Pub Date : 2024-01-11DOI: 10.1021/acsmeasuresciau.3c00062
Tingyuan Yang, Shuli Tang, Jiaxin Feng and Xin Yan*,
Changes in the levels of lipid sn-positional isomers are associated with perturbation of the physiological environment within the biological system. Consequently, knowing the concentrations of these lipids holds significant importance for unraveling their involvement in disease diagnosis and pathological mechanisms. However, existing methods for lipid quantification often fall short in accuracy due to the structural diversity and isomeric forms of lipids. To address this challenge, we have developed an aziridine-based isobaric tag labeling strategy that allows (i) differentiation and (ii) enhanced relative quantification of lipid sn-positional isomers from distinct samples in a single run. The methodology enabled by aziridination, isobaric tag labeling, and lithiation has been applied to various phospholipids, enabling the determination of the sn-positions of fatty acyl chains and enhanced relative quantification. The analysis of Escherichia coli lipid extracts demonstrated the enhanced determination of the concentration ratios of lipid isomers by measuring the intensity ratios of mass reporters released from sn-positional diagnostic ions. Moreover, we applied the method to the analysis of human colon cancer plasma. Intriguingly, 17 PC lipid sn-positional isomers were identified and quantified simultaneously, and among them, 7 showed significant abundance changes in the colon cancer plasma, which can be used as potential plasma markers for diagnosis of human colon cancer.
脂质 Sn 位异构体水平的变化与生物系统内生理环境的干扰有关。因此,了解这些脂质的浓度对于揭示它们在疾病诊断和病理机制中的参与具有重要意义。然而,由于脂质的结构多样性和异构形式,现有的脂质定量方法往往不够准确。为了应对这一挑战,我们开发了一种基于氮丙啶的异构体标签标记策略,可在一次运行中(i)区分和(ii)增强来自不同样本的脂质 Sn-位置异构体的相对定量。氮丙啶化、同位标签标记和石碳酸化方法已应用于多种磷脂,可确定脂肪酰基链的 sn 位置并提高相对定量。对大肠杆菌脂质提取物的分析表明,通过测量 Sn 位置诊断离子释放的质量报告强度比,可以更好地确定脂质异构体的浓度比。此外,我们还将该方法应用于人类结肠癌血浆的分析。有趣的是,我们同时鉴定并定量了17种PC脂质sn-定位异构体,其中7种在结肠癌血浆中显示出显著的丰度变化,可作为诊断人类结肠癌的潜在血浆标记物。
{"title":"Lipid Isobaric Mass Tagging for Enhanced Relative Quantification of Unsaturated sn-Positional Isomers","authors":"Tingyuan Yang, Shuli Tang, Jiaxin Feng and Xin Yan*, ","doi":"10.1021/acsmeasuresciau.3c00062","DOIUrl":"10.1021/acsmeasuresciau.3c00062","url":null,"abstract":"<p >Changes in the levels of lipid <i>sn</i>-positional isomers are associated with perturbation of the physiological environment within the biological system. Consequently, knowing the concentrations of these lipids holds significant importance for unraveling their involvement in disease diagnosis and pathological mechanisms. However, existing methods for lipid quantification often fall short in accuracy due to the structural diversity and isomeric forms of lipids. To address this challenge, we have developed an aziridine-based isobaric tag labeling strategy that allows (i) differentiation and (ii) enhanced relative quantification of lipid <i>sn</i>-positional isomers from distinct samples in a single run. The methodology enabled by aziridination, isobaric tag labeling, and lithiation has been applied to various phospholipids, enabling the determination of the <i>sn</i>-positions of fatty acyl chains and enhanced relative quantification. The analysis of <i>Escherichia coli</i> lipid extracts demonstrated the enhanced determination of the concentration ratios of lipid isomers by measuring the intensity ratios of mass reporters released from <i>sn</i>-positional diagnostic ions. Moreover, we applied the method to the analysis of human colon cancer plasma. Intriguingly, 17 PC lipid <i>sn</i>-positional isomers were identified and quantified simultaneously, and among them, 7 showed significant abundance changes in the colon cancer plasma, which can be used as potential plasma markers for diagnosis of human colon cancer.</p>","PeriodicalId":29800,"journal":{"name":"ACS Measurement Science Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsmeasuresciau.3c00062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139420672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1021/acsmeasuresciau.3c00066
Jingqin Mao, Yahya Atwa, Zhenxun Wu, David McNeill and Hamza Shakeel*,
In this study, a micro helium dielectric barrier discharge (μHDBD) plasma device fabricated using 3D printing and molding techniques was coupled with a mini spectrometer to detect and identify different classes of volatile organic compounds (VOCs) using optical emission spectrometry (OES). We tested 11 VOCs belonging to three different classes (straight-chain alkanes, aromatics, and polar organic compounds). Our results clearly demonstrate that the optical emission spectra of different classes of VOCs show clear differences, and therefore, can be used for identification. Additionally, the emission spectra of VOCs with a similar structure (such as n-pentane, n-hexane, n-heptane, n-octane, and n-nonane) have similar optical emission spectrum shape. Acetone and ethanol also have similar emission wavelengths, but they show different line intensities for the same concentrations. We also found that the side-chain group of aromatics will also affect the emission spectra even though they have a similar structure (all have a benzene ring). Moreover, our μHDBD-OES system can also identify multiple compounds in VOC mixtures. Our work also demonstrates the possibility of identifying different classes of VOCs by the OES shape.
在这项研究中,利用三维打印和成型技术制造的微型氦介质阻挡放电(μHDBD)等离子体装置与微型光谱仪相结合,使用光学发射光谱法(OES)检测和识别不同类别的挥发性有机化合物(VOCs)。我们测试了属于三个不同类别(直链烷烃、芳烃和极性化合物)的 11 种挥发性有机化合物。我们的结果清楚地表明,不同类别的挥发性有机化合物的光学发射光谱显示出明显的差异,因此可用于识别。此外,具有相似结构的挥发性有机化合物(如正戊烷、正己烷、正庚烷、正辛烷和正壬烷)的发射光谱具有相似的光学发射光谱形状。丙酮和乙醇也具有相似的发射波长,但在浓度相同的情况下,它们显示出不同的线强度。我们还发现,芳烃的侧链基团也会影响发射光谱,尽管它们具有相似的结构(都有一个苯环)。此外,我们的 μHDBD-OES 系统还能识别挥发性有机化合物混合物中的多种化合物。我们的工作还证明了通过 OES 形状识别不同类别挥发性有机化合物的可能性。
{"title":"Identification of Different Classes of VOCs Based on Optical Emission Spectra Using a Dielectric Barrier Helium Plasma Coupled with a Mini Spectrometer","authors":"Jingqin Mao, Yahya Atwa, Zhenxun Wu, David McNeill and Hamza Shakeel*, ","doi":"10.1021/acsmeasuresciau.3c00066","DOIUrl":"10.1021/acsmeasuresciau.3c00066","url":null,"abstract":"<p >In this study, a micro helium dielectric barrier discharge (μHDBD) plasma device fabricated using 3D printing and molding techniques was coupled with a mini spectrometer to detect and identify different classes of volatile organic compounds (VOCs) using optical emission spectrometry (OES). We tested 11 VOCs belonging to three different classes (straight-chain alkanes, aromatics, and polar organic compounds). Our results clearly demonstrate that the optical emission spectra of different classes of VOCs show clear differences, and therefore, can be used for identification. Additionally, the emission spectra of VOCs with a similar structure (such as <i>n</i>-pentane, <i>n</i>-hexane, <i>n</i>-heptane, <i>n</i>-octane, and <i>n</i>-nonane) have similar optical emission spectrum shape. Acetone and ethanol also have similar emission wavelengths, but they show different line intensities for the same concentrations. We also found that the side-chain group of aromatics will also affect the emission spectra even though they have a similar structure (all have a benzene ring). Moreover, our μHDBD-OES system can also identify multiple compounds in VOC mixtures. Our work also demonstrates the possibility of identifying different classes of VOCs by the OES shape.</p>","PeriodicalId":29800,"journal":{"name":"ACS Measurement Science Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsmeasuresciau.3c00066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139078672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-28DOI: 10.1021/acsmeasuresciau.3c00064
Jacob Heiss, and , Hossein Tavana*,
The main cause of mortality among cancer patients is metastatic disease. Metastasis develops from cancer cells that invade the stromal tissue and intravasate the circulatory or lymphatic systems to eventually form new tumors in other organs. Blocking cancer cell invasion can potentially prevent or reduce the metastatic progression of cancers. Testing different chemical compounds against cell invasion in three-dimensional cultures is a common laboratory technique. The efficacy of the treatments is often evaluated from confocal microscopic images of the cells using image processing. However, the analysis approaches are often subject to variations and inconsistencies due to user decisions that must be made while processing each image. To overcome this limitation, we developed a fully automated method to quantify the invasion of cancer cells from a 3D tumor spheroid into the surrounding extracellular matrix. We demonstrated that this method resolves cell invasion from spheroids of different shapes and sizes and from cells that invade as a cluster or individually. We also showed that this approach can help quantify the dose-dependent anti-invasive effects of a commonly used chemotherapy drug. Our automated method significantly reduces the time and increases the consistency and accuracy of cancer cell invasion analysis in three-dimensional cultures.
{"title":"Automated Analysis of Extracellular Matrix Invasion of Cancer Cells from Tumor Spheroids","authors":"Jacob Heiss, and , Hossein Tavana*, ","doi":"10.1021/acsmeasuresciau.3c00064","DOIUrl":"10.1021/acsmeasuresciau.3c00064","url":null,"abstract":"<p >The main cause of mortality among cancer patients is metastatic disease. Metastasis develops from cancer cells that invade the stromal tissue and intravasate the circulatory or lymphatic systems to eventually form new tumors in other organs. Blocking cancer cell invasion can potentially prevent or reduce the metastatic progression of cancers. Testing different chemical compounds against cell invasion in three-dimensional cultures is a common laboratory technique. The efficacy of the treatments is often evaluated from confocal microscopic images of the cells using image processing. However, the analysis approaches are often subject to variations and inconsistencies due to user decisions that must be made while processing each image. To overcome this limitation, we developed a fully automated method to quantify the invasion of cancer cells from a 3D tumor spheroid into the surrounding extracellular matrix. We demonstrated that this method resolves cell invasion from spheroids of different shapes and sizes and from cells that invade as a cluster or individually. We also showed that this approach can help quantify the dose-dependent anti-invasive effects of a commonly used chemotherapy drug. Our automated method significantly reduces the time and increases the consistency and accuracy of cancer cell invasion analysis in three-dimensional cultures.</p>","PeriodicalId":29800,"journal":{"name":"ACS Measurement Science Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsmeasuresciau.3c00064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139055641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-15DOI: 10.1021/acsmeasuresciau.3c00063
Jaqueline F. Rocha, Julia C. de Oliveira, Jefferson Bettini, Mathias Strauss, Guilherme S. Selmi, Anderson K. Okazaki, Rafael F. de Oliveira, Renato S. Lima and Murilo Santhiago*,
Electrochemical paper-based analytical devices represent an important platform for portable, low-cost, affordable, and decentralized diagnostics. For this kind of application, chemical functionalization plays a pivotal role to ensure high clinical performance by tuning surface properties and the area of electrodes. However, controlling different surface properties of electrodes by using a single functionalization route is still challenging. In this work, we attempted to tune the wettability, chemical composition, and electroactive area of carbon-paper-based devices by thermally treating polydopamine (PDA) at different temperatures. PDA films were deposited onto pyrolyzed paper (PP) electrodes and thermally treated in the range of 300–1000 °C. After deposition of PDA, the surface is rich in nitrogen and oxygen, it is superhydrophilic, and it has a high electroactive area. As the temperature increases, the surface becomes hydrophobic, and the electroactive area decreases. The surface modifications were followed by Raman, X-ray photoelectron microscopy (XPS), laser scanning confocal microscopy (LSCM), contact angle, scanning electron microscopy (SEM-EDS), electrical measurements, transmission electron microscopy (TEM), and electrochemical experiments. In addition, the chemical composition of nitrogen species can be tuned on the surface. As a proof of concept, we employed PDA-treated surfaces to anchor [AuCl4]− ions. After electrochemical reduction, we observed that it is possible to control the size of the nanoparticles on the surface. Our route opens a new avenue to add versatility to electrochemical interfaces in the field of paper-based electrochemical biosensors.
{"title":"Tuning the Chemical and Electrochemical Properties of Paper-Based Carbon Electrodes by Pyrolysis of Polydopamine","authors":"Jaqueline F. Rocha, Julia C. de Oliveira, Jefferson Bettini, Mathias Strauss, Guilherme S. Selmi, Anderson K. Okazaki, Rafael F. de Oliveira, Renato S. Lima and Murilo Santhiago*, ","doi":"10.1021/acsmeasuresciau.3c00063","DOIUrl":"10.1021/acsmeasuresciau.3c00063","url":null,"abstract":"<p >Electrochemical paper-based analytical devices represent an important platform for portable, low-cost, affordable, and decentralized diagnostics. For this kind of application, chemical functionalization plays a pivotal role to ensure high clinical performance by tuning surface properties and the area of electrodes. However, controlling different surface properties of electrodes by using a single functionalization route is still challenging. In this work, we attempted to tune the wettability, chemical composition, and electroactive area of carbon-paper-based devices by thermally treating polydopamine (PDA) at different temperatures. PDA films were deposited onto pyrolyzed paper (PP) electrodes and thermally treated in the range of 300–1000 °C. After deposition of PDA, the surface is rich in nitrogen and oxygen, it is superhydrophilic, and it has a high electroactive area. As the temperature increases, the surface becomes hydrophobic, and the electroactive area decreases. The surface modifications were followed by Raman, X-ray photoelectron microscopy (XPS), laser scanning confocal microscopy (LSCM), contact angle, scanning electron microscopy (SEM-EDS), electrical measurements, transmission electron microscopy (TEM), and electrochemical experiments. In addition, the chemical composition of nitrogen species can be tuned on the surface. As a proof of concept, we employed PDA-treated surfaces to anchor [AuCl<sub>4</sub>]<sup>−</sup> ions. After electrochemical reduction, we observed that it is possible to control the size of the nanoparticles on the surface. Our route opens a new avenue to add versatility to electrochemical interfaces in the field of paper-based electrochemical biosensors.</p>","PeriodicalId":29800,"journal":{"name":"ACS Measurement Science Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsmeasuresciau.3c00063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138681741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-12DOI: 10.1021/acsmeasuresciau.3c00050
Ada Raucci, Antonella Miglione, Wanda Cimmino, Alessia Cioffi, Sima Singh, Michele Spinelli, Angela Amoresano, Giacomo Musile* and Stefano Cinti*,
Nitrite is a compound used as a food additive for its preservative action and coloring capability, as well as an industrial agent for its antifreezing action and for preventing corrosion, and it is also used as a pharmaceutical in cyanide detoxification therapy. However, even recently, because of its high toxicity, it has been used as a murder and suicidal agent due to its affordability and ready availability. In this technical report, we describe an electrochemical paper-based device for selectively determining nitrite in complex biofluids, such as blood, cadaveric blood, vitreous humor, serum, plasma, and urine. The approach was validated in terms of the linearity of response, selectivity, and sensitivity, and the accuracy of the determination was verified by comparing the results with a chromatographic instrumental method. A linear response was observed in the micromolar range; the sensitivity of the method expressed as the limit of detection was 0.4 μM in buffer measurements. The simplicity of use, the portability of the device, and the performance shown make the approach suitable for detecting nitrite in complex biofluids, including contexts of forensic interest, such as murders or suicides in which nitrite is used as a toxic agent. Limits of detection of ca. 1, 2, 4, 5, 3, and 4 μM were obtained in vitreous humor, urine, serum and plasma, blood, and cadaveric blood, also highlighting a satisfactory accuracy comprised between 91 and 112%.
{"title":"Technical Evaluation of a Paper-Based Electrochemical Strip to Measure Nitrite Ions in the Forensic Field","authors":"Ada Raucci, Antonella Miglione, Wanda Cimmino, Alessia Cioffi, Sima Singh, Michele Spinelli, Angela Amoresano, Giacomo Musile* and Stefano Cinti*, ","doi":"10.1021/acsmeasuresciau.3c00050","DOIUrl":"10.1021/acsmeasuresciau.3c00050","url":null,"abstract":"<p >Nitrite is a compound used as a food additive for its preservative action and coloring capability, as well as an industrial agent for its antifreezing action and for preventing corrosion, and it is also used as a pharmaceutical in cyanide detoxification therapy. However, even recently, because of its high toxicity, it has been used as a murder and suicidal agent due to its affordability and ready availability. In this technical report, we describe an electrochemical paper-based device for selectively determining nitrite in complex biofluids, such as blood, cadaveric blood, vitreous humor, serum, plasma, and urine. The approach was validated in terms of the linearity of response, selectivity, and sensitivity, and the accuracy of the determination was verified by comparing the results with a chromatographic instrumental method. A linear response was observed in the micromolar range; the sensitivity of the method expressed as the limit of detection was 0.4 μM in buffer measurements. The simplicity of use, the portability of the device, and the performance shown make the approach suitable for detecting nitrite in complex biofluids, including contexts of forensic interest, such as murders or suicides in which nitrite is used as a toxic agent. Limits of detection of ca. 1, 2, 4, 5, 3, and 4 μM were obtained in vitreous humor, urine, serum and plasma, blood, and cadaveric blood, also highlighting a satisfactory accuracy comprised between 91 and 112%.</p>","PeriodicalId":29800,"journal":{"name":"ACS Measurement Science Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsmeasuresciau.3c00050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138580771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-11DOI: 10.1021/acsmeasuresciau.3c00061
Robert D. Crapnell, Prashanth S. Adarakatti and Craig E. Banks*,
Mesalamine, known as 5-aminosalicylic acid, is a medication used primarily in the treatment of inflammatory bowel disease, including ulcerative colitis and Crohn’s disease. 5-Aminosalicylic acid can be measured using various benchtop laboratory techniques which involve liquid chromatography–mass spectroscopy, but these are sophisticated and large, meaning that they cannot be used on-site because transportation of the samples, chemicals, and physical and biological reactions can potentially occur, which can affect the sample’s composition and potentially result in inaccurate results. An alternative approach is the use of electrochemical based sensing platforms which has the advantages of portability, cost-efficiency, facile miniaturization, and rapid analysis while nonetheless providing sensitivity and selectivity. We provide an overview of the use of the electroanalytical techniques for the sensing of 5-aminosalicylic acid and compare them to other laboratory-based measurements. The applications, challenges faced, and future opportunities for electroanalytical based sensing platforms are presented in this review.
{"title":"Electroanalytical Overview: The Sensing of Mesalamine (5-Aminosalicylic Acid)","authors":"Robert D. Crapnell, Prashanth S. Adarakatti and Craig E. Banks*, ","doi":"10.1021/acsmeasuresciau.3c00061","DOIUrl":"10.1021/acsmeasuresciau.3c00061","url":null,"abstract":"<p >Mesalamine, known as 5-aminosalicylic acid, is a medication used primarily in the treatment of inflammatory bowel disease, including ulcerative colitis and Crohn’s disease. 5-Aminosalicylic acid can be measured using various benchtop laboratory techniques which involve liquid chromatography–mass spectroscopy, but these are sophisticated and large, meaning that they cannot be used on-site because transportation of the samples, chemicals, and physical and biological reactions can potentially occur, which can affect the sample’s composition and potentially result in inaccurate results. An alternative approach is the use of electrochemical based sensing platforms which has the advantages of portability, cost-efficiency, facile miniaturization, and rapid analysis while nonetheless providing sensitivity and selectivity. We provide an overview of the use of the electroanalytical techniques for the sensing of 5-aminosalicylic acid and compare them to other laboratory-based measurements. The applications, challenges faced, and future opportunities for electroanalytical based sensing platforms are presented in this review.</p>","PeriodicalId":29800,"journal":{"name":"ACS Measurement Science Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsmeasuresciau.3c00061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138577084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-07DOI: 10.1021/acsmeasuresciau.3c00052
Muhammad Saqib*, Mariam Zafar, Mohamed Ibrahim Halawa, Shahzad Murtaza, Ghulam Mustafa Kamal and Guobao Xu,
Single-particle-level measurements, during the reaction, avoid averaging effects that are inherent limitations of conventional ensemble strategies. It allows revealing structure–activity relationships beyond averaged properties by considering crucial particle-selective descriptors including structure/morphology dynamics, intrinsic heterogeneity, and dynamic fluctuations in reactivity (kinetics, mechanisms). In recent years, numerous luminescence (optical) techniques such as chemiluminescence (CL), electrochemiluminescence (ECL), and fluorescence (FL) microscopies have been emerging as dominant tools to achieve such measurements, owing to their diversified spectroscopy principles, noninvasive nature, higher sensitivity, and sufficient spatiotemporal resolution. Correspondingly, state-of-the-art methodologies and tools are being used for probing (real-time, operando, in situ) diverse applications of single particles in sensing, medicine, and catalysis. Herein, we provide a concise and comprehensive perspective on luminescence-based detection and imaging of single particles by putting special emphasis on their basic principles, mechanistic pathways, advances, challenges, and key applications. This Perspective focuses on the development of emission intensities and imaging based individual particle detection. Moreover, several key examples in the areas of sensing, motion, catalysis, energy, materials, and emerging trends in related areas are documented. We finally conclude with the opportunities and remaining challenges to stimulate further developments in this field.
{"title":"Nanoscale Luminescence Imaging/Detection of Single Particles: State-of-the-Art and Future Prospects","authors":"Muhammad Saqib*, Mariam Zafar, Mohamed Ibrahim Halawa, Shahzad Murtaza, Ghulam Mustafa Kamal and Guobao Xu, ","doi":"10.1021/acsmeasuresciau.3c00052","DOIUrl":"10.1021/acsmeasuresciau.3c00052","url":null,"abstract":"<p >Single-particle-level measurements, during the reaction, avoid averaging effects that are inherent limitations of conventional ensemble strategies. It allows revealing structure–activity relationships beyond averaged properties by considering crucial particle-selective descriptors including structure/morphology dynamics, intrinsic heterogeneity, and dynamic fluctuations in reactivity (kinetics, mechanisms). In recent years, numerous luminescence (optical) techniques such as chemiluminescence (CL), electrochemiluminescence (ECL), and fluorescence (FL) microscopies have been emerging as dominant tools to achieve such measurements, owing to their diversified spectroscopy principles, noninvasive nature, higher sensitivity, and sufficient spatiotemporal resolution. Correspondingly, state-of-the-art methodologies and tools are being used for probing (real-time, operando, in situ) diverse applications of single particles in sensing, medicine, and catalysis. Herein, we provide a concise and comprehensive perspective on luminescence-based detection and imaging of single particles by putting special emphasis on their basic principles, mechanistic pathways, advances, challenges, and key applications. This Perspective focuses on the development of emission intensities and imaging based individual particle detection. Moreover, several key examples in the areas of sensing, motion, catalysis, energy, materials, and emerging trends in related areas are documented. We finally conclude with the opportunities and remaining challenges to stimulate further developments in this field.</p>","PeriodicalId":29800,"journal":{"name":"ACS Measurement Science Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsmeasuresciau.3c00052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138545847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-07DOI: 10.1021/acsmeasuresciau.3c00055
Wei Wang, Carmen R. de Nier, Manfred Wuhrer and Guinevere S.M. Lageveen-Kammeijer*,
Prostate-specific antigen (PSA) is a well-known clinical biomarker in prostate cancer (PCa) diagnosis, but a better test is still needed, as the serum-level-based PSA quantification exhibits limited specificity and comes with poor predictive value. Prior to PSA, prostatic acid phosphatase (PAP) was used, but it was replaced by PSA because PSA improved the early detection of PCa. Upon revisiting PAP and its glycosylation specifically, it appears to be a promising new biomarker candidate. Namely, previous studies have indicated that PAP glycoforms differ between PCa and non-PCa individuals. However, an in-depth characterization of PAP glycosylation is still lacking. In this study, we established an in-depth glycoproteomic assay for urinary PAP by characterizing both the micro- and macroheterogeneity of the PAP glycoprofile. For this purpose, PAP samples were analyzed by capillary electrophoresis coupled to mass spectrometry after affinity purification from urine and proteolytic digestion. The developed urinary PAP assay was applied on a pooled DRE (digital rectal examination) urine sample from nine individuals. Three glycosylation sites were characterized, namely N94, N220, and N333, via N-glycopeptide analysis. Taking sialic acid linkage isomers into account, a total of 63, 27, and 4 N-glycan structures were identified, respectively. The presented PAP glycoproteomic assay will enable the determination of potential glycomic biomarkers for the early detection and prognosis of PCa in cohort studies.
前列腺特异性抗原(PSA)是诊断前列腺癌(PCa)的著名临床生物标志物,但由于基于血清水平的 PSA 定量特异性有限且预测价值不高,因此仍需要更好的检测方法。在 PSA 之前,人们使用前列腺酸性磷酸酶(PAP),但由于 PSA 提高了 PCa 的早期检测率,PAP 被 PSA 所取代。重新审视前列腺酸性磷酸酶及其糖基化特性后,它似乎是一个很有希望的候选生物标记物。也就是说,以前的研究表明 PCa 患者和非 PCa 患者的 PAP 糖基化形式不同。然而,目前仍缺乏对 PAP 糖基化的深入研究。在本研究中,我们通过表征 PAP 糖型的微观和宏观异质性,建立了尿液 PAP 的深入糖蛋白组学检测方法。为此,在对尿液进行亲和纯化和蛋白水解消化后,采用毛细管电泳结合质谱法对 PAP 样品进行了分析。所开发的尿液 PAP 检测方法适用于来自九个人的 DRE(数字直肠检查)尿液样本。通过 N-糖肽分析,确定了三个糖基化位点,即 N94、N220 和 N333。考虑到半乳淀粉酸连接异构体,共鉴定出 63、27 和 4 个 N-糖结构。所介绍的 PAP 糖蛋白组测定方法将有助于确定潜在的糖生物标记物,以便在队列研究中对 PCa 进行早期检测和预后判断。
{"title":"In-Depth Glycoproteomic Assay of Urinary Prostatic Acid Phosphatase","authors":"Wei Wang, Carmen R. de Nier, Manfred Wuhrer and Guinevere S.M. Lageveen-Kammeijer*, ","doi":"10.1021/acsmeasuresciau.3c00055","DOIUrl":"10.1021/acsmeasuresciau.3c00055","url":null,"abstract":"<p >Prostate-specific antigen (PSA) is a well-known clinical biomarker in prostate cancer (PCa) diagnosis, but a better test is still needed, as the serum-level-based PSA quantification exhibits limited specificity and comes with poor predictive value. Prior to PSA, prostatic acid phosphatase (PAP) was used, but it was replaced by PSA because PSA improved the early detection of PCa. Upon revisiting PAP and its glycosylation specifically, it appears to be a promising new biomarker candidate. Namely, previous studies have indicated that PAP glycoforms differ between PCa and non-PCa individuals. However, an in-depth characterization of PAP glycosylation is still lacking. In this study, we established an in-depth glycoproteomic assay for urinary PAP by characterizing both the micro- and macroheterogeneity of the PAP glycoprofile. For this purpose, PAP samples were analyzed by capillary electrophoresis coupled to mass spectrometry after affinity purification from urine and proteolytic digestion. The developed urinary PAP assay was applied on a pooled DRE (digital rectal examination) urine sample from nine individuals. Three glycosylation sites were characterized, namely N<sub>94</sub>, N<sub>220</sub>, and N<sub>333</sub>, via <i>N</i>-glycopeptide analysis. Taking sialic acid linkage isomers into account, a total of 63, 27, and 4 <i>N</i>-glycan structures were identified, respectively. The presented PAP glycoproteomic assay will enable the determination of potential glycomic biomarkers for the early detection and prognosis of PCa in cohort studies.</p>","PeriodicalId":29800,"journal":{"name":"ACS Measurement Science Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsmeasuresciau.3c00055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138552272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-05DOI: 10.1021/acsmeasuresciau.3c00051
Jana M. Carpenter, Hannah M. Hynds, Kingsley Bimpeh and Kelly M. Hines*,
Although MALDI-ToF platforms for microbial identifications have found great success in clinical microbiology, the sole use of protein fingerprints for the discrimination of closely related species, strain-level identifications, and detection of antimicrobial resistance remains a challenge for the technology. Several alternative mass spectrometry-based methods have been proposed to address the shortcomings of the protein-centric approach, including MALDI-ToF methods for fatty acid/lipid profiling and LC-MS profiling of metabolites. However, the molecular diversity of microbial pathogens suggests that no single “ome” will be sufficient for the accurate and sensitive identification of strain- and susceptibility-level profiling of bacteria. Here, we describe the development of an alternative approach to microorganism profiling that relies upon both metabolites and lipids rather than a single class of biomolecule. Single-phase extractions based on butanol, acetonitrile, and water (the BAW method) were evaluated for the recovery of lipids and metabolites from Gram-positive and -negative microorganisms. We found that BAW extraction solutions containing 45% butanol provided optimal recovery of both molecular classes in a single extraction. The single-phase extraction method was coupled to hydrophilic interaction liquid chromatography (HILIC) and ion mobility-mass spectrometry (IM-MS) to resolve similar-mass metabolites and lipids in three dimensions and provide multiple points of evidence for feature annotation in the absence of tandem mass spectrometry. We demonstrate that the combined use of metabolites and lipids can be used to differentiate microorganisms to the species- and strain-level for four of the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa) using data from a single ionization mode. These results present promising, early stage evidence for the use of multiomic signatures for the identification of microorganisms by liquid chromatography, ion mobility, and mass spectrometry that, upon further development, may improve upon the level of identification provided by current methods.
{"title":"HILIC-IM-MS for Simultaneous Lipid and Metabolite Profiling of Bacteria","authors":"Jana M. Carpenter, Hannah M. Hynds, Kingsley Bimpeh and Kelly M. Hines*, ","doi":"10.1021/acsmeasuresciau.3c00051","DOIUrl":"10.1021/acsmeasuresciau.3c00051","url":null,"abstract":"<p >Although MALDI-ToF platforms for microbial identifications have found great success in clinical microbiology, the sole use of protein fingerprints for the discrimination of closely related species, strain-level identifications, and detection of antimicrobial resistance remains a challenge for the technology. Several alternative mass spectrometry-based methods have been proposed to address the shortcomings of the protein-centric approach, including MALDI-ToF methods for fatty acid/lipid profiling and LC-MS profiling of metabolites. However, the molecular diversity of microbial pathogens suggests that no single “ome” will be sufficient for the accurate and sensitive identification of strain- and susceptibility-level profiling of bacteria. Here, we describe the development of an alternative approach to microorganism profiling that relies upon both metabolites and lipids rather than a single class of biomolecule. Single-phase extractions based on butanol, acetonitrile, and water (the BAW method) were evaluated for the recovery of lipids and metabolites from Gram-positive and -negative microorganisms. We found that BAW extraction solutions containing 45% butanol provided optimal recovery of both molecular classes in a single extraction. The single-phase extraction method was coupled to hydrophilic interaction liquid chromatography (HILIC) and ion mobility-mass spectrometry (IM-MS) to resolve similar-mass metabolites and lipids in three dimensions and provide multiple points of evidence for feature annotation in the absence of tandem mass spectrometry. We demonstrate that the combined use of metabolites and lipids can be used to differentiate microorganisms to the species- and strain-level for four of the ESKAPE pathogens (<i>Enterococcus faecium</i>, <i>Staphylococcus aureus</i>, <i>Acinetobacter baumannii</i>, and <i>Pseudomonas aeruginosa</i>) using data from a single ionization mode. These results present promising, early stage evidence for the use of multiomic signatures for the identification of microorganisms by liquid chromatography, ion mobility, and mass spectrometry that, upon further development, may improve upon the level of identification provided by current methods.</p>","PeriodicalId":29800,"journal":{"name":"ACS Measurement Science Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsmeasuresciau.3c00051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138539140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-05DOI: 10.1021/acsmeasuresciau.3c00049
Nipunika H. Godage, Song S. Qian, Erasmus Cudjoe and Emanuela Gionfriddo*,
This study addresses the challenges of matrix effects and interspecies plasma protein binding (PPB) on measurement variability during method validation across diverse plasma types (human, rat, rabbit, and bovine). Accurate measurements of small molecules in plasma samples often require matrix-matched calibration approaches with the use of specific plasma types, which may have limited availability or affordability. To mitigate the costs associated with human plasma measurements, we explore in this work the potential of cross-matrix-matched calibration using Bayesian hierarchical modeling (BHM) to correct for matrix effects associated with PPB. We initially developed a targeted quantitative approach utilizing biocompatible solid-phase microextraction coupled with liquid chromatography–mass spectrometry for xenobiotic analysis in plasma. The method was evaluated for absolute matrix effects across human, bovine, rat, and rabbit plasma comparing pre- and postmatrix extraction standards. Absolute matrix effects from 96 to 108% for most analytes across plasma sources indicate that the biocompatibility of the extraction phase minimizes interference coextraction. However, the extent of PPB in different media can still affect the accuracy of the measurement when the extraction of small molecules is carried out via free concentration, as in the case of microextraction techniques. In fact, while matrix-matched calibration revealed high accuracy, cross-matrix calibration (e.g., using a calibration curve generated from bovine plasma) proved inadequate for precise measurements in human plasma. A BHM was used to calculate correction factors for each analyte within each plasma type, successfully mitigating the measurement bias resulting from diverse calibration curve types used to quantify human plasma samples. This work contributes to the development of cost-effective, efficient calibration strategies for biofluids. Leveraging easily accessible plasma sources, like bovine plasma, for method optimization and validation prior to analyzing costly plasma (e.g., human plasma) holds substantial advantages applicable to biomonitoring and pharmacokinetic studies.
{"title":"Enhancing Quantitative Analysis of Xenobiotics in Blood Plasma through Cross-Matrix Calibration and Bayesian Hierarchical Modeling","authors":"Nipunika H. Godage, Song S. Qian, Erasmus Cudjoe and Emanuela Gionfriddo*, ","doi":"10.1021/acsmeasuresciau.3c00049","DOIUrl":"10.1021/acsmeasuresciau.3c00049","url":null,"abstract":"<p >This study addresses the challenges of matrix effects and interspecies plasma protein binding (PPB) on measurement variability during method validation across diverse plasma types (human, rat, rabbit, and bovine). Accurate measurements of small molecules in plasma samples often require matrix-matched calibration approaches with the use of specific plasma types, which may have limited availability or affordability. To mitigate the costs associated with human plasma measurements, we explore in this work the potential of cross-matrix-matched calibration using Bayesian hierarchical modeling (BHM) to correct for matrix effects associated with PPB. We initially developed a targeted quantitative approach utilizing biocompatible solid-phase microextraction coupled with liquid chromatography–mass spectrometry for xenobiotic analysis in plasma. The method was evaluated for absolute matrix effects across human, bovine, rat, and rabbit plasma comparing pre- and postmatrix extraction standards. Absolute matrix effects from 96 to 108% for most analytes across plasma sources indicate that the biocompatibility of the extraction phase minimizes interference coextraction. However, the extent of PPB in different media can still affect the accuracy of the measurement when the extraction of small molecules is carried out via free concentration, as in the case of microextraction techniques. In fact, while matrix-matched calibration revealed high accuracy, cross-matrix calibration (e.g., using a calibration curve generated from bovine plasma) proved inadequate for precise measurements in human plasma. A BHM was used to calculate correction factors for each analyte within each plasma type, successfully mitigating the measurement bias resulting from diverse calibration curve types used to quantify human plasma samples. This work contributes to the development of cost-effective, efficient calibration strategies for biofluids. Leveraging easily accessible plasma sources, like bovine plasma, for method optimization and validation prior to analyzing costly plasma (e.g., human plasma) holds substantial advantages applicable to biomonitoring and pharmacokinetic studies.</p>","PeriodicalId":29800,"journal":{"name":"ACS Measurement Science Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsmeasuresciau.3c00049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138539128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}