Analytical Chemistry最新文献

{"title":"Monitoring of Doxorubicin-Mediated Mitochondria–Lysosome Crosstalk by In Situ Raman Spectroscopy: The Molecular Mechanism during Apoptosis and Implications for Cardiotoxicity","authors":"Li Song,&nbsp;Zeyi Wang,&nbsp;Yaqiang Chen,&nbsp;Wei Li,&nbsp;Jinyu Zhu,&nbsp;Linjun Cai,&nbsp;Xiao Xia Han","doi":"10.1021/acs.analchem.6c03083","DOIUrl":"10.1021/acs.analchem.6c03083","url":null,"abstract":"<p>Doxorubicin is among the most commonly used chemotherapeuticagentsfor a wide range of cancers. Despite its effectiveness, it poses long-termcardiotoxic risks that elevate mortality among cancer patients. Inthis study, doxorubicin-mediated mitochondria–lysosome crosstalkin apoptosis and the underlying molecular mechanism are explored.The interactions between organelle-specific phospholipids and doxorubicin,and their structural basis, are investigated using comprehensive spectroscopyand molecular dynamics simulations. Our results by in situ Raman spectroscopyreveal that doxorubicin can directly trigger mitochondrial and lysosomalpermeabilization, facilitating the release of key apoptotic modulators.Besides phospholipids, doxorubicin is found to interact with cytochromec and boost its proapoptotic effect. Further study indicates thatprotecting cardiolipin is sufficient to inhibit doxorubicin-induceddisruption of CL conformation. Accordingly, the molecular mechanismunderlying doxorubicin-mediated mitochondria–lysosome crosstalkin apoptosis is proposed, paving the way for the rational design ofcardioprotective agents targeting mitochondria and lysosomes for cancerpatients.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"98 41","pages":"29529–29540"},"PeriodicalIF":7.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149003345","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":"Drug Metabolism and Drug–Drug Interactions Studied Using High-Throughput Ambient Mass Spectrometry","authors":"Mousumi Saha,&nbsp;Nari Talaty,&nbsp;Nicolás M. Morato,&nbsp;Mahdiyeh Shahi,&nbsp;Christopher J. Welch,&nbsp;Yunfei Feng,&nbsp;Christina R. Ferreira,&nbsp;David Wagner,&nbsp;Andreas Kaerner,&nbsp;Robert Graham Cooks","doi":"10.1021/acs.analchem.6c04039","DOIUrl":"10.1021/acs.analchem.6c04039","url":null,"abstract":"<p>Rapid characterization of drug metabolism and drug–druginteractions (DDIs) with quantitative rigor remains challenging dueto complex samples and labor-intensive workflows. We present a high-throughput(HT) ambient mass spectrometry (MS) approach using desorption electrosprayionization (DESI) that unites three complementary capabilities availableusing two different mass spectrometers: (A) untargeted screening tosurvey the metabolic space, (B) product ion scan tandem MS to characterizenovel metabolites, and (C) multiple reaction monitoring (MRM) to deliverprecise quantitation of substrates and metabolites. Applying the methodologyto diverse <em>in vitro</em> systems, we track substrate depletion,metabolite formation, and DDIs with quantitative accuracy (error &lt;9%for MRM quantitation) validated against liquid chromatography (LC)MS. The method operates two to three orders of magnitude faster (1s/sample) than traditional LC–MS methods. This allows hundredsof substrate–enzyme–DDI combinations to be followedin time-resolved fashion using ∼4 × 10⁴ individualDESI-MS measurements, acquired at a rate of &gt;3,000 measurements/hour.By combining HT screening and targeted monitoring, the DESI-MS approachdelivers metabolic discovery with robust quantitation, overcominga central bottleneck in large-scale drug metabolism studies. Thisinvestigation aims to provide a high-throughput analytical approachwith broad utility in drug discovery, toxicology, and precision medicineworkflows.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"98 41","pages":"29604–29615"},"PeriodicalIF":7.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019599","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":"Quantifying Viscosity of Semisolid Submicrometer and Nanosized Individual Aerosols Using Atomic Force Microscopy with Varying Cantilever Velocity","authors":"Ruwini A. Weerasinghe,&nbsp;Chamika K. Madawala,&nbsp;Alexei V. Tivanski","doi":"10.1021/acs.analchem.6c02398","DOIUrl":"10.1021/acs.analchem.6c02398","url":null,"abstract":"<p>Atmospheric aerosol viscosity governs diffusion timescales ofreactive gases into aerosols, thereby influencing gas uptake, heterogeneouschemistry, and atmospheric aging. However, direct viscosity measurementsof individual semisolid aerosols have been restricted to a relativelyhigh viscosity range and submicrometer size. Herein, a new atomicforce microscopy-based nanorheological experimental approach is presentedthat utilizes force–indentation distance and indentation ratemeasurements at varying cantilever velocities to quantify the viscosityof individual semisolid aerosols as a function of relative humidity(RH). Using glucose and sucrose as model systems, we demonstrate accuratesingle particle viscosity quantification spanning ∼10²·⁵ to 10⁷ Pa s under atmospherically relevantRH conditions. We establish an iterative cantilever velocity frameworkthat enables the determination of the appropriate velocity requiredfor accurate viscosity characterization of aerosols without priorknowledge of their composition. Additionally, we demonstrate thatthe method enables accurate viscosity quantification of individualsub-100 nm aerosols. We anticipate that future viscosity measurementsof atmospheric aerosols from various sources at different RHs willprovide valuable insights into aerosol viscosity variability and revealthe extent of particle-to-particle heterogeneity.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"98 41","pages":"29471–29480"},"PeriodicalIF":7.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149091825","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":"SPRINT-Cas12a: A Single Leading-Hairpin Probe-Enabled Dual-Pathway Activation Strategy for Sensitive miRNA Detection","authors":"Qian Li,Junda Liu,Mo Xue,Jiahao Wang,Youfei Zhang,Luzhen Huai,Xingzhou Zhu,Xiaoyan Liu,Jie Wang","doi":"10.1021/acs.analchem.6c06144","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c06144","url":null,"abstract":"CRISPR−Cas12a possesses robust trans-cleavage activity and has emerged as a powerful tool for nucleic acid detection. However, the efficient integration of Cas12a trans-cleavage with direct miRNA recognition and signal amplification remains challenging, particularly because conventional assay designs often rely on multiple probes or a single activation pathway. Here, we developed SPRINT-Cas12a, a single-probe RNA-triggered integrated trans-cleavage platform for sensitive miRNA detection. In this design, a leading hairpin probe (L-HP) specifically recognizes the target miRNA and initiates polymerase-mediated cascade isothermal amplification, synchronously generating two structurally distinct Cas12a-activating products: an RNA−DNA complex and a long-chain micro-hairpin probe (L-MHP). These products provide complementary activation pathways for Cas12a, thereby promoting reporter cleavage and fluorescence signal generation. The single-probe architecture simplifies probe design while enabling synergistic signal amplification through dual-pathway Cas12a activation. The platform was successfully adapted for the detection of miR-21 and miR-122, two miRNAs with distinct sequences, demonstrating its modularity and sequence versatility. Using miR-192 as a hepatocellular carcinoma-associated target, the method achieved sensitive detection in serum samples and distinguished patients with hepatocellular carcinoma from healthy controls, with results consistent with stem-loop quantitative reverse-transcription PCR. In addition, the platform was coupled with a lateral flow assay to provide an instrument-free visual readout. Depending on the amplification and readout format, the assay could be completed within 90 min to 120 min using simple laboratory equipment. Overall, SPRINT-Cas12a provides a single-probe, dual-pathway strategy for Cas12a-mediated miRNA detection and shows promise for portable molecular diagnostics and point-of-care testing.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"13 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221674","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":"AI Agent-Enabled Development of Enhanced DataYee for Robust and Efficient AFM Force Spectroscopy Analysis","authors":"Guojin Tang,Bin Zheng,Shihao Lin,Yifeng Tian,Yuhan Ma,Peng Zheng","doi":"10.1021/acs.analchem.6c05091","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c05091","url":null,"abstract":"High-throughput atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS) produces large, heterogeneous data sets that require force−curve screening, polymer model fitting, molecular event annotation, and expert verification. These interconnected operations limit analytical throughput and can introduce uncertainty when noisy or nonideal trajectories are processed. Here, we report the expert-supervised, AI agent-enabled development of DataYee, an integrated platform for AFM-SMFS analysis. The previously developed platform is referred to as original DataYee, whereas the version developed in this study is referred to as enhanced DataYee. During development, the AI agent assisted with literature retrieval, codebase navigation, coordinated modification of multiple software modules, refactoring, and debugging. Researchers defined the analytical requirements and verified the physical models, parameter constraints, software behavior, and experimental outputs. Enhanced DataYee combines convolutional neural network-based prescreening with support vector machine classification using interpretable mechanical features, noise-adaptive fitting window selection, worm-like regime crossover-informed multi-start worm-like chain fitting, and domain annotation constrained jointly by contour-length increments and unfolding forces. Functional refinements further improve data import, curve management, exception handling, and routine operation. Evaluation using a representative AFM-SMFS data set showed that enhanced DataYee improved the fitting and retention of noisy or nonideal trajectories while substantially reducing the number of curves requiring expert review. Following targeted expert verification, the resulting unfolding-force distribution remained consistent with manual analysis while including more validated molecular events. Enhanced DataYee therefore provides an efficient and traceable expert-in-the-loop workflow for high-throughput SMFS analysis and demonstrates how AI agents can support the scientifically supervised development of laboratory analytical software.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"29 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221670","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":"NOX2-Targeted Immunocapture Enables High-Specificity Lysosome Isolation from Low Cell Numbers","authors":"Anniek L. de Jager,Julia Berdasco-García,Sara Kassem,Alesha Louis,Brigitta A. E. Naber,Inge F. de Laat,Bas de Mooij,Kyra van der Pan,Jacques J. M. van Dongen,Cristina Teodosio,Paula Díez","doi":"10.1021/acs.analchem.6c01372","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c01372","url":null,"abstract":"Research on lysosomal composition and function is critical for understanding cellular homeostasis and pathogenesis of diverse diseases, including cancer. However, current isolation methods often require millions of input cells, limiting their application to rare cell populations or clinical samples. Here, we present Lysolation, a high-specificity antibody-based isolation method optimized for low cell numbers. By combining digitonin-mediated selective plasma membrane permeabilization with immunocapture targeting the lysosomal membrane protein NOX2, we developed both magnetic bead- and plate-based isolation formats. We first identified clone 7D5 as the superior antibody for capturing native lysosomal NOX2 across multiple cell types. In the bead-based workflow, we demonstrated near-exhaustive recovery of lysosomes (>99.5%) even from targets with low epitope density. To further downscale input requirements, we implemented a plate-based system combined with papain-mediated proteolytic release, achieving an isolation efficiency of 60.1% from as few as 15,000 cells. Overall, Lysolation provides a robust, tag-free platform for the isolation of intact, functional lysosomes from limited clinical samples and rare material, bridging the gap between standard biochemical assays and low-input sample availability.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"22 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221710","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":"Physics-Informed Machine Learning Overcomes Particle-Size Nonlinearities That Confound the Raman Spectrometry of Granular Carbonaceous Materials","authors":"Ginger W. Brown,&nbsp;Natalia V. Solomatova,&nbsp;Matthew D. Kowal,&nbsp;Miayan Larose,&nbsp;Calum Cole,&nbsp;Nicola Jurinovic,&nbsp;Sadegh Shokatian,&nbsp;Edward Grant","doi":"10.1021/acs.analchem.6c02307","DOIUrl":"10.1021/acs.analchem.6c02307","url":null,"abstract":"<p>Raman spectroscopy supports multivariate regression modelsthatcan offer a rapid and nondestructive approach to quantifying the compositionof granular materials. Soils constitute a class of such materialsfor which chemical analysis provides vital information for agricultureand environmental stewardship. However, soil samples typically presenthighly heterogeneous mixtures of varying particle size and diverseoptical properties owing to light-absorbing constituents. Althoughparticle-size effects on Raman spectrometry in scattering media havelong been considered in the context of pharmaceutical analytical technology,the quantitative influence of particle size in opaque, absorbing materialsremains poorly understood. Here, we investigate the effect of particlesize and light absorption in controlled mixture systems that mimicsoils. These mixtures, containing particles of varying sizes and opticalproperties, isolate the ways in which fluorescence, granularity andlight absorption affect the accuracy of machine learning regressionmodels. Using a dual-laser Raman system, we collected both conventionalRaman and Shifted-Excitation Raman Difference Spectroscopy (SERDS)spectra, showing that light-absorbing compounds attenuate Raman intensitiesnonlinearly to an extent that varies with particle size. Multivariateregression models link this behavior to optical extinction governedby the surface area of the absorbing grains. We account for this behaviorin terms of a simple physical model that incorporates the physicsof light scattering and absorption in heterogeneous systems of varyingparticle size. This hybrid, physics-informed machine learning frameworkoutperforms purely data-driven approaches in predicting sample compositionfrom Raman spectra, highlighting the importance of physical characteristicsin the analysis of light-absorbing granular materials.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"98 41","pages":"29459–29470"},"PeriodicalIF":7.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149049911","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":"Permeability-Based Measurement of Nanobody Binding to Nuclear Pore Complexes by Transient Scanning Electrochemical Microscopy","authors":"Moghitha Parandhaman,&nbsp;Siao-Han Huang,&nbsp;Kathryn G. Dzurik,&nbsp;W. Seth Childers,&nbsp;Shigeru Amemiya","doi":"10.1021/acs.analchem.6c04319","DOIUrl":"10.1021/acs.analchem.6c04319","url":null,"abstract":"<p>Nucleocytoplasmic macromolecular transport through thenuclearpore complex (NPC) is mediated selectively and efficiently by protein–proteininteractions, thereby regulating gene expression and the cell cycle.The NPC transport barrier is formed by biomolecular condensates ofnucleoporins (nups) rich in hydrophobic phenylalanine–glycine(FG) repeats. Herein, we develop the transient mode of scanning electrochemicalmicroscopy (SECM) to measure NPC interactions with a nanobody proteintargeting the non-FG site of the crucial barrier-forming FG-rich nup,Nup98. The small nanobody, which was recombinantly expressed and purified,diffuses into the NPC and partially blocks the transport of an FG-bindingpolycationic peptide, protamine. The lowered permeability is measuredmore sensitively by transient SECM than by the traditional steady-statecounterpart under our experimental conditions. A dissociation equilibriumconstant between the nanobody and Nup98 in the authentic NPC is determinedfrom the dependence of polypeptide permeability on nanobody concentration.The resulting dissociation constant of 7.7 nM is significantly higherthan that of 1.7 nM measured for isolated Nup98 with the nanobodyattached to the optical sensor surface in biolayer interferometry.The higher dissociation constant of nanobody–Nup98 interactionsin the NPC is consistent with the enthalpically and entropically unfavorablepartitioning of the nanobody into the condensate of hydrophobic anddisordered nups. The powerful SECM method will be applicable to investigatea variety of NPC-binding proteins with the authentic NPC, therebyadvancing our understanding of protein–NPC interactions andfunctions.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"98 41","pages":"29639–29647"},"PeriodicalIF":7.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149049987","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":"Simultaneous Quantification of Lanthanoid Ions in Solution by Magnetic Anisotropy-Assisted 19F NMR","authors":"Mo-Han Li,&nbsp;Xing Zhang,&nbsp;Xun-Cheng Su","doi":"10.1021/acs.analchem.6c02571","DOIUrl":"10.1021/acs.analchem.6c02571","url":null,"abstract":"<p>Lanthanoid are indispensable for modern technologiesincludinghigh-performance magnets, electronics, renewable energy, and medicalimaging. However, their similar ionic radii and chemical propertiesmake it inherently challenging for existing chemical, biochemical,and optical probes to distinguish individual Ln³⁺ ionsin mixtures. It is even more difficult to simultaneously quantifymultiple Ln³⁺ ions in solution. Due to their distinct magneticanisotropy, Ln³⁺ ions and their complexes exhibit a widerange of magnetic anisotropies (except for La³⁺, Gd³⁺, and Lu³⁺) and exert differential effects onthe NMR signals of nuclear spins surrounding the metal center. Designinghigh-performance probes for Ln³⁺ ion binding and discriminationis a great challenge because of their high coordination numbers andtheir tendency to form multiple conformations. Here, we designed andsynthesized two chemical-magnetic probes (CF₃-TDA and F-TDA),each containing a ¹⁹F reporter and metal chelating moiety,for simultaneous discrimination and quantification of Ln³⁺ ions in solution thanks to the distinct magnetic anisotropy of Ln³⁺ ions. These probes form stable lanthanoid complexes, generatingwell-resolved ¹⁹F NMR chemical shifts induced by the distinctmagnetic anisotropy of Ln³⁺. This strategy enables thesimultaneous identification and quantification of individual Ln³⁺ in mixtures, even in the presence of competing common metalions. This approach combines the metal-chelating property and distinctmagnetic anisotropy for lanthanoid ion quantification by NMR. It providesa conceptually innovative and broadly applicable platform for preciselanthanoid assays, facilitating the monitoring of critical elementsin industrial and strategic contexts.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"98 41","pages":"29481–29492"},"PeriodicalIF":7.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149092676","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":"Electrochemical Dual-Sensing Platform for HLA-B*13:01 Detection to Prevent Severe Cutaneous Adverse Reactions (SCARs) Induced by Dapsone and Cotrimoxazole","authors":"Jirapat Attapong,&nbsp;Chollanot Kaset,&nbsp;Nontaya Nakkam,&nbsp;Wichittra Tassaneeyakul,&nbsp;Wichayaporn Kamsong,&nbsp;Chanpen Karuwan,&nbsp;Chonlaphat Sukasem,&nbsp;Sirinart Chomean","doi":"10.1021/acs.analchem.6c03379","DOIUrl":"10.1021/acs.analchem.6c03379","url":null,"abstract":"<p>The <em>HLA-B*13:01</em> allele is a critical biomarkerfor dapsone- and cotrimoxazole-induced severe cutaneous adverse reactions(SCARs). Overcoming the limitations of centralized laboratory screening,we developed a portable electrochemical dual-sensing platform (EDP)for the simultaneous, ultrasensitive detection of <em>HLA-B*13:01</em> alongside a <em>TIMP-1</em> internal control. On screen-printedcarbon electrodes (SPCEs), <em>TIMP-1</em> is captured throughrobust biotin–streptavidin interactions, while <em>HLA-B*13:01</em> relies on sequence-specific ssDNA hybridization. Crucially, thesystem utilizes methylene blue (MB) to precisely modulate both electrostaticrepulsion and physical steric hindrance, enhancing signal discrimination.The platform demonstrates exceptional limits of detection, reaching0.992 pg and 65.5 fg when evaluated by electrochemical impedance spectroscopy(EIS) and cyclic voltammetry (CV), respectively. Notably, accountingfor genomic copy number, this corresponds to a practical detectionlimit of ∼3 HLA-B gene copies (1 × 10^–2 ng genomic DNA), several orders of magnitude below conventionalgel electrophoresis. Validated against 100 blinded clinical samples,the EDP achieved 100% sensitivity, specificity, and accuracy usingROC-derived cut-offs. By delivering a highly scalable, portable post-PCRscreening tool, this work provides a high-performance alternativeto standard methods, effectively mitigating SCAR risks and advancingthe global accessibility of precision medicine.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"98 41","pages":"29565–29578"},"PeriodicalIF":7.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019587","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}