Manuel Gutiérrez-Capitán, Eva Balada, Anna Aviñó, Lluïsa Vilaplana, Roger Galve, Alícia Lacoma, Antonio Baldi, Antonio Alcamí, Véronique Noé, Carlos J. Ciudad, Ramón Eritja, María-Pilar Marco, César Fernández-Sánchez
{"title":"Unraveling the Amplification-Free Quantitative Detection of Viral RNA in Nasopharyngeal Swab Samples Using a Compact Electrochemical Rapid Test Device","authors":"Manuel Gutiérrez-Capitán, Eva Balada, Anna Aviñó, Lluïsa Vilaplana, Roger Galve, Alícia Lacoma, Antonio Baldi, Antonio Alcamí, Véronique Noé, Carlos J. Ciudad, Ramón Eritja, María-Pilar Marco, César Fernández-Sánchez","doi":"10.1021/acs.analchem.5c01605","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c01605","url":null,"abstract":"Providing viral load numbers of infection events aids in the identification of disease severity and in the effective overall patient management. Gold-standard polymerase chain reaction (PCR) techniques make this possible but cannot be applied at the point of need and in low-resource settings. Here, we report on the development of a compact analytical platform that can detect a conserved sequence of the RNA of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in 40 min in nasopharyngeal swab samples without the need for any previous purification or gene amplification steps. It combines electrochemical and paper fluidic approaches together with a sandwich hybridization assay performed on magnetic nanoparticles (MNPs) modified with a tailor-designed capture DNA hairpin. The device proves to quantitatively detect viral RNA in a retrospective study carried out with nasopharyngeal swab samples. A sensitivity of 100% and a specificity of 93% were estimated by the receiver operating characteristic (ROC) analysis. However, although molar concentration values of the target RNA sequence are provided, these estimates do not fully correlate with the viral load numbers estimated by RT-qPCR over the whole Ct sample range. Empirical studies have been carried out that have provided clear insights into this hurdle and simple solutions to overcome it, without depriving the device of the features required for potential use in a point-of-care (PoC) environment.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"71 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177198","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}
Haibin Si, Qing Xu, Yan Sun, Dexin Du, Yiguo Wang, Simin Li, Lu Li, Bo Tang
{"title":"Fusion of Molecular and Mechanical Phenotypes Enables High-Purity and Low-Loss Reacquisition of Viable CTCs for Transcriptome Analysis","authors":"Haibin Si, Qing Xu, Yan Sun, Dexin Du, Yiguo Wang, Simin Li, Lu Li, Bo Tang","doi":"10.1021/acs.analchem.5c01806","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c01806","url":null,"abstract":"The high-purity and low-loss reacquisition of viable circulating tumor cells (CTCs) is crucial for enabling downstream omics analysis of CTCs and currently represents key challenges limiting their application in clinical diagnosis and pathological research. Given the limitations of traditional methods that rely solely on a molecular or mechanical phenotype for CTCs acquisition, this study introduces an innovative approach that fuses the inherent molecular and mechanical phenotypes of CTCs into a new mechanical phenotype, thereby achieving high-purity preconcentration and low-loss reacquisition of CTCs. Specifically, CTCs in blood are immunomodified using calcium carbonate microspheres (CCMSs) conjugated with antibodies, transforming the molecular phenotype (membrane protein expression) into an additional mechanical phenotype (increased size and reduced deformability). This transformation enhances the mechanical phenotype distinctions between CTCs and white blood cells, enabling high-purity preconcentration of CTCs on a single-cell trapping array chip. Since CCMSs can be reversibly eliminated under weak acid, captured CTCs can be nondestructively reacquired with 93.10% in microliter-scale solution, allowing for subsequent omics analysis. In a breast cancer mouse model, the counts and transcriptome analysis of CTCs provide valuable insights into assessing tumor occurrence and progression.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"43 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177199","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":"Dual Ratiometric Single-Molecule Theranostic Probes for Photothermal Therapy and Real-Time Quantitative Evaluation of Therapeutic Efficacy In Vivo","authors":"Shuping Zhang, Xingyue Liu, Bang-Ping Jiang, Shi-Chen Ji, Hua Chen, Xing-Can Shen","doi":"10.1021/acs.analchem.5c02253","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c02253","url":null,"abstract":"Tracking the quantitative evaluation of therapeutic efficiency in tumors is essential for the precision management of cancer patients. Theranostic probes, which integrate diagnostic molecular imaging and therapeutic capabilities into a single entity, can be used to monitor the treatment process and reflect the therapeutic effect. However, current theranostic probes lack precise quantitative evaluations <i>in vivo</i> due to the use of single-wavelength imaging during tumor therapy. Here we present a portal library of dual ratiometric single-molecule theranostic probes for precise tumor therapy through photothermal therapy (PTT) and quantitative evaluation of tumor cell death <i>in vivo</i> via ratiometric near-infrared fluorescence (NIRF) and ratiometric photoacoustic (PA) imaging. One optimal single-molecule dye is further modified into an activatable probe (AF-1F-NO<sub>2</sub>), whose dual ratiometric NIRF/PA signal and photothermal activity are only activated in the presence of a tumor biomarker (nitroreductase). By eliciting a dual ratiometric response (NIRF/PA: NIRF<sub>850</sub>/NIRF<sub>750</sub>; PA<sub>770</sub>/PA<sub>670</sub>) to tumor hypoxia, the new probe acts as a hypoxia-activated PTT theranostic agent, enabling real-time quantitative evaluation <i>in vivo</i> during PTT. Thus, this study not only presents the first dual ratiometric single-molecule theranostic probe for PTT and real-time quantitative evaluation of therapeutic efficacy <i>in vivo</i>, but also opens up a promising paradigm for engineering other single-molecule dual ratiometric theranostic probes in combination with more therapeutic modalities for precision medicine.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"52 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177200","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}
Lukasz Polewski, Daria Dymnikova, Weronika Malicka, Maike Lettow, Gert von Helden, Christian Teutloff, Matthias Ballauff, Matthias Taupitz, Robert Bittl, Kevin Pagel
{"title":"Glycan-Induced Transchelation of Gadolinium from Magnetic Resonance Imaging Contrast Agent-Complexes","authors":"Lukasz Polewski, Daria Dymnikova, Weronika Malicka, Maike Lettow, Gert von Helden, Christian Teutloff, Matthias Ballauff, Matthias Taupitz, Robert Bittl, Kevin Pagel","doi":"10.1021/acs.analchem.4c06624","DOIUrl":"https://doi.org/10.1021/acs.analchem.4c06624","url":null,"abstract":"Glycosaminoglycans (GAGs) are linear, highly acidic polysaccharides that serve as essential extracellular matrix components. There has been increasing evidence that GAGs can release gadolinium ions from complexes of magnetic resonance imaging contrast agents. This unintended release of gadolinium might be an initial step leading to gadolinium deposition disease, as observed in some patients after intravenous injection of such contrast agents. However, the molecular details of the release remain poorly understood. In this work, we provide direct evidence for gadolinium binding by GAGs using synthetic model substance Fondaparinux (FPX), a heparin mimetic. We observed FPX–gadolinium complexes in mass spectrometry experiments and electron paramagnetic resonance spectroscopy (EPR) and characterized the binding by EPR, isothermal titration calorimetry, and gas-phase infrared (IR) spectroscopy. Finally, we were able to follow the transchelation process on a molecular level by utilizing collision-induced dissociation experiments.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"35 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184012","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}
Troy R. Scoggins IV, Yingchan Guo, Paul Zerebinski, Boone M. Prentice
{"title":"Ozonolysis Dissociation Kinetics for the Relative Quantification of Geometrical Phosphatidylcholine Isomers","authors":"Troy R. Scoggins IV, Yingchan Guo, Paul Zerebinski, Boone M. Prentice","doi":"10.1021/acs.analchem.5c00670","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c00670","url":null,"abstract":"The structural diversity of lipids presents significant challenges for accurate identification and characterization, necessitating advanced analytical tools. Among these challenges is the differentiation between cis and trans isomers of lipids, which differ only by the geometry of a carbon–carbon double bond. This study employs ozonolysis kinetics to distinguish these isomers based on the reactivity of their gas phase ions with ozone. To achieve precise differentiation, it is essential to use an ion adduct that enhances reactivity, thereby improving the sensitivity of the kinetic assays. We evaluated various ion types, including protonated lipids as well as lipids cationized with lithium, sodium, and potassium, using a modified quadrupole ion trap mass spectrometer. Our results demonstrate that lithium-adducted lipids exhibit the highest reaction efficiency and greatest sensitivity for distinguishing between cis and trans isomers. Subsequent analysis of cis and trans isomer mixtures of PC 18:1/18:1 (Δ9), PC 16:1/16:1 (Δ9), and PC 14:1/14:1 (Δ9) confirmed the method’s robustness.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"41 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183810","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}
Gabriely S. Folli, Anne Louise S. Torres, Matthews Martins, Luiz Ricardo Rodrigues Silva, Vinícius Bermond Marques, Maria Tereza Carneiro, Larissa Dias Roriz, Leonardo dos Santos, Wanderson Romão, Francis L. Martin, Paulo R. Filgueiras, Valério G. Barauna
{"title":"One-Drop Serum Screening Test to Monitor Tissue Iron Accumulation","authors":"Gabriely S. Folli, Anne Louise S. Torres, Matthews Martins, Luiz Ricardo Rodrigues Silva, Vinícius Bermond Marques, Maria Tereza Carneiro, Larissa Dias Roriz, Leonardo dos Santos, Wanderson Romão, Francis L. Martin, Paulo R. Filgueiras, Valério G. Barauna","doi":"10.1021/acs.analchem.5c00778","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c00778","url":null,"abstract":"Although iron is an essential element for vital body functions, iron overload (IO) is accompanied by significant cellular damage due to its accumulation within organs. Thus, early diagnosis and accurate identification of the affected organs are critical for preventing irreversible damage and improving patient survival rates. Diagnosing tissue iron deposits relieves invasive biopsies with atomic absorption spectrometry (reserved for specific cases) or noninvasive but costly and time-consuming imaging techniques like computerized tomography and magnetic resonance, which provide limited analytical data and are unsuitable for routine screening. As an alternative, Fourier transform infrared spectroscopy combined with machine learning has emerged as a promising approach for supporting medical decision-making. In this study, we developed a minimally invasive method to identify IO and quantify iron levels in blood and tissues (heart, liver, spleen, and kidney) without biopsies. PLS-DA classification models and PLS regression models were constructed based on samples categorized into a control group (<i>n</i> = 10) and three iron-administered groups at 250 mg kg<sup>–1</sup> (<i>n</i> = 14), 500 mg·kg<sup>–1</sup> (<i>n</i> = 13), and 1000 mg·kg<sup>–1</sup> (<i>n</i> = 15). Iron levels were measured in blood samples and tissue biopsies (spleen, heart, liver, and kidney). The binary classification models (control vs iron-administered) and multiclass models (control, 250, 500, and 1000 mg·kg<sup>–1</sup>) demonstrated satisfactory performance into train and validation groups. PLS regression models for quantifying iron concentrations in blood and tissues exhibited excellent linearity and low associated errors across both calibration and test groups. Permutation tests confirmed that all models found a real class structure in the data, were not random, and were built using true chemical information. The chemical insights from the spectra may reflect adaptations associated with iron-induced dysregulation. Alterations in biomolecules could reflect systemic stress responses and may result from free radicals generated by the iron-induced Fenton reaction. Moreover, key spectral regions revealed functional interrelationships, particularly between spleen and liver, and heart and kidneys. In summary, the findings support the potential of this innovative for future research to identify IO and quantify iron levels in human blood and different human tissues using only a single drop of blood without tissue biopsies.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"81 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184014","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}
Barbora Svobodová, David Št’astný, Hans Blom, Ilya Mikhalyov, Natalia Gretskaya, Alena Balleková, Erdinc Sezgin, Martin Hof, Radek Šachl
{"title":"Revised Diffusion Law Permits Quantitative Nanoscale Characterization of Membrane Organization","authors":"Barbora Svobodová, David Št’astný, Hans Blom, Ilya Mikhalyov, Natalia Gretskaya, Alena Balleková, Erdinc Sezgin, Martin Hof, Radek Šachl","doi":"10.1021/acs.analchem.5c00021","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c00021","url":null,"abstract":"The formation of functional nanoscopic domains is an inherent property of plasma membranes. Stimulated emission depletion combined with fluorescence correlation spectroscopy (STED-FCS) has been previously used to identify such domains; however, the information obtained by STED-FCS has been limited to the presence of such domains while crucial parameters have not been accessible, such as size (<i>R</i><sub>d</sub>), the fraction of occupied membrane surface (<i>f</i>), in-membrane lipid diffusion inside (<i>D</i><sub>in</sub>) and outside (<i>D</i><sub>out</sub>) the nanodomains as well as their self-diffusion (<i>D</i><sub>d</sub>). Here, we introduce a quantitative approach based on a revised interpretation of the diffusion law. By analyzing experimentally recorded STED-FCS diffusion law plots using a comprehensive library of simulated diffusion law plots, we extract these five parameters from STED-FCS data. That approach is verified on ganglioside nanodomains in giant unilamellar vesicles, validating the Saffman-Delbrück assumption for <i>D</i><sub>d</sub>. STED-FCS data in both plasma membranes of living PtK2 cells and giant plasma membrane vesicles are examined, and a quantitative framework for molecular diffusion modes in biological membranes is presented.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"49 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165368","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}
Yu-shuang Jin, Li Chen, Yi-Fei Chen, Ruo Yuan, Ya-Qin Chai, Jia-li Liu
{"title":"Dual-Mode Photoelectrochemical/ColoriMetric Biosensor with a Broad Linear Range for the Sensitive Detection of Enrofloxacin in Aquatic Products","authors":"Yu-shuang Jin, Li Chen, Yi-Fei Chen, Ruo Yuan, Ya-Qin Chai, Jia-li Liu","doi":"10.1021/acs.analchem.5c00991","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c00991","url":null,"abstract":"In this study, an integrated dual-mode biosensor combining photoelectrochemical (PEC) and colorimetric (CL) methods was proposed to broaden the linear detection range of enrofloxacin (ENR), thus enabling sensitive detection of ENR in aquatic products. Compared to traditional PEC/CL dual-mode biosensors that rely on the same sensitizer for both PEC and CL signals, this biosensor expanded the linear range and enhanced sensitivity by separating the sensitizer of PEC and the signal label of CL. Specifically, the PEC detection platform employed a Z-type heterojunction of iron indium sulfide (FeIn<sub>2</sub>S<sub>4</sub>) and cadmium sulfide (CdS) to significantly improve the photoelectric conversion efficiency for the sensitivity of PEC detection. Furthermore, based on an entropy-driven catalytic nucleic acid circuit (ETSD) strategy mediated by aptamers, ENR was converted into a mass of output DNA. Subsequently, the output DNA triggered a strand displacement reaction mediated by a palindrome-catalyzed DNA assembly (NEPA) to form a three-dimensional gold nanoparticle-DNA nanocomposite for the adsorption of methylene blue (3D Au-DNA NC-MB). The resulting 3D Au-DNA NC-MB biomolecular nanocarrier was then used in PEC detection for trace ENR with a linear detection range of 10<sup>–5</sup>–10<sup>2</sup> ng·mL<sup>–1</sup>. Concurrently, the unadsorbed MB solution was used in CL detection for a high level of ENR with a linear detection range from 10<sup>–1</sup> to 10<sup>4</sup> ng·mL<sup>–1</sup>. Finally, the method was successfully applied to detect ENR in aquatic products with higher sensitivity and a wider linear range than most reported detection methods, which is anticipated for use in food safety and environmental surveillance.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"148 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165372","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}
Xin Xu, Dan Wang, Cailin Zhou, Yuhang Xing, Tianpei Cai, Xinlei Yang, Ruilin Yang, Peijie Xie, Fei Liu, Zeyang Jia, Xueli Zhai, Lu Liu, Donghao Li
{"title":"High-Efficient and Controllable Purification of Protein by Cyclic Injection in an Orthogonal Micro-Free-Flow Electrophoresis","authors":"Xin Xu, Dan Wang, Cailin Zhou, Yuhang Xing, Tianpei Cai, Xinlei Yang, Ruilin Yang, Peijie Xie, Fei Liu, Zeyang Jia, Xueli Zhai, Lu Liu, Donghao Li","doi":"10.1021/acs.analchem.5c00436","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c00436","url":null,"abstract":"High-abundance proteins (HAPs) in plasma significantly interfere with the purification of low-abundance proteins (LAPs). This study proposed a unique orthogonality microfluidic free-flow electrophoresis (OMFFE) platform and then set up a self-made device that can perform cyclic injection for protein purification. The OMFFE device consists of a focusing channel, an orthogonal separation channel, and two sets of voltage-controlled electrodes. In the scan voltage mode, the voltage and deflection angle are positively correlated for proteins, allowing the determination of the separation voltage for the target protein. In the selective voltage mode, proteins with a specific mass-to-charge ratio could be deflected into a specific channel, enabling selective separation of proteins. When the 75 V voltage was applied, the optimal resolution of the device between HAPs (human serum albumin, HSA, and immunoglobulin IgG) and LAP (green fluorescent protein, GFP) was achieved with Rs = 0.37. The OMFFE device achieved a removal rate of 94.7 ± 4.1% for HSA and IgG and a recovery rate of 95.3 ± 3.7% for GFP. The purity of GFP has increased by approximately 32 times. Furthermore, in human plasma, the removal rates of HAPs (HSA and IgG) and the recovery rates of LAP (GFP) are as high as 83.2 ± 3.9 and 76.3 ± 7.5%, respectively. The OMFFE device can achieve the removal and purification of proteins, hence posing promising potential in proteomics, protein function analysis, and medical diagnostics.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"2 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177239","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}
Dong Wang, I Wayan Ardyan Sudharta Putra, Hiroko Oshima, Han Gia Nguyen, Ayhan Yurtsever, Alexis Borowiak, Linhao Sun, Masanobu Oshima, Shinji Watanabe
{"title":"Characterizing for Subcellular Physical Property Changes of Chemotherapy Drug-Resistant Malignant Cancer Cells","authors":"Dong Wang, I Wayan Ardyan Sudharta Putra, Hiroko Oshima, Han Gia Nguyen, Ayhan Yurtsever, Alexis Borowiak, Linhao Sun, Masanobu Oshima, Shinji Watanabe","doi":"10.1021/acs.analchem.5c01597","DOIUrl":"https://doi.org/10.1021/acs.analchem.5c01597","url":null,"abstract":"Recently, scanning ion conductance microscopy (SICM) as a noncontact nanoprobe tool has offered great advantages for applications in revealing biophysicochemical properties of soft biological samples, specifically for living cells. These physical properties, e.g., stiffness, of the cell surface provide an efficient label-free biomarker for differing tumor from normal cells, leading to gradually increasing interest in cancer biological studies. However, expanding potential application of SICM for cancer treatment, especially targeting chemotherapy facing a challenge in drug resistance, is still rarely explored. In addition, in biology, some clues indicate that the physical factors (matrix stiffness and stress) can contribute to tumor drug resistance. Meanwhile, fundamental studies to quantify these unique physical properties of drug-resistant cancer cells correlated with leverage for targeted therapy are less known. Here, we utilized chemotherapy drugs, 5-fluorouracil (5-FU) and oxaliplatin (OXA), to establish three drug-resistant cell lines from human colorectal cancer, including DLD1, SW620, and HT29 cells. High-speed SICM measurements were performed to visualize surface characteristics of subcellular physical properties (heights, roughness, and stiffness) on the control (ctrl) sample and drug-resistant samples derived from ctrl samples. Statistical analysis of stiffness showed a reduced change from drug-resistant samples, especially those resistant to 5-FU and OXA simultaneously, in comparison to ctrl samples. This work sheds light on subcellular physical properties of drug-resistant cell lines. The SICM technique as an important strategy would provide useful assistance in biomedicine in leveraging for targeted therapy.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"1 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165376","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}