enzymes are crucial in biological systems and widely used in biology and medicine, but their disadvantages, such as insufficient stability and high-cost, have limited their wide application. Since Fe 3 O 4 nanoparticles were found to show peroxidase-like activity, researchers have designed and developed a growing number of nanozymes that mimic the activity of natural enzymes. Nanozymes can compensate for the defects of natural enzymes and show higher stability with lower cost. Iron, a nontoxic and low-cost transition metal, has been used to synthesize a variety of iron-based nanozymes with unique structural and physicochemical properties to obtain different enzymes mimicking catalytic properties. In this perspective, catalytic mechanisms, activity modulation, and their recent research progress in sensing, tumor therapy, and antibacterial and anti-inflammatory applications are systematically presented. The challenges and perspectives on the development of iron-based nanozymes are also analyzed and discussed.

Untargeted metabolomics is an analytical approach with numerous applications serving as an effective metabolic phenotyping platform to characterize small molecules within a biological system. Data quality can be challenging to evaluate and demonstrate in metabolomics experiments. This has driven the use of pooled quality control (QC) samples for monitoring and, if necessary, correcting for analytical variance introduced during sample preparation and data acquisition stages. Described herein is a scoping literature review detailing the use of pooled QC samples in published untargeted liquid chromatography-mass spectrometry (LC-MS) based metabolomics studies. A literature query was performed, the list of papers was filtered, and suitable articles were randomly sampled. In total, 109 papers were each reviewed by at least five reviewers, answering predefined questions surrounding the use of pooled quality control samples. The results of the review indicate that use of pooled QC samples has been relatively widely adopted by the metabolomics community and that it is used at a similar…

Scanning electrochemical probe microscopies (SEPMs) have played a key role in advancing small-scale electrochemistry. SEPMs use an electrochemical probe (micro/nanoelectrode or pipet) to quantify and map local interfacial fluxes of electroactive species and have found increasingly wide applications. Our contribution to the Fundamental and Applied Reviews in Analytical Chemistry 2019 discussed how advances in SEPMs converged towards nanoscale electrochemical mapping. This inflection in experimental capability has opened up myriad opportunities for SEPMs in many types of systems, from material and energy sciences to the life sciences. The enhancement in the spatial resolution of imaging techniques, and instrumental developments, have resulted in significant increases in the size of electrochemical datasets from a typical experiment and served to speed up measurement throughput. Next generation nanoelectrochemistry will thus see an emphasis on “big data”, its analysis, storage and curation, high throughput analysis and parallelization, “intelligent” instruments and experiments, active…

Abnormal changes occurring in the mitochondrial microenvironment are important markers indicating mitochondrial and cell dysfunction. Herein, we designed and synthesized a multifunctional fluorescent probe DPB that responds to polarity, viscosity, and peroxynitrite (ONOO – ). DPB is composed of an electron donor (diethylamine group) and electron acceptor (coumarin, pyridine cations, and phenylboronic acid esters), in which the pyridine group with a positive charge is responsible for targeting to mitochondria. D-π– A structure with strong intramolecular charge transfer (ICT) and twisted intramolecular charge transfer (TICT) properties give rise to respond to polarity and viscosity. The introduction of cyanogroup and phenylboronic acid esters increases the electrophilicity of the probe, which is prone to oxidation triggered by ONOO – . The integrated architecture satisfies the multiple response requirements. As the polarity increases, the fluorescence intensity of probe DPB at 470 nm is quenched by 97%. At 658 nm, the fluorescence intensity of DPB increases with viscosity and…

Developing highly active and sensitive nanozymes for biothiol analysis is of vital significance due to their essential roles in disease diagnosis. Herein, two metal ion-doped carbon dots (M-CDs) with high peroxidase-like activity were designed and prepared for biothiol detection and identification through the colorimetric sensor array technique. The two M-CDs can strongly catalyze the decomposition of H 2 O 2, accompanied by color changes of 3,3′,5,5′-tetramethylbenzidine (TMB) from colorless to blue, indicating peroxidase-mimicking activities of M-CDs. Compared with pure carbon dots (CDs), M-CDs exhibited enhanced peroxidase-like activity owing to the synergistic effect between metal ions and CDs. However, due to the strong binding affinity between biothiols and metal ions, the catalytic activities of M-CDs could be inhibited by different biothiols to diverse degrees. Therefore, using TMB as a chromogenic substrate in the presence of H 2 O 2, the developed colorimetric sensor array can form differential fingerprints for the three most important biothiols (i.e., cysteine (Cys),…

Hepatic lipid droplets (LDs) and peroxynitrite (ONOO – ) levels are closely related to nonalcoholic fatty liver disease (NAFLD). Additionally, some drug-induced liver injury (DILI) is often associated with ONOO – . Here, we constructed and screened the quasi-LDs-targeted and ONOO – -responsive fluorescent probe MBDP-Py + to investigate the interaction of NAFLD with DILI. By monitoring the upregulation of the ONOO – levels and the accumulation of LDs, MBDP-Py + was more sensitive and efficient than tissue staining and serum markers detection in evaluating the early toxicity of NAFLD and diagnosing the anticancer-DILI. More importantly, the sensitive enhancement of fluorescence signals demonstrated that in different stages of NAFLD, the dominant element of liver injury was different in the NAFLD combined with DILI mice models. As the degree of NAFLD deepens, the synergistic effect of the two will lead to more serious liver damage.

The analysis of ultralow input samples or even individual cells is essential to answering a multitude of biomedical questions, but current proteomic workflows are limited in their sensitivity and reproducibility. Here, we report a comprehensive workflow that includes improved strategies for all steps, from cell lysis to data analysis. Thanks to convenient-to-handle 1 μL sample volume and standardized 384-well plates, the workflow is easy for even novice users to implement. At the same time, it can be performed semi-automatized using CellenONE, which allows for the highest reproducibility. To achieve high throughput, ultrashort gradient lengths down to 5 min were tested using advanced μ-pillar columns. Data-dependent acquisition (DDA), wide-window acquisition (WWA), data-independent acquisition (DIA), and commonly used advanced data analysis algorithms were benchmarked. Using DDA, 1790 proteins covering a dynamic range of four orders of magnitude were identified in a single cell. Using DIA, proteome coverage increased to more than 2200 proteins identified from single-cell level input…

Based on the controllable instantaneous self-assembly ability of long-chain branched DNA nanostructures and the synergistic effect between nucleic acid amplification without enzymes, a highly sensitive and highly specific self-powered biosensing platform is developed. Two-dimensional graphdiyne is prepared, modified on flexible carbon cloth, and then functionalized with gold nanoparticles. When DNA mi-tubes are applied on it, target thalassemia gene CD122 triggers a dual-catalytic hairpin assembly reaction. The generated nanoscale DNA is precisely captured by the DNA mi-tube, exposing binding sites and activating the hybridization chain reaction to form long-chain branched DNA. Double-stranded DNA, along with dendritic DNA carrying a large number of guanine bases, precisely captures the signal molecule methylene blue (MB), generating a significant electrochemical signal. The redox reaction of MB also causes a proportional change in the system’s color, achieving a colorimetric detection functionality. An efficient dual-mode self-powered sensing platform, therefore, is established for…

While great progress in nanozyme-enabled analytical chemistry has been made, most current nanozyme-based biosensing platforms are based on peroxidase-like nanozymes. However, peroxidase-like nanozymes with multienzymatic activities can influence the detection sensitivity and accuracy, while the use of unstable hydrogen peroxide (H 2 O 2 ) in a peroxidase-like catalytic reaction may result in the reproducibility challenge of sensing signals. We envision that constructing biosensing systems by using oxidase-like nanozymes can address these limitations. Herein, we reported that platinum–nickel nanoparticles (Pt–Ni NPs) with Pt-rich shells and Ni-rich cores possessed high oxidase-like catalytic efficiency, exhibiting a 2.18-fold higher maximal reaction velocity ( v max ) than initial pure Pt NPs. The oxidase-like Pt–Ni NPs were applied to develop a colorimetric assay for the determination of total antioxidant capacity (TAC). The antioxidant levels of four bioactive small molecules, two antioxidant nanomaterials, and three cells were successfully measured. Our work not only provides new…

Digitized telemedicine tools with the Internet of Things (IoT) started advancing into our daily lives and have been incorporated with commercial wearable gadgets for noninvasive remote health monitoring. The newly established tools have been steered toward a new era of decentralized healthcare. The advancement of a telemedicine wearable monitoring system has attracted enormous interest in the multimodal big data acquisition of real-time physiological and biochemical information via noninvasive methods for any health-related industries. The expectation of telemedicine wearable creation has been focused on early diagnosis of multiple diseases and minimizing the cost of high-tech and invasive treatments. However, only limited progress has been directed toward the development of telemedicine wearable sensors. This Perspective addresses the advancement of these wearable sensors that encounter multiple challenges on the forefront and technological gaps hampering the realization of health monitoring at molecular levels related to smart materials mostly limited to single use, issues of…

Laser-induced breakdown spectroscopy (LIBS) is a versatile analytical tool for studying the elemental composition of any kind of sample, such as solids, liquids or gases.One of the latest developments in this technique is the ability to use it for elemental imaging, that is to say spatially resolved surface analysis.LIBS imaging is becoming a very attractive and popular technique for the qualitative and/or quantitative spectrochemical characterization of specimens for a wide range of applications.Because of its unique set of intrinsic advantages, LIBS imaging is frequently preferred over competitive and complementary techniques for elemental imaging.This review recapitulates the technical fundamentals of LIBS imaging and focuses on significant applications that have received the most promising attention and have undergone major advances during the last three years in the industrial, geological and biomedical fields.We also discuss the current limitations that hinder the further development of LIBS imaging, as well as perspectives on the use of LIBS as a part of multimodal imaging…

A rational design of high-efficiency electrocatalysts and thus achieving sensitive electrochemical sensing remains a great challenge. In this work, single-atom indium anchored on nitrogen-doped carbon (In 1 –N–C) with an In–N 4 configuration is prepared successfully through a high-temperature annealing strategy; the product can serve as an advanced electrocatalyst for sensitive electrochemical sensing of dopamine (DA). Compared with In nanoparticle catalysts, In 1 –N–C exhibits high catalytic performance for DA oxidation. The theoretical calculation reveals that In 1 –N–C has high adsorption energy for hydroxy groups and a low energy barrier in the process of DA oxidation compared to In nanoparticles, indicating that In 1 –N–C with atomically dispersed In–N 4 sites possesses enhanced intrinsic activity. An electrochemical sensor for DA detection is established as a concept application with high sensitivity and selectivity. Furthermore, we also verify the feasibility of In 1 –N–C catalysts for the simultaneous detection of uric acid, ascorbic acid, and DA. This work extends the…

The sensitive detection of neuron-specific enolase (NSE) as a biomarker for lung cancer at an early stage is critical but has long been a challenge. The emergence of polarity-switchable photoelectrochemical (PEC) bioanalysis has opened up new avenues for developing highly sensitive NSE sensors. In this study, we present such a biosensor depending on the bioinduced AgI transition on MOF-on-MOF-derived semiconductor heterojunctions. Specifically, treatment of ZnO@In 2 O 3 @AgI by bioproduced H 2 S can in situ generate the ZnO@In 2 O 3 @In 2 S 3 @Ag 2 S heterojunction, with the photocurrent switching from the cathodic to anodic one due to the changes in the carrier transfer pathway. Linking an NSE-targeted sandwich immunorecognition with labeled alkaline phosphatase (ALP) catalyzed generation of H 2 S, such a phenomenon was correlated to NSE concentration with good performance in terms of selectivity and sensitivity and a low detection limit of 0.58 pg/mL. This study offered a new perspective on the use of MOF-on-MOF-derived heterostructures for advanced polarity-switchable PEC…

FeOOH nanorods, as one-dimensional nanomaterials, have been widely used in many fields due to their stable properties, low cost, and easy synthesis, but their application in the field of chemiluminescence (CL) is rarely reported. In this work, FeOOH nanorods were synthesized by a simple and environmentally friendly one-pot hydrothermal method and used for the first time as a catalyst for generating strong CL with luminol without additional oxidant. Remarkably, luminol-FeOOH exhibits about 250 times stronger CL than the luminol-H 2 O 2 system. Its CL intensity was significantly quenched by uric acid. We established a simple, rapid, sensitive, and selective CL method for the detection of uric acid with a linear range of 20–1000 nM and a detection limit of 6.3 nM (S/N = 3). In addition, we successfully applied this method to the detection of uric acid in human serum, and the standard recoveries were 95.6–106.4%.

High Resolution Image Download MS PowerPoint Slide In this Perspective, we discuss the current status and advances in spatial transcriptomics technologies, which allow high-resolution mapping of gene expression in intact cell and tissue samples. Spatial transcriptomics enables the creation of high-resolution maps of gene expression patterns within their native spatial context, adding an extra layer of information to the bulk sequencing data. Spatial transcriptomics has expanded significantly in recent years and is making a notable impact on a range of fields, including tissue architecture, developmental biology, cancer, and neurodegenerative and infectious diseases. The latest advancements in spatial transcriptomics have resulted in the development of highly multiplexed methods, transcriptomic-wide analysis, and single-cell resolution utilizing diverse technological approaches. In this Perspective, we provide a detailed analysis of the molecular foundations behind the main spatial transcriptomics technologies, including methods based on microdissection, in situ sequencing,…

Intracellular peroxynitrite anions (ONOO – ) and microenvironments (such as viscosity and polarity) play an important role in maintaining redox homeostasis, regulating diffusion, transportation, and signal transduction in living cells. The abnormality of these factors is often closely related to various physiological/pathological processes. However, owing to the lack of suitable probes, the simultaneous visualization of ONOO –, viscosity, and polarity in ferroptosis and cancer models has not been achieved. To meet urgent needs, we presented a multifunctional near-infrared (NIR) fluorescent probe, named MQA-P, for simultaneously detecting ONOO –, viscosity, and polarity within mitochondria. The probe exhibited a remarkable turn-on response to ONOO – with the far-red emission of about 645 nm and was highly sensitive to viscosity/polarity in the NIR channel with λ em > 704 nm. Facilitated by MQA-P, for the first time, we revealed that erastin-induced ferroptosis was accompanied by a significant upregulation of ONOO – and an increase of viscosity (or decrease of polarity) at the same…

Electrochemical biosensors provide powerful tools for dissecting the dynamically changing neurochemical signals in the living brain, which contribute to the insight into the physiological and pathological processes of the brain, due to their high spatial and temporal resolutions. Recent advances in the integration of in vivo electrochemical sensors with cross-disciplinary advances have reinvigorated the development of in vivo sensors with even better performance. In this Review, we summarize the recent advances in molecular design, electrode materials, and electrochemical devices for in vivo electrochemical sensors from molecular to macroscopic dimensions, highlighting the methods to obtain high performance for fulfilling the requirements for determination in the complex brain through flexible and smart design of molecules, materials, and devices. Also, we look forward to the development of next-generation in vivo electrochemical biosensors.

Mitophagy is a vital cellular process playing vital roles in regulating cellular metabolism and mitochondrial quality control. Mitochondrial viscosity is a key microenvironmental index, closely associated with mitochondrial status. To monitor mitophagy and mitochondrial viscosity, three molecular rotors ( Mito-1, Mito-2, and Mito-3 ) were developed. All probes contain a cationic quinolinium unit and a C 12 chain so that they can tightly bind mitochondria and are not affected by the mitochondrial membrane potential. Optical studies showed that all probes are sensitive to viscosity changes with an off–on fluorescence response, and Mito-3 shows the best fluorescence enhancement. Bioimaging studies showed that all these probes can not only tightly locate and visualize mitochondria with near-infrared fluorescence but also effectively monitor the mitochondrial viscosity changes in cells. Moreover, Mito-3 was successfully applied to visualize the mitophagy process induced by starvation, and mitochondrial viscosity was found to show an increase during mitophagy. We expect Mito-3 to become a…

Peroxidase-mimetic materials are intensively applied to establish multienzyme systems because of their attractive merits. However, almost all of the nanozymes explored exhibit catalytic capacity only under acidic conditions. The pH mismatch between peroxidase mimics in acidic environments and bioenzymes under neutral conditions significantly restricts the development of enzyme–nanozyme catalytic systems especially for biochemical sensing. To solve this problem, here amorphous Fe-containing phosphotungstates (Fe-PTs) featuring high peroxidase activity at neutral pH were explored to fabricate portable multienzyme biosensors for pesticide detection. The strong attraction of negatively charged Fe-PTs to positively charged substrates as well as the accelerated regeneration of Fe 2+ by the Fe/W bimetallic redox couples was demonstrated to play important roles in endowing the material with peroxidase-like activity in physiological environments. Consequently, integrating the developed Fe-PTs with acetylcholinesterase and choline oxidase led to an enzyme–nanozyme tandem platform with good…

Fluorine nuclear magnetic resonance ( 19 F-NMR) spectroscopy has been shown to be a powerful tool capable of quantifying the total per- and polyfluoroalkyl substances (PFAS) in a complex sample. The technique relies on the characteristic terminal −CF 3 shift (−82.4 ppm) in the alkyl chain for quantification and does not introduce bias due to sample preparation or matrix effects. Traditional quantitative analytical techniques for PFAS, such as liquid chromatography–mass spectrometry (LC-MS) and combustion ion chromatography (CIC), contain inherent limitations that make total fluorine analysis challenging. Here, we report a sensitive 19 F-NMR method for the analysis of total PFAS, with a limit of detection of 99.97 nM, or 50 μg/L perfluorosulfonic acid. To demonstrate the capabilities of 19 F-NMR, the technique was compared to two commonly used methods for PFAS analysis: total oxidizable precursor (TOP) assay and LC-high resolution MS analysis for targeted quantification and suspect screening. In both cases, the 19 F-NMR analyses detected higher total PFAS quantities than either the…

This research delves into investigating ion transport behavior within nanochannels, enhanced through modification with a negatively charged polyelectrolyte layer (PEL), aimed at achieving superior control. The study examines two types of electric fields─direct current and alternating current with square, sinusoidal, triangular, and sawtooth waveforms─to understand their impact on ion transport. Furthermore, the study compares symmetric (cylindrical) and asymmetric (conical) nanochannel geometries to assess the influence of overlapping electrical double layers (EDLs) in generating specific electrokinetic behaviors such as ionic current rectification (ICR) and ion selectivity. The research employs the finite element method to solve the coupled Poisson–Nernst–Planck and Navier–Stokes equations under unsteady-state conditions. By considering factors such as electrolyte concentration, soft layer charge density, and electric field type, the study evaluates ion transport performance in charged nanochannels, investigating effects on concentration polarization, electroosmotic flow (EOF), ion…

The rational design of efficient nanozymes and the immobilization of enzymes are of great significance for the construction of high-performance biosensors based on nano-/bioenzyme catalytic systems. Herein, a novel V-TCPP(Fe) metal–organic framework nanozyme with a two-dimensional nanosheet morphology is rationally designed by using V 2 CT x MXene as a metal source and iron tetrakis(4-carboxyphenyl)porphine (FeTCPP) ligand as an organic linker. It exhibits enhanced peroxidase- and catalase-like activities and luminol–H 2 O 2 chemiluminescent (CL) behavior. Based on the experimental and theoretical results, these excellent enzyme-like activities are derived from the two-site synergistic effect between V nodes and FeTCPP ligands in V-TCPP(Fe). Furthermore, a confined catalytic system is developed by zeolitic imidazole framework (ZIF) coencapsulation of the V-TCPP(Fe) nanozyme and bioenzyme. Using the acetylcholinesterase (AChE) as a model, our constructed V-TCPP(Fe)/AChE@ZIF confined catalytic system was successfully used for the colorimetric/CL dual-mode visual biosensing of…

Expanding sensing modes and improving catalytic performance of nanozyme-based analytical chemistry are beneficial to realizing the desired biosensing of analytes. Herein, Schiff-base chemistry coupled with a novel catechol oxidase-like nanozyme (CHzyme) is designed and constructed, exhibiting two main advantages, including (1) improving catalytic performance by nearly 2-fold compared with only the oxidase-like role of CHzyme; (2) increasing the designability of the output signal by signal transduction of cascade reaction. Thereafter, the substrate sensing modes based on a cascade reaction between the CHzyme-catalyzed reaction and Schiff-base chemistry are proposed and comprehensively studied, containing catalytic substrate sensing mode, competitive substrate sensing mode, and generated substrate sensing mode, expecting to be employed in environmental monitoring, food analyses, and clinical diagnoses, respectively. More meaningfully, the generated substrate sensing mode is successfully applied to construct a cascade reaction coupling ratiometric fluorescent immunoassay for the…

Interest in wearable and stretchable multifunctional sensors has grown rapidly in recent years. The sensing elements must accurately detect external stimuli to expand their applicability as sensors. However, the sensor's self-healing and adhesion to a target object have been major challenges in developing such practical and versatile devices. In this study, we prepared a hydrogel (LM-SA-PAA) composed of liquid metal (LM), sodium alginate (SA), and poly(acrylic acid) (PAA) with ultrastretchable, excellent self-healing, self-adhesive, and high-sensitivity sensing capabilities that enable the conformal contact between the sensor and skin even during dynamic movements. The excellent self-healing performance of the hydrogel stems from its double cross-linked networks, including physical and chemical cross-linked networks. The physical cross-link formed by the ionic interaction between the carboxyl groups of PAA and gallium ions provide the hydrogel with reversible autonomous repair properties, whereas the covalent bond provides the hydrogel with a stable and strong chemical network.…

The theory of aggregation-induced electrochemiluminescence (AIECL) has introduced new vitality into preparing new electrochemiluminescence (ECL) emitters. However, the progress in the application of biosensing analysis has been slow owing to the lack of AIECL-based functional nanomaterials. Herein, a biosensor was fabricated using mesoporous silica nanosphere (MSN) matrix-confined 1,1,2,2-tetra(4-carboxylphenyl)ethylene (TPE) as a well-ordered ECL emitter and self-designed WHPWSYC (WC-7) heptapeptide as the target capturer for CD44 detection. TPE and its co-reactant, triethylamine (TEA), were encapsulated in the MSN nanomatrix to enhance the radiation transition by limiting the intramolecular rotation of TPE molecule benefit from the spatial confinement effect, and the ECL intensity is self-enhanced by replacing electron free diffusion in the conventional ECL system. MSN-TPE-TEA can act as satisfactory sensing substrates that improve the reproducibility and batch-to-batch consistency of biosensors and functions as a stable signal label for trace analysis of biomarkers. As a…

Timely identification of human papillomavirus (HPV) infection is crucial for the prevention of cervical cancer. Current HPV detection methods mainly rely on polymerase chain reaction (PCR), which often requires bulky equipment and a long assay time. In this work, we report a heating-membrane-assisted multiplexed microfluidics platform that couples recombinase polymerase amplification (RPA) and CRISPR technology (termed M3-CRISPR) for fast and low-cost detection of multiple HPV subtypes. The heating membrane can provide convenient temperature control for the on-chip RPA and CRISPR assays. This stand-alone system allows simultaneous detection of HPV16 and HPV18 with high specificity and detection sensitivity (0.5 nM and 1 × 10 –18 M for unamplified and amplified plasmids, respectively) in 30 min with a fluorescence-based readout. Furthermore, we introduced an optimized lateral flow dipstick (LFD) into the portable system to allow visualized detection of HPV DNA. The LFD-based readout also reached a detection sensitivity of 1 × 10 –18 M for amplified plasmids and realized successful…

Mass spectrometry imaging (MSI) is a powerful tool for label-free mapping of the spatial distribution of proteins in biological tissues. We have previously demonstrated imaging of individual proteoforms in biological tissues using nanospray desorption electrospray ionization (nano-DESI), an ambient liquid extraction-based MSI technique. Nano-DESI MSI generates multiply charged protein ions, which is advantageous for their identification using top-down proteomics analysis. In this study, we demonstrate proteoform mapping in biological tissues with a spatial resolution down to 7 μm using nano-DESI MSI. A substantial decrease in protein signals observed in high-spatial-resolution MSI makes these experiments challenging. We have enhanced the sensitivity of nano-DESI MSI experiments by optimizing the design of the capillary-based probe and the thickness of the tissue section. In addition, we demonstrate that oversampling may be used to further improve spatial resolution at little or no expense to sensitivity. These developments represent a new step in MSI-based spatial proteomics, which…

Sweat wearable sensors enable noninvasive and real-time metabolite monitoring in human health management but lack accuracy and wearable applicability. The rational design of sensing electrode materials will be critical yet challenging. Herein, we report a dual aerogel-based nonenzymatic wearable sensor for the sensitive and selective detection of uric acid (UA) in human sweat. The three-dimensional porous dual-structural aerogels composed of Au nanowires and N-doped graphene nanosheets (noted as N-rGO/Au DAs) provide a large active surface, abundant access to the target, rapid electron transfer pathways, and a high intrinsic activity. Thus, a direct UA electro-oxidation is demonstrated at the N-rGO/Au DAs with a much higher activity than those at the individual gels (i.e., Au and N-rGO). Moreover, the resulting sensing chip displays high performance with a good anti-interfering ability, long-term stability, and excellent flexibility toward the UA detection. With the assistance of a wireless circuit, a wearable sensor is successfully applied in the real-time UA monitoring on human…

Recently, a novel technology was published, utilizing the strengths of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) and immunohistochemistry (IHC), achieving highly multiplexed, targeted imaging of biomolecules in tissue. This new technique, called MALDI-IHC, opened up workflows to target molecules of interest using MALDI-MSI that are usually targeted by standard IHC. In this paper, the utility of targeted MALDI-IHC and its complementarity with untargeted on-tissue bottom-up spatial proteomics is explored using breast cancer tissue. Furthermore, the MALDI-2 effect was investigated and demonstrated to improve MALDI-IHC. Formalin-fixed paraffin-embedded (FFPE) human breast cancer tissue sections were stained for multiplex MALDI-IHC with six photocleavable mass-tagged (PC-MT) antibodies constituting a breast cancer antibody panel (CD20, actin-αSM, HER2, CD68, vimentin, and panCK). K-means spatial clusters were created based on the MALDI-IHC images and cut out using laser-capture microdissection (LMD) for further untargeted LC-MS-based bottom-up…

Monitoring acetylcholinesterase (AChE) and its inhibitors is of importance for early diagnosis and therapy of neurological diseases. Herein, N-doped carbon nanotubes supported Fe–Mn dual-single-atoms (FeMn DSAs/N-CNTs) were fabricated by a simple pyrolysis, as thoroughly figured out by a series of the characterization techniques. The peroxidase-like activity of FeMn DSAs/N-CNTs was investigated by catalytic oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) to generate rich hydroxyl radicals (·OH) in the H 2 O 2 system, which effectively catalyzed colorless TMB oxidation to blue oxidized TMB (ox-TMB). Besides, the peroxidase-like activity was greatly weakened by thiocholine (derived from AChE), accompanied by making blue ox-TMB fade. Impressively, the highly improved peroxidase-like property is further evidenced by density functional theory (DFT) calculations, where the dual-single atoms show a lower energy barrier (0.079 eV) and their interactions with the N-CNTs played critical roles for producing the oxygen radicals. By virtue of the nanozyme, a low-cost, specific, and sensitive…

Metabolite identification represents a major bottleneck in contemporary metabolomics research and a step where critical errors may occur and pass unnoticed. This is especially the case for studies employing liquid chromatography-mass spectrometry technology, where there is increased concern on the validity of the proposed identities. In the present perspective article, we describe the issue and categorize the errors into two types: identities that show poor biological plausibility and identities that do not comply with chromatographic data and thus to physicochemical properties (usually hydrophobicity/hydrophilicity) of the proposed molecule. We discuss the problem, present characteristic examples, and propose measures to improve the situation.

In this paper, a photoelectrochemical (PEC)-surface-enhanced Raman scattering (SERS) dual-mode biosensor is constructed coupled with a dual-recognition binding-induced DNA walker with a carbon nitride nanosheet (C 3 N 4 )/MXene-gold nanoparticles (C/M-Au NPs) accelerator, which is reliable and capable for sensitive and accurate detection of Staphylococcus aureus ( S. aureus ). Initially, a photoactive heterostructure is formed by combining C 3 N 4 and MXene via a simple electrostatic self-assembly as they possess well-matched band-edge energy levels. Subsequently, in situ growth of gold nanoparticles on the formed surface results in better PEC performance and SERS activity, because of the synergistic effects of surface plasmon resonance and Schottky barrier. Furthermore, a three-dimensional, bipedal, and dual-recognition binding-induced DNA walker is introduced with the formation of Pb 2+ -dependent DNAzyme. In the presence of S. aureus, a significant quantity of intermediate DNA (I-DNA) is generated, which can open the hairpin structure of Methylene Blue-tagged hairpin DNA (H-MB)…

Herein, a chemiluminescence (CL) biosensor based on CRISPR-Cas12a and cation exchange reaction was constructed to detect the biomarker microRNA-21 (miRNA-21). The rolling circle amplification (RCA) reaction was introduced to convert each target RNA strand into a long single-stranded DNA with repeated sequences, which acted as triggers to initiate the transcleavage activity of CRISPR-Cas12a. The activated Cas12a could cleave the biotinylated linker DNA of CuS nanoparticles (NPs) to inhibit the binding of CuS NPs to streptavidin immobilized on the surface of the microplate, which strongly reduced the generation of Cu 2+ from a cation exchange between CuS NPs and AgNO 3, and thus efficiently suppressed the CL of Cu 2+ -luminol-H 2 O 2 system, giving a “signal off” biosensor. With the multiple amplification, the detection limit of the developed sensor for miRNA-21 reached 16 aM. In addition, this biosensor is not only suitable for a professional chemiluminescence instrument but also for a smartphone used as a detection tool for the purpose of portable and low-cost assay. This method…

Nanozymes can imitate the catalytic properties of natural enzymes while overcoming the limitations of natural enzymes such as high cost, poor robustness, and difficulty in recycling. However, rational design and facile preparation of nanozymes are still in demand. Inspired by the chemical structure of laccase, we report an amorphous metal–organic coordination nanocomposite named CuNAD, which is composed of copper ions and nicotinamide adenine dinucleotide (NAD + ) via a simple coordinating coassembly process. As a single-site nanozyme, CuNAD exhibits excellent robustness under extreme conditions, significantly stronger catalytic activity for phenolic compounds, and 4.02-fold higher sensitivity for epinephrine detection than laccase. Furthermore, by breaking through the functional constraints of laccase, CuNAD is also able to activate H 2 O 2 at neutral pH, benefiting a one-step chromogenic detection platform for cholesterol. This facile approach demonstrates the potential to develop single-site nanozymes by biomimicking natural enzymes and may boost more insights into the…

An ultralow-potential electrochemiluminescence (ECL) aptasensor has been designed for zearalenone (ZEN) assay based on a resonance energy transfer (RET) system with SnS 2 QDs/g-C 3 N 4 as a novel luminophore and CuO/NH 2 -UiO-66 as a dual-quencher. SnS 2 QDs were loaded onto g-C 3 N 4 nanosheets and enhanced the ECL luminescence via strong synergistic effects under an ultralow potential. The UV–vis absorption spectrum of CuO/NH 2 -UiO-66 exhibits considerable overlap with the ECL emission spectrum of SnS 2 QDs/g-C 3 N 4, an important consideration for the RET process. In order to stimulate RET, the ZEN aptamer and complementary DNA are introduced for conjugation between the donor and the acceptor. With the binding interaction between ZEN by its aptamer, CuO/NH 2 -UiO-66 is removed from the electrode surface, resulting in the inhibition of the RET system and an increase in the ECL signal. Under optimal conditions, the as-prepared aptasensor quantified ZEN from 0.5 μg·mL –1 to 0.1 fg·mL –1 with a low limit of detection of 0.085 fg·mL –1, and it exhibited good stability, excellent…

Early detection of foodborne bacteria is urgently needed to ensure food quality and to avoid the outbreak of foodborne bacterial diseases. Here, a kind of metal–organic framework (Zr-MOF) modified with Pt nanoparticles (Pt-PCN-224) was designed as a peroxidase-like signal amplifier for microfluidic biosensing of foodborne bacteria. Taking Escherichia coli ( E. coli ) O157:H7 as a model, a linear range from 2.93 × 10 2 to 2.93 × 10 8 CFU/mL and a limit of detection of 2 CFU/mL were obtained. The whole detection procedure was integrated into a single microfluidic chip. Water, milk, and cabbage samples were successfully detected, showing consistency with the results of the standard culture method. Recoveries were in the range from 90 to 110% in spiked testing. The proposed microfluidic biosensor realized the specific and sensitive detection of E. coli O157:H7 within 1 h, implying broad prospects of MOF with biomimetic enzyme activities for biosensing.

Simultaneous detection of different disease markers is significant for clinical diagnosis. In this work, a dual-signal electrochemiluminescence (ECL) immunosensor was constructed for the simultaneous detection of carbohydrate antigen 125 (CA125) and human epithelial protein 4 (HE4) markers of ovarian cancer. The results showed that the Eu metal–organic framework-loaded isoluminol–Au nanoparticles (Eu MOF@Isolu–Au NPs) could generate a strong anodic ECL signal through synergistic interaction; as cathodic luminophore, the composite of carboxyl-functionalized CdS quantum dots and N-doped porous carbon-anchored Cu single-atom catalyst could catalyze H 2 O 2 co-reactant to produce a large amount of • OH and O 2 •–, making the anodic and cathodic ECL signals significantly increase and become stable. Based on the enhancement strategy, a sandwich immunosensor was constructed for the simultaneous detection of ovarian cancer-associated CA125 and HE4 markers by combining antigen–antibody specific recognition and magnetic separation technique. The resulting ECL immunosensor displayed high…

Foodborne illnesses caused by the ingestion of contaminated foods or beverages are a serious concern due to the millions of reported cases per year. It is essential to develop sensitive and rapid detection methods of foodborne pathogens to ensure food safety for producers and consumers. Unfortunately, current detection techniques still suffer from time-consuming operations and the need for highly skilled personnel. Here, we introduce a highly sensitive dual colorimetric/electrochemical detection approach for Salmonella enterica serovar typhimurium ( S. typhimurium) based on a laser-induced graphene-integrated lateral flow immunoassay (LIG–LFIA) strip. The LIG electrode was fabricated by laser engraving on a polyimide tape containing a pseudo silver/silver chloride reference electrode from silver sintering and chlorination. Using double-sided tape inserted into the strip, automatic sequential reagent delivery was enabled for the dual-mode signal readout by single-sample loading. A gold-deposited gold nanoparticle strategy was first employed to simultaneously obtain a colorimetric…

Nanozymes are functional nanomaterials with enzyme-like activities, which have good stability and specific nanoscale properties. Among them, peroxidase-like (POD-like) nanozymes with two substrates are the biggest chunk and have been widely applied in biomedical and environmental fields. Maximum velocity (Vmax) is an essential kinetic parameter, accurate measurements of which can help in activity comparisons, mechanism studies, and nanozyme improvements. At present, the standardized assay determines the catalytic kinetics of POD-like nanozymes by a single fitting based on the Michaelis–Menten equation. However, the true Vmax cannot be confirmed by this method due to the test condition that the concentration of a fixed substrate is finite. Here, a double fitting method to determine the intrinsic Vmax of POD-like nanozymes is presented, which breaks through the limited concentration of the fixed substrate by an additional Michaelis–Menten fitting. Furthermore, a comparison of the Vmax among five typical POD-like nanozymes validates the accuracy and feasibility of our method. This work…

In this work, a sensitive signal-on electrochemiluminescence biosensor using liposome-encapsuled 1,1,2,2-tetra(4-carboxylphenyl)ethylene (TPE) as a promising aggregation-induced electrochemiluminescence (AIECL) emitter for detection of biomarkers was developed. Aggregation-induced enhancement occurs internally through the spatial confinement effect and intramolecular self-encapsulation of encapsulating TPE and triethylamine (TEA) molecules in liposome cavities. Peptide sequence WTGWCLNPEESTWGFCTGSF (WF-20) was used to replace the antibody for reducing the steric hindrance of the sensing surface while taking into account the affinity. The proposed sensing strategies showed satisfactory properties for detection of human epidermal growth factor receptor 2 (HER2) ranging from 0.01 to 500 ng/mL with a limit of detection of 6.65 pg/mL. The results confirmed that encapsulation of luminescent molecules in the vesicle structure for triggering the AIECL phenomenon is a promising method to prepare a signal label for a trace detection biomarker.

The trans-cleavage activity of Cas12a has been widely used with various applications. Here, we report that the trans-cleavage activity of Cas12a can be significantly affected by the fluorescent probe length and reaction buffer. The optimal probe length for Cas12a is found to be 15 nucleotides, and the optimal buffer is NEBuffer 4. Compared to the popularly used reaction conditions, the activity of Cas12a is improved by about 50-fold. In addition, the detection limit of Cas12a for DNA targets has been reduced by nearly three orders of magnitude. Our method provides a powerful tool for Cas12a trans-cleavage activity applications.

Nanozymes have drawn much attention as an enzyme mimetic with low cost and stability in enhancing analytical performance. Herein, a peroxidase-mimicking nanozyme-improved enzyme-linked immunosorbent assay (ELISA) was developed employing the bimetallic PdRu nanozyme to replace the natural enzymes as a catalytic carrier for the sensing of Escherichia coli O157:H7 ( E. coli O157:H7). The PdRu nanozyme displayed ultrahigh catalytic activity, possessing a catalytic rate that was 5-fold higher than horseradish peroxidase (HRP). In addition, PdRu exhibited great biological affinity with antibody (affinity constant was about 6.75 × 10 12 M) and high stability. All those advantages ensure the successful establishment and the construction of a novel colorimetric biosensor for E. coli O157:H7 detection. PdRu-based ELISA not only achieved an ultrasensitive detection sensitivity (8.7 × 10 2 CFU/mL) by approximately 288-fold as compared to the traditional HRP-based ELISA and also possessed satisfactory specificity and reproducibility (relative standard deviation (RSD) < 10%). Furthermore, the…

In this paper, a micro-quartz crystal tuning fork (M-QCTF) was first demonstrated for developing a low-cost, highly sensitive quartz tuning fork photodetector array for spectroscopic applications. A gas sensing system based on the M-QCTF photodetector and highly sensitive wavelength modulation spectroscopy was developed. Typically, an atmospheric greenhouse gas methane (CH 4 ) molecule was selected as the target analyte for evaluating the M-QCTF and standard commercial QCTF detectivity. The results indicate that the M-QCTF photodetector exhibits ∼3.3 times sensitivity enhancement compared to the standard commercial QCTF. The long-term stability was evaluated by using the Allan deviation analysis method; a minimum detection limit of 1.2 ppm was achieved with an optimal integration time of 85 s, and the corresponding normalized noise equivalent absorption coefficient was calculated to be 4.45 × 10 –10 cm –1 W/√Hz. Finally, a two-M-QCTF array detection scheme was experimentally demonstrated, and a signal-to-noise ratio enhancement factor of more than 1.7 times compared to that achieved…

Drug-induced liver injury (DILI) is a major clinical issue associated with the majority of commercial drugs. During DILI, the peroxynitrite (ONOO – ) level is upregulated in the liver. However, traditional methods are unable to timely monitor the dynamic changes of the ONOO – level during DILI in vivo . Therefore, ONOO – -activated near-infrared (NIR) fluorescent probes with high sensitivity and selectivity are key to the early diagnosis of DILI in situ . Herein, we report a novel ONOO – -responsive NIR fluorescent probe, QCy7-DP, which incorporates a donor-dual-acceptor π-electron cyanine skeleton with diphenyl phosphinate. The ONOO – -mediated highly selective hydrolytic cleavage via an addition-elimination pathway of diphenyl phosphinate produced the deprotonated form of QCy7 in physiological conditions with a distinctive extended conjugated π-electron system and ∼200-fold enhancement in NIR fluorescence emission at 710 nm. Moreover, the probe QCy7-DP was successfully used for the imaging of the endogenous and exogenous ONOO – concentration changes in living cells. Importantly,…

Ultra-sensitive detection of cancer-related biomarkers in serum is of great significance for early diagnosis, treatment, prognosis, and staging of cancer. In this work, we proposed a surface-enhanced Raman scattering and fluorescence (SERS/FL) dual-mode biosensor for hepatocellular carcinoma (HCC)-related miRNA (miR-224) detection using the composition of well-arranged Au nanoarrays (Au NAs) substrate coupled with the target-catalyzed hairpin assembly (CHA) strategy. The hot spots densely and uniformly distributed on the Au array offers considerably enhanced and reproducible SERS signals, along with their wide and open surface to facilitate miR-224 adsorption. By this sensing strategy, the target miR-224 can be detected in a wide linear range (1 fM to 1 nM) with a limit of detection of 0.34 fM in the SERS mode and 0.39 fM in the FL mode. Meanwhile, this biosensor with exceptional specificity and anti-interference ability can discriminate target miR-224 from other interference miRNAs. Practical analysis of human blood samples also demonstrated considerable reliability and…

Extracellular vesicles (EVs) are crucial mediators of intercellular communication and can be classified based on their physical properties, biomolecular structure, and origin. Among EVs, exosomes have garnered significant attention due to their potential as therapeutic and diagnostic tools. Exosomes are released via fusion of multivesicular bodies on plasma membranes and can be isolated from various biofluids using methods such as differential ultracentrifugation, immune affinity capture, ultrafiltration, and size exclusion chromatography. Herein, an overview of different techniques for exosome characterization and isolation, as well as the diverse applications of exosome detection, including their potential use in drug delivery and disease diagnosis, is provided. Additionally, we discuss the emerging field of exosome detection by sensors, which offers an up-and-coming avenue for point-of-care diagnostic tools development. Overall, this review aims to provide a exhaustive and up-to-date summary of the current state of exosome research.

In this work, an ingenious sensor technology was established by integrating the EBFCs on a flexible paper strip carrier (PE) that was used for simultaneous detection of tumor markers in complex samples. Adopting high performance ultrathin graphdiyne (U-GDY) as the substrate can increase the enzyme load, accelerate the electron transfer rate, and significantly enhance the detection sensitivity. A homologous DNA nanomanager strategy cleverly uses signal switches to recycle and amplify target miRNAs, while the smartphone receives real-time instantaneous current values to realize multivariate detection. Electrochemical data show that the detection limits (LODs) of miRNA-21 and miRNA-155 are 0.09 and 0.15 fM in the wide concentration range. The results confirm that the tailored sensor platform provides a strategy for the early cancer diagnosis and lays the foundation for the construction of a flexible wearable platform.

Isothermal, enzyme-free amplification techniques, such as the hybridization chain reaction (HCR) and catalytic hairpin assembly (CHA), have gained increasing attention for miRNA analysis. However, current methodological challenges, including slow kinetics, low amplification efficiency, difficulties in efficient cellular internalization of DNA probes, and concerns regarding the intracellular stability of nucleic acids, need to be addressed. To this end, we propose a novel strategy for sensitive miRNA detection based on a three-dimensional (3D) CHA-HCR system. This system comprises two DNA nanospheres, named DS-13 and DS-24, which are functionalized with CHA and HCR hairpins. Target miR-21 initiates CHA between the two nanospheres, thereby activating downstream HCR and bringing cyanine 3 (Cy3) and cyanine 5 (Cy5) into proximity. The 3D CHA-HCR process leads to the formation of large DNA aggregates and the generation of fluorescence resonance energy transfer signals. In this strategy, the employment of a cascaded reaction and spatial confinement effect improve sensitivity and kinetics,…

Mitochondrial viscosity affects metabolite diffusion and mitochondrial metabolism and is associated with many diseases. However, the accuracy of mitochondria-targeting fluorescent probes in measuring viscosity is unsatisfactory because these probes can diffuse from mitochondria during mitophagy with a decreased mitochondrial membrane potential (MMP). To avoid this problem, by incorporating different alkyl side chains into dihydroxanthene fluorophores (denoted as DHX ), we developed six near-infrared (NIR) probes for the accurate detection of mitochondrial viscosity, and the sensitivity to viscosity and the mitochondrial targeting and anchoring capability of these probes increased by increasing the alkyl chain length. Among them, DHX-V-C 12 had a highly selective response to viscosity variations with minimum interference from polarity, pH, and other biologically relevant species. Furthermore, DHX-V-C 12 was used to monitor the mitochondrial viscosity changes of HeLa cells treated by ionophores (nystatin, monensin) or under starvation conditions. We hope that this mitochondrial…

Rapid and sensitive detection of foodborne bacteria is of great significance in guaranteeing food safety and preventing foodborne diseases. A bifunctional Au@Pt core–shell nanozyme with excellent catalytic properties and high surface-enhanced Raman scattering (SERS) activity was developed for the highly sensitive detection of Salmonella typhimurium based on a label-free SERS strategy. The ultrathin Pt shell (about 1 nm) can catalyze Raman-inactive molecules into Raman-active reporters, greatly amplifying the amount of signal molecules. Moreover, the Au core serves as an active SERS substrate to enhance the signal of reporter molecules, further significantly improving the detection sensitivity. Benefiting from the excellent properties, such a bifunctional Au@Pt nanozyme was integrated with a magnetic immunoassay to construct a label-free SERS platform for the highly sensitive detection of S. typhi with a low detection limit of 10 CFU mL –1 . Also, the Au@Pt-based SERS platform exhibited excellent selectivity and was successfully utilized for the detection of S. typhi in milk samples…

Dual-channel fluorescent probes could respond to a specific target and emit different wavelengths of fluorescence before and after the response. Such probes could alleviate the influence caused by the variation of the probe concentration, excitation intensity, and so on. However, for most dual-channel fluorescent probes, the probe and fluorophore faced spectral overlap, which reduced sensitivity and accuracy. Herein, we introduced a cysteine (Cys)-responsive and near-infrared (NIR) emissive AIEgen (named TSQC ) with good biocompatibility to dual-channel monitor Cys in mitochondria and lipid droplets (LDs) during cell apoptosis through wash-free fluorescence bio-imaging. TSQC can label mitochondria with bright fluorescence around 750 nm, and after reacting with Cys, the reaction product TSQ could spontaneously target LDs with emissions around 650 nm. Such spatially separated dual-channel fluorescence responses could significantly improve detection sensitivity and accuracy. Furthermore, the Cys-triggered dual-channel fluorescence imaging in LDs and mitochondria during apoptosis…

Visual wearable devices can rapid intuitively monitor biomarkers in body fluids to indicate the human health status and provide valuable reference for further medical diagnosis. However, unavoidable interference factors such as skin color, natural light, and background luminescence can interfere with the visualization accuracy of flexible wearable devices, limiting their practical sensing application. Here, we designed a wearable sensing patch via an embedded upconversion optical probe in a 3D porous polyacrylamide hydrogel, exhibiting a multiplex chroma response to urea based on the inner filter effect, which overcomes the susceptibility to external conditions due to its near-infrared excited luminescence and improves the resolution and accuracy of visual sensing. Furthermore, a highly compatible portable sensing platform combined with a smartphone was designed to achieve in situ rapid quantitative analysis of urea. The limit of detection values of the upconversion optical probe and hydrogel sensor are as low as 1.4 and 30 μM respectively, exhibiting the practicality in different…

Sensitive, portable methods of detection for foodborne pathogens hold great significance for the early warning and prevention of foodborne diseases and environmental pollution. Restricted by a complicated matrix and limited signaling strategies, developing a ready-to-use sensing platform with ultrahigh sensitivity remains challenging. In this work, near-infrared (NIR) light-responsive AgBiS 2 nanoflowers (NFs) and Cu 2 O nanocubes (NCs) were introduced to construct a novel target-induced photocurrent-polarity-switchable system and verified for the development of an all-in-one, ready-to-use photoelectrochemical (PEC) immunosensor. NIR-responsive n-type AgBiS 2 NFs and p-type Cu 2 O NCs producing anodic and cathodic photocurrents were conjugated with monoclonal (MAb 1 ) and polyclonal antibodies (PAb 2 ), respectively. Using a sandwich-type immunocomplex bridged by Escherichia coli O157:H7, an efficient photocurrent-polarity-switching PEC system was formed on a paper-based working electrode (PWE). Owing to the spatial separation of the photogenerated carriers and the elimination of…

The ever-growing modern industry promotes the evolution of gas sensors for environmental monitoring and safety inspection. However, traditional chemiresistive gas sensors still suffer from drawbacks of high power consumption and detection limit, mainly due to the insufficient charge-transfer ability of gas-sensing materials. Here, an optoelectronic gas sensor that can detect ppb-level ammonia at room temperature is constructed based on core–shell g-C 3 N 4 @WO 3 heterocomposites. The growth of WO 3 nanosheets on graphitic g-C 3 N 4 nanosheets was precisely controlled, achieving well-defined g-C 3 N 4 @WO 3 core–shell architectures. Based on the synergism between light activation and the amplification effect of in situ-formed heterojunctions, the g-C 3 N 4 @WO 3 sensor exhibits improved sensing characteristics for reliable ammonia detection. As compared with the pristine g-C 3 N 4 sensor, the sensor response toward ammonia is enhanced 21 times and the detection limit is reduced from 308 to 108 ppb. This work provides a successful approach for the in situ formation of core–shell g-C 3…

Although near-infrared responsive photoelectrochemical (PEC) biosensors have less damage to biological components compared to UV–visible light, they still reveal an inferior response due to the rapid recombination of photogenerated electron–hole. In this study, a near-infrared-driven PEC biosensor is fabricated for microRNA (miRNA) detection via integrating photoelectricity and pyroelectricity. Upon the introduction of target miRNA-21, the exponential DNA amplifier is triggered based on enzyme-assisted strand displacement amplification (SDA), releasing multiple Ag 2 S reporter probes to hybridize with capture probes immobilized on a CdS-2-mercaptobenzimidazole (2MBI)-modified photoelectrode. As a result, under the stimulation of NIR, the photoelectric conversion of Ag 2 S NPs generates the photocurrents. In addition, due to the strong hole acceptor ability of MBI, the pyroelectric effect of CdS-2MBI nanocomposites is enhanced, which generates highly pyroelectro-induced charge separation efficiency and induces the pyroelectric current benefited from the spontaneous polarization of…

High Resolution Image Download MS PowerPoint Slide Mixing of graphite and carbon black (CB) alongside recycled poly(lactic acid) and castor oil to create an electrically conductive additive manufacturing filament without the use of solvents is reported herein. The additively manufactured electrodes (AMEs) were electrochemically benchmarked against a commercial conductive filament and a bespoke filament utilizing only CB. The graphite/CB produced a heterogeneous rate constant, k 0, of 1.26 (±0.23) × 10 –3 cm s –1 and resistance of only 155 ± 15 Ω, compared to 0.30 (±0.03) × 10 –3 cm s –1 and 768 ± 96 Ω for the commercial AME. Including graphite within the filament reduced the cost of printing each AME from £0.09, with the CB-only filament, to £0.05. The additive manufacturing filament was successfully used to create an electroanalytical sensing platform for the detection of oxalate within a linear range of 10–500 μM, achieving a sensitivity of 0.0196 μA/μM, LOD of 5.7 μM and LOQ of 18.8 μM was obtained. Additionally, the cell was tested toward the detection of oxalate within a spiked…

Credible and on-site detection of organophosphorus pesticides (OPs) in complex matrixes is significant for food security and environmental monitoring. Herein, a novel COF/methylene blue@MnO 2 (COF/MB@MnO 2 ) composite featured abundant signal loading, a specific recognition unit, and robust oxidase-like activity was successfully prepared through facile assembly processes. The multifunctional composite acted as a homogeneous electrochemical and photothermal dual-mode sensing platform for OPs detection through stimuli-responsive regulation. Without the presence of OPs, the surface MnO 2 coating could recognize thiocholine (TCh), originating from acetylcholinesterase (AChE)-catalyzed hydrolysis of acetylthiocholine (ATCh), and exhibited a distinctly amplified diffusion current due to the release of plentiful MB; while the residual MnO 2 nanosheets could only catalyze less TMB into oxidized TMB (oxTMB) with a typical near-infrared (NIR) absorption, enabling NIR-driven photothermal assay with a low temperature using a portable thermometer. Based on the inhibitory effect of OPs on AChE…

Cancer is a worldwide health problem. Revealing the changes in the microenvironment after cell carcinogenesis is helpful to understand cancer and develop sensitive methods for cancer diagnosis. We developed herein a viscosity-responsive plasma membrane probe (TPA-S) that was successfully used to probe the viscosity difference between normal and tumor cell plasma membranes for the first time. The probe shows AIE properties with good water solubility, significant near-infrared (NIR) fluorescence responses to viscosity with high sensitivity, and excellent cell membrane location performance. With these features, our experiments showed that TPA-S could selectively visualize cancer cell plasma membranes, revealing that the plasma membrane of tumor cells is more viscous than that of normal cells. In addition, TPA-S was successfully applied to specifically light up tumors. Altogether, this work explored the changes of cell membrane viscosity after canceration, provided a new method for selective visualization of tumor cells, and opened up a new approach for cancer diagnosis.

In this paper, a novel donor–acceptor pair was creatively proposed based on the principle of electrochemiluminescence resonance energy transfer (ECL-RET): luminol immobilized on polyethyleneimine (PEI)-functionalized manganese-based single-atom nanozymes (Mn SANE/PEI-luminol, donor) and a PtCu-grafted hollow metal polydopamine framework (PtCu/h-MPF, acceptor). A quenched ECL immunosensor was constructed for the ultrasensitive analysis of carcinoembryonic antigen (CEA). Mn SANE, as an efficient novel coreaction accelerator with the outstanding performance of significantly activating H 2 O 2 to produce large amounts of ROS, was further modified by the coreactant PEI, which efficiently immobilized luminol to form a self-enhanced emitter. As a result, the electron transport distance was effectively shortened, the energy loss was reduced, and luminol achieved a high ECL efficiency. More importantly, PtCu-grafted h-MPF (PtCu/h-MPF) was proposed as a novel quencher. The UV–vis spectra of PtCu/h-MPF partially overlap with the ECL spectra of Mn SANE/PEI-luminol, which can effectively trigger…

Fast, simplified, and multiplexed detection of human papillomaviruses (HPVs) is of great importance for both clinical management and population screening. However, current HPV detection methods often require sophisticated instruments and laborious procedures to detect multiple targets. In this work, we developed a simple microfluidic dual-droplet device (M-D3) for the simultaneous detection of HPV16 and HPV18 by combining the CRISPR-Cas12a system and multiplexed recombinase polymerase amplification (RPA) assay. A new approach of combining pressure/vacuum was proposed for efficient droplet generation with minimal sample consumption. Two groups of droplets that separately encapsulate the relevant Cas12a/crRNA and the fluorescent green or red reporters are parallelly generated, followed by automatic imaging to discriminate the HPV subtypes based on the specific fluorescence of the droplets. The M-D3 platform performs with high sensitivity (∼0.02 nM for unamplified plasmids) and specificity in detecting HPV16 and HPV18 DNA. By combining the RPA and Cas12a assay, M-D3 allows on-chip…

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTIon-Exchange Chromatography Coupled to Mass Spectrometry in Life Science, Environmental, and Medical ResearchJudith B. NgereJudith B. NgereDepartment of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.More by Judith B. NgereView Biographyhttps://orcid.org/0000-0003-2288-7215, Kourosh H. EbrahimiKourosh H. EbrahimiInstitute of Pharmaceutical Science, King's College London, London SE1 9NH, U.K.More by Kourosh H. EbrahimiView Biography, Rachel WilliamsRachel WilliamsDepartment of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.More by Rachel WilliamsView Biography, Elisabete PiresElisabete PiresDepartment of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.More by Elisabete PiresView Biography, John Walsby-TickleJohn Walsby-TickleDepartment of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.More by John Walsby-TickleView Biographyhttps://orcid.org/0000-0002-1287-9580, and James S. O. McCullagh*James S. O. McCullaghDepartment of Chemistry, University of Oxford,…

CRISPR/Cas12a has been believed to be powerful in molecular detection and diagnostics due to its amplified trans-cleavage feature. However, the activating specificity and multiple activation mechanisms of the Cas12a system are yet to be elucidated fully. Herein, a "synergistic activator effect" is discovered, which supports an activation mechanism that a synergistic incorporation of two short ssDNA activators can promote the trans-cleavage of CRISPR/Cas12a, while either of them is too short to work independently. As a proof-of-concept example, the synergistic activator-triggered CRISPR/Cas12a system has been successfully harnessed in the AND logic operation and the discrimination of single-nucleotide variants, requiring no signal conversion elements or other amplified enzymes. Moreover, a single-nucleotide specificity has been achieved for the detection of single-nucleotide variants by pre-introducing a synthetic mismatch between crRNA and the "helper" activator. The finding of "synergistic activator effect" not only provides deeper insight into CRISPR/Cas12a but also may facilitate…

Homogeneous immunoassays represent an attractive alternative to traditional heterogeneous assays due to their simplicity and high efficiency. Homogeneous electrochemical assays, however, are not commonly accessed due to the requirement of electrode immobilization of the recognition elements. Herein, we demonstrate a new homogeneous electrochemical immunoassay based on the aggregation-collision strategy for the quantification of tumor protein biomarker alpha-fetoprotein (AFP). The detection principle relies on the aggregation of AgNPs induced by the molecular biorecognition between AFP and AgNPs-anti-AFP probes, which leads to an increased AgNP size and decreased AgNP concentration, allowing an accurate self-validated dual-mode immunoassay by performing nanoimpact electrochemistry (NIE) of the oxidation of AgNPs. The intrinsic one-by-one analytical capability of NIE as well as the participation of all of the atoms of the AgNPs in signal transduction greatly elevates the detection sensitivity. Accordingly, the current sensor enables a limit of detection (LOD) of 5 pg/mL for AFP…

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTAdvances in Microfluidics: Technical Innovations and Applications in Diagnostics and TherapeuticsGuillaume AubryGuillaume AubrySchool of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United StatesMore by Guillaume AubryView Biographyhttps://orcid.org/0000-0001-7828-8508, Hyun Jee LeeHyun Jee LeeSchool of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United StatesMore by Hyun Jee LeeView Biographyhttps://orcid.org/0000-0001-9662-2063, and Hang Lu*Hang LuSchool of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United StatesPetit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, United States*Email: [email protected]More by Hang LuView Biographyhttps://orcid.org/0000-0002-6881-660XCite this: Anal. Chem. 2023, 95, 1, 444–467Publication Date (Web):January 10, 2023Publication History Published online10 January 2023Published inissue 10 January…

Point-of-care (POC) diagnostics in particular focuses on the timely identification of harmful conditions close to the patients' needs. For future healthcare these diagnostics could be an invaluable tool especially in a digitalized or telemedicine-based system. However, while paper-based POC tests, with the most prominent example being the lateral flow assay (LFA), have been especially successful due to their simplicity and timely response, the COVID-19 pandemic highlighted their limitations, such as low sensitivity and ambiguous responses. This perspective discusses strategies that are currently being pursued to evolve such paper-based POC tests toward a superior diagnostic tool that provides high sensitivities, objective result interpretation, and multiplexing options. Here, we pinpoint the challenges with respect to (i) measurability and (ii) public applicability, exemplified with select cases. Furthermore, we highlight promising endeavors focused on (iii) increasing the sensitivity, (iv) multiplexing capability, and (v) objective evaluation to also ready the technology for…

Chemical nerve agents are highly toxic organophosphorus compounds that are easy to obtain and can be utilized by terrorists to threaten homeland security and human safety. Those organophosphorus nerve agents contain nucleophilic ability that can react with acetylcholinesterase leading to muscular paralysis and human death. Therefore, there is great importance to explore a reliable and simple method to detect chemical nerve agents. Herein, the o -phenylenediamine-linked dansyl chloride as a colorimetric and fluorescent probe has been prepared to detect specific chemical nerve agent stimulants in the solution and vapor phase. The o -phenylenediamine unit serves as a detection site that can react with diethyl chlorophosphate (DCP) in a rapid response within 2 min. A satisfied relationship line was obtained between fluorescent intensity and the concentration of DCP in the range of 0–90 μM. In the optimized conditions, we conducted the fluorescent titration to measure the limits of detection (0.082 μM) with the fluorescent enhancement up to 18-fold. Fluorescence titration and NMR studies…

Aberrant mitochondrial viscosity is closely associated with many diseases and cellular malfunctions. Thus, the development of reliable methods for monitoring mitochondrial viscosity variations has attracted considerable attention. Herein, through stepwise structural modulation of the dihydroxanthene fluorophore ( DHX ), we developed three NIR fluorescent probes, named DHX-V-1–3, for detecting mitochondrial viscosity. Among them, DHX-V-3 displayed the highest signal-to-noise ratio (67-fold) for viscosity with outstanding selectivity and showed excellent mitochondria targeting and immobilization ability. At the cellular level, the DHX-V-3 probe was successfully applied to image the mitochondrial viscosity in live cells upon treatment with lipopolysaccharide (LPS) or nystatin. Moreover, benefiting from its NIR emission and the increased depth of tissue imaging, DHX-V-3 demonstrated the ability to visualize the increased viscosity in LPS-treated mice.

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTEmerging Wearable Chemical Sensors Enabling Advanced Integrated Systems toward Personalized and Preventive MedicineTianyiyi HeTianyiyi HeDepartment of Electrical and Computer Engineering, National University of Singapore, 4 Engineering Drive 3, Singapore 117583, SingaporeCenter for Intelligent Sensors and MEMS, National University of Singapore, Block E6 #05-11, 5 Engineering Drive 1, Singapore 117608, SingaporeMore by Tianyiyi HeView Biography, Feng WenFeng WenDepartment of Electrical and Computer Engineering, National University of Singapore, 4 Engineering Drive 3, Singapore 117583, SingaporeCenter for Intelligent Sensors and MEMS, National University of Singapore, Block E6 #05-11, 5 Engineering Drive 1, Singapore 117608, SingaporeMore by Feng WenView Biography, Yanqin YangYanqin YangDepartment of Electrical and Computer Engineering, National University of Singapore, 4 Engineering Drive 3, Singapore 117583, SingaporeCenter for Intelligent Sensors and MEMS, National University of Singapore, Block E6 #05-11, 5 Engineering Drive 1, Singapore…

The level of cortisol can reflect people’s psychological stress, help diagnose adrenal gland diseases, and is also related to several mental diseases. In this study, we developed a cortisol monoclonal antibody-oriented approach to modify an immunosensor for wearable label-free and persistent sweat cortisol detection. On such an antibody-oriented immunosensor, the fragment crystallizable (Fc) region is partially inserted within the metal–organic framework (MOF), and antibody-binding regions of the cortisol monoclonal antibody (C mab ) were exposed on the MOF surface via selective growth and self-assembly. Such ordered and oriented embedding of antibodies in the MOF resulted in excellent antibody activity and improved stability and antigen-binding capacity. We also engineered the full integrated system for on-body sweat cortisol biosensing performance in several volunteers, and the results indicated that this wearable sensor is suitable for practical cortisol detection with a good linear detection range from 1 pg/mL to 1 μg/mL with a lower limit of detection of 0.26 pg/mL. Moreover,…

Rapid and sensitive antigen detection using a lateral flow immunoassay (LFIA) is crucial for diagnosing infectious diseases due to its simplicity, speed, and user-friendly features. However, it remains a critical issue to explore specific biorecognition elements and powerful signal amplification. In this study, taking SARS-CoV-2 as a proof of concept, a specific peptide, WFLNDSELIML, binding to the SARS-CoV-2 spike (S) antigen was identified by a nonamplified biopanning method, which exhibited high affinity to the target, with a dissociation constant of 9.29 ± 1.55 nM. Molecular docking analysis reveals that this peptide binds to the N-terminal domain of the SARS-CoV-2 S antigen. Then, using this peptide as a capture probe and angiotensin-converting enzyme 2 as a detection probe, a peptide-based lateral flow immunoassay (pLFIA) for the sensitive detection of the SARS-CoV-2 S antigen without any antibody was developed, for which a polydopamine nanosphere (PDA)@MnO 2 nanocomposite with excellent oxidase-like activity was used as a colorimetric label, exhibiting dual-mode remarkable…

The research on lipid droplets (LDs) has attracted great attention in the field of biomedical science in recent years. LD malfunction is found to be associated with the development of acute kidney injury (AKI). To monitor this biological process and explain related pathological behavior, the development of excellent LD fluorescent probes with a polarity-sensitive character would provide a desirable strategy. Herein, we designed a new polarity-susceptible fluorescent probe named LD-B with LD targetability, which exhibits very weak fluorescence in highly polar solvents based on the twisted intramolecular charge transfer effect but enhanced fluorescence in low polar environments, enabling us to visualize polarity alteration. The probe LD-B also possesses the merits of intense near-infrared (NIR) emission, good photostability, large Stokes shift, low toxicity, faster metabolic rate, and wash-free ability; thereby, it would contribute to efficient LD fluorescence visualization application. Using LD-B via confocal laser scanning fluorescence imaging and a small-animal imaging system in…

Accurate and sensitive detection of multicomponent trace gases below the parts-per-million (ppm) level is needed in a variety of medical, industrial, and environmental applications. Raman spectroscopy can identify multiple molecules in the sample simultaneously and has excellent potential for fast diagnosis of various samples, but applications are often limited by its sensitivity. In this contribution, we report the development of a cavity-enhanced Raman spectroscopy instrument using a narrow-line width 532 nm laser locked with a high-finesse cavity through a Pound-Drever-Hall locking servo, which allows continuous measurement in a broad spectral range. An intracavity laser power of up to 1 kW was achieved with an incident laser power of about 240 mW, resulting in a significant enhancement of the Raman signal in the range of 200–5000 cm –1 and a sub-ppm sensitivity for various molecules. The technique is applied in the detection of different samples, including ambient air, natural gas, and reference gas of sulfur hexafluoride, demonstrating its capability for the quantitative…

Nanozymes are nanomaterials with enzyme-mimetic activity. It is known that DNA can interact with various nanozymes in different ways, enhancing or inhibiting the activity of nanozymes, which can be used to develop various biosensors. In this work, we synthesized a photosensitive covalent–organic framework (Tph-BT) as a nanozyme, and its oxidase and peroxidase activities could be reversely regulated by surface modification of single-stranded DNA (ssDNA) for the colorimetric detection of UO 2 2+ . Tph-BT exhibits excellent oxidase activity and weak peroxidase activity, and it is surprising to find that the UO 2 2+ -specific DNA aptamer can significantly inhibit the oxidase activity while greatly enhancing the peroxidase activity. The present UO 2 2+ interacts with the DNA aptamer to form secondary structures and detaches from the surface of Tph-BT, thereby restoring the enzymatic activity of Tph-BT. Based on the reversed regulation effects of the DNA aptamer on the two types of enzymatic activities of Tph-BT, a novel “off-on” and “on-off” sensing platform can be constructed for the…

We designed and implemented a photoacoustic (PA) sensor for H 2 S detection in SF 6 background gas based on a multi-pass differential photoacoustic cell (MDPC) and a near-infrared distributed feedback (DFB) laser. In the MDPC apparatus, two resonators with identical geometric parameters were vertically and symmetrically embedded. The differential processing algorithm of two phase-reversed signals realized the effective enhancement of the PA signal and suppressed the flow noise in the dynamic sampling process. In addition, the λ/4 buffer chamber in the MDPC was utilized as a muffler to further reduce the flow noise and realize the dynamic detection of H 2 S. The collimated excitation light was reflected 30 times in a multi-pass structure constituted of two gold-plated concave mirrors, and an absorption path length of 4.92 m was achieved. Due to the high gas density of SF 6, the relationship between the signal-to-noise ratio (SNR) and the gas flow was different between SF 6 and N 2 background gases. The maximum flow rate of the characteristic gas components detected in the SF 6…

Herein, an electrochemiluminescence (ECL) and electrochemical (EC) dual-mode biosensor platform with a self-powered DNAzyme walking machine was established for accurate and sensitive detection of miRNA-21. By employing a magnesium ion (Mn 2+ )-dependent DNAzyme cleavage cycling reaction, the walking machine was built by assembling DNAzyme walking strands and ferrocene (Fc)-labeled substrate strands on the Au nanoparticles and graphitic carbon nitride nanosheet (g-C 3 N 4 NS)-covered electrode. The DNAzyme walking strand was first prohibited by a blocker strand. After the addition of target miRNA-21 and Mn 2+, the DNAzyme walker could be activated and produce autonomous movements along the electrode track fueled by Mn 2+ -dependent DNAzyme-catalyzed substrate cleavage without additional energy supply. Notably, each walking step resulted in the cleavage of a substrate strand and the release of a Fc-labeled DNA strand fragment, allowing us to acquire an extreme ECL signal recovery of g-C 3 N 4 inhibited by Fc. Meanwhile, numerous Fc-labeled DNA fragments escaped from the surface of the…

Parkinson’s disease (PD) is one of the major neurodegenerative diseases caused by complex pathological processes. As a signal molecule, formaldehyde is closely linked to nervous systems, but the relationship between PD and formaldehyde levels remains largely unclear. We speculated that formaldehyde might be a potential biomarker for PD. To prove it, we constructed the first near-infrared (NIR) lysosome-targeted formaldehyde fluorescent probe (named NIR-Lyso-FA ) to explore the relationship between formaldehyde and PD. The novel fluorescent probe achieves formaldehyde detection in vitro and in vivo, thanks to its excellent properties such as NIR emission, large Stokes shift, and fast response to formaldehyde. Crucially, utilizing the novel probe NIR-Lyso-FA, formaldehyde overexpression was discovered for the first time in cellular, zebrafish, and mouse PD models, supporting our guess that formaldehyde can function as a possible biomarker for PD. We anticipate that this finding will offer insightful information for PD pathophysiology, diagnosis, medication development, and treatment.

Biomarkers detection in blood with high accuracy is crucial for the diagnosis and treatment of many diseases. In this study, the proof-of-concept fabrication of a dual-mode sensor based on a single probe (Re-BChE) using a dual-signaling electrochemical ratiometric strategy and a “turn-on” fluorescent method is presented. The probe Re-BChE was synthesized in a single step and demonstrated dual mode response toward butyrylcholinesterase (BChE), a promising biomarker of Alzheimer’s disease (AD). Due to the specific hydrolysis reaction, the probe Re-BChE demonstrated a turn-on current response for BChE at −0.28 V, followed by a turn-off current response at −0.18 V, while the fluorescence spectrum demonstrated a turn-on response with an emission wavelength of 600 nm. The developed ratiometric electrochemical sensor and fluorescence detection demonstrated high sensitivity with BChE concentrations with a low detection limit of 0.08 μg mL –1 and 0.05 μg mL –1, respectively. Importantly, the dual-mode sensor presents the following advantages: (1) dual-mode readout can correct the impact of…

Exosomal microRNAs (exomiRNAs) have emerged as ideal biomarkers for early clinical diagnostics. The accurate detection of exomiRNAs plays a crucial role in facilitating clinical applications. Herein, an ultrasensitive electrochemiluminescent (ECL) biosensor was constructed using three-dimensional (3D) walking nanomotor-mediated CRISPR/Cas12a and tetrahedral DNA nanostructures (TDNs)-modified nanoemitters (TCPP-Fe@HMUiO@Au-ABEI) for exomiR-155 detection. Initially, the 3D walking nanomotor-mediated CRISPR/Cas12a strategy could effectively convert the target exomiR-155 into amplified biological signals for improving the sensitivity and specificity. Then, TCPP-Fe@HMUiO@Au nanozymes with excellent catalytic performance were used to amplify ECL signals because of the enhanced mass transfer and increased catalytic active sites, originating from its high surface areas (601.83 m 2 /g), average pore size (3.46 nm), and large pore volumes (0.52 cm 3 /g). Meanwhile, the TDNs as the scaffold to fabricate “bottom-up” anchor bioprobes could improve the trans -cleavage efficiency of Cas12a.…

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTOn the Road from Single-Atom Materials to Highly Sensitive Electrochemical Sensing and BiosensingLei JiaoLei JiaoKey Laboratory of Pesticide and Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan, Hubei 430079, P. R. ChinaInstitute of Molecular Metrology, College of Chemistry and Chemical Engineering, Qingdao University, Qingdao 266071, P. R. ChinaMore by Lei JiaoView Biography, Weiqing XuWeiqing XuKey Laboratory of Pesticide and Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan, Hubei 430079, P. R. ChinaMore by Weiqing XuView Biography, Yu WuYu WuKey Laboratory of Pesticide and Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan,…

The increasing pressure and unhealthy lifestyle are gradually eroding the physical and mental health of modern people. As a key hormone responsible for maintaining the normal functioning of human systems, cortisol plays a vital role in regulating physiological activities. Moreover, cortisol can serve as a marker for monitoring psychological stress. The development of cortisol detection sensors carries immense potential, as they not only facilitate timely adjustments and treatments by detecting abnormal physiological indicators but also provide comprehensive data for conducting research on the correlation between cortisol and several potential diseases. Here, we report a molecularly imprinted polymer (MIP) electrochemical biosensor that utilizes a porous composite (MXG) modified electrode. MXG composite is prepared by combining Ti 3 C 2 T x -MXene sheets and graphene (Gr). MXG composite material with high conductive properties and large electroactive surface area promotes the charge transfer capability of the electrode surface, expands the effective surface area of the sensor, and…

The interpretation of spectral data, including mass, nuclear magnetic resonance, infrared, and ultraviolet-visible spectra, is critical for obtaining molecular structural information. The development of advanced sensing technology has multiplied the amount of available spectral data. Chemical experts must use basic principles corresponding to the spectral information generated by molecular fragments and functional groups. This is a time-consuming process that requires a solid professional knowledge base. In recent years, the rapid development of computer science and its applications in cheminformatics and the emergence of computer-aided expert systems have greatly reduced the difficulty in analyzing large quantities of data. For expert systems, however, the problem-solving strategy must be known in advance or extracted by human experts and translated into algorithms. Gratifyingly, the development of artificial intelligence (AI) methods has shown great promise for solving such problems. Traditional algorithms, including the latest neural network algorithms, have shown great potential…

Peroxynitrite (ONOO – ) is one type of important reactive oxygen/nitrogen species (ROS/RNS) and plays a vital role in many physiological activities. Excessive ONOO – is associated with many diseases including inflammation, arthritis, inflammatory bowel disease, cancer, and neurodegenerative diseases. However, a chemiluminescent probe capable of detecting endogenous ONOO – at the acidic condition that might be applied for sensitive diagnosis of inflammation-related disease has not been reported. Hence, we designed and synthesized a chemiluminescence (CL) probe, B-PD, to detect endogenous ONOO – both in vitro and in vivo . B-PD demonstrated a quick response toward ONOO – with a limit of detection of 201 nM. In vivo CL imaging results showed that, 30 min postinjection, B-PD could effectively locate early stage inflammation tissue with an imaging contrast up to 6.2. These results suggest that B-PD holds great promise for highly sensitive diagnosis of inflammation-related diseases in the future.

High Resolution Image Download MS PowerPoint Slide Non-targeted liquid chromatography–tandem mass spectrometry (LC–MS/MS) is a widely used tool for metabolomics analysis, enabling the detection and annotation of small molecules in complex environmental samples. Data-dependent acquisition (DDA) of product ion spectra is thereby currently one of the most frequently applied data acquisition strategies. The optimization of DDA parameters is central to ensuring high spectral quality, coverage, and number of compound annotations. Here, we evaluated the influence of 10 central DDA settings of the Q Exactive mass spectrometer on natural organic matter samples from ocean, river, and soil environments. After data analysis with classical and feature-based molecular networking using MZmine and GNPS, we compared the total number of network nodes, multivariate clustering, and spectrum quality-related metrics such as annotation and singleton rates, MS/MS placement, and coverage. Our results show that automatic gain control, microscans, mass resolving power, and dynamic exclusion are the most…