Analytical Chemistry最新文献_第8页

Single-Cell 5 μm-Resolution Dual-Polarity MALDI-MS Imaging without Matrix Reapplication. 单细胞5 μm分辨率双极性MALDI-MS成像，无需重新应用矩阵。

IF 7.4 1区化学

Analytical Chemistry Pub Date : 2025-07-29 DOI: 10.1021/acs.analchem.5c03289

Yanyan Chen,Rui Shi,Jianing Wang,Chengyi Xie,Yuanyuan Song,Ruxin Li,Luyao Wen,Thomas Ka-Yam Lam,Zhu Yang,Zongwei Cai

{"title":"Single-Cell 5 μm-Resolution Dual-Polarity MALDI-MS Imaging without Matrix Reapplication.","authors":"Yanyan Chen,Rui Shi,Jianing Wang,Chengyi Xie,Yuanyuan Song,Ruxin Li,Luyao Wen,Thomas Ka-Yam Lam,Zhu Yang,Zongwei Cai","doi":"10.1021/acs.analchem.5c03289","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c03289","url":null,"abstract":"High-resolution mass spectrometry imaging (MSI) plays a vital role in lipidomics, yet challenges persist in analyzing lipids at the single-cell level due to limitations in spatial resolution and lipid coverage. While existing strategies based on a single matrix application step for dual-polarity provide high lipid coverage from the same sample and enable easy sample preparation, matrix depletion limits their spatial resolution to 10 μm, preventing their application to single-cell imaging. Here, we present a single-cell/subcellular resolution strategy for dual-polarity matrix-assisted laser desorption and ionization mass spectrometry imaging (MALDI-MSI) that eliminates the need for matrix reapplication. This approach achieves 5 μm spatial resolution while maintaining lipid coverage comparable to multistep single-cell imaging methods. This is enabled by a fine-tuned matrix deposition technique that fully utilizes the high sensitivity of N-(1-naphthyl)-ethylenediamine dihydrochloride (NEDC) in dual polarities and optimized acquisition conditions, allowing single-deposition workflows without the need for washing, repreparation, or image recalibration. This single-cell resolution MALDI-MSI strategy successfully imaged a broader range of lipid species with distinctive spatial detail in mouse kidney tissue and lung carcinoma cells (A549). Using spatial probabilistic latent semantic analysis (PLSA), we identified three distinct lipid distribution patterns within a single-cell population in both polarities, and histogram analysis revealed substantial cell-to-cell lipidomic heterogeneity. This strategy overcomes limitations of traditional dual-polarity MSI and provides a powerful tool for advancing cellular lipidomics, elucidating disease mechanisms, and investigating environmental toxicology.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"35 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719902","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}

引用次数: 0

Molecular Editing-Biolayer Interferometry Technique for Sensitive, Rapid, and High-Throughput Detection of Multiple Steroid Environmental Estrogens. 灵敏、快速、高通量检测多种甾类环境雌激素的分子编辑-生物层干涉测量技术。

IF 7.4 1区化学

Analytical Chemistry Pub Date : 2025-07-29 DOI: 10.1021/acs.analchem.5c03778

Dilnur Dilxat,Wei Zhang,Jing-Jing Deng,Wei-Kang Wang,Juan Xu

{"title":"Molecular Editing-Biolayer Interferometry Technique for Sensitive, Rapid, and High-Throughput Detection of Multiple Steroid Environmental Estrogens.","authors":"Dilnur Dilxat,Wei Zhang,Jing-Jing Deng,Wei-Kang Wang,Juan Xu","doi":"10.1021/acs.analchem.5c03778","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c03778","url":null,"abstract":"The simultaneous detection of multiple steroid environmental estrogens (SEEs, E1, E2, EE2 for instance) is critical for comprehensively assessing environmental risks and safeguarding public health. In this study, we developed a novel molecular editing-biolayer interferometry (BLI) technology for the sensitive, rapid, and high-throughput detection of multiple SEEs in various water samples. An oligonucleotide sequence editing technique was employed to precisely tailor the molecular structures of aptamers P1 and P2. Aptamer P1 was immobilized on the BLI biosensor, while aptamer P2 was premixed with water samples containing SEEs. Results from spectroscopic experiments, isothermal titration calorimetry, and molecular docking simulation revealed significant improvements in the binding interactions between the edited aptamers and SEEs. The formation of a stable ternary structure between P1 and the P2-SEEs complex further amplified changes in the optical thickness of the molecular layer on the BLI biosensor, endowing this molecular editing-BLI technology with superior sensitivity and selectivity for detecting low molecular weight SEEs. This method effectively detected low concentrations of individual and mixed SEEs within the 0.001-1 nM range, achieving a remarkable 7 orders of magnitude increase in recognition efficiency compared to the original aptamer-SEEs interactions. Without the need for sample pretreatment, this multichannel sensing method simultaneously detected SEEs concentrations in 8 water samples within just 7 min. This study provides a powerful tool for the effective monitoring of SEEs in the environment, contributing to the protection of human health and the ecological environment.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"144 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737246","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}

引用次数: 0

Ion-Pairing Hydrophilic Interaction Chromatography for Impurity Profiling of Therapeutic Phosphorothioated Oligonucleotides. 离子配对亲水性相互作用色谱法用于治疗性磷硫化寡核苷酸杂质谱分析。

IF 6.7 1区化学

Analytical Chemistry Pub Date : 2025-07-29 Epub Date: 2025-07-17 DOI: 10.1021/acs.analchem.5c01407

Luca Tutiš, Paul D Ferguson, David Benstead, Adrian Clarke, Carl Heatherington, Chris Gripton, Christina J Vanhinsbergh, Govert W Somsen, Andrea F Gargano

{"title":"Ion-Pairing Hydrophilic Interaction Chromatography for Impurity Profiling of Therapeutic Phosphorothioated Oligonucleotides.","authors":"Luca Tutiš, Paul D Ferguson, David Benstead, Adrian Clarke, Carl Heatherington, Chris Gripton, Christina J Vanhinsbergh, Govert W Somsen, Andrea F Gargano","doi":"10.1021/acs.analchem.5c01407","DOIUrl":"10.1021/acs.analchem.5c01407","url":null,"abstract":"Therapeutic oligonucleotides (ONs) may contain many closely related impurities. Using conventional liquid chromatography (LC) modes, the separation of impurities comprising the same number of nucleotides as the ON product remains a challenge. In this study, we investigated the performance of ion-pairing HILIC (IP-HILIC) as an alternative mass-spectrometry (MS)-compatible LC mode for ON impurity profiling. A fully phosphorothioated, N-acetylgalactosamine-conjugated 16-mer antisense ON (full-length product; FLP) served as a model compound, along with shortmer, longmer, PS-PO converted, deaminated (DA) and nonconjugated (NC) products, which are potential impurities. We describe the effect of ion-pairing reagent (IPR) hydrophobicity, eluent pH, and column temperature on IP-HILIC performance, with IPRs reducing the relative contribution of the phosphate moiety on retention, thereby increasing separation selectivity based on the nature of nucleobases and conjugated groups. For a poly(dT) ladder, the effective peak capacity was reduced from 35 to 22 when introducing triethylamine as IPR; however, improved separations were observed for PS ONs. By employing an eluent containing 25 mM triethylamine acetate (pH 6.3) and a column temperature of 80 °C, IP-HILIC successfully resolved the DA impurities from both the FLP and the NC-FLP. This is noteworthy, as current MS-compatible, one-dimensional LC methods cannot resolve the DA impurity from the FLP, and MS resolution is often insufficient to differentiate the FLP and DA due to a mass difference of less than 1 Da. The proposed IP-HILIC method shows the potential for ON impurity profiling.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":" ","pages":"15717-15726"},"PeriodicalIF":6.7,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647959","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}

引用次数: 0

High-Throughput Fluorescence-Guided Sequential Single-Cell MALDI-ICC Mass Spectrometry. 高通量荧光引导序贯单细胞MALDI-ICC质谱分析。

IF 6.7 1区化学

Analytical Chemistry Pub Date : 2025-07-29 Epub Date: 2025-07-21 DOI: 10.1021/acs.analchem.5c02092

Marisa Asadian, Seth W Croslow, Timothy J Trinklein, Stanislav S Rubakhin, Fan Lam, Jonathan V Sweedler

{"title":"High-Throughput Fluorescence-Guided Sequential Single-Cell MALDI-ICC Mass Spectrometry.","authors":"Marisa Asadian, Seth W Croslow, Timothy J Trinklein, Stanislav S Rubakhin, Fan Lam, Jonathan V Sweedler","doi":"10.1021/acs.analchem.5c02092","DOIUrl":"10.1021/acs.analchem.5c02092","url":null,"abstract":"Lipids are a diverse class of biomolecules essential for brain function, yet their cell-type-specific distributions remain underexplored, presenting significant knowledge gaps in the era of single-cell biology. Traditional bulk measurements provide valuable insights into lipid composition across brain regions but lack the resolution to distinguish lipid profiles at the single-cell level. To address this, we introduce fluorescence-guided sequential single-cell mass spectrometry (SSMS), an automated workflow combining untargeted lipid profiling with antibody-targeted protein detection via photocleavable mass tags, enabling neurolipidomic classification of cell types and cell states. We applied this approach to rodent hippocampal cells, analyzing over a thousand single cells and annotating more than a hundred lipid species with complementary liquid chromatography-mass spectrometry (LC-MS/MS) measurements. Our findings show that phosphatidylcholine (PC) species are predominantly enriched in oligodendrocytes and neurons compared to astrocytes, while hexosylceramide (HexCer) species are differentially expressed across these cell types. Furthermore, neuronal state analysis revealed an enrichment of phosphatidylethanolamines (PEs) in presynaptic neurons, while nonpresynaptic neurons exhibited a more diverse lipid composition, including HexCer, PC, sphingomyelin, triacylglycerol, and PE. Our findings provide new insights into brain lipid heterogeneity with cell-type and cell-state specificity and extend-capabilities of next-generation single-cell mass spectrometry to map brain biochemistry.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":" ","pages":"15864-15872"},"PeriodicalIF":6.7,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673317","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}

引用次数: 0

IF 6.7 1区化学