The 50 most-cited articles in Analytical Chemistry, 2020

Green analytical chemistry focuses on making analytical procedures more environmentally benign and safer to humans. The amounts and toxicity of reagents, generated waste, energy requirements, the number of procedural steps, miniaturization, and automation are just a few of the multitude of criteria considered when assessing an analytical methodology's greenness. The use of greenness assessment criteria requires dedicated tools. We propose the Analytical GREEnness calculator, a comprehensive, flexible, and straightforward assessment approach that provides an easily interpretable and informative result. The assessment criteria are taken from the 12 principles of green analytical chemistry (SIGNIFICANCE) and are transformed into a unified 0-1 scale. The final score is calculated based on the SIGNIFICANCE principles. The result is a pictogram indicating the final score, performance of the analytical procedure in each criterion, and weights assigned by the user. Freely available software makes the assessment procedure straightforward. It is open-source and downloadable from…

Abstract The World Health Organization has declared the outbreak of a novel coronavirus (SARS-CoV-2 or 2019-nCoV) as a global pandemic. However, the mechanisms behind the coronavirus infection are not yet fully understood, nor are there any targeted treatments or vaccines. In this study, we identified high-binding-affinity aptamers targeting SARS-CoV-2 RBD, using an ACE2 competition-based aptamer selection strategy and a machine learning screening algorithm. The Kd values of the optimized CoV2-RBD-1C and CoV2-RBD-4C aptamers against RBD were 5.8 nM and 19.9 nM, respectively. Simulated interaction modeling, along with competitive experiments, suggests that two aptamers may have partially identical binding sites at ACE2 on SARS-CoV-2 RBD. These aptamers present an opportunity for generating new probes for recognition of SARS-CoV-2 and could provide assistance in the diagnosis and treatment of SARS-CoV-2 while providing a new tool for in-depth study of the mechanisms behind the coronavirus infection.

The outbreak of 2019 coronavirus disease (COVID-19) has been a challenge for hospital laboratories because of the huge number of samples that must be tested for the presence of the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Simple and rapid immunodiagnostic methods are urgently needed to identify positive cases. Here we report the development of a rapid and sensitive lateral flow immunoassay (LFIA) that uses lanthanide-doped polysterene nanoparticles (LNPs) to detect anti-SARV-CoV-2 IgG in human serum. A recombinant nucleocapsid phosphoprotein of SARS-CoV-2 was dispensed onto a nitrocellulose membrane to capture specific IgG. Mouse anti-human IgG antibody was labeled with self-assembled LNPs that served as a fluorescent reporter. A 100-μL aliquot of serum samples (1:1000 dilution) was used for this assay and the whole detection process took 10 min. The results of the validation experiment met the requirements for clinical diagnostic reagents. A value of 0.0666 was defined as the cutoff value by assaying 51 normal samples. We tested 7 samples…

Molecular diagnosis of COVID-19 primarily relies on the detection of RNA of the SARS-CoV-2 virus, the causative infectious agent of the pandemic. Reverse transcription polymerase chain reaction (RT-PCR) enables sensitive detection of specific sequences of genes that encode the RNA dependent RNA polymerase (RdRP), nucleocapsid (N), envelope (E), and spike (S) proteins of the virus. Although RT-PCR tests have been widely used and many alternative assays have been developed, the current testing capacity and availability cannot meet the unprecedented global demands for rapid, reliable, and widely accessible molecular diagnosis. Challenges remain throughout the entire analytical process, from the collection and treatment of specimens to the amplification and detection of viral RNA and the validation of clinical sensitivity and specificity. We highlight the main issues surrounding molecular diagnosis of COVID-19, including false negatives from the detection of viral RNA, temporal variations of viral loads, selection and treatment of specimens, and limiting factors in detecting viral…

Horseradish peroxidase (HRP)-based assays feature particular interests because of the simple colorimetric readout. In these assays, 3,3′,5,5′-tetramethylbenzidine (TMB) is the most widely used chromogenic substrates for HRP. The later research in nanozyme and DNAzyme also used TMB (the chosen substrate) because they are both HRP-mimics. It should be noted that the substrate of HRP is not just limited to TMB but, in fact, a broad range of benzidine derivatives. However, except decreased carcinogenicity due to tetrasubstitution of benzidine, the rationale for the chosen substrate TMB is not clear yet. Here, we addressed such a fundamental issue from the chemistry point of view. Nine benzidine derivatives featuring varied properties (different substitution groups and varied number of substitutions) were selected and investigated with four typical TMB-involved chromogenic systems. Among the existing benzidine substrates that are used for peroxidase-based assays, TMB exhibited the highest sensitivity, better color purity of colored products, and reasonable stability of oxidation…

The SARS-CoV-2 pandemic has created an unprecedented need for rapid diagnostic testing to enable the efficient treatment and mitigation of COVID-19. The primary diagnostic tool currently employed is reverse transcription polymerase chain reaction (RT-PCR), which can have good sensitivity and excellent specificity. Unfortunately, implementation costs and logistical problems with reagents during the global SARS-CoV-2 pandemic have hindered its universal on demand adoption. Lateral flow assays (LFAs) represent a class of diagnostic that, if sufficiently clinically sensitive, may fill many of the gaps in the current RT-PCR testing regime, especially in low- and middle-income countries (LMICs). To date, many serology LFAs have been developed, though none meet the performance requirements necessary for diagnostic use cases, primarily due to the relatively long delay between infection and seroconversion. However, on the basis of previously reported results from SARS-CoV-1, antigen-based SARS-CoV-2 assays may have significantly better clinical sensitivity than serology assays. To date, only…

Fallacies about the nature of biases have shadowed a proper cognitive understanding of biases and their sources, which in turn lead to ways that minimize their impact. Six such fallacies are presented: it is an ethical issue, only applies to "bad apples", experts are impartial and immune, technology eliminates bias, blind spot, and the illusion of control. Then, eight sources of bias are discussed and conceptualized within three categories: (A) factors that relate to the specific case and analysis, which include the data, reference materials, and contextual information, (B) factors that relate to the specific person doing the analysis, which include past experience base rates, organizational factors, education and training, and personal factors, and lastly, (C) cognitive architecture and human nature that impacts all of us. These factors can impact what the data are (e.g., how data are sampled and collected, or what is considered as noise and therefore disregarded), the actual results (e.g., decisions on testing strategies, how analysis is conducted, and when to stop testing), and…

A self-powered temperature sensor based on Seebeck effect transduction was designed for photothermal–thermoelectric coupled immunoassay of α-fetoprotein (AFP). In this system, glucose oxidase (GOx)-conjugated detection antibody was first captured onto the microplate by target-induced sandwich-type immunoreaction. Thereafter, the as-generated hydrogen peroxide via the GOx–glucose system oxidized 3,3′,5,5′-tetrametylbenzidine (TMB) into photothermal product oxidized TMB (ox-TMB). Under near-infrared (NIR) laser irradiation, the temperature change of ox-TMB was read out in an electrical signal by the flexible thermoelectric module in a 3D-printed integrated detection device. Under optimal conditions, the photothermal–thermoelectric coupled immunoassay exhibited a limit of detection of 0.39 ng mL –1 AFP over a dynamic linear range from 0.5 to 60 ng mL –1 . Impressively, such a strategy presented herein offers tremendous potentials for applying many other high-efficiency thermoelectric materials in ultrasensitive biosensors.

As smaller particle sizes are increasingly included in microplastic research, it is critical to chemically characterize microparticles to identify whether particles are indeed microplastics. To increase the accessibility of methods for characterizing microparticles via Raman spectroscopy, we created an application-based library of Raman spectroscopy parameters specific to microplastics based on color, morphology, and size. We also created two spectral libraries that are representative of microplastics found in environmental samples. Here, we present SLoPP, a spectral library of plastic particles, consisting of 148 reference spectra, including a diversity of polymer types, colors, and morphologies. To account for the effects of aging on microplastics and associated changes to Raman spectra, we present a spectral library of plastic particles aged in the environment (SLoPP-E). SLoPP-E includes 113 spectra, including a diversity of types, colors, and morphologies. The microplastics used to make SLoPP-E include environmental samples obtained across a range of matrices, geographies, and…

In this study, a cellulose acetate (CA) membrane is formed as an interference rejection membrane on a glucose sensor to measure glucose in saliva. Glucose in saliva is successfully measured in vivo without any pretreatment of human saliva. A mouthguard (MG) glucose sensor is developed to monitor salivary glucose, which is reported to be correlated with the blood glucose level. Salivary components of ascorbic acid (AA) and uric acid (UA) hinder the accurate measurement of the glucose concentration of human saliva. CA-coated electrodes are prepared to investigate the interference rejection membrane. To measure hydrogen peroxide, which is a reaction product of glucose oxidase, effects of AA and UA are examined. Characteristics of the fabricated biosensor are examined on the basis of artificial saliva. The as-developed MG sensor can quantify the glucose concentration in the range of 1.75-10 000 μmol/L, which includes a salivary sugar concentration of 20-200 μmol/L. For the measurement of saliva samples collected from healthy subjects, the output corresponding to the concentration is…

Full-scan, data-dependent acquisition (DDA), and data-independent acquisition (DIA) are the three common data acquisition modes in high resolution mass spectrometry-based untargeted metabolomics. It is an important yet underrated research topic on which acquisition mode is more suitable for a given untargeted metabolomics application. In this work, we compared the three data acquisition techniques using a standard mixture of 134 endogenous metabolites and a human urine sample. Both hydrophilic interaction and reversed-phase liquid chromatographic separation along with positive and negative ionization modes were tested. Both the standard mixture and urine sample generated consistent results. Full-scan mode is able to capture the largest number of metabolic features, followed by DIA and DDA (53.7% and 64.8% respective features fewer on average in urine than full-scan). Comparing the MS 2 spectra in DIA and DDA, spectra quality is higher in DDA with average dot product score 83.1% higher than DIA in Urine(H), and the number of MS 2 spectra (spectra quantity) is larger in DIA (on…

Single-atom nanozymes (SAzymes), as novel nanozymes with atomically dispersed active sites, are of great importance in the development of nanozymes for their high catalytic activities, the maximum utilization efficiency of metal atoms, and the simple model of active sites. Herein, the peroxidase-like SAzymes with high-concentration Cu sites on carbon nanosheets (Cu-N-C) were synthesized through a salt-template strategy. With the densely distributed active Cu atoms (∼5.1 wt %), the Cu-N-C SAzymes exhibit remarkable activity to mimic natural peroxidase. Integrating Cu-N-C SAzymes with natural acetylcholinesterase and choline oxidase, three-enzyme-based cascade reaction system was constructed for the colorimetric detection of acetylcholine and organophosphorus pesticides. This work not only provides a strategy to synthesize SAzymes with abundant active sites but also gives some new insights for robust nanozyme biosensing systems.

Cell Adherence 314 Operational Units 314 Pumping 314 Valves 315 Gradient Formation 316 Mixing 316 Filtration and Separation 316 Filtration 316 Separation 316 Droplet Microfluidics and Digital Microfluidics 317 Droplet Generation 317 Droplet Sorting 317 Droplet Storage 317 Droplet Interfaces 317 In-Droplet Manipulation 318 Digital Microfluidics 318 Detection 319 Electroanalytical Methods 319 Raman Spectroscopy 320 Optical Methods 321 Mass Spectrometry (MS) 321 Other Methods 321 Selected Applications in Bioanalysis and Diagnostics 322 Cell Manipulation 322 Cytometry and Cell Sorting 322 Analysis of Secreted Compounds 324 Diagnostic Applications 324 Blood Cell Separation 324 Point-of-Care Devices for the Detection of Biomarkers 324 Extracellular Vesicles (EV) 324 Identification of Pathogens and Antibiotic

Pesticides, widely used for pest control and plant growth regulation, have posed a threat to the environment and human health. Conventional methods to analyze pesticide residues are not applied to resource-limited areas because of their high cost, complexity, and requirements for expensive instruments (such as GC/MS and LC/MS). To address these challenges, herein we fabricated colorimetric nanozyme sensor arrays based on heteroatom-doped graphene for detection of aromatic pesticides. The active sites of nanozymes could be differentially masked when different pesticides were adsorbed on the graphene, which in turn resulted in the decrease of their peroxidase-mimicking activities. On the basis of this principle, five pesticides (i.e., lactofen, fluoroxypyr-meptyl, bensulfuron-methyl, fomesafen, and diafenthiuron) from 5 to 500 μM were successfully discriminated by the sensor arrays. In addition, discrimination for different concentrations of each pesticide and different ratios of two mixed pesticides were also demonstrated. The practical application of the sensor arrays was further…

Bisphenol A, an endocrine disrupting compound, is widely used in food and beverage packaging, and it then leaches in food and source water cycles, and thus must be monitored. Here, we report a simple, low-cost and sensitive electrochemical sensor using graphene oxide and β-cyclodextrin functionalized multiwalled carbon nanotubes for the detection of BPA in water. This sensor electrode system combines the high surface area of graphene oxide and carbon nanotubes, and the superior host-guest interaction capability of β-cyclodextrin. A diffusion-controlled oxidation reaction involving equal numbers of protons and electrons facilitated the electrochemical sensing of BPA. The sensor showed a two-step linear response from 0.05 to 5 μM and 5-30 μM with a limit of detection of 6 nM. The sensors also exhibited a reproducible and stable response over one month with negligible interference from common inorganic and organic species, and an excellent recovery with real water samples. The proposed electrochemical sensor can be promising for the development of simple low-cost water quality…

We have developed a single-tube assay for SARS-CoV-2 in patient samples. This assay combined advantages of reverse transcription (RT) loop-mediated isothermal amplification (LAMP) with clustered regularly interspaced short palindromic repeats (CRISPRs) and the CRISPR-associated (Cas) enzyme Cas12a. Our assay is able to detect SARS-CoV-2 in a single tube within 40 min, requiring only a single temperature control (62 °C). The RT-LAMP reagents were added to the sample vial, while CRISPR Cas12a reagents were deposited onto the lid of the vial. After a half-hour RT-LAMP amplification, the tube was inverted and flicked to mix the detection reagents with the amplicon. The sequence-specific recognition of the amplicon by the CRISPR guide RNA and Cas12a enzyme improved specificity. Visible green fluorescence generated by the CRISPR Cas12a system was recorded using a smartphone camera. Analysis of 100 human respiratory swab samples for the N and/or E gene of SARS-CoV-2 produced 100% clinical specificity and no false positive. Analysis of 50 samples that were detected positive using reverse…

Tumor exosomes are promising biomarkers for early cancer diagnosis in a noninvasive manner. However, precise capture and direct analysis of tumor-specific exosomes in complex biological samples are still challenging. Herein, we present a highly efficient dual-aptamer recognition system for precisely isolating and quantifying tumor exosomes from the complex biological environment based on hyperbranched DNA superstructure-facilitated signal amplification and ratiometric dual-signal strategies. When tumor exosomes were captured by the dual-aptamer recognition system, the cholesterol-modified DNA probe was anchored on the surface of the exosomes, activating DNA tetrahedron-based hyperbranched hybridization chain reaction to generate a sandwich complex. Then, the sandwich complex could bind a large number of Ru(NH 3 ) 6 3+ (Ru(III)), leading to a small amount of unbound Ru(III) left in the supernatant after magnetic separation. Hence, the redox reaction between Ru(II) and [Fe(CN) 6 ] 3– (Fe(III)) was significantly prevented, causing an obviously enhanced I Fe(III) / I Ru(III) value.…

Abstract Colorimetric gene detection based on gold nanoparticles (AuNPs) is an attractive detection format due to its simplicity. Here, we report a new design for a colorimetric gene-sensing platform based on the CRISPR/Cas system that has improved specificity, sensitivity, and universality. CRISPR/Cas12a and CRISPR/Cas13a have two distinct catalytic activities and are used for specific target gene recognition. Programmable recognition of DNA by Cas12a/crRNA and RNA by Cas13a/crRNA with a complementary sequence activates the nonspecific trans -ssDNA or -RNA cleavage, respectively, thus degrading the ssDNA or RNA linkers which are designed as a hybridization template for the AuNP-DNA probe pair. Target-induced trans -ssDNA or RNA cleavage leads to a distance-dependent color change for the AuNP-DNA probe pair. In this platform, naked eye detection of transgenic rice, African swine fever virus (ASFV), and a miRNA can be completed within 1 hour. Our colorimetric gene-sensing method shows superior characteristics, such as probe universality, isothermal reaction conditions, on-site…

Unidentified peaks remain a major problem in untargeted metabolomics by LC-MS/MS. Confidence in peak annotations increases by combining MS/MS matching and retention time. We here show how retention times can be predicted from molecular structures. Two large, publicly available data sets were used for model training in machine learning: the Fiehn hydrophilic interaction liquid chromatography data set (HILIC) of 981 primary metabolites and biogenic amines,and the RIKEN plant specialized metabolome annotation (PlaSMA) database of 852 secondary metabolites that uses reversed-phase liquid chromatography (RPLC). Five different machine learning algorithms have been integrated into the Retip R package: the random forest, Bayesian-regularized neural network, XGBoost, light gradient-boosting machine (LightGBM), and Keras algorithms for building the retention time prediction models. A complete workflow for retention time prediction was developed in R. It can be freely downloaded from the GitHub repository (https://www.retip.app). Keras outperformed other machine learning algorithms in the test…

In this work, an ultrasensitive electrogenerated chemiluminescence (ECL) biosensor for exosomes and their surface proteins was developed by the in situ formation of gold nanoparticles (AuNPs) decorated Ti 3 C 2 MXenes hybrid with aptamer modification (AuNPs-MXenes-Apt). In this strategy, the exosomes were efficiently captured on an exosome recognized CD63 aptamer modified electrode interface. Meanwhile, in situ formation of gold nanoparticles on single layer Ti 3 C 2 MXenes with aptamer (MXenes-Apt) modification was obtained, in which MXenes acted as both reductants and stabilizer, and no additional reductant and stabilizer involved. The in situ formed AuNPs-MXenes-Apt hybrid not only presented highly efficient recognition of exosomes specifically, but also provide naked catalytic surface with high electrocatalytic activity of gold nanoparticles with predominated (111) facets that significantly improved the ECL signal of luminol. In this way, a highly sensitive ECL biosensor for exosomes detection was constructed ascribing to the synergistic effects of large surface area, excellent…

Transition metal carbides, known as MXenes, are generated via the selective etching of “A” layers from their layered, ternary parent compounds, MAX phases, where M corresponds to early d -transition metal, A being a main group sp -element from either Group 13 or 14 and carbon or nitrogen being denoted by X. MXenes are being recognized as a new and uprising class of 2D materials with extraordinary physical and electrochemical properties. The huge specific surface area and outstanding electrical conductivity of MXenes, make them ideal candidates for sensing and energy applications. Herein, we demonstrated the successful incorporation of pristine MXene, Ti 3 C 2 produced via HF etching and subsequent delamination with TBAOH, as a transducer platform toward the development of a second generation electrochemical glucose biosensor. Chronoamperometric studies demonstrate that the proposed biosensing system exhibits high selectivity and excellent electrocatalytic activity toward the detection of glucose, spanning over wide linear ranges of 50–27 750 μM and possess a low limit of detection…

Recently, CRISPR-Cas technology has opened a new era of nucleic acid-based molecular diagnostics. However, current CRISPR-Cas-based nucleic acid biosensing has a lack of the quantitative detection ability and typically requires separate manual operations. Herein, we reported a dynamic aqueous multiphase reaction (DAMR) system for simple, sensitive and quantitative one-pot CRISPR-Cas12a based molecular diagnosis by taking advantage of density difference of sucrose concentration. In the DAMR system, recombinase polymerase amplification (RPA) and CRISPR-Cas12a derived fluorescent detection occurred in spatially separated but connected aqueous phases. Our DAMR system was utilized to quantitatively detect human papillomavirus (HPV) 16 and 18 DNAs with sensitivities of 10 and 100 copies within less than 1 h. Multiplex detection of HPV16/18 in clinical human swab samples were successfully achieved in the DAMR system using 3D-printed microfluidic device. Furthermore, we demonstrated that target DNA in real human plasma samples can be directly amplified and detected in the DAMR system…

Mercury detection remains an important task because of its high toxicity. Herein a new dual-signal probe based on a boric acid (BA)-functionalized lanthanide metal–organic framework (BA-Eu-MOF) was developed for the detection of Hg 2+ and CH 3 Hg + ions for the first time. The BA-Eu-MOF was synthesized by coordination of Eu 3+ with 5-boronobezene-1, 3-dicarboxylic acid (5-bop) through a one-pot method. The 5-bop ligand not only acted as the “antenna” to sensitize the luminescence of Eu 3+ but also provided reaction sites for Hg 2+ and CH 3 Hg + . Owing to the electron-withdrawing effect of the BA group, the “antenna” effect of the ligand was passivating and the BA-Eu-MOF showed weak red emission in water. Upon addition of Hg 2+ or CH 3 Hg + into the system, a transmetalation reaction took place, i.e., BA groups were replaced by Hg 2+ or CH 3 Hg +; therefore, the “antenna” effect of the ligand was triggered, leading to the enhancement of red emission. As Hg 2+ or CH 3 Hg + concentration increased, the red emission was gradually enhanced, and the color change was also observed with…

Collection of nasopharyngeal samples using swabs followed by the transfer of the virus into a solution and an RNA extraction step to perform reverse transcription polymerase chain reaction (PCR) is the primary method currently used for the diagnosis of COVID-19. However, the need for several reagents and steps and the high cost of PCR hinder its worldwide implementation to contain the outbreak. Here, we report a cotton-tipped electrochemical immunosensor for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus antigen. Unlike the reported approaches, we integrated the sample collection and detection tools into a single platform by coating screen-printed electrodes with absorbing cotton padding. The immunosensor was fabricated by immobilizing the virus nucleocapsid (N) protein on carbon nanofiber-modified screen-printed electrodes which were functionalized by diazonium electrografting. The detection of the virus antigen was achieved via swabbing followed by competitive assay using a fixed amount of N protein antibody in the solution. A square wave…

ADVERTISEMENT RETURN TO ISSUEReviewNEXTElectrochemical Sensing at a Confined SpaceSi-Min LuSi-Min LuState Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. ChinaMore by Si-Min LuView Biography, Yue-Yi PengYue-Yi PengState Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. ChinaMore by Yue-Yi PengView Biography, Yi-Lun YingYi-Lun YingState Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. ChinaMore by Yi-Lun YingView Biographyhttp://orcid.org/0000-0001-6217-256X, and Yi-Tao Long*Yi-Tao LongState Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China*Email: [email protected]More by Yi-Tao LongView Biographyhttp://orcid.org/0000-0003-2571-7457Cite this: Anal. Chem. 2020, 92, 8, 5621–5644Publication Date…

The outbreak of SARS-CoV-2 is posing serious global public health problems. Facing the emergence of this pandemic, we established a portable microfluidic immunoassay system for easy-to-use, sensitive, rapid (<15 min), multiple, and on-site detection of IgG/IgM/Antigen of SARS-CoV-2 simultaneously. This integrated method was successfully applied for detecting SARS-CoV-2 IgM and IgG antibodies in clinical human serum as well as SARS-CoV-2 antigen in pharyngeal swabs from 26 patients with COVID-19 infection and 28 uninfected people. The assay demonstrated high sensitivity and specificity, which is promising for the diagnosis and monitoring as well as control of SARS-CoV-2 worldwide.

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTPotentiometric SensingElena Zdrachek*Elena ZdrachekDepartment of Inorganic and Analytical Chemistry, University of Geneva, Quai Ernest-Ansermet 30, CH-1211 Geneva, Switzerland*Email: [email protected]More by Elena ZdrachekView Biographyhttp://orcid.org/0000-0003-1593-7843 and Eric BakkerEric BakkerDepartment of Inorganic and Analytical Chemistry, University of Geneva, Quai Ernest-Ansermet 30, CH-1211 Geneva, SwitzerlandMore by Eric BakkerView Biographyhttp://orcid.org/0000-0001-8970-4343Cite this: Anal. Chem. 2021, 93, 1, 72–102Publication Date (Web):October 27, 2020Publication History Published online27 October 2020Published inissue 12 January 2021https://pubs.acs.org/doi/10.1021/acs.analchem.0c04249https://doi.org/10.1021/acs.analchem.0c04249review-articleACS PublicationsCopyright © 2020 American Chemical Society. This publication is licensed under CC-BY-NC-ND 4.0. License Summary*You are free to share (copy and redistribute) this article in any medium or format within the parameters below:Creative Commons (CC): This is a Creative Commons…

Reference standardization was developed to address quantification and harmonization challenges for high-resolution metabolomics (HRM) data collected across different studies or analytical methods. Reference standardization relies on the concurrent analysis of calibrated pooled reference samples at predefined intervals and enables a single-step batch correction and quantification for high-throughput metabolomics. Here, we provide quantitative measures of approximately 200 metabolites for each of three pooled reference materials (220 metabolites for Qstd3, 211 metabolites for CHEAR, 204 metabolites for NIST1950) and show application of this approach for quantification supports harmonization of metabolomics data collected from 3677 human samples in 17 separate studies analyzed by two complementary HRM methods over a 17-month period. The results establish reference standardization as a method suitable for harmonizing large-scale metabolomics data and extending capabilities to quantify large numbers of known and unidentified metabolites detected by high-resolution mass spectrometry…

Abstract Drug-induced liver injury (DILI) is considered gradually as a serious public health issue, and hepatotoxicity has been regarded as the main clinical problem caused by it. We suspected that both the intracellular viscosity and peroxynitrite (ONOO–) levels in drug-induced hepatotoxicity tissue are higher than those in a healthy liver. For this reason, we have presented a fluorescent probe VO for multichannel imaging viscosity and ONOO– simultaneously. Experimental results showed that VO has satisfactory detection performance for both viscosity and ONOO–, and based on the advantages of its lower cytotoxicity and pH-stabilities, VO was successfully employed to image viscosity and ONOO– in living cells and animals. More importantly, we use the probe to successfully showcase drug-induced hepatotoxicity by imaging viscosity and ONOO– induced by acetaminophen (APAP). All the results indicate that VO has great potential for the detection of viscosity and ONOO– and to assay drug-induced hepatotoxicity. Overall, this work offers a new detection tool/method for a deeper understanding…

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTElectrochemical Sensing Directions for Next-Generation Healthcare: Trends, Challenges, and FrontiersJuan F. Hernández-RodríguezJuan F. Hernández-RodríguezDepartment of Analytical Chemistry, Physical Chemistry and Chemical Engineering, Faculty of Sciences, University of Alcalá, E-28871 Alcalá de Henares, Madrid, SpainMore by Juan F. Hernández-RodríguezView Biographyhttp://orcid.org/0000-0001-5035-6791, Daniel RojasDaniel RojasDepartment of Analytical Chemistry, Physical Chemistry and Chemical Engineering, Faculty of Sciences, University of Alcalá, E-28871 Alcalá de Henares, Madrid, SpainFaculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, 64100 Teramo, ItalyMore by Daniel RojasView Biographyhttp://orcid.org/0000-0002-4404-4668, and Alberto Escarpa*Alberto EscarpaDepartment of Analytical Chemistry, Physical Chemistry and Chemical Engineering, Faculty of Sciences, University of Alcalá, E-28871 Alcalá de Henares, Madrid, SpainChemical Research Institute Andres M. del Rio, University of Alcalá,…

Microplastics have been observed in indoor and outdoor air. This raises concern for human exposure, especially should they occur in small enough sizes, which if inhaled, reach the central airway and distal lung. As yet, methods for their detection have not spectroscopically verified the chemical composition of microplastics in this size-range. One proposed method is an automated spectroscopic technique, Raman spectral imaging; however, this generates large and complex data sets. This study aims to optimize Raman spectral imaging for the identification of microplastics (≥2 μm) in ambient particulate matter, using different chemometric techniques. We show that Raman spectral images analyzed using chemometric statistical approaches are appropriate for the identification of both virgin and environmental microplastics ≥2 μm in size. On the basis of the sensitivity, we recommend using the developed Pearson's correlation and agglomerative hierarchical cluster analysis for the identification of microplastics in spectral data sets. Finally, we show their applicability by identifying airborne…

A rapid and accurate method for detection of virus (SARS-CoV-2)-specific antibodies is important to contain the 2019 coronavirus disease (COVID-19) outbreak, which is still urgently needed. Here, we develop a colorimetric-fluorescent dual-mode lateral flow immunoassay (LFIA) biosensor for rapid, sensitive, and simultaneous detection of SARS-CoV-2-specific IgM and IgG in human serum using spike (S) protein-conjugated SiO 2 @Au@QD nanobeads (NBs) as labels. The assay only needs 1 μL of the serum sample, can be completed within 15 min, and is 100 times more sensitive than the colloidal gold-based LFIA. Two detection modes of our biosensor are available: the colorimetric mode for rapid screening of the patients with suspected SARS-CoV-2 infection without any special instrument and the fluorescent mode for sensitive and quantitative analyses to determine the concentrations of specific IgM/IgG in human serum and detect the infection early and precisely. We validated the proposed method using 16 positive serum samples from patients with COVID-19 and 41 negative samples from patients with…

Microplastics are defined as microscopic plastic particles in the range from few micrometers and up to 5 mm. These small particles are classified as primary microplastics when they are manufactured in this size range, whereas secondary microplastics arise from the fragmentation of larger objects. Microplastics are widespread emerging pollutants, and investigations are underway to determine potential harmfulness to biota and human health. However, progress is hindered by the lack of suitable analytical methods for rapid, routine, and unbiased measurements. This work aims to develop an automated analytical method for the characterization of small microplastics (<100 μm) using micro-Fourier transform infrared (μ-FTIR) hyperspectral imaging and machine learning tools. Partial least squares discriminant analysis (PLS-DA) and soft independent modeling of class analogy (SIMCA) models were evaluated, applying different data preprocessing strategies for classification of nine of the most common polymers produced worldwide. The hyperspectral images were also analyzed to quantify particle…

Synthesis of red emissive carbon dots (CDs) is highly desirable for sensing applications, as they still remain as bottlenecks in terms of precursor synthesis and product purification. Herein, we have designed a new strategy for realizing efficient red emissive CD optimal emission at 610 nm (fluorescence quantum yield ca. 24.0%) based on solvothermal treatment of citric acid and thiourea using dimethylformamide as solvent. Further investigations reveal that the conjugating sp 2 -domain controlling the incorporation of nitrogen and surface engineering are mainly responsible for the obtained red emission of CDs. Taking advantage of optical properties and abundant surface functional groups, CDs were considered to facilely construct a ratiometric fluorescent platform for quantifying trace levels of organophosphorus pesticides (OPs). Combining the acetylcholinesterase-mediated polymerization of dopamine and the inhibition of pesticide toward the enzyme, the degree of polymerization of dopamine rationally depends on the concentration of OPs. By measuring the fluorescence intensity ratio,…

In vitro diagnosis requires target biomarkers to be reliably detected at an ultralow level. A dual-signal strategy permits self-calibration to overcome the interferences of experimental and environmental factors, and thus is regarded as a promising approach. However, currently reported works mainly concentrated on the same forms of energy of output signals. Herein, we propose a one-step strategy for synthesis of methylene blue-encapsulated zeolitic imidazolate framework-90 (MB@ZIF-90) with high loading, unique dual-signal property, exceptional recognition capability, and good stability, and we further pioneer MB@ZIF-90 as a dual-signal biosensor for label-free, enzyme-free, and ultrasensitive detection of adenosine triphosphate (ATP) by integration of fluorescence and homogeneous electrochemical techniques. The recognition of MB@ZIF-90 by target ATP spurs the decomposition of ZIF-90, subsequently permitting MB to be released into a supernatant. As compared to the case where ATP does not exist, obviously increased intensities in fluorescence and differential pulse voltammetry current…

Herein, we report on a two-dimensional amino-functionalized Ti 3 C 2 -MXene (N–Ti 3 C 2 -MXene)-based surface plasmon resonance (SPR) biosensor for detecting carcinoembryonic antigen (CEA) utilizing a sandwich format signal amplification strategy. Our biosensor employs an N-Ti 3 C 2 -MXene nanosheet-modified sensing platform and a signal enhancer comprising N-Ti 3 C 2 -MXene-hollow gold nanoparticles (HGNPs)-staphylococcal protein A (SPA) complexes. Ultrathin Ti 3 C 2 -MXene nanosheets were synthesized and functionalized with aminosilane to provide a hydrophilic-biocompatible nanoplatform for covalent immobilization of the monoclonal anti-CEA capture antibody (Ab 1 ). The N-Ti 3 C 2 -MXene/HGNPs nanohybrids were synthesized and further decorated with SPA to immobilize the polyclonal anti-CEA detection antibody (Ab 2 ) and serve as signal enhancers. The capture of CEA followed by the formation of the Ab 2 -conjugated SPA/HGNPs/N-Ti 3 C 2 -MXene sandwiched nanocomplex on the SPR chip results in the generation of a response signal. The fabricated N-Ti 3 C 2 -MXene-based SPR biosensor…

Glioblastoma (GBM) is one of the most fatal tumors in the brain, and its early diagnosis remains technically challenging due to the complex repertoires of oncogenic alterations and blood-brain barrier (BBB). GBM-derived specific exosomes can cross the BBB and circulate in body fluids, so they can be noninvasive biomarkers for the early diagnosis of GBM. Herein, we propose a sensitive and label-free electrochemical biosensor designed by using Zr-based metal–organic frameworks (Zr-MOFs) for the detection of GBM-derived exosomes with practical application. In the design, a peptide ligand can specifically bind with human epidermal growth factor receptor (EGFR) and EGFR variant (v) III mutation (EGFRvIII), which are overexpressed on the GBM-derived exosomes. Meanwhile, Zr-MOFs encapsulated with methylene blue can absorb on the surface of the exosomes due to the interaction between Zr 4+ and the intrinsic phosphate groups outside of exosomes. Consequently, the concentration of exosomes can be directly quantified by monitoring the electroactive molecules inside MOFs, ranging from 9.5 × 10…

A simple, low-cost, and universal gold nanoparticle (AuNP) aggregation-induced photothermal biosensing platform has been developed for the first time and applied for the visual quantitative genetic detection using a common thermometer. By exploiting the photothermal effect of target-induced gold nanoparticle aggregation, visual quantitative biochemical analysis can be achieved by simply recording temperature signals using a common thermometer. Compared to conventional genetic testing methods, it is label- and amplification-free and can be completed in 40 min without the aid of any advanced analytical instruments. Mycobacterium tuberculosis ( MTB ) DNA was used as a model target to demonstrate the application of this photothermal biosensing platform. Although no costly instrument was used, high sensitivity and specificity were achieved with the limit of detection (LOD) of 0.28 nM, which was nearly 10-fold lower than that of the colorimetric method using a spectrometer. This AuNP aggregation-induced photothermal biosensing strategy provides a simple, low-cost, and universal platform…

Design of highly active carbon nanozymes and further establishment of ultrasensitive biosensors remain a challenge. Herein, hierarchically porous carbon nanozymes with sulfur (S)/nitrogen (N) codoping (SNC) were developed. Compared with N-doped carbon (NC) nanozymes, SNC nanozymes have a smaller Michaelis-Menten constant and higher specific activities, demonstrating that the S-doping in SNC nanozymes could not only enhance their affinity toward substrates but also improve their catalytic performance. These results may be caused by the synergistic effect of heteroatoms (S and N). Because of the good enzyme-like activity, the proposed SNC nanozymes were exploited to the colorimetric detection of the total antioxidant capacity (TAC) using ascorbic acid as a typical model with a limit of detection of 0.08 mM. Because of its high sensitivity and selectivity and encouraging performance, the detection method presented practical feasibility for the TAC assay in commercial beverages. This work paves a way to design the highly active carbon nanozymes and expand their applications in the…

A compact multigas sensor system based on a single quartz crystal tuning fork (QCTF) and multifrequency synchronous modulation strategy is proposed for trace gas detection. To demonstrate the novel detection technique, three near-infrared continuous-wave (CW) distributed feedback (DFB) diode lasers with center wavelengths of near 1391, 1574, and 1653 nm and a standard 32 kHz QCTF were integrated for simultaneous detection of H 2 O, CO 2, and CH 4, respectively. Wavelength modulation spectroscopy with second harmonic detection (WMS-2 f ) was selected for enhancing sensitivity. Design of the sensor configuration and primary performance between the traditional single-frequency modulation and the proposed tri-frequency modulation were experimentally investigated and compared in detail. The results indicate that the proposed sensing technique has significant advantages of cost effectiveness, portability, and ease-of-use, and detection limits of 1.4, 353, and 3.1 ppm for simultaneously measuring H 2 O, CO 2, and CH 4, respectively, are obtained, corresponding to the normalized noise…

Untargeted molecular analyses of complex mixtures are relevant for many fields of research, including geochemistry, pharmacology, and medicine. Ultrahigh-resolution mass spectrometry is one of the most powerful tools in this context. The availability of open scripts and online tools for specific data processing steps such as noise removal or molecular formula assignment is growing, but an integrative tool where all crucial steps are reproducibly evaluated and documented is lacking. We developed a novel, server-based tool (ICBM-OCEAN, I nstitute for C hemistry and B iology of the M arine Environment, O ldenburg– c omplex molecular mixtures, e valuation & an alysis) that integrates published and novel approaches for standardized processing of ultrahigh-resolution mass spectrometry data of complex molecular mixtures. Different from published approaches, we offer diagnostic and validation tools for all relevant steps. Among other features, we included objective and reproducible reduction of noise and systematic errors, spectra recalibration and alignment, and identification of likeliest…

Here, we discovered that rigidifying the tetraphenylethylene (TPE)-based ligand H 4 TCBPE (H 4 TCBPE = 1,1,2,2-tetra(4-carboxylbiphenyl)ethylene) into Hf-based metal–organic framework (Hf-TCBPE) could lead to a stronger electrochemiluminescence (ECL) emission in comparison to H 4 TCBPE aggregates and H 4 TCBPE monomers. Due to the lack of close-packed TCBPE chromophores in Hf-TCBPE, which was required for aggregation-induced ECL (AI-ECL) enhancement, we defined this unprecedented phenomenon as matrix coordination-induced ECL (MCI-ECL) enhancement. The strong ECL intensity of Hf-TCBPE not only originated from the fixation of the TCBPE ligand between Hf 6 clusters that restricted the intramolecular free motions of TCBPE and suppressed the nonradiative relaxation but also stemmed from the high porosity of Hf-TCBPE that rendered both internal and external TCBPE chromophores able to be excited. Considering the unique ECL characteristic of Hf-TCBPE, we combined the new ECL indicator of Hf-TCBPE as well as the phosphate-terminal ferrocene (Fc)-labeled hairpin DNA (Fc-HP3) aptamer together…

RETURN TO ISSUEPREVReviewNEXTRecurrent Topics in Mass Spectrometry-Based Metabolomics and Lipidomics—Standardization, Coverage, and ThroughputEvelyn RamplerEvelyn RamplerDepartment of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Währinger Str. 38, 1090 Vienna, AustriaVienna Metabolomics Center (VIME), University of Vienna, Althanstraße 14, 1090 Vienna, AustriaUniversity of Vienna, Althanstraße 14, 1090 Vienna, AustriaMore by Evelyn RamplerView Biographyhttp://orcid.org/0000-0002-9429-7663, Yasin El AbieadYasin El AbieadDepartment of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Währinger Str. 38, 1090 Vienna, AustriaMore by Yasin El AbieadView Biography, Harald SchoenyHarald SchoenyDepartment of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Währinger Str. 38, 1090 Vienna, AustriaMore by Harald SchoenyView Biographyhttp://orcid.org/0000-0001-8696-481X, Mate RuszMate RuszDepartment of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Währinger Str. 38, 1090 Vienna, AustriaInstitute of Inorganic Chemistry,…

A method for the detection and quantification of nanoplastics (NPTs) at environmentally relevant concentrations was developed. It is based on conjugating nanoplastics with functionalized metal (Au)-containing nanoparticles (NPs), thus making them detectable by highly sensitive inductively coupled plasma mass spectrometry (ICP-MS) operated in single particle (SP) mode. The selectivity of the method was achieved by the coupling of negatively charged carboxylate groups present at the surface of nanoplastics with a positively charged gelatin attached to the custom-synthesized AuNPs. The adsorbed Au produced a SP-ICP-MS signal allowing the counting of individual nanoplastic particles, and hence their accurate quantification (<5% error). Polystyrene (PS) particle models with controlled surface functionalization mimicking the nanoplastics formed during natural degradation of plastic debris were used for the method development. The nanoplastic number concentration quantification limit was calculated at 8.4 × 10 5 NPTs L –1 and the calibration graph was linear up to 3.5 × 10 8 NPTs L –1 .…

Escherichia coli O157:H7 has been reported as an important pathogenic bacteria causing serious infection and economic loss. However, detection of Escherichia coli O157:H7 needs improvement, given its current complexity and sensitivity. Herein, we attempt to build a fluorescence sensing method to detect Escherichia coli O157:H7 with easy operation and high efficiency. The target virulence gene sequences are recognized and cleaved by the CRISPR-Cas9 system, and trigger strand displacement amplification and rolling circle amplification. After amplification reactions, massive products can hybridize with the probes, the fluorescence of which are quenched based on a metal–organic framework platform, leading to the fluorescence recovery at typical excitation/emission wavelengths of 480/518 nm. This method exhibits high sensitivity with the detection limit at 4.0 × 10 1 CFU mL –1 and a wide range from 1.3 × 10 2 CFU mL –1 to 6.5 × 10 4 CFU mL –1 . Meanwhile, this assay also shows significant specificity and applies to practical samples with high accuracy. Therefore, our method would have…

Single-cell proteomics can provide unique insights into biological processes by resolving heterogeneity that is obscured by bulk measurements. Gains in the overall sensitivity and proteome coverage through improvements in sample processing and analysis increase the information content obtained from each cell, particularly for less abundant proteins. Here we report on improved single-cell proteome coverage through the combination of the previously developed nanoPOTS platform with further miniaturization of liquid chromatography (LC) separations and implementation of an ultrasensitive latest generation mass spectrometer. Following nanoPOTS sample preparation, protein digests from single cells were separated using a 20 μm i.d. in-house-packed nanoLC column. Separated peptides were ionized using an etched fused-silica emitter capable of stable operation at the ∼20 nL/min flow rate provided by the LC separation. Ultrasensitive LC-MS analysis was achieved using the Orbitrap Eclipse Tribrid mass spectrometer. An average of 362 protein groups were identified by tandem mass spectrometry…

Despite the recent developments on the construction of point-of-care testing (POCT) devices, it is still a big challenge to build portable POCT tools for simple, sensitive, selective, and quantitative determination of disease-related biomarkers. With this in mind, we developed a simple and user-friendly POCT tool for onsite analysis of DNA adenine methyltransferase (Dam) activity by using DNA tetrahedra-based hydrogel to trap glucose-producing enzymes for target recognition and signal transduction. The enzyme-encapsulated DNA hydrogel and the substrate of enzyme were separately modified on papers and then combined onto a commercial glucose test strip for the sensitive evaluation of Dam activity via using a personal glucose meter (PGM) for quantitative signal readout. Taking advantage of the great amount of enzyme entrapped in DNA hydrogel and the high signal amplification ability of enzyme, this POCT tool is capable of highly sensitive and selective determination of Dam activity with a direct detection limit down to 0.001 U/mL, which is superior to that of most previously reported…

The noninvasive continuous analysis of human sweat is of great significance for improved healthcare diagnostics and treatment in the future, for which a wearable potentiometry-based ion-selective electrode (ISE) has attracted increasing attention, particularly involving ion detection. Note that traditional solid-state ISE electrodes are rigid ion-to-electron transducers that are not conformal to soft human skin and cannot function under stretched states. Here, we demonstrated that vertically aligned mushroom-like gold nanowires (v-AuNW) could serve as stretchable and wearable ion-to-electron transducers for multiplexed, in situ potentiometric analysis of pH, Na +, and K + in sweat. By modifying v-AuNW electrodes with polyaniline, Na ionophore X, and a valinomycin-based selective membrane, we could specifically detect pH, Na +, and K +, respectively, with high selectivity, reproducibility, and stability. Importantly, the electrochemical performance could be maintained even under 30% strain and during stretch-release cycles without the need of extrinsic structural design. Furthermore,…

Target-directed aptamer adsorption by gold nanoparticles (AuNPs) has been widely used to develop label-free colorimetric biosensors. However, the potential interactions between target molecules and AuNPs have not been considered, which may lead to misinterpretation of analytical results. In this work, the detection of dopamine, melamine, and K + was studied as model systems to address this problem. First, dopamine and two control molecules all induced the aggregation of citrate-capped AuNPs with apparent K d ’s of 5.8 μM dopamine, 51.6 μM norepinephrine, and 142 μM tyramine. Isothermal titration calorimetry measured the aptamer K d to be 1.9 μM dopamine and 16.8 μM norepinephrine, whereas tyramine cannot bind. Surface enhanced Raman spectroscopy confirmed direct adsorption of dopamine, and the adsorbed dopamine inhibited the adsorption of DNA. Using a typical salt-induced colorimetric detection protocol, a similar color response was observed regardless of the sequence of DNA, indicating the observed color change reflected the adsorption of dopamine by the AuNPs instead of the…

Abstract Point-of-care testing for nucleic acid that combines amplification and readout is in great demand. This report integrates recombinase-aided amplification (RAA) with the clustered regularly interspaced short palindromic repeats (CRISPR)–Cas12a system in a centrifugal microfluidic point-of-care test. We overcome the difficulty in the integration of these two processes, which mainly lies in the fact that Cas12a can digest the template DNA. We further integrate all reagents into the centrifugal microfluidics to automate the entire process. The Cas12a-assisted straightforward microfluidic equipment for analysis of nucleic acid (CASMEAN) enables us to rapidly and conveniently detect nucleic acid within 1.5 h. An application for detecting Pseudomonas aeruginosa confirms the excellent compatibility between RAA and the Cas12a system, which ensures the superior performance of CASMEAN, such as capabilities of point-of-care detection, high sensitivity, and high specificity. CASMEAN is a genetic detection platform with great potential.