Analytical Chemistry最新文献

{"title":"Modular Cell-Surface-to-Solution CRISPR-Cas12a Platform for Wash-Free Quantification of Cell−Surface Proteins on Living Cells","authors":"Xiao-Yun Hou,Man-Ying Li,Wen-Bo Sun,Shun-Li Wu,Yan Tan,Qi-Fan Yang,Kai-Di Li,Qing-Nan Li,Li-Na Zhu,De-Ming Kong","doi":"10.1021/acs.analchem.6c05289","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c05289","url":null,"abstract":"Abstract Cell−surface proteins are important biomarkers for cell phenotyping, disease diagnosis, therapeutic evaluation, and drug screening. However, their quantitative analysis on intact living cells remains challenging because conventional methods often require cell lysis, fixation, repeated washing, extensive sample processing, or bulky instrumentation. Herein, we developed a modular and reconfigurable cell-surface-to-solution CRISPR-Cas12a platform for wash-free quantitative analysis of cell−surface proteins on intact living cells. Aptamer recognition of extracellularly accessible targets deblocks a DNA activator, thereby activating Cas12a trans-cleavage in solution and converting localized cell−surface recognition into amplified fluorescence while maintaining a low background in the absence of targets. Using EpCAM as a model target, we engineered a split dual-aptamer architecture that enabled cooperative target recognition, efficient activator deblocking, and low-background signal amplification. The platform achieved sensitive EpCAM detection with a limit of detection of 32 fM and enabled live-cell analysis down to 2 cells/μL. It distinguished cell populations with different surface EpCAM levels and quantitatively monitored epithelial−mesenchymal transition-associated changes in cell−surface EpCAM abundance. Coordinated redesign of the target-responsive nucleic acid components extended the platform to PTK7 detection and the analysis of drug-induced cell−surface PTK7 remodeling. Coupling the system to a lateral flow readout enabled portable visual detection. This work establishes a modular and reconfigurable CRISPR-Cas12a sensing strategy for wash-free amplified quantification of cell−surface proteins on living cells, providing a convenient tool for investigating their dynamic remodeling during physiological and pathological processes and therapeutic responses, as well as for drug screening.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"12 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209960","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":"Rapid Screening and Etiological Stratification of Inherited Dyslipidemias by Infrared Microspectroscopy","authors":"Leiying Xie,Min Wang,Mengna Huang,Ke Huang,Chaochun Zou,Yingke Xu","doi":"10.1021/acs.analchem.6c05084","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c05084","url":null,"abstract":"Abstract Inherited dyslipidemias, including familial hypercholesterolemia (FH) and sitosterolemia (STSL), present overlapping clinical manifestations but require distinct therapeutic interventions. Current diagnosis relies on genetic sequencing and mass spectrometry-based sterol profiling, which are accurate but costly, time-consuming, and unsuitable for large-scale first-line screening. Infrared (IR) microspectroscopy offers a rapid, label-free alternative for biochemical phenotyping; however, its clinical application is challenged by the spatial heterogeneity of biological samples and spectral variability. Here, we present an IR microspectroscopic phenotyping framework for rapid screening and etiological stratification of inherited dyslipidemias. The framework combines multi-pixel IR microspectroscopy, batch-effect correction, and participant-level spectral integration to achieve reproducible cross-batch phenotyping while preserving disease-associated biochemical signatures. Quantitative models predicted FH-associated lipid biomarkers, whereas qualitative classifiers identified STSL-associated sterol biomarkers. A cascade decision framework integrating IR-based phenotypic classification with biomarker profiling further enabled etiological discrimination among healthy controls, FH, and STSL. The framework achieved an average participant-level sensitivity of approximately 93% and yielded detection rates of 97.7% for FH and 85.7% for STSL, compared with 93.2% and 60.7%, respectively, with conventional clinical screening. Co-importance and consensus feature analyses identified 2837 cm−1 as a prominent discriminatory spectral feature. Measurements of β-sitosterol reference standards revealed a characteristic absorption band near 2834 cm−1, supporting a possible association between this spectral region and β-sitosterol-related biochemical variation. This internally validated proof-of-concept study supports the potential of IR microspectroscopy for rapid etiological stratification of inherited dyslipidemias, complementing genetic sequencing and mass spectrometry.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"14 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209964","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":"APE1-Responsive Adaptive DNA Nanomachines for Prolonged Intracellular Bioanalysis and Sustained Gene Silencing","authors":"Xiao-Qiong Li,Ye Zhu,Zhi-Fan Ye,Jianhao Wang,Jing-Juan Xu","doi":"10.1021/acs.analchem.6c05976","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c05976","url":null,"abstract":"Abstract Rapid cellular clearance severely restricts the effective analytical and functional windows of intracellular probes. Herein, we developed an endogenous enzyme-driven adaptive DNA nanomachine (TRZL) that synchronizes target recognition with in situ morphological transformation to overcome premature cellular clearance for prolonged intracellular theranostics. Specifically, a spatially confined hybridization chain reaction (HCR) circuit and an apurinic/apyrimidinic endonuclease 1 (APE1)-responsive module, which initially locks a DNAzyme, are integrated onto a rigid DNA prism framework. In tumor cells, APE1 recognition triggers the HCR circuit accompanied by fluorescence recovery, enabling sensitive APE1 detection with an ultralow limit of detection (LOD) of 9.60 × 10−4 U/mL. Concurrently, the continuous extension of the HCR polymers drives an in situ hydrodynamic size expansion from 37 nm monomers into 479 nm 3-dimensional networks. The resulting steric hindrance effectively mitigates rapid cellular clearance, successfully extending the signal retention window by maintaining 85.34% of the APE1-triggered signal over 24 h. Furthermore, benefiting from this aggregation-driven retention, the synchronously released DNAzyme can continuously cleave survivin mRNA to achieve sustained protein downregulation, thereby extending the functional window. Ultimately, this programmable size-adaptive strategy provides a highly versatile theranostic platform for precise bioanalysis and long-acting intervention.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"69 2 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210063","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":"Aptamer-Based Fluorescent Assays for Detection of the Host-Response Viral Biomarker 3′-Deoxy-3′,4′-Didehydro-Cytidine","authors":"Ravi Mehta,Sondes Ben-Aissa,Kyungae Yang,Elena Chekmeneva,Maria Valdivia-Garcia,Lynn Maslen,Trevor Ferris,Kamil Skirlo,Ewurabena Mills,Vincenzo Sgro,Shiranee Sriskandan,Anthony E. G. Cass","doi":"10.1021/acs.analchem.6c04805","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c04805","url":null,"abstract":"Abstract Improved viral diagnostics are urgently needed to strengthen pandemic preparedness and combat antimicrobial resistance, highlighting the importance of 3′-deoxy-3′,4′-didehydro-cytidine (ddhC), a host-derived, pan-viral biomarker that addresses key limitations of PCR-based diagnostics. Current methods for ddhC measurement rely on liquid chromatography-mass spectrometry (LC−MS) or nuclear magnetic resonance spectroscopy, which are accurate but costly and impractical for rapid or point-of-care testing. Here, we report the development of aptamer-based fluorescent assays for selective ddhC detection. Low-micromolar-affinity DNA aptamers were isolated using capture-systematic evolution of ligands by exponential enrichment (SELEX) and characterised by isothermal titration calorimetry. Using a common core aptamer sequence, three fluorescence assay formats−strand displacement, molecular beacon, and dye displacement−were developed and evaluated. Independent LC−MS analysis demonstrated a strong correlation between creatinine-normalised urinary and serum ddhC concentrations in inpatient samples (R = 0.98, p <0.0001), supporting urine as a non-invasive matrix for ddhC detection. Among the three aptamer-based formats tested, the dye displacement assay exhibited the lowest functional Kd but was limited in urine by inner filter effects, whereas a Cy5-labelled strand displacement assay overcame this limitation and detected ddhC in patient urine with moderate correlation to LC−MS (R = 0.76, p = 0.001). Together, these results establish aptamer-based sensing approaches for ddhC and demonstrate their feasibility in clinical urine samples, providing a foundation for further optimisation toward accessible, non-invasive, and rapid detection of acute viral infection.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"160 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209329","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-Label Sequentially Released DNA Probe for Self-Powered PEC-RGB Sensing of Coexisting Mycotoxins","authors":"Yanru Zhang,Yutong Fu,Xue Fan,Hongye Liu,Jingyao Peng,Ying Sun,Xuechen Zhang,Wenbo Song,Daqian Song","doi":"10.1021/acs.analchem.6c05916","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c05916","url":null,"abstract":"Abstract On-site assay of multiple coexisting mycotoxins is critical for securing food safety and safeguarding public health. Photoelectrochemical (PEC) sensing meets the demand of on-site analysis owing to the advantages of easy miniaturization, rapid response, and low cost. However, existing signal discrimination strategies for multiplexed PEC detection typically rely on complex electrode modification and external instrumentation, limiting their on-site applicability. To address this issue, we developed a dual-label sequentially released DNA probe (DSRDP) and constructed an ion exchange-mediated modification-free self-powered sensing platform, which enables on-site PEC red-green-blue (RGB) sensing of dual targets. The DSRDP was formed by assembling Ag NPs-terminated double-stranded DNA and PC-Linker-modified hairpin DNA bearing CuO NPs on the magnetic beads’ surface. Upon the simultaneous recognition of two targets, the first signal label (Ag NPs) was obtained in the supernatant through magnetic separation, and the other signal label (CuO NPs) was released via UV-induced photocleavage of the photocleavable linker (PC-Linker). Subsequently, acidification of each signal label triggered the ion exchange (Ag+ or Cu2+) with the MgIn2S4 photoanode, which quenched the photocurrent resulting from the heterostructure formation. Meanwhile, Ag+ or Cu2+ also induced a color change of Na2S solution, which provided the visual RGB signal for the dual-target assay using a smartphone. The PEC-RGB sensor exhibited linear ranges of 1 fg/mL−100 ng/mL of aflatoxin B1 (AFB1) and ochratoxin A (OTA) with LODs of 0.24 fg/mL and 0.33 fg/mL in PEC mode, respectively, and linear ranges of 1 pg/mL−100 ng/mL of AFB1 and OTA with LODs of 10.96 fg/mL and 3.63 fg/mL in RGB mode, respectively. Featuring convenient target separation, rapid signal transduction, and self-powered detection, this work may pave the way for portable on-site detection of coexisting mycotoxins for food safety assessment and environmental monitoring.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"16 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210010","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":"Fluorescence “Turn-On” Detection of Bisulfite via Specific CN Bond Cleavage: Reactivity, Structure−Property Relationship, and Bioimaging Applications","authors":"Xin Wang,Wenhui Xue,Penghui Xia,Qian Wang,Shance Sun,Mengxin Zhang,Keting Zhu,Wenjun Xue,Bo Dong,Wenzhang Xiong,Jie Chen,Changqing Qu,Cuibing Bai,Rui Qiao","doi":"10.1021/acs.analchem.6c04900","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c04900","url":null,"abstract":"Abstract It is essential to detect HSO3− for ensuring food safety, preventing environmental pollution, and safeguarding human health. We report a new approach for the fluorescence recognition of HSO3−. The key principle lies in exploiting the specific and irreversible cleavage of the CN bond in the probe’s Schiff base structure by HSO3− to achieve signal transduction. Compared with conventional recognition modes, this probe undergoes a specific structural cleavage upon HSO3− triggering, releasing a strongly fluorescent aromatic amine moiety and thereby yielding a fluorescence “turn-on” response with a high signal-to-noise ratio. By systematically tuning the electronic properties of the molecular termini, the reactivity of the imine bond and the corresponding recognition performance can be effectively modulated. Furthermore, the structure−activity relationship between the molecular electronic structure and the sensing performance has been thoroughly elucidated, providing a theoretical basis for the design of highly selective probes. The platform constructed based on this approach exhibits excellent sensitivity and a low detection limit and enables the visual detection of HSO3− in complex matrices, live-cell imaging, and an acute liver injury model, confirming the reliability and application potential of the probe in real biological and environmental samples. This work not only offers a novel and efficient chemical tool for the effective detection of HSO3− but also provides new insight into the development of fluorescence sensing strategies based on covalent bond cleavage.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"33 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210007","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":"3D DNA Framework-Encoded Multicolor DNA Amplifiers Permit Dual-Modal Simultaneous Imaging of Intracellular Multiplexed mRNAs","authors":"Chengxin Tian,Huiyan Du,Ping Nie,Ensheng Xu,Yanrong Qian,Xia Li,Qingwang Xue,Nan Zhang,Jibin Song","doi":"10.1021/acs.analchem.6c04196","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c04196","url":null,"abstract":"Abstract High-sensitivity, simultaneous visualization of multiple low-abundance intracellular mRNAs is appealed to elucidating their synergistic functions and guiding cancer diagnosis and treatment. Engineered nanoprobes integrating anti-enzymatic degradation, efficient signal amplification, and multimodal output are highly desirable for sensitive and accurate in situ imaging in living cells. Herein, we design a 3D tetrahedral DNA-encoded four-color entropy-driven amplifiers (TFEA) for simultaneous fluorescence/surface-enhanced Raman scattering (FL-SERS) dual-modal imaging of four intracellular mRNAs. Target mRNA binding activates the TFEA to simultaneously trigger a multi-path entropy-driven DNA circuit, resulting in the disassociation of multicolor fluorophore-tagged DNAs and the aggregation of gold nanobipyramids (Au NBPs) mediated by tetrahedral DNA (TDN) nanostructures, thus producing strong FL and SERS signals that directly report on the location and concentration of the mRNAs. The TDN assembles equal amounts of different entropy-driven amplifier probes on a single nanostructure, confers potent resistance to nuclease degradation, maintains structural integrity in complex biological systems, and facilitates amplifier probe delivery. Impressively, the multiple Au NBPs assembled by TDN promote the formation of dense plasmonic hotspots in TDN-confined spaces, thereby eliciting a significant boost in the SERS signal. The amplifiers are endowed with potent delivery, high sensitivity, and desirable stability and can simultaneously monitor the four types of cellular mRNAs with FL-SERS dual-modal imaging, thus providing accurate information on localization and concentration of targets. Notably, it can distinguish the expression signatures of multiplex mRNAs in different cells and in tissues from healthy controls and liver cancer patients, offering a promising platform for clinical diagnosis and biomedical research.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"12 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210012","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":"Lock-in Biosensing beyond the Analog Ensemble Detection Limits","authors":"Chen Wang,Yifei Zhang,Zhuoyin Liu,Qiang Zeng,Hui Yu,Xinping Guan,Yuting Yang","doi":"10.1021/acs.analchem.6c04649","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c04649","url":null,"abstract":"Abstract Clinical assessment of biomarkers via “analog” ensemble detection of molecular signals is fundamentally limited by the background noise from a detector and nonspecific binding. Although digital assays have emerged as a solution, their clinical translation remains challenging due to their reliance on sophisticated single-molecule sensing technologies. Here, we demonstrate that these analog limitations can be overcome using lock-in detection of ensemble signals. By modulating endpoint molecular binding events into periodic optical fluctuations, our approach amplifies weak molecular signals above the background noise floor. Experimental validation demonstrates a three-fold increase in the limit of sensitivity for single-stranded DNA and a one-order-of-magnitude increase for interleukin-6 (IL-6), achieving a limit of detection at the femtomolar level. Compatible with existing assay platforms, this ensemble lock-in biosensing strategy offers a simple yet effective route for the clinical detection of low-abundance biomarkers.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"51 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209962","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":"Beyond Co-Localization: DeepCoEx Learns Exclusion-Aware Spatial Representations in Mass Spectrometry Imaging via Dual-Contrastive Learning","authors":"Jingjing Xu,Xin Diao,Siyang Liu,Thomas Ka-Yam Lam,Yusong Zhang,Shuang Gao,Lingli Deng,Weiji Chen,Lei Guo,Zongwei Cai,Jiyang Dong","doi":"10.1021/acs.analchem.6c02338","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c02338","url":null,"abstract":"Abstract Mass spectrometry imaging (MSI) provides spatially resolved molecular profiles, yet the existing computational workflows are heavily biased toward co-localization and remain limited in characterizing exclusion-like spatial relationships, especially when reliable negative labels are scarce. To address this challenge, we present DeepCoEx (Deep Co-localization and Exclusion), a self-supervised framework that learns exclusion-aware spatial representations through dual-contrastive learning for spatial metabolomics analysis. Instead of relying on large collections of annotated negative ion pairs, DeepCoEx embeds positive spatial consistency and exclusion-aware separation into a unified representation space. This design enables the model to preserve spatially coherent ion patterns while improving the separability of spatially complementary distributions. Compared with conventional similarity metrics and dimensionality reduction baselines, DeepCoEx provides more consistent and interpretable retrieval of candidate negative spatial associations. In representative control and PM2.5-exposed rat brains, the framework reveals localized spatial redistribution patterns and brainstem-related complementary ion associations that are not readily captured by conventional correlation-based analysis. In barley seeds, the learned embeddings help resolve chemically related ion species, including protonated and sodiated adducts of phosphatidylcholine species and glycosylated hordatine derivatives. Furthermore, DeepCoEx supports subregion-specific network construction, enabling exploratory analysis of localized molecular association patterns under different tissue or treatment contexts. By establishing an exclusion-aware representation learning strategy for MSI, DeepCoEx expands spatial metabolomics beyond co-localization and provides a practical workflow for analyzing complementary molecular organization in complex tissues.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"24 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210011","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":"Machine Learning Prediction of Molar Mass Distribution of Polymers Forming Fibrous Structures","authors":"Nashwa L. Attallah,Kourosh Mobredi,Isaac Y. Miranda-Valdez,Valentina Guccini,Vishnu Arumughan,Juha Koivisto,Mikko J. Alava,Eero Kontturi","doi":"10.1021/acs.analchem.6c04366","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c04366","url":null,"abstract":"Abstract Molecular weight parameters, such as molar mass distribution (MMD), are core characteristics of polymer materials. While MMD is routinely measured by gel permeation chromatography (GPC), the procedure takes time and resources and requires specific, relatively costly instruments. Polysaccharides such as cellulose and chitin are particularly difficult to dissolve. Herein, we report on the potential of combining hyperspectral imaging (HSI) with machine learning (ML) to predict, at different length scales, the MMDs of these sparingly soluble fibrous polymers from visible-range HS images (420−730 nm) of the solid substrate. A Gaussian process regression model was trained on principal component representations of the HS cubes against MMDs measured by GPC. HCl-vapor hydrolysis served as a controlled degradation pathway that altered the degree of polymerization without detectable morphological change. Although samples appear identical to the eye and under electron microscopy, HSI captures systematic optical differences that can be empirically related to GPC-measured MMD within the investigated hydrolyzed samples. Predicted distributions matched the GPC reference, with curve RMSEs of 0.009−0.027 (native cellulose paper), 0.017−0.050 (cellulose nanopaper), and 0.016−0.029 (chitin nanopaper). The principal features of the bimodal MMD of cellulose nanopaper and the leveling-off degree of polymerization were both recovered. The workflow uses a microscope, a tunable bandpass filter, and a digital camera, completing HSI acquisition and prediction in a few minutes per sample. This approach provides a non-destructive, solvent-free complement to traditional analytical techniques. The presented case study is a proof-of-concept, calibrated against GPC reference data for the specific materials and protocols studied here. Expanding to other polymer systems would require establishing a similar chromatographic reference for each new system.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"26 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210013","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}