Pub Date : 2025-01-08DOI: 10.1021/acs.analchem.4c04913
Qinjingwen Cao, John Guan, Delia Li, Jennifer Zhang, Riley Togashi, Elizabeth J. Johnson, Wayman Chan, Jia Guo, Peilu Liu, Yiran Liang, Lance Cadang, Anna Mah, John Briggs, Bing Zhang, Stephan Galvan, Monica Sadek, Kevin M. Legg, K. Ilker Sen, Maria Basanta-Sanchez, Luis Fernández Ruiz, Feng Yang
New peak detection (NPD) is a significant component of the multiattribute method (MAM) for MS use to facilitate the detection of quality attributes exhibiting abnormal ratio changes, vanishing attributes, or newly emerging attributes. However, challenges remain to get a balanced sensitivity and minimize false positives in NPD. In this study, we have developed a robust NPD and identification method to enhance sensitivity 10-fold (0.5% spike-in) compared to previously reported work while maintaining controlled false positives via a statistics-driven experimental design utilizing three control samples and a product-specific peptide library. This method not only enables MAM to replace conventional analytical methods for quality attribute control, but also provides a new and objective way of performing differential analysis of LC-MS-based experiments at different stages of the biopharmaceutics process development.
{"title":"A Robust and Sensitive New Peak Detection and Identification Method for Mass Spectrometry-Based Differential Analysis in Biologics Characterization","authors":"Qinjingwen Cao, John Guan, Delia Li, Jennifer Zhang, Riley Togashi, Elizabeth J. Johnson, Wayman Chan, Jia Guo, Peilu Liu, Yiran Liang, Lance Cadang, Anna Mah, John Briggs, Bing Zhang, Stephan Galvan, Monica Sadek, Kevin M. Legg, K. Ilker Sen, Maria Basanta-Sanchez, Luis Fernández Ruiz, Feng Yang","doi":"10.1021/acs.analchem.4c04913","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c04913","url":null,"abstract":"New peak detection (NPD) is a significant component of the multiattribute method (MAM) for MS use to facilitate the detection of quality attributes exhibiting abnormal ratio changes, vanishing attributes, or newly emerging attributes. However, challenges remain to get a balanced sensitivity and minimize false positives in NPD. In this study, we have developed a robust NPD and identification method to enhance sensitivity 10-fold (0.5% spike-in) compared to previously reported work while maintaining controlled false positives via a statistics-driven experimental design utilizing three control samples and a product-specific peptide library. This method not only enables MAM to replace conventional analytical methods for quality attribute control, but also provides a new and objective way of performing differential analysis of LC-MS-based experiments at different stages of the biopharmaceutics process development.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"104 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937564","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}
Pub Date : 2025-01-08DOI: 10.1021/acs.analchem.4c04419
Xindi Xu, Wei-Yi Zhang, Xian-Yin Ma, Xianxian Qin, Tian-Wen Jiang, Hong Li, Yanliang Zhang, Kun Jiang, Wen-Bin Cai
To address the pressing demand for hyphenated in situ characterization of the electrode–electrolyte interfaces at the molecular level, we report herein a technical note to demonstrate the hyphenation of in situ electrochemical surface-enhanced infrared absorption spectroscopy (SEIRAS) and shell-isolated nanoparticle enhanced Raman spectroscopy (SHINERS). The core setup incorporates a top-down configured Raman optic fiber head loaded on a 3-dimension positioning module and a bottom-up configured attenuated total reflection infrared spectroscopy (ATR-IR) spectroelectrochemical cell accommodated in a custom-designed optical accessory. The feasibility of this integrated design is initially validated by the simultaneous measurement of two model systems, namely, potential dependent adsorption of pyridine on a Au film electrode and the CO2 reduction reaction on a Cu film electrode by in situ SEIRAS and SHINERS, yielding distinct and complementary spectral information.
{"title":"Toward Hyphenated In Situ Infrared and Raman Spectroscopies in Interfacial Electrochemistry","authors":"Xindi Xu, Wei-Yi Zhang, Xian-Yin Ma, Xianxian Qin, Tian-Wen Jiang, Hong Li, Yanliang Zhang, Kun Jiang, Wen-Bin Cai","doi":"10.1021/acs.analchem.4c04419","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c04419","url":null,"abstract":"To address the pressing demand for hyphenated <i>in situ</i> characterization of the electrode–electrolyte interfaces at the molecular level, we report herein a technical note to demonstrate the hyphenation of <i>in situ</i> electrochemical surface-enhanced infrared absorption spectroscopy (SEIRAS) and shell-isolated nanoparticle enhanced Raman spectroscopy (SHINERS). The core setup incorporates a top-down configured Raman optic fiber head loaded on a 3-dimension positioning module and a bottom-up configured attenuated total reflection infrared spectroscopy (ATR-IR) spectroelectrochemical cell accommodated in a custom-designed optical accessory. The feasibility of this integrated design is initially validated by the simultaneous measurement of two model systems, namely, potential dependent adsorption of pyridine on a Au film electrode and the CO<sub>2</sub> reduction reaction on a Cu film electrode by <i>in situ</i> SEIRAS and SHINERS, yielding distinct and complementary spectral information.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"35 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936465","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}
Pub Date : 2025-01-08DOI: 10.1021/acs.analchem.4c05669
Shuda Liu, Na Dong, Shuyun Meng, Yuye Li, Yuqing Li, Siyuan Wang, Dong Liu, Tianyan You
Comprehending the biosensing mechanism of the biosensor interface is crucial for sensor development, yet accurately reflecting interfacial interactions within actual detection environments remains an unsolved challenge. An operando photoelectrochemical surface-enhanced Raman spectroscopy (PEC-SERS) biosensing platform was developed, capable of simultaneously capturing photocurrent and SERS signals, allowing operando characterization of the interfacial biosensing behavior. Porphyrin-based MOFs (Zr-MOF) served as bifunctional nanotags, providing a photocurrent and stable Raman signal output under 532 nm laser irradiation. Aptamer was used to bridge the Zr-MOF and the silver-encased gold nanodumbbells (AuNDs@AgNPs). The simultaneous in situ acquisition of target-induced PEC and SERS signal responses facilitated the correlation of electron transfer information from the photocurrent with the distance information from the SERS signal. It revealed the biosensing mechanism in which target-induced aptamer conformational bending drove the Zr-MOF to approach the electrode. However, the increase in charge transfer observed through conventional electrochemical methods contradicts the conclusions drawn from the operando PEC-SERS analysis. Comprehensive analysis indicated that redox probes introduced during the non-in-situ measurement process became adsorbed within the MOF pores, potentially affecting the judgment of the biosensing mechanism. In addition, the operando PEC-SERS biosensor simultaneously obtained two independent signals, providing self-verification to improve the accuracy and reliability of patulin detection. The linear ranges were 1 pg mL–1–10 ng mL–1 for the PEC method and 1 pg mL–1–100 ng mL–1 for the SERS method, respectively. This work provides a powerful tool for determining the interface characteristics of biosensors.
{"title":"Operando Photoelectrochemical Surface-Enhanced Raman Spectroscopy: Interfacial Mechanistic Insights and Simultaneous Detection of Patulin","authors":"Shuda Liu, Na Dong, Shuyun Meng, Yuye Li, Yuqing Li, Siyuan Wang, Dong Liu, Tianyan You","doi":"10.1021/acs.analchem.4c05669","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c05669","url":null,"abstract":"Comprehending the biosensing mechanism of the biosensor interface is crucial for sensor development, yet accurately reflecting interfacial interactions within actual detection environments remains an unsolved challenge. An operando photoelectrochemical surface-enhanced Raman spectroscopy (PEC-SERS) biosensing platform was developed, capable of simultaneously capturing photocurrent and SERS signals, allowing operando characterization of the interfacial biosensing behavior. Porphyrin-based MOFs (Zr-MOF) served as bifunctional nanotags, providing a photocurrent and stable Raman signal output under 532 nm laser irradiation. Aptamer was used to bridge the Zr-MOF and the silver-encased gold nanodumbbells (AuNDs@AgNPs). The simultaneous in situ acquisition of target-induced PEC and SERS signal responses facilitated the correlation of electron transfer information from the photocurrent with the distance information from the SERS signal. It revealed the biosensing mechanism in which target-induced aptamer conformational bending drove the Zr-MOF to approach the electrode. However, the increase in charge transfer observed through conventional electrochemical methods contradicts the conclusions drawn from the operando PEC-SERS analysis. Comprehensive analysis indicated that redox probes introduced during the non-in-situ measurement process became adsorbed within the MOF pores, potentially affecting the judgment of the biosensing mechanism. In addition, the operando PEC-SERS biosensor simultaneously obtained two independent signals, providing self-verification to improve the accuracy and reliability of patulin detection. The linear ranges were 1 pg mL<sup>–1</sup>–10 ng mL<sup>–1</sup> for the PEC method and 1 pg mL<sup>–1</sup>–100 ng mL<sup>–1</sup> for the SERS method, respectively. This work provides a powerful tool for determining the interface characteristics of biosensors.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"19 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937528","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}
Hepatic fibrosis, a chronic liver response to injury with potential severe outcomes like cirrhosis and liver cancer, necessitates urgent noninvasive diagnostic techniques to halt disease progression. We herein for the first time developed a single-chain peptide probe targeting pathological collagen for in vivo magnetic resonance imaging (MRI) of hepatic fibrosis. The novel (GhypO)10 probe, distinguished by its unique monomeric conformation achieved through Pro to (2S,4S)-hydroxyproline (hyp) substitution and subsequent disruption of hydrogen bonding, exhibits selectivity for pathological collagen over its intact counterpart in connective tissues. Fluorescence imaging of liver specimens from fibrotic models displayed a discernible relationship between pathological collagen levels and fibrosis stage. Moreover, T1-weighted MR images post Gd-GhypO administration revealed progressive signal enhancement congruent with fibrosis severity, corroborated by a corresponding increase in the contrast-to-noise ratio (ΔCNR). Biodistribution analysis indicates that Gd-GhypO has low Gd retention in the main organs 24 h postinjection, ensuring the probe’s safety for molecular imaging. The Gd-GhypO probe therefore emerges as a potent tool for the precise, noninvasive delineation of hepatic fibrosis stages, offering significant implications for the diagnosis and management of liver fibrosis.
{"title":"A Single-Chain Peptide Probe Targeting Pathological Collagen for Precise Staging of Hepatic Fibrosis by MR Imaging","authors":"Linge Nian, Zhao Liu, Xiangdong Cai, Bo Wang, Qianqian Zhang, Junqiang Lei, Jianxi Xiao","doi":"10.1021/acs.analchem.4c03601","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c03601","url":null,"abstract":"Hepatic fibrosis, a chronic liver response to injury with potential severe outcomes like cirrhosis and liver cancer, necessitates urgent noninvasive diagnostic techniques to halt disease progression. We herein for the first time developed a single-chain peptide probe targeting pathological collagen for in vivo magnetic resonance imaging (MRI) of hepatic fibrosis. The novel (GhypO)<sub>10</sub> probe, distinguished by its unique monomeric conformation achieved through Pro to (2<i>S</i>,4<i>S</i>)-hydroxyproline (hyp) substitution and subsequent disruption of hydrogen bonding, exhibits selectivity for pathological collagen over its intact counterpart in connective tissues. Fluorescence imaging of liver specimens from fibrotic models displayed a discernible relationship between pathological collagen levels and fibrosis stage. Moreover, T1-weighted MR images post Gd-GhypO administration revealed progressive signal enhancement congruent with fibrosis severity, corroborated by a corresponding increase in the contrast-to-noise ratio (ΔCNR). Biodistribution analysis indicates that Gd-GhypO has low Gd retention in the main organs 24 h postinjection, ensuring the probe’s safety for molecular imaging. The Gd-GhypO probe therefore emerges as a potent tool for the precise, noninvasive delineation of hepatic fibrosis stages, offering significant implications for the diagnosis and management of liver fibrosis.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"4 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936467","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}
Pub Date : 2025-01-08DOI: 10.1021/acs.analchem.4c05406
Naizhong Zhang, Ivan Prokhorov, Nico Kueter, Gang Li, Béla Tuzson, Paul M. Magyar, Volker Ebert, Malavika Sivan, Mayuko Nakagawa, Alexis Gilbert, Yuichiro Ueno, Naohiro Yoshida, Thomas Röckmann, Stefano M. Bernasconi, Lukas Emmenegger, Joachim Mohn
Mid-infrared laser absorption spectroscopy enables rapid and nondestructive analysis of methane clumped isotopes. However, current analytical methods require a sample size of 20 mL STP (0.82 mmol) of pure CH4 gas, which significantly limits its application to natural samples. To enhance the performance of spectroscopic measurement of methane clumped isotopes, we established a laser spectroscopic platform with newly selected spectral windows for clumped isotope analysis: 1076.97 cm–1 for 12CH2D2 and 1163.47 cm–1 for 13CH3D, and a custom-built gas inlet system. These spectral windows were identified through an extensive spectral survey on newly recorded high-resolution Fourier transform infrared (FTIR) spectra across the wavelength range of 870–3220 cm–1, thereby addressing gaps for 12CH2D2 in existing spectral databases. In addition, we implemented several key technological advances, which result in superior control and performance of sample injection and analysis. We demonstrate that for small samples ranging from 3 to 10 mL (0.12–0.41 mmol) of CH4 gas, a measurement precision comparable to high-resolution isotope ratio mass spectrometry for Δ12CH2D2 (∼1.5‰) can be achieved through 3 to 8 repetitive measurements using a recycle-refilling system within a few hours. Samples larger than 10 mL can be quantified in under 20 min. At the same time, for Δ13CH3D analysis a repeatability of 0.05‰, superior to mass spectrometry, was realized. These advancements in reducing sample size and shortening analysis time significantly improve the practicality of the spectroscopic technique for determining the clumped isotope signatures of natural methane samples, particularly for applications involving low CH4 concentrations or requiring consecutive analyses, which are feasible in conjunction with an automated preconcentration system.
{"title":"Rapid High-Sensitivity Analysis of Methane Clumped Isotopes (Δ13CH3D and Δ12CH2D2) Using Mid-Infrared Laser Spectroscopy","authors":"Naizhong Zhang, Ivan Prokhorov, Nico Kueter, Gang Li, Béla Tuzson, Paul M. Magyar, Volker Ebert, Malavika Sivan, Mayuko Nakagawa, Alexis Gilbert, Yuichiro Ueno, Naohiro Yoshida, Thomas Röckmann, Stefano M. Bernasconi, Lukas Emmenegger, Joachim Mohn","doi":"10.1021/acs.analchem.4c05406","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c05406","url":null,"abstract":"Mid-infrared laser absorption spectroscopy enables rapid and nondestructive analysis of methane clumped isotopes. However, current analytical methods require a sample size of 20 mL STP (0.82 mmol) of pure CH<sub>4</sub> gas, which significantly limits its application to natural samples. To enhance the performance of spectroscopic measurement of methane clumped isotopes, we established a laser spectroscopic platform with newly selected spectral windows for clumped isotope analysis: 1076.97 cm<sup>–1</sup> for <sup>12</sup>CH<sub>2</sub>D<sub>2</sub> and 1163.47 cm<sup>–1</sup> for <sup>13</sup>CH<sub>3</sub>D, and a custom-built gas inlet system. These spectral windows were identified through an extensive spectral survey on newly recorded high-resolution Fourier transform infrared (FTIR) spectra across the wavelength range of 870–3220 cm<sup>–1</sup>, thereby addressing gaps for <sup>12</sup>CH<sub>2</sub>D<sub>2</sub> in existing spectral databases. In addition, we implemented several key technological advances, which result in superior control and performance of sample injection and analysis. We demonstrate that for small samples ranging from 3 to 10 mL (0.12–0.41 mmol) of CH<sub>4</sub> gas, a measurement precision comparable to high-resolution isotope ratio mass spectrometry for Δ<sup>12</sup>CH<sub>2</sub>D<sub>2</sub> (∼1.5‰) can be achieved through 3 to 8 repetitive measurements using a recycle-refilling system within a few hours. Samples larger than 10 mL can be quantified in under 20 min. At the same time, for Δ<sup>13</sup>CH<sub>3</sub>D analysis a repeatability of 0.05‰, superior to mass spectrometry, was realized. These advancements in reducing sample size and shortening analysis time significantly improve the practicality of the spectroscopic technique for determining the clumped isotope signatures of natural methane samples, particularly for applications involving low CH<sub>4</sub> concentrations or requiring consecutive analyses, which are feasible in conjunction with an automated preconcentration system.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"31 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937526","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}
Early prediction of the neoadjuvant therapy efficacy for HER2-positive breast cancer is crucial for personalizing treatment and enhancing patient outcomes. Exosomes, which play a role in tumor development and treatment response, are emerging as potential biomarkers for cancer diagnosis and efficacy prediction. Despite their promise, current exosome detection and isolation methods are cumbersome and time-consuming and often yield limited purity and quantity. In this study, we employed Raman spectroscopy to analyze the molecular changes in exosomes from the sera of HER2-positive breast cancer patients before and after two cycles of neoadjuvant therapy. Utilizing machine learning techniques (PCA, LDA, and SVM), we developed a predictive model with an AUC value exceeding 0.89. Additionally, we introduced an innovative HER2-positive exosome capture and detection system, termed Magnetic beads@HER2-Exos@HER2-SERS detection nanoprobes (HER2-MEDN). This system enabled us to efficiently extract and analyze HER2-positive exosomes, refining our predictive model to achieve an accuracy greater than 0.94. Our study has demonstrated the potential of the HER2-MEDN system in accurately predicting early treatment response, offering novel insights and methodologies for assessing the efficacy of neoadjuvant therapy in HER2-positive breast cancer.
{"title":"Raman Spectroscopy and Exosome-Based Machine Learning Predicts the Efficacy of Neoadjuvant Therapy for HER2-Positive Breast Cancer","authors":"Yining Jia, Yongqi Li, Xintong Bai, Liyuan Liu, Ying Shan, Fei Wang, Zhigang Yu, Chao Zheng","doi":"10.1021/acs.analchem.4c05833","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c05833","url":null,"abstract":"Early prediction of the neoadjuvant therapy efficacy for HER2-positive breast cancer is crucial for personalizing treatment and enhancing patient outcomes. Exosomes, which play a role in tumor development and treatment response, are emerging as potential biomarkers for cancer diagnosis and efficacy prediction. Despite their promise, current exosome detection and isolation methods are cumbersome and time-consuming and often yield limited purity and quantity. In this study, we employed Raman spectroscopy to analyze the molecular changes in exosomes from the sera of HER2-positive breast cancer patients before and after two cycles of neoadjuvant therapy. Utilizing machine learning techniques (PCA, LDA, and SVM), we developed a predictive model with an AUC value exceeding 0.89. Additionally, we introduced an innovative HER2-positive exosome capture and detection system, termed Magnetic beads@HER2-Exos@HER2-SERS detection nanoprobes (HER2-MEDN). This system enabled us to efficiently extract and analyze HER2-positive exosomes, refining our predictive model to achieve an accuracy greater than 0.94. Our study has demonstrated the potential of the HER2-MEDN system in accurately predicting early treatment response, offering novel insights and methodologies for assessing the efficacy of neoadjuvant therapy in HER2-positive breast cancer.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"56 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937529","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}
It is significant but challenging to develop polarity sensors that can measure multiscenario polarity in a modular, customized, sensitive, and accurate manner. In this work, we proposed a polarity sensor based on multivariate lanthanide metal–organic framework (Ln-MOF) nanoclusters through the modular programming design of ligands. This multivariate Ln-MOF combines the advantages of modularity, ease of design, high flexibility and low cost, and can be precisely customized for different polarity systems. The MOF Eu0.1Tb0.9-isophthalic acid (IPA) and Eu0.3Tb0.7-o-phthalic acid (OPA) are suitable for the detection of trace water in dimethylsulfoxide (DMSO) and hyaluronidase activity, respectively. Especially, Eu0.3Tb0.7-OPA can achieve high-sensitivity detection of hyaluronidase activity within 8 min, with the limit of detection as low as 0.016 U/L. The results enable us to break through our previous understanding of polarity parameter, allowing us to develop more polarity-related biosensing platforms. Ln-MOFs are believed to utilize their adjustable polar intermolecular interactions to achieve the optimal compatibility and high sensitivity in polarity sensing systems, which is supported by experiments and density functional theory calculations. These polarity sensors based on multivariate Ln-MOF nanoclusters offer significant potential in biosensing and medical diagnostics, overcoming traditional biosensor limitations in synthesis and customization.
{"title":"Polarity Sensor Based on Multivariate Lanthanide Metal–Organic Framework for Constructing Biosensing Platform","authors":"Long Yu, Qi Xu, Ling Huang, Lixiang Feng, Yumin Feng, Gaosong Wu, Yuxiu Xiao","doi":"10.1021/acs.analchem.4c06080","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c06080","url":null,"abstract":"It is significant but challenging to develop polarity sensors that can measure multiscenario polarity in a modular, customized, sensitive, and accurate manner. In this work, we proposed a polarity sensor based on multivariate lanthanide metal–organic framework (Ln-MOF) nanoclusters through the modular programming design of ligands. This multivariate Ln-MOF combines the advantages of modularity, ease of design, high flexibility and low cost, and can be precisely customized for different polarity systems. The MOF Eu<sub>0.1</sub>Tb<sub>0.9</sub>-isophthalic acid (IPA) and Eu<sub>0.3</sub>Tb<sub>0.7</sub>-<i>o</i>-phthalic acid (OPA) are suitable for the detection of trace water in dimethylsulfoxide (DMSO) and hyaluronidase activity, respectively. Especially, Eu<sub>0.3</sub>Tb<sub>0.7</sub>-OPA can achieve high-sensitivity detection of hyaluronidase activity within 8 min, with the limit of detection as low as 0.016 U/L. The results enable us to break through our previous understanding of polarity parameter, allowing us to develop more polarity-related biosensing platforms. Ln-MOFs are believed to utilize their adjustable polar intermolecular interactions to achieve the optimal compatibility and high sensitivity in polarity sensing systems, which is supported by experiments and density functional theory calculations. These polarity sensors based on multivariate Ln-MOF nanoclusters offer significant potential in biosensing and medical diagnostics, overcoming traditional biosensor limitations in synthesis and customization.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"56 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936475","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}
The integrative multiomics characterization of minute amounts of clinical tissue specimens has become increasingly important. Here, we present an approach called Integral-Omics, which enables sequential extraction of metabolites, lipids, genomic DNA, total RNA, proteins, and phosphopeptides from a single biopsy-level tissue specimen. We benchmarked this method with various samples, applied the workflow to perform multiomics profiling of tissues from six patients with colorectal cancer, and found that tumor tissues exhibited suppressed ferroptosis pathways at multiomics levels. Together, this study presents a methodology that enables sequential extraction and profiling of metabolomics, lipidomics, genomics, transcriptomics, proteomics, and phosphoproteomics using biopsy tissue specimens.
{"title":"Integral-Omics: Serial Extraction and Profiling of Metabolome, Lipidome, Genome, Transcriptome, Whole Proteome and Phosphoproteome Using Biopsy Tissue","authors":"Wei Li, Jing Sun, Rui Sun, Yujuan Wei, Junke Zheng, Yi Zhu, Tiannan Guo","doi":"10.1021/acs.analchem.4c04421","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c04421","url":null,"abstract":"The integrative multiomics characterization of minute amounts of clinical tissue specimens has become increasingly important. Here, we present an approach called Integral-Omics, which enables sequential extraction of metabolites, lipids, genomic DNA, total RNA, proteins, and phosphopeptides from a single biopsy-level tissue specimen. We benchmarked this method with various samples, applied the workflow to perform multiomics profiling of tissues from six patients with colorectal cancer, and found that tumor tissues exhibited suppressed ferroptosis pathways at multiomics levels. Together, this study presents a methodology that enables sequential extraction and profiling of metabolomics, lipidomics, genomics, transcriptomics, proteomics, and phosphoproteomics using biopsy tissue specimens.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"9 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936473","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}
Smart-responsive materials have attracted much attention in the enrichment of post-translational modifications of proteins. In this work, for the first time, we developed a smart enrichment strategy (MNPs-l-DOPA/PEI-SP) based on the change in hydrophilic properties of spiropyran under the regulation of light and pH to realize the controllable enrichment and release of intact glycopeptides. The enrichment mechanism and possible binding mechanism were verified by theoretical calculations. The smart enrichment platform based on MNPs-l-DOPA/PEI-SP was used to screen glycoprotein biomarkers for hepatocellular carcinoma (HCC) to evaluate its cancer diagnostic and monitoring performance. A total of 3,864 intact N-glycopeptides containing 166 N-glycoproteins were successfully identified in serum samples of early-stage HCC patients, while 3,266 intact N-glycopeptides containing 193 glycoproteins were identified in normal control (NC) serum samples. This work not only provides new ideas for the efficient enrichment of intact glycopeptides with smart-responsive material, but also broadens the research possibilities for biomarker discovery in HCC serum liquid biopsies.
{"title":"Light-/pH-Regulated Spiropyran Smart-Responsive Hydrophilic Separation Platform for the Identification of Serum Glycopeptides from Hepatocellular Carcinoma Patients","authors":"Yanqing Zhao, Hongbin Li, Haijiao Zheng, Qiong Jia","doi":"10.1021/acs.analchem.4c04025","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c04025","url":null,"abstract":"Smart-responsive materials have attracted much attention in the enrichment of post-translational modifications of proteins. In this work, for the first time, we developed a smart enrichment strategy (MNPs-<span>l</span>-DOPA/PEI-SP) based on the change in hydrophilic properties of spiropyran under the regulation of light and pH to realize the controllable enrichment and release of intact glycopeptides. The enrichment mechanism and possible binding mechanism were verified by theoretical calculations. The smart enrichment platform based on MNPs-<span>l</span>-DOPA/PEI-SP was used to screen glycoprotein biomarkers for hepatocellular carcinoma (HCC) to evaluate its cancer diagnostic and monitoring performance. A total of 3,864 intact <i>N</i>-glycopeptides containing 166 <i>N</i>-glycoproteins were successfully identified in serum samples of early-stage HCC patients, while 3,266 intact <i>N</i>-glycopeptides containing 193 glycoproteins were identified in normal control (NC) serum samples. This work not only provides new ideas for the efficient enrichment of intact glycopeptides with smart-responsive material, but also broadens the research possibilities for biomarker discovery in HCC serum liquid biopsies.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"82 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936469","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}
Pub Date : 2025-01-07DOI: 10.1021/acs.analchem.4c06038
Hua Pan, Shelby M. Klein, Akalanka Gunaratne, Martin F. Jarrold, David E. Clemmer
Charge detection mass spectrometry (CD-MS) is used to monitor the dissociation of large (300 kDa to 20 MDa) protein complexes in droplets heated with a 10.6 μm CO2 laser. In this approach, electrospray ionization (ESI) is used to produce charged droplets containing macromolecular complexes. As the droplets travel from the ESI capillary tip to the entrance of the CD-MS instrument, they pass through a variable-power laser field, where they are rapidly heated and dissociate to produce fragments. The approach is illustrated for three model systems: glutamate dehydrogenase (GDH), a 334 kDa hexameric protein complex, which dissociates into protein monomers, dimers, and tetramers; the ∼3 MDa T = 3, and ∼4 MDa T = 4 hepatitis B virus VLPs (virus-like particles) that produce a distribution of protein dimer clusters; and the ∼20 MDa T = 7 human papillomavirus VLP, which dissociates primarily into small capsid protein clusters that are not well-resolved by CD-MS. The fragments produced by in-droplet activation provide information that is useful for characterizing the structures of the intact antecedent complexes. A discussion of the advantages and current limitations of this approach is presented.
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