Analytical Chemistry最新文献

{"title":"Development of a Novel Hydroxylamine-Based Stable Isotope Labeling Reagent for Profiling Aldehyde Metabolic Biomarkers in Diabetes Using LC-MS/MS and Machine Learning","authors":"Chuanyuan Du, Yuxin Zhang, Wenjie Zhu, Xiang Liu, Nian Liu, Zhenyu He, Junling Liu, Yawei Lin, Xiaosong Hu","doi":"10.1021/acs.analchem.5c04501","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c04501","url":null,"abstract":"Aldehyde compounds are significantly associated with diabetes mellitus. The metabolic profile of aldehydes can enhance understanding of the mechanisms underlying development of diabetes. This study employed a pair of stable isotope labeling (SIL) reagents, <i>N</i>-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)hydroxylamine (PTMH) and <i>N</i>-((1-(phenyl-d5)-1H-1,2,3-triazol-4-yl)methyl)hydroxylamine (PTMH-d5), for aldehyde profiling, address challenges related to selectivity, isomer formation, and transamination that occur with conventional labels, such as hydrazide or amine reagents. The metabolic profiling of 28 aldehydes on the serum samples of patients with type 2 diabetes mellitus (T2DM, <i>n</i> = 39) and gestational diabetes mellitus (GDM, <i>n</i> = 37) was carried out using PTMH/PTMH-d5. Furthermore, comparative metabolomic analyses of T2DM and GDM against healthy controls were performed. Moreover, advanced informatics approaches, including PCA, ROC, and PLS-DA, were employed for statistical evaluation. A machine learning classification model was also developed. The results revealed that 4-hydroxyhexenal, methylglyoxal, and trans-2-pentenal may serve as potential biomarkers for T2DM, whereas 4-hydroxyhexenal, methylglyoxal, heptanal, 5-hydroxymethylfurfural, and trans-2-octenal can be employed as potential biomarkers for GDM. The established model demonstrated significant potential as a prototype for early and accurate diagnosis of T2DM and GDM and may be translated into routine clinical diagnostics.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"26 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxygen Isotope Analyses of Phosphate and Organophosphorus Compounds by Electrospray Ionization Orbitrap Mass Spectrometry","authors":"Nora M. Bernet, Cleo Soldini, Timo M. O. Felder, Kristýna Lapčíková, Cajetan Neubauer, Wendy L. Queen, Ralf Kaegi, Federica Tamburini, Thomas B. Hofstetter","doi":"10.1021/acs.analchem.5c04367","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c04367","url":null,"abstract":"Orbitrap mass spectrometry with electrospray ionization (ESI-Orbitrap MS) enables ¹⁸O/¹⁶O ratio measurements in phosphate and organophosphorus compounds, which offers promising avenues for the study of metabolic, biogeochemical, and environmental processes. While the instrumental feasibility of such ¹⁸O/¹⁶O ratio measurements has been shown, the applicability of such analyses in aqueous matrices on multipurpose mass spectrometers remains unaddressed. Here, we (i) evaluated the interplay between instrument parameters and the long-term accuracy and precision of ESI-Orbitrap MS for the determination of δ¹⁸O(PO₄) from H₂PO₄^– vs PO₃^– fragments of phosphate, (ii) identified properties of methanolic sample solutions that are critical for accurate and precise measurements, and (iii) propose a sample purification procedure for the elimination of matrix-based interferences. In 10 measurement campaigns over two years, we observed a long-term reproducibility of δ¹⁸O(PO₄) within ±2.8‰. Results of in-source fragmentation experiments of H₂PO₄^– to PO₃^– show excellent agreement of δ¹⁸O and offer promising opportunities to probe for ¹⁸O/¹⁶O ratios in organophosphorus compounds. By investigating the effect of the aqueous matrix and interfering anions on ¹⁸O/¹⁶O ratio measurements, we found that a water content exceeding 50 vol % and the presence of oxyanions such as nitrate and sulfate limit measurement accuracy due to interferences of matrix constituents in the ESI source. To overcome these challenges, we evaluated selective phosphate extraction with a zirconium-based metal–organic framework (MOF) as sorbent. The resulting purification procedure allowed for successful extraction and recovery of phosphate from nitrate- and sulfate-containing aqueous solutions, resulting in methanolic phosphate samples that enabled accurate analyses of δ¹⁸O(PO₄) by ESI-Orbitrap MS.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"6 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 19F-Labeled Isothiocyanate Derivatizing Agent for the Chiral Discrimination of Cyclic Secondary Amines","authors":"Xiao-Juan Wang, Shuai-Hua Shi, Jie Zhang, Wei-Kang Zhai, Xing-Hua Wang, Yuan-Yuan Gao, Wen-Jun Han, Lan-Tao Liu, Xinxiang Lei, Gao-Wei Li","doi":"10.1021/acs.analchem.5c04345","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c04345","url":null,"abstract":"Due to the widespread applications of cyclic secondary amines in drug development, rapid methods for detecting and distinguishing chiral cyclic secondary amines have become increasingly important. In this study, we successfully present a derivatizing strategy employing ¹⁹F-labeled isothiocyanate for the enantiomeric analysis of various cyclic secondary amines, including piperidines, pyrrolidines, piperazines, and morpholines (28 examples). The distinguishable chemical shift produced by the novel chiral ¹⁹F-labeled probe permits simultaneous differentiation of three pairs of cyclic secondary amines in a mixture. This approach eliminates the cumbersome purification steps of covalent modification of substrates, enabling rapid analysis of these chiral <i>N</i>-heterocyclic compounds with clear signals and high resolution. Besides, the mechanism of derivatizing interaction between a novel chiral ¹⁹F-labeled probe and the analytes was first verified by single-crystal X-ray analysis and DFT calculations, which generates a pair of diastereomeric thioureas with distinct ¹⁹F NMR signals. This technology provides an efficient, sensitive, and versatile solution for the analysis of chiral cyclic <i>sec</i>-amines, demonstrating significant value, particularly in the development of pharmaceutical synthesis processes.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"27 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Spatial Confinement Effect-Based \"Swing Probe\" In Situ Entropy-Driven Assembly for the Sensitive Ratiometric Electrochemical Detection of Exosomal miRNA.","authors":"Guanyu Chen,Lilan Xu,Ning Yang,Jiayan Wu,Lifang Lin,Mingzhu Chen,Xiaobing Huang,Jinghua Chen,Xu Yao,Fang Wu","doi":"10.1021/acs.analchem.5c03792","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c03792","url":null,"abstract":"Electrochemical biosensors based on DNA assembly signal amplification have emerged as powerful tools for exosomal miRNA detection, demonstrating broad application potential in accurate early cancer diagnosis. However, due to the passivation of the electrode by DNA nanostructures and inherent limitations in assembly reaction efficiency, electrochemical biosensors still face challenges in the sensitive and rapid detection of exosomal miRNA. Herein, we propose a novel spatial confinement effect based \"swing probe\" in situ entropy-driven assembly strategy. By constraining two auxiliary probes in a specific space with a T-type structure, the target miRNA can induce rapid in situ swinging of the probe at the electrode interface, facilitating the assembly of the auxiliary probes and the dissociation of labeled methylene blue (MB) signal probes. Therefore, the rapid and sensitive detection of miRNA can be achieved by analyzing the signal ratio between MB and ferrocene (Fc). The [Fe(CN)6]3--mediated electrocatalytic signal amplification reaction was further employed to realize significant signal response by utilizing the DNA nanostructures' passivation effect on the electrode. The developed biosensor exhibited an ultralow LOD of 4.08 fM and successfully distinguished hepatocellular carcinoma (HCC) patients from healthy donors. Overall, this study provides a novel approach for exosomal miRNA detection and holds promise for advancing miRNA-based liquid biopsy in early cancer diagnosis.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"114 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinspired Nanofluidic Synapse Capable of Dopamine Sensing with an Inverted-U Dose-Response Function.","authors":"Xian Zhang,Jian-Xiang Pang,Yu-Han Kang,Yi-Feng Wang,Wei-Wei Zhao,Jing-Juan Xu","doi":"10.1021/acs.analchem.5c03531","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c03531","url":null,"abstract":"In biology, synaptic sensing of neurotransmitter dopamine (DA) has proven to exhibit a characteristic inverted-U shaped dose-response function on cognitive performance and working memory in the prefrontal cortex. With this inspiration, we present a nanofluidic synapse capable of simulating such an intricate behavior by a rationally designed DNA-based DA-responsive nanosensor with good selectivity, reversibility, and stability. The presence of DA could cause gradual DNA collapse and thus regulation of ion flux passing through the nanofluidic synapse, leading to unique DA-mediated hysteresis and synaptic characteristics of an inverted-U manner, based on which artificial neural network-enabled image recognition is done with an inverted-U shaped efficiency and accuracy.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"17 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visual Whole-Process Monitoring Dynamic Phase Separation of Autophagic Lysosomes in Alzheimer's Disease by a Lysosome-Targeted pH-Activated Fluorescence Probe.","authors":"Fei Gao,Wanquan Lin,Tingting Zhao,Jinlong Zhang,Dong Pei,Duolong Di,Zhongxiong Fan,Lichao Yang,Jun Hai","doi":"10.1021/acs.analchem.5c02994","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c02994","url":null,"abstract":"Although liquid-liquid phase separation (LLPS) of amyloid-β (Aβ) aggregates is a critical driver of Alzheimer's disease (AD) progression, the role of lysosomal acidification defects remains poorly understood during this process. Herein, we successfully develop a synthetic strategy involving the construction of pH-activated probe backbones by the atom transfer radical polymerization technique with methacrylates with different substituents as monomers. Subsequently, a fluorescence probe is prepared by integrating hydrophobic aggregation-induced luminescence (AIE) fluorescence dyes and aggregation-induced bursting (ACQ) dyes into ACQ/AIE ratio imaging nanoparticles through covalent bonding and self-assembly techniques. Such AIE probe can monitor lysosomal acidification defects in AD and elucidate their role in Aβ phase separation. Interestingly, our new findings reveal that Aβ accumulation synergizes with lysosomal dysfunction (the pH value itself has not changed) to induce pathological LLPS, thereby providing a novel approach for phase modulation and attenuating AD progression. Taken together, our design concept provides a novel strategy to regulate phase separation, potentially reducing or delaying Aβ aggregation and AD progression.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"114 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probabilistic-Guided Dynamic Fusion Multitask (PDFM) Framework for Mass Spectrometry Classification.","authors":"Yinchu Wang,Wei Zhang,Zilong Liu,Lin Guo,Xingchuang Xiong","doi":"10.1021/acs.analchem.5c04933","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c04933","url":null,"abstract":"Traditional deep learning models (e.g., convolutional neural networks (CNNs) and transformers) often rely on deterministic feature representations, fixed feature fusion mechanisms, and single-task optimization, which limit their effectiveness in accurately classifying mass spectrometry (MS) data. This study proposes PDFM, a progressive framework for MS data classification, implemented via the VAE-TDW architecture. VAE models latent distributions to guide peak attention, while dynamic weights adaptively fuse global (VAE) and local (Transformer) features. A reconstruction branch and adversarial samples enhance robustness. The multiobjective loss integrates classification, reconstruction, and distribution alignment. Evaluations show a 4.73% accuracy gain on six batch-effect-free data sets; 3.49%-4.66% cross-batch improvement; and up to a 44.07% F1-score boost for rare categories in small samples. PDFM represents a novel approach for the precise analysis of mass spectrometry data, demonstrating substantial potential to advance translational applications in biomedicine and clinical diagnostics.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"125 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical Factors Affecting Digital PCR Quantification Accuracy in HBV DNA Reference Material for In Vitro Diagnostics.","authors":"Ning Ma,Manyu Li,Xiaotian Hao,Alimire Abulikemu,Zeyu Song,Pengfei Wang,Liang Li,Haiwei Zhou","doi":"10.1021/acs.analchem.5c03430","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c03430","url":null,"abstract":"Digital PCR, as an advanced technique for absolute nucleic acid quantification, has been widely used in the value assignment and characterization of reference materials, including in vitro diagnostic reference standards. However, few studies have systematically evaluated the impact of different digital PCR platforms and nucleic acid extraction kits on the quantification of reference materials. In this study, we established a highly specific and reproducible digital PCR assay for the hepatitis B virus and systematically evaluated the influences of commercial digital PCR platforms, primer-probe sets, and nucleic acid extraction kits on reference materials quantification. Results demonstrated good consistency in quantitative measurements across mainstream commercial digital PCR platforms based on different technical principles, with a mean interplatform coefficient of variation (CV) of 9.05%. Notably, nucleic acid extraction efficiency demonstrated the greatest impact on quantification accuracy, with a mean CV across different extraction kits of 76.66%. Primer-probe design also contributed substantially to the measurement uncertainty. These findings provide important insights that support the standardization of digital PCR protocols for reference materials quantification.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"30 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interference Effect of Tubular Colloidal Crystal Films and Their Biosensing Applications.","authors":"Xiaoling Zheng,Bo Zhang,Liming Liu,Yizhen Wan,Tianze Wang,Yu Zhang,Weiping Qian","doi":"10.1021/acs.analchem.5c03478","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c03478","url":null,"abstract":"Accurate in vitro lumen models are critical for simulating physiological microenvironments, as numerous biological processes are intrinsically linked to lumen structure. However, current models are difficult to simulate the curvature-dependent biomechanics and dynamic flow conditions of luminal systems, limiting their utility in complex biological matrices. In this study, tubular colloidal crystal films are prepared by combining biomimetic microstructures with photonic crystal technology and utilized its unique interference effect to achieve dynamic monitoring of biomolecular interactions. The interference effects are observed in highly ordered and structurally uniform tubular films prepared based on solvent evaporation-induced self-assembly. By adjusting the inner diameter of the glass tube and the concentration of the colloidal suspension and simultaneously measuring the optical thickness and refractive index response of the film to ethanol gradients, the curvature tunability, structural stability, and functional feasibility of the tubular films were evaluated. Furthermore, Staphylococcus aureus protein A (SPA)-functionalized tubular films combined with an ordered porous layer interferometry system enable in situ real-time monitoring of human immunoglobulin G binding and release from SPA-modified materials, validating the platform's feasibility. This strategy of integrating curvature bionic design with photonic crystal technology provides a dynamic biomimicry, real-time response, and visualization analysis platform for studying physiological microenvironments.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"24 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Real-Time Monitoring System for the Adherent Human Keratinocyte Metabolism by Live-Cell Metabolic NMR with Illumination.","authors":"Makoto Uyama,Yuki Umino,Fumio Matsuda,Ayako Furukawa,Kenji Sugase,Takahisa Ikegami","doi":"10.1021/acs.analchem.5c03872","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c03872","url":null,"abstract":"Our skin is constantly exposed to the external environment, and the epidermis, in particular, responds to various external stimuli by producing biomolecules, including proteins, lipids, and metabolites. Therefore, a real-time metabolic monitoring system for living keratinocytes is essential. Metabolomics, one of the key fields in omics research, has emerged as a powerful tool for the comprehensive characterization and quantification of biological molecule pools. However, most conventional metabolomics studies rely on cell quenching or lysis methods, which may introduce artifactual stimuli and potentially alter the metabolite profiles of living cells, as fast signaling events such as phosphorylation can occur within milliseconds to seconds. Consequently, conducting omics research on living organisms in real time is of great value, as it can provide unique insights that are not achievable through conventional methods. In this study, we established a novel, noninvasive, real-time metabolic monitoring system termed \"live-cell metabolic NMR with illumination\". This innovative technique enables the evaluation of the metabolic responses of living human keratinocytes to various external stimuli, allowing for the investigation of real-time metabolic dynamics in a physiologically relevant environment.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"90 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}