The 50 most-cited articles in Analytical Chemistry, 2016

Compound identification from accurate mass MS/MS spectra is a bottleneck for untargeted metabolomics. In this study, we propose nine rules of hydrogen rearrangement (HR) during bond cleavages in low-energy collision-induced dissociation (CID). These rules are based on the classic even-electron rule and cover heteroatoms and multistage fragmentation. We evaluated our HR rules by the statistics of MassBank MS/MS spectra in addition to enthalpy calculations, yielding three levels of computational MS/MS annotation: "resolved" (regular HR behavior following HR rules), "semiresolved" (irregular HR behavior), and "formula-assigned" (lacking structure assignment). With this nomenclature, 78.4% of a total of 18506 MS/MS fragment ions in the MassBank database and 84.8% of a total of 36370 MS/MS fragment ions in the GNPS database were (semi-) resolved by predicted bond cleavages. We also introduce the MS-FINDER software for structure elucidation. Molecular formulas of precursor ions are determined from accurate mass, isotope ratio, and product ion information. All isomer structures of the…

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTRecent Advances in Electrochemiluminescence AnalysisLingling Li†, Ying Chen†, and Jun-Jie Zhu*View Author Information State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, P. R. China*E-mail: [email protected]Cite this: Anal. Chem. 2017, 89, 1, 358–371Publication Date (Web):November 30, 2016Publication History Published online13 December 2016Published inissue 3 January 2017https://pubs.acs.org/doi/10.1021/acs.analchem.6b04675https://doi.org/10.1021/acs.analchem.6b04675review-articleACS PublicationsCopyright © 2016 American Chemical SocietyRequest reuse permissionsArticle Views13579Altmetric-Citations468LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref…

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTPaper-Based Microfluidic Devices: Emerging Themes and ApplicationsYuanyuan Yang†, Eka Noviana†, Michael P. Nguyen†, Brian J. Geiss‡, David S. Dandy§, and Charles S. Henry*†§View Author Information† Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States‡ Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado 80523, United States§ Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, Colorado 80523, United States*E-mail: [email protected]. Phone: +1-970-491-2852.Cite this: Anal. Chem. 2017, 89, 1, 71–91Publication Date (Web):December 7, 2016Publication History Published online12 December 2016Published inissue 3 January 2017https://pubs.acs.org/doi/10.1021/acs.analchem.6b04581https://doi.org/10.1021/acs.analchem.6b04581review-articleACS PublicationsCopyright © 2016 American Chemical SocietyRequest reuse permissionsArticle Views12459Altmetric-Citations418LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant…

The efficient extraction of targets from complex surfaces is vital for technological applications ranging from environmental pollutant monitoring to analysis of explosive traces and pesticide residues. In our present study, we proposed a proof-of-concept surface enhance Raman scattering (SERS) active substrate serving directly to the rapid extraction and detection of target molecules. The novel substrate was constructed by decorating the commercial tape with colloidal gold nanoparticles (Au NPs), which simultaneously provides SERS activity and "sticky" of adhesive. The utility of SERS tape was demonstrated by directly extracting pesticide residues in fruits and vegetables via a simple and viable "paste and peel off" approach. The obtained strong and easily distinguishable SERS signals allow us to detect various pesticide residues such as parathion-methyl, thiram, and chlorpyrifos in the real samples with complex surfaces including green vegetable, cucumber, orange, and apple.

Dereplication represents a key step for rapidly identifying known secondary metabolites in complex biological matrices. In this context, liquid-chromatography coupled to high resolution mass spectrometry (LC-HRMS) is increasingly used and, via untargeted data-dependent MS/MS experiments, massive amounts of detailed information on the chemical composition of crude extracts can be generated. An efficient exploitation of such data sets requires automated data treatment and access to dedicated fragmentation databases. Various novel bioinformatics approaches such as molecular networking (MN) and in-silico fragmentation tools have emerged recently and provide new perspective for early metabolite identification in natural products (NPs) research. Here we propose an innovative dereplication strategy based on the combination of MN with an extensive in-silico MS/MS fragmentation database of NPs. Using two case studies, we demonstrate that this combined approach offers a powerful tool to navigate through the chemistry of complex NPs extracts, dereplicate metabolites, and annotate analogues of…

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTNanopore SensingWenqing Shi, Alicia K. Friedman, and Lane A. Baker*View Author Information Department of Chemistry, Indiana University, 800 E. Kirkwood Avenue, Bloomington, Indiana 47405, United States*E-mail: [email protected]. Phone: (812) 856-1873. Fax: (812) 856-8300.Cite this: Anal. Chem. 2017, 89, 1, 157–188Publication Date (Web):November 6, 2016Publication History Published online18 November 2016Published inissue 3 January 2017https://pubs.acs.org/doi/10.1021/acs.analchem.6b04260https://doi.org/10.1021/acs.analchem.6b04260review-articleACS PublicationsCopyright © 2016 American Chemical SocietyRequest reuse permissionsArticle Views12503Altmetric-Citations337LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more…

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTNucleic Acid Biosensors: Recent Advances and PerspectivesYan Du and Shaojun Dong*View Author Information State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, Jilin China*E-mail: [email protected]Cite this: Anal. Chem. 2017, 89, 1, 189–215Publication Date (Web):November 14, 2016Publication History Published online22 November 2016Published inissue 3 January 2017https://pubs.acs.org/doi/10.1021/acs.analchem.6b04190https://doi.org/10.1021/acs.analchem.6b04190review-articleACS PublicationsCopyright © 2016 American Chemical SocietyRequest reuse permissionsArticle Views11927Altmetric-Citations331LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily.…

Circulating antibodies (Ab) that specifically bind polyethylene glycol (PEG), a biocompatible polymer routinely used in protein and nanoparticle therapeutics, have been associated with reduced efficacy of and/or adverse reactions to therapeutics modified with or containing PEG. Unlike most antidrug antibodies that are induced following initial drug dosing, anti-PEG Ab can be found in treatment-naïve individuals (i.e., individuals who have never undergone treatment with PEGylated drugs but most likely have been exposed to PEG through other means). Unfortunately, the true prevalence, quantitative levels, and Ab isotype of pre-existing anti-PEG Ab remain poorly understood. Here, using rigorously validated competitive ELISAs with engineered chimeric anti-PEG monoclonal Ab standards, we quantified the levels of anti-PEG IgM and different subclasses of anti-PEG IgG (IgG1-4) in both contemporary and historical human samples. We unexpectedly found, with 90% confidence, detectable levels of anti-PEG Ab in ∼72% of the contemporary specimens (18% IgG, 25% IgM, 30% both IgG and IgM). The vast…

A simple and sensitive fluorescent assay for detecting alkaline phosphatase (ALP) based on the inner filter effect (IFE) has been proven, which is conceptually different from the previously reported ALP fluorescent assays. In this sensing platform, N-doped carbon dots (CDs) with a high quantum yield of 49% were prepared by one-pot synthesis and were directly used as a fluorophore in IFE. p-Nitrophenylphosphate (PNPP) was employed to act as an ALP substrate, and its enzyme catalytic product (p-nitrophenol (PNP)) was capable of functioning as a powerful absorber in IFE to influence the excitation of fluorophore (CDs). When in the presence of ALP, PNPP was transformed into PNP and induced the absorption band transition from 310 to 405 nm, which resulted in the complementary overlap between the absorption of PNP and the excitation of CDs. Because of the competitive absorption, the excitation of CDs was significantly weakened, resulting in the quenching of CDs. The present IFE-based sensing strategy showed a good linear relationship from 0.01 to 25 U/L (R(2) = 0.996) and provided an…

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTRecent Advances in Analytical Chemistry by 3D PrintingBethany Gross, Sarah Y. Lockwood, and Dana M. Spence*View Author Information Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States*E-mail: [email protected]. Phone: 517-355-9715 ext. 174.Cite this: Anal. Chem. 2017, 89, 1, 57–70Publication Date (Web):November 14, 2016Publication History Published online30 November 2016Published inissue 3 January 2017https://pubs.acs.org/doi/10.1021/acs.analchem.6b04344https://doi.org/10.1021/acs.analchem.6b04344review-articleACS PublicationsCopyright © 2016 American Chemical SocietyRequest reuse permissionsArticle Views9169Altmetric-Citations264LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily.…

In this tutorial, we discuss the motivations for doing two-dimensional liquid chromatography (2D-LC) and describe the commonly used implementations of the method. We review important guiding principles for method development, discuss the state of the art in 2D-LC performance as measured by peak capacity, and describe example applications from different fields that we hope will inspire new users to adopt 2D-LC for their analytical problems.

Nanozymes, the nanostructures with enzymatic activities, have attracted considerable attention because, in comparison with natural enzymes, they offer the possibility of lowered cost, improved stability, and excellent recyclability. However, the specificity and catalytic activity of current nanozymes are still far lower than that of their natural counterparts, which in turn has limited their use such as in bioanalysis. To address these challenges, herein we report the design and development of integrated nanozymes (INAzymes) by simultaneously embedding two cascade catalysts (i.e., a molecular catalyst hemin and a natural enzyme glucose oxidase, GOx) inside zeolitic imidazolate framework (ZIF-8) nanostructures. Such integrated design endowed the INAzymes with major advantage in improved catalytic efficiency as the first enzymatic reaction occurred in close (nanoscale) proximity to the second enzyme, so products of the first reaction can be used immediately as substrates for the second reaction, thus overcoming the problems of diffusion-limited kinetics and product instability. The…

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTRecent Advances in Electrochemical ImmunosensorsWei Wen†§, Xu Yan†§, Chengzhou Zhu†, Dan Du*†‡, and Yuehe Lin*†View Author Information† School of Mechanical and Material Engineering, Washington State University, Pullman, Washington 99164, United States‡ Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, Hubei 430079, P.R. China*E-mail: [email protected]*E-mail: [email protected]Cite this: Anal. Chem. 2017, 89, 1, 138–156Publication Date (Web):November 9, 2016Publication History Published online5 December 2016Published inissue 3 January 2017https://pubs.acs.org/doi/10.1021/acs.analchem.6b04281https://doi.org/10.1021/acs.analchem.6b04281review-articleACS PublicationsCopyright © 2016 American Chemical SocietyRequest reuse permissionsArticle Views7941Altmetric-Citations256LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These…

The recent outbreak of Zika virus (ZIKV) infection in the Americas and its devastating impact on fetal development have prompted the World Health Organization (WHO) to declare the ZIKV pandemic as a Public Health Emergency of International Concern. Rapid and reliable diagnostics for ZIKV are vital because ZIKV-infected individuals display no symptoms or nonspecific symptoms similar to other viral infections. Because immunoassays lack adequate sensitivity and selectivity and are unable to identify active state of infection, molecular diagnostics are an effective means to detect ZIKV soon after infection and throughout pregnancy. We report on a highly sensitive reverse-transcription loop-mediated, isothermal amplification (RT-LAMP) assay for rapid detection of ZIKV and its implementation in a simple, easy-to-use, inexpensive, point-of-care (POC) disposable cassette that carries out all the unit operations from sample introduction to detection. For thermal control of the cassette, we use a chemically heated cup without a need for electrical power. Amplification products are detected…

Here, we report that boric acid is used to tune the optical properties of lanthanide metal–organic frameworks (LMOFs) for dual-fluorescence emission and improves the selectivity of LMOFs for the determination of F – ions. The LMOFs are prepared with 5-boronoisophthalic acid (5-bop) and Eu 3+ ions as the precursors. Emission mechanism study indicates that 5-bop is excited with UV photons to produce its triplet state, which then excites Eu 3+ ions for their red emission. This is the general story of the antenna effect, but electron-deficient boric acid decreases the energy transfer efficiency from the triplet state of 5-bop to Eu 3+ ions, so dual emission from both 5-bop and Eu 3+ ions is efficiently excited at the single excitation of 275 nm. Moreover, boric acid is used to identify fluoride specifically as a free accessible site. The ratiometric fluorescent detection of F – ions is validated with the dual emission at single excitation. The LMOFs are very monodisperse, so the determination of aqueous F – ions is easily achieved with high selectivity and a low detection limit (2 μM).…

Improved analytical technologies and data extraction algorithms enable detection of >10 000 reproducible signals by liquid chromatography-high-resolution mass spectrometry, creating a bottleneck in chemical identification. In principle, measurement of more than one million chemicals would be possible if algorithms were available to facilitate utilization of the raw mass spectrometry data, especially low-abundance metabolites. Here we describe an automated computational framework to annotate ions for possible chemical identity using a multistage clustering algorithm in which metabolic pathway associations are used along with intensity profiles, retention time characteristics, mass defect, and isotope/adduct patterns. The algorithm uses high-resolution mass spectrometry data for a series of samples with common properties and publicly available chemical, metabolic, and environmental databases to assign confidence levels to annotation results. Evaluation results show that the algorithm achieves an F1-measure of 0.8 for a data set with known targets and is more robust than previously…

Measuring pH in living cells is of great importance for better understanding cellular functions as well as providing pivotal assistance for early diagnosis of diseases. In this work, we report the first use of a novel kind of label-free carbon dots for intracellular ratiometric fluorescence pH sensing. By simple one-pot hydrothermal treatment of citric acid and basic fuchsin, the carbon dots showing dual emission bands at 475 and 545 nm under single-wavelength excitation were synthesized. It is demonstrated that the fluorescence intensities of the as-synthesized carbon dots at the two emissions are pH-sensitive simultaneously. The intensity ratio (I475 nm/I545 nm) is linear against pH values from 5.2 to 8.8 in buffer solution, affording the capability as ratiometric probes for intracellular pH sensing. It also displays that the carbon dots show excellent reversibility and photostability in pH measurements. With this nanoprobe, quantitative fluorescence imaging using the ratio of two emissions (I475 nm/I545 nm) for the detection of intracellular pH were successfully applied in HeLa…

As diabetes is considered one of the biggest health care challenges of the coming decades substantial effort is being made to develop novel glucose monitoring systems, this includes thousands of articles which are being published every year. To the question in the title, we answer an unequivocal "yes" but maybe not necessarily in the areas where most of the published research is focused.

Nitrogen and sulfur codoped carbon-based dots (N,S-CDs) with strong blue light emission are encapsulated into red light-emitting europium metal-organic frameworks (Eu-MOFs) to form two color light-emitting nanohybrids (Eu-MOFs/N,S-CDs). In organic solvents, the encapsulated N,S-CDs are aggregated and confined in the cavities of the Eu-MOFs, exhibiting only a very weak photoluminescence (PL) signal. Therefore, the nanohybrids show red light emission of the Eu-MOFs. Contrarily, when the Eu-MOFs/N,S-CDs are dispersed in water, the encapsulated N,S-CDs are released into solution while the red light emission of the Eu-MOFs is quenched due to the effect of O-H oscillators. The nanohybrids are used as the probe for the water content in organic solvents. Take ethanol as an example; as the water content is increased from 0.2 to 30%, the nanoprobe provides distinguishable PL color change. The ratio of light intensity at 420 nm to that at 623 nm (I420/I623) increases linearly with increasing water content in the range from 0.05 to 4% with a low detection limit of 0.03%.

A critical question facing the field of metabolomics is whether data obtained from different centers can be effectively compared and combined. An important aspect of this is the interlaboratory precision (reproducibility) of the analytical protocols used. We analyzed human samples in six laboratories using different instrumentation but a common protocol (the AbsoluteIDQ p180 kit) for the measurement of 189 metabolites via liquid chromatography (LC) or flow injection analysis (FIA) coupled to tandem mass spectrometry (MS/MS). In spiked quality control (QC) samples 82% of metabolite measurements had an interlaboratory precision of <20%, while 83% of averaged individual laboratory measurements were accurate to within 20%. For 20 typical biological samples (serum and plasma from healthy individuals) the median interlaboratory coefficient of variation (CV) was 7.6%, with 85% of metabolites exhibiting a median interlaboratory CV of <20%. Precision was largely independent of the type of sample (serum or plasma) or the anticoagulant used but was reduced in a sample from a patient with…

A new class of surface-enhanced Raman scattering (SERS)-based lateral flow assay (LFA) biosensor has been developed for the simultaneous detection of dual DNA markers. The LFA strip in this sensor was composed of two test lines and one control line. SERS nano tags labeled with detection DNA probes were used for quantitative evaluation of dual DNA markers with high sensitivity. Target DNA, associated with Kaposi's sarcoma-associated herpesvirus (KSHV) and bacillary angiomatosis (BA), were tested to validate the detection capability of this SERS-based LFA strip. Characteristic peak intensities of SERS nano tags on two test lines were used for quantitative evaluations of KSHV and BA. The limits of detection for KSHV and BA, determined from our SERS-based LFA sensing platform, were estimated to be 0.043 and 0.074 pM, respectively. These values indicate approximately 10 000 times higher sensitivity than previously reported values using the aggregation-based colorimetric method. We believe that this is the first report of simultaneous detection of two different DNA mixtures using a…

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTRecent Advances in the Development of Highly Luminescent Semiconducting Polymer Dots and Nanoparticles for Biological Imaging and MedicineJiangbo Yu, Yu Rong, Chun-Ting Kuo, Xing-Hua Zhou, and Daniel T. Chiu*View Author Information Department of Chemistry, University of Washington, Seattle, Washington 98195, United States*E-mail: [email protected]Cite this: Anal. Chem. 2017, 89, 1, 42–56Publication Date (Web):November 28, 2016Publication History Published online8 December 2016Published inissue 3 January 2017https://pubs.acs.org/doi/10.1021/acs.analchem.6b04672https://doi.org/10.1021/acs.analchem.6b04672review-articleACS PublicationsCopyright © 2016 American Chemical SocietyRequest reuse permissionsArticle Views6146Altmetric-Citations220LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles…

There is a growing interest in developing high-performance sensors monitoring organophosphate pesticides, primarily due to their broad usage and harmful effects on mammals. In the present study, a colorimetric sensor array consisting of citrate-capped 13 nm gold nanoparticles (AuNPs) has been proposed for the detection and discrimination of several organophosphate pesticides (OPs). The aggregation-induced spectral changes of AuNPs upon OP addition has been analyzed with pattern recognition techniques, including hierarchical cluster analysis (HCA) and linear discriminant analysis (LDA). In addition, the proposed sensor array has the capability to identify individual OPs or mixtures of them in real samples.

A dual mode fluorescent probe, which is based on an integration of fluorescein and coumarin fluorophores, was developed for the discrimination of Cys from Hcy and GSH. This probe ( 2 ) shows the advantage of quick reaction (5 min) with Cys, resulting in a strong fluorescence turn-on response when excited at 450 nm. Notably, it also demonstrates the ratiometric fluorescence property while excited by a shorter wavelength (332 nm). All of results suggest probe 2 has a high selectivity toward Cys even in the presence of other amino acids, cations and anions. The detection limit of Cys was calculated as 0.084 μM, which was much lower than the intracellular concentration. 1 H NMR, MS and DFT calculation were used to reveal the detection mechanism further. Finally, this low cytotoxic probe was successfully applied in bioimaging within HepG2 cells.

In this study, we developed a turn-on mitochondria-targeting hydrogen sulfide, "probe 1", based on the selective thiolysis of 7-nitro-1,2,3-benzoxadiazole amine moiety attached to the piperazine-based naphthalimide scaffold. Probe 1 exhibited excellent properties with 68-fold fluorescence enhancement, a low detection limit (2.46 μM), a low cytotoxicity, and a good selectivity toward hydrogen sulfide. The success of intracellular imaging indicated that probe 1 could be used in further applications for the investigation of biological functions and pathological roles of H2S in living systems.

Filter aided sample preparation (FASP) and related methods gain increasing popularity for proteomic sample preparation. Nevertheless, the originally published FASP method has been criticized by several authors, who reported low digestion performance. In this work, we re-evaluate FASP and the related multienzyme digestion (MED) FASP method. We use different types of animal tissues and cultured cells and test the performance of the method under various conditions. We analyze the protein to peptide conversion by assessing the yield of peptides, frequency of peptides with missed cleavage sites, and the reproducibility of FASP. We identify conditions allowing efficient protein processing with high peptide yields and demonstrate advantages of the two step digestion strategy over single step digestion with trypsin. In addition, we show that FASP outperforms in-solution cleavage strategies. Our results clearly demonstrate that the performance of digestion varies between different types of samples. We show that MED FASP in combination with the total protein approach provides highly…

Acidic pH is a critical physiological factor for controlling the activities and functions of lysosome. Herein, we report a novel dual site-controlled and lysosome-targeted intramolecular charge transfer-photoinduced electron transfer-Fluorescence resonance energy transfer (ICT-PET-FRET) fluorescent probe (CN-pH), which was essentially the combination of a turn-on pH probe (CN-1) and a turn-off pH probe (CN-2) by a nonconjugated linker. Coumarin and naphthalimide fluorophores were selected as donor and acceptor to construct the FRET platform. Hydroxyl group and morpholine were simultaneously employed as the two pH sensing sites and controlled the fluorescence of coumarin and naphthalimide units by ICT and PET, respectively. The sensing mechanism of CN-pH to pH was essentially an integration of ICT, PET, and FRET processes. Meanwhile, the morpholine also can serve as a lysosome-targeted group. By combining the two data analysis approaches of the ratios of the two emission intensities (R) and the reverse ratio R' (R' = 1/R), the fluorescent ratio of CN-pH can show proportional…

Tip-enhanced Raman spectroscopy (TERS), a combination of Raman spectroscopy and apertureless near-field scanning optical microscopy using a metallic tip which resonates with the local mode of the surface plasmon, can provide a high-sensitive and high-spatial-resolution optical analytical approach. The basic principle of TERS, common experimental setups, various SPM technologies, and excitation/collection configurations are introduced as well as recent research progress with respect to TERS.

Polyethylene glycol (PEG) is a biocompatible polymer that is often attached to therapeutic molecules to improve bioavailability and therapeutic efficacy. Although antibodies with specificity for PEG may compromise the safety and effectiveness of PEGylated medicines, the prevalence of pre-existing anti-PEG antibodies in healthy individuals is unclear. Chimeric human anti-PEG antibody standards were created to accurately measure anti-PEG IgM and IgG antibodies by direct ELISA with confirmation by a competition assay in the plasma of 1504 healthy Han Chinese donors residing in Taiwan. Anti-PEG antibodies were detected in 44.3% of healthy donors with a high prevalence of both anti-PEG IgM (27.1%) and anti-PEG IgG (25.7%). Anti-PEG IgM and IgG antibodies were significantly more common in females as compared to males (32.0% vs 22.2% for IgM, p < 0.0001 and 28.3% vs 23.0% for IgG, p = 0.018). The prevalence of anti-PEG IgG antibodies was higher in younger (up to 60% for 20 year olds) as opposed to older (20% for >50 years) male and female donors. Anti-PEG IgG concentrations were negatively…

Continual monitoring of secreted biomarkers from organ-on-a-chip models is desired to understand their responses to drug exposure in a noninvasive manner. To achieve this goal, analytical methods capable of monitoring trace amounts of secreted biomarkers are of particular interest. However, a majority of existing biosensing techniques suffer from limited sensitivity, selectivity, stability, and require large working volumes, especially when cell culture medium is involved, which usually contains a plethora of nonspecific binding proteins and interfering compounds. Hence, novel analytical platforms are needed to provide noninvasive, accurate information on the status of organoids at low working volumes. Here, we report a novel microfluidic aptamer-based electrochemical biosensing platform for monitoring damage to cardiac organoids. The system is scalable, low-cost, and compatible with microfluidic platforms easing its integration with microfluidic bioreactors. To create the creatine kinase (CK)-MB biosensor, the microelectrode was functionalized with aptamers that are specific to…

Herein, gold-silver bimetallic nanoclusters (Au-Ag NCs) with the high fluorescent intensity were first synthesized successfully and utilized for the fabrication of sensitive and specific sensing probes toward inorganic pyrophosphatase (PPase) activity with the help of copper ion (Cu(2+)) and inorganic pyrophosphate ion (PPi). Cu(2+) was used as the quencher of fluorescent Au-Ag NC, while PPi was employed as the hydrolytic substrate of PPase. The system consisted of PPi, Cu(2+) ion, and bovine serum albumin (BSA)-stabilized Au-Ag NC. The detection was carried out by enzyme-induced hydrolysis of PPi to liberate copper ion from the Cu(2+)-PPi complex. In the absence of target PPase, free copper ions were initially chelated with inorganic pyrophosphate ions to form the Cu(2+)-PPi complexes via the coordination chemistry, thus preserving the natural fluorescent intensity of the Au-Ag NCs. Upon addition of target PPase into the detection system, the analyte hydrolyzed PPi into phosphate ions and released Cu(2+) ion from the Cu(2+)-PPi complex. The dissociated copper ions readily quenched…

It is highly attractive to construct a natural enzyme-free electrode for sensitive and selective detection of glucose. In this Letter, we report that a Ni2P nanoarray on conductive carbon cloth (Ni2P NA/CC) behaves as an efficient three-dimensional catalyst electrode for glucose electrooxidation under alkaline conditions. Electrochemical measurements demonstrate that the Ni2P NA/CC, when used as a nonenzymatic glucose sensor, offers superior analytical performances with a short response time of 5 s, a wide detection range of 1 μM to 3 mM, a low detection limit of 0.18 μM (S/N = 3), a response sensitivity of 7792 μA mM(-1) cm(-2), and satisfactory selectivity, specificity, and reproducibility. Moreover, it can also be used for glucose detection in human blood serum, promising its application toward determination of glucose in real samples.

Abstract Synthetic cannabinoids (SCs) are the largest group of compounds currently monitored in Europe by the EU Early Warning System on new psychoactive substances. Emerging recreational use of these products has led to multiple cases of adverse health effects and even death. In contrast to marijuana, where Δ9-tetrahydrocannabinol (Δ9THC) is metabolized to only one major active metabolite, it has been reported that several major phase I metabolites of SCs remain biologically active, exerting cannabinoid (CB) receptor affinity, potency, and efficacy greater than those of Δ9THC. It is therefore reasonable that more SCs can also be biotransformed into molecules with various levels of CB activity. Here, we developed and applied a new G-protein coupled receptor (GPCR) activation assay based on NanoLuc binary technology (Promega). More specifically, by demonstrating CB1 and CB2 receptor activation by JWH-018 and a selection of its metabolites, we are the first to show the suitability of the newly developed bioassay for monitoring GPCR-mediated activity. We also successfully applied this…

Hypochlorous acid (HOCl) acts as a weak acid distributed mainly in acidic organelle lysosomes of phagocytes and plays a crucial role in the immune defense. The elaborate interrelation between the variations of HOCl levels in lysosomes and different physiological and pathological processes remains unclear. Thus, the accurate determination of lysosomal HOCl in living cells and in vivo is very important. Because of extremely low concentration and difficulty in distinguishing HOCl from OCl – under the physiological environment, it is still a great challenge to specifically monitor the intracellular intrinsic HOCl levels without exogenous stimulation, which impedes an exact understanding of its biological roles. In this paper, based on the electrophilic addition of Cl + to sulfide moiety, we have developed a two-photon fluorescent probe O -( N -butyl-1,8-naphthalimide)-4-yl- N, N -dimethylthiocarbamate ( NDMTC ) for the specific determination of HOCl over OCl – and other bioactive molecules. Our results show that NDMTC possesses a detection limit of 7.6 pM, and it is the first…

This perspective presents recent developments in the application of surface-enhanced Raman spectroscopy (SERS) to biosensing, with a focus on in vivo diagnostics. We describe the concepts and methodologies developed to date and the target analytes that can be detected. We also discuss how SERS has evolved from a "point-and-shoot" stand-alone technique in an analytical chemistry laboratory to an integrated quantitative analytical tool for multimodal imaging diagnostics. Finally, we offer a guide to the future of SERS in the context of clinical diagnostics.

Mycotoxins, highly toxic secondary metabolites produced by many invading species of filamentous fungi, contaminate different agricultural commodities under favorable temperature and humidity conditions. Herein, we successfully devised a novel signal-on photoelectrochemical immunosensing platform for the quantitative monitoring of mycotoxins (aflatoxin B1, AFB1, used as a model) in foodstuffs on the basis of silver nanolabels-assisted ion-exchange reaction with CdTe quantum dots (QDs) mediated hole-trapping. Initially, a competitive-type immunoreaction was carried out on a high-binding microplate by using silver nanoparticle (AgNP)-labeled AFB1-bovine serum albumin (AFB1-BSA) conjugates as the tags. Then, the carried AgNPs with AFB1-BSA were dissolved by acid to release numerous silver ions, which could induce ion-exchange reaction with the CdTe QDs immobilized on the electrode, thus resulting in formation of surface exciton trapping. Relative to pure CdTe QDs, the formed exciton trapping decreased the photocurrent of the modified electrode. In contrast, the detectable photocurrent…

Gold nanoparticles (AuNPs) have been frequently utilized for the construction of diverse colorimetric biosensors. Normally, AuNPs with sharp edges could have better sensitivity. However, the poor monodipersity of AuNPs with sharp edges seriously confines their utility for colorimetric biosensing. Herein, we demonstrate the utility of highly uniform gold nanobipyramids (Au NBPs) for ultrasensitive colorimetric detection of H 5 N 1 virus. The proposed method is based on the fact that alkaline phosphatase (ALP) could catalyze the decomposition of 4-aminophenyl phosphate (4-APP) to generate 4-aminophenol (4-AP), which would then reduce silver nitrate to metal silver and then deposited on Au NBPs. The metal silver shell coated on the Au NBPs changed the refractive index of gold and thus resulted in a blue shift of longitudinal localized surface plasmon resonance (LSPR) and accompanied a vivid color change. This method exhibited a higher sensitivity than that of other Au NPs such as gold nanorods due to the high-index-faceted on the tips of the Au NBPs. This method was used to detect the…

The rapid development of metabolomics has significantly advanced health and disease related research. However, metabolite identification remains a major analytical challenge for untargeted metabolomics. While the use of collision cross-section (CCS) values obtained in ion mobility-mass spectrometry (IM-MS) effectively increases identification confidence of metabolites, it is restricted by the limited number of available CCS values for metabolites. Here, we demonstrated the use of a machine-learning algorithm called support vector regression (SVR) to develop a prediction method that utilized 14 common molecular descriptors to predict CCS values for metabolites. In this work, we first experimentally measured CCS values (Ω N2 ) of ∼400 metabolites in nitrogen buffer gas and used these values as training data to optimize the prediction method. The high prediction precision of this method was externally validated using an independent set of metabolites with a median relative error (MRE) of ∼3%, better than conventional theoretical calculation. Using the SVR based prediction method, a…

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTAtmospheric Aerosol Chemistry: Spectroscopic and Microscopic AdvancesAndrew P. Ault*†‡ and Jessica L. Axson‡View Author Information† Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States‡ Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan 48109, United States*E-mail: [email protected]. Phone: 734-763-4212.Cite this: Anal. Chem. 2017, 89, 1, 430–452Publication Date (Web):November 28, 2016Publication History Published online28 November 2016Published inissue 3 January 2017https://pubs.acs.org/doi/10.1021/acs.analchem.6b04670https://doi.org/10.1021/acs.analchem.6b04670review-articleACS PublicationsCopyright © 2016 American Chemical SocietyRequest reuse permissionsArticle Views5290Altmetric-Citations135LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations…

A disposable, equipment-free, versatile point-of-care testing platform, microfluidic distance readout sweet hydrogel integrated paper-based analytical device (μDiSH-PAD), was developed for portable quantitative detection of different types of targets. The platform relies on a target-responsive aptamer cross-linked hydrogel for target recognition, cascade enzymatic reactions for signal amplification, and microfluidic paper-based analytic devices (μPADs) for visual distance-based quantitative readout. A "sweet" hydrogel with trapped glucoamylase (GA) was synthesized using an aptamer as a cross-linker. When target is present in the sample, the "sweet" hydrogel collapses and releases enzyme GA into the sample, generating glucose by amylolysis. A hydrophilic channel on the μPADs is modified with glucose oxidase (GOx) and colorless 3,3'-diaminobenzidine (DAB) as the substrate. When glucose travels along the channel by capillary action, it is converted to H2O2 by GOx. In addition, DAB is converted into brown insoluble poly-3,3'-diaminobenzidine [poly(DAB)] by horseradish peroxidase,…

Crystalline 2D hexagonal boron nitride (2D-hBN) nanosheets are explored as a potential electrocatalyst toward the electroanalytical sensing of dopamine (DA). The 2D-hBN nanosheets are electrically wired via a drop-casting modification process onto a range of commercially available carbon supporting electrodes, including glassy carbon (GC), boron-doped diamond (BDD), and screen-printed graphitic electrodes (SPEs). 2D-hBN has not previously been explored toward the electrochemical detection/electrochemical sensing of DA. We critically evaluate the potential electrocatalytic performance of 2D-hBN modified electrodes, the effect of supporting carbon electrode platforms, and the effect of "mass coverage" (which is commonly neglected in the 2D material literature) toward the detection of DA. The response of 2D-hBN modified electrodes is found to be largely dependent upon the interaction between 2D-hBN and the underlying supporting electrode material. For example, in the case of SPEs, modification with 2D-hBN (324 ng) improves the electrochemical response, decreasing the electrochemical…

Sensitive and quantitative detection of protein biomarkers with a point-of-care (POC) assay is significant for early diagnosis, treatment, and prognosis of diseases. In this paper, a quantitative lateral flow assay with high sensitivity for protein biomarkers was established by utilizing fluorescent nanospheres (FNs) as reporters. Each fluorescent nanosphere (FN) contains 332 ± 8 CdSe/ZnS quantum dots (QDs), leading to its superstrong luminescence, 380-fold higher than that of one QD. Then a detection limit of 27.8 pM C-reaction protein (CRP) could be achieved with an immunofluorescent nanosphere (IFN)-based lateral flow test strip. The assay was 257-fold more sensitive than that with a conventional Au-based lateral flow test strip for CRP detection. Besides, the fluorescence intensity of FNs and bioactivity of IFNs were stable during 6 months of storage. Hence, the assay owns good reproducibility (intra-assay variability of 5.3% and interassay variability of 6.6%). Furthermore, other cancer biomarkers (PSA, CEA, AFP) showed negative results by this method, validating the excellent…

Extracellular vesicles (EVs), namely, exosomes and microvesicles, are important mediators of intercellular communication pathways. Since EVs can be detected in a variety of biofluids and contain a specific set of biomarkers which are reminiscent of their parental cells, they show great promise in clinical diagnostics as EV analysis can be performed in minimally invasive liquid biopsies. However, reliable, fast and cost-effective methods for their determination are still needed, especially if decentralized analysis is intended. In this study, we developed an electrochemical biosensor which works with 1.5 μL sample volume and can detect as low as 200 exosomes per microliter, with a linear range spanning almost 4 orders of magnitude. The sensor is specific and readily differentiates exosomes from microvesicles in samples containing 1000-fold excess of the latter. Capability of detecting exosomes in real samples (diluted serum) was shown. This was achieved by immobilizing rabbit antihuman CD9 antibodies on gold substrates and using monoclonal antibodies against CD9 for detection of…

A sensitive and selective fluorescence "turn-off" sensor to detect heparin using water-soluble silicon nanoparticles (Si NPs) was developed for the first time. The Si NPs were synthesized by a simple one-step procedure, which did not need high-temperature and complex modification. The as-prepared Si NPs featured strong fluorescence, favorable biocompatibility, and robust photo- and pH stability. Significantly, the Si NPs were induced to assemble or aggregate via hydrogen bonding, which resulted in the fluorescence of Si NPs quenched. Under the optimized conditions, the linear range was obtained from 0.02 to 2.0 μg/mL, with a limit of detection of 18 ng/mL (equal to 0.004 U/mL). It was lower than the proper therapeutic level of heparin during cardiovascular surgery and long-term therapy. This proposed method was relatively free of interference from heparin analogues, which commonly existed in heparin samples and could possibly affect heparin detection. Moreover, it did not need to introduce any control medium. As expected, the method was successfully applied to detect heparin in…

In this paper, we report a benzothiazole-functionalized cyanine fluorescence probe and demonstrate that it is selectively reactive to bisulfite, an intermediate indicator for oxidative stress. The selective reaction can be monitored by distinct ratiometric fluorescence variation favorable for cell imaging and visualization. The original probe can be regenerated in high yield through the elimination of bisulfite from the product by peroxides such as hydrogen peroxide, accompanied by fluorescence turning on at 590 nm, showing a potential application for the detection of peroxides. We successfully applied this probe for fluorescence imaging of bisulfite in cancer cells (MCF-7) treated with bisulfite and hydrogen peroxide as well as a selective detection limit of 0.34 μM bisulfite in aqueous solution.

An international project developed, quality-tested, and determined isotope-δ values of 19 new organic reference materials (RMs) for hydrogen, carbon, and nitrogen stable isotope-ratio measurements, in addition to analyzing pre-existing RMs NBS 22 (oil), IAEA-CH-7 (polyethylene foil), and IAEA-600 (caffeine). These new RMs enable users to normalize measurements of samples to isotope-δ scales. The RMs span a range of δ(2)H(VSMOW-SLAP) values from -210.8 to +397.0 mUr or ‰, for δ(13)C(VPDB-LSVEC) from -40.81 to +0.49 mUr and for δ(15)N(Air) from -5.21 to +61.53 mUr. Many of the new RMs are amenable to gas and liquid chromatography. The RMs include triads of isotopically contrasting caffeines, C16 n-alkanes, n-C20-fatty acid methyl esters (FAMEs), glycines, and l-valines, together with polyethylene powder and string, one n-C17-FAME, a vacuum oil (NBS 22a) to replace NBS 22 oil, and a (2)H-enriched vacuum oil. A total of 11 laboratories from 7 countries used multiple analytical approaches and instrumentation for 2-point isotopic normalization against international primary measurement…

Concentration and separation of particles and biological specimens are fundamental functions of micro/nanofluidic systems. Acoustic streaming is an effective and biocompatible way to create rapid microscale fluid motion and induce particle capture, though the >100 MHz frequencies required to directly generate acoustic body forces on the microscale have traditionally been difficult to generate and localize in a way that is amenable to efficient generation of streaming. Moreover, acoustic, hydrodynamic, and electrical forces as typically applied have difficulty manipulating specimens in the submicrometer regime. In this work, we introduce highly focused traveling surface acoustic waves (SAW) at high frequencies between 193 and 636 MHz for efficient and highly localized production of acoustic streaming vortices on microfluidic length scales. Concentration occurs via a novel mechanism, whereby the combined acoustic radiation and streaming field results in size-selective aggregation in fluid streamlines in the vicinity of a high-amplitude acoustic beam, as opposed to previous acoustic…

We present a new glucose oxidase (GOx)-mediated strategy for detecting glucose based on carbon nanodots supported on silver nanoparticles (C-dots/AgNPs) as nanocomplexes. The strategy involves three processes: quenching of C-dots’ fluorescence by AgNPs, production of H 2 O 2 from GOx-catalyzed oxidation of glucose, and H 2 O 2 -induced etching of AgNPs. In the C-dots/AgNPs complex, AgNPs act as a “nanoquencher” to decrease C-dots fluorescence by surface plasmon-enhanced energy transfer (SPEET) from C-dots (donor) to AgNPs (acceptor). The H 2 O 2 formed by GOx-catalyzed oxidation of glucose etches the AgNPs to silver ions, thus freeing the C-dots from the AgNPs surfaces and restoring the C-dots’ fluorescence. Therefore, the increase in fluorescence depends directly on the concentration of H 2 O 2, which, in turn, depends on the concentration of glucose. The strategy allows the quantitative analysis of glucose with a detection limit of 1.39 μM. The method based on C-dots/AgNPs offers the following advantages: simplicity of design and facile preparation of nanomaterials, as well as low…

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTIn Vivo Analysis with Electrochemical Sensors and BiosensorsTongfang Xiao†‡, Fei Wu†‡, Jie Hao†‡, Meining Zhang†‡, Ping Yu†‡, and Lanqun Mao*†‡View Author Information† Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems and Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China‡ University of Chinese Academy of Sciences, Beijing 100049, China*E-mail: [email protected]. Fax: (86)-10-62559373.Cite this: Anal. Chem. 2017, 89, 1, 300–313Publication Date (Web):November 7, 2016Publication History Published online17 November 2016Published inissue 3 January 2017https://pubs.acs.org/doi/10.1021/acs.analchem.6b04308https://doi.org/10.1021/acs.analchem.6b04308review-articleACS PublicationsCopyright © 2016 American Chemical SocietyRequest reuse permissionsArticle Views6478Altmetric-Citations168LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all…