Clinica Chimica Acta最新文献

{"title":"Multiplexed protease activity profiling for host response-based Sepsis diagnosis.","authors":"Emily R Caton, Yezhi Pan, Kiana M Kiser, Caroline R Haddaway, Wayne A Bryden, Michael McLoughlin, Marek A Mirski, Robert H Christenson, Cindy C Sevilla, Shuo Chen, Sheng Feng, Dapeng Chen","doi":"10.1016/j.cca.2026.122903","DOIUrl":"https://doi.org/10.1016/j.cca.2026.122903","url":null,"abstract":"<p><p>Human proteases play major roles in various pathological conditions, including dysregulated immune responses in sepsis, making them strong candidates for developing diagnostic markers. Despite this potential, the process of developing protease-based diagnostic tools has remained slow due to significant technical barriers associated with measuring protease activity, mainly stemming from the vast diversity of human proteases and the lack of substrate specificity, which complicates the interpretation of activity profiles. In this work, we advanced the current state of assay development by engineering substrate molecules and implementing an analytical approach based on mass spectrometry. Specifically, we developed a novel approach to chemically modify protease substrates for human neutrophil elastase (HNE) and matrix metalloproteinases (MMPs) to enhance specificity and generate unique mass-to-charge signatures, allowing the deconvolution of protease activities. We then integrated the modified substrates into a mass spectrometry-based platform for quantifying multiple protease activities within a single analytical run. We applied the assay to spared plasma samples and demonstrated that the assay detects distinct protease activity profiles. We further demonstrated that the assay achieved a diagnostic sensitivity of 88% and specificity of 87% for sepsis detection within a three-hour timeframe. ONE SENTENCE SUMMARY: We developed a novel multiplexed protease activity profiling approach to quantify immune responses and improve sepsis diagnosis.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"122903"},"PeriodicalIF":4.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Familial glycerol kinase deficiency uncovered by triglyceride-lipemic index discordance.","authors":"Carla Fernández-Prendes, Álvaro Piedra-Aguilera, Andrea Ros, Alejandra Pérez-Itza, Analia Ramos, Sandra Bonache, Ignacio Blanco","doi":"10.1016/j.cca.2026.122914","DOIUrl":"https://doi.org/10.1016/j.cca.2026.122914","url":null,"abstract":"<p><strong>Background: </strong>Pseudohypertriglyceridemia caused by elevated free glycerol is an uncommon analytical interference that may lead to misdiagnosis and unnecessary treatment. Because most routine enzymatic triglyceride assays do not incorporate glycerol blanking, triglyceride concentrations may be overestimated in patients with hyperglycerolemia. Recognition of triglyceride-lipemic index (L-index) discordance may facilitate the identification of glycerol interference in clinical laboratory practice.</p><p><strong>Methods: </strong>We investigated a patient with persistent severe hypertriglyceridemia who repeatedly showed a negative L-index. The unexpected absence of lipemia prompted investigation for glycerol interference.</p><p><strong>Results: </strong>A 78-year-old man showed persistently elevated triglyceride concentrations ranging from 844 to 1864 mg/dL over a five-year period despite lipid-lowering therapy, while L-index remained consistently negative. Markedly elevated free glycerol (12,600 μmol/L) confirmed pseudohypertriglyceridemia due to hyperglycerolemia. Exome sequencing identified a previously unreported hemizygous likely pathogenic GK variant (NM_001205019.2:c.1 A > G), affecting the translation initiation codon. Targeted familial testing identified the same variant in an affected maternal nephew with a concordant biochemical phenotype.</p><p><strong>Conclusions: </strong>Triglyceride-L-index discordance represents an easily recognizable analytical pattern that can be incorporated into routine laboratory workflows. We propose a practical laboratory algorithm to facilitate recognition of pseudohypertriglyceridemia and earlier diagnosis of glycerol kinase deficiency.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"122914"},"PeriodicalIF":4.1,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional characterization of compound heterozygous HLCS variants reveals exon skipping and impaired biotin responsiveness in holocarboxylase synthetase deficiency.","authors":"Jin-Kyu Kang, Eui-Jeon Woo, Sook-Za Kim, Haing-Woon Baik","doi":"10.1016/j.cca.2026.122913","DOIUrl":"https://doi.org/10.1016/j.cca.2026.122913","url":null,"abstract":"<p><p>Holocarboxylase synthetase deficiency (HLCSD) is a rare inherited metabolic disorder caused by variants in the HLCS gene. Functional characterization can aid the interpretation of rare HLCS variants. Clinical, biochemical, genetic, transcriptional, functional, and structural analyses were performed, including urine organic acid analysis, targeted next-generation sequencing, Sanger validation, RT-PCR, cDNA sequencing, fibroblast propionyl-CoA carboxylase (PCC) activity before and after biotin treatment, and AlphaFold3-based structural modeling. A 29-month-old child with late-onset HLCSD presented with severe metabolic acidosis. Urine organic acid analysis revealed elevated levels of lactic acid, 3-hydroxyisovaleric acid, 3-methylcrotonylglycine, propionylglycine, and methylcitric acid. PCC activity increased from 34 to 142 pmol/min/mg protein following biotin supplementation, confirming preserved biotin responsiveness. The patient showed marked clinical and metabolic improvement after treatment. Genetic analysis identified compound heterozygous HLCS variants: a novel splice-acceptor site variant, c.1796-2 A > G, paternal, and a previously reported missense variant, c.2126C > T, p.(Pro709Leu), maternal. RT-PCR and cDNA sequencing demonstrated exon 11 skipping caused by c.1796-2 A > G, predicting a truncated protein. Comparative AlphaFold3-based structural modeling of wild-type and p.(Pro709Leu) HLCS suggested variant-associated local conformational changes affecting the HLCS-substrate interaction interface and active-site architecture, providing additional structural evidence supporting the pathogenicity of p.(Pro709Leu). These findings support the pathogenicity of the novel splice-site variant, provide new structural evidence for the previously reported p.(Pro709Leu) variant, and expand the molecular and functional spectrum of HLCSD.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"122913"},"PeriodicalIF":4.1,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the commutability of control materials for C-peptide proficiency testing.","authors":"M D Sooho Yu, Soye Jung, M D Yong Kwan Lim, M D Soo Jin Yoo, Hyung-Doo Park","doi":"10.1016/j.cca.2026.122908","DOIUrl":"https://doi.org/10.1016/j.cca.2026.122908","url":null,"abstract":"<p><strong>Background: </strong>Commutability refers to the consistency of measurement results between reference materials (RMs) and patient samples across different measurement procedures. C-peptide is essential for diabetes classification and management, however, inter-assay variability persists despite ongoing harmonization efforts. The use of commutable materials is therefore critical for calibration and external quality assessment (EQA). This study evaluated the commutability of pooled human serum and commercial control materials using CLSI- and IFCC-based approaches.</p><p><strong>Methods: </strong>Commutability was evaluated using 30 clinical samples and six RMs, including three serum-based in-house prepared materials and three commercial materials. C-peptide was measured in triplicate using four major measurement procedures in Korea; Alinity i (Abbott Diagnostics), cobas e801 (Roche Diagnostics), UniCel DxI 800 (Beckman Coulter), and Atellica IM 1600 (Siemens Healthineers). Commutability was assessed using the CLSI EP14-ED4 Deming regression-based approach with 95% prediction intervals (PIs) and the IFCC difference-in-bias approach with expanded uncertainty, applying a total allowable error of 7.1% and a coverage factor of 1.9.</p><p><strong>Results: </strong>Three clinical samples were excluded from the analyses after being identified as outliers in scatter plots. Using the CLSI approach with the remaining 27 clinical samples, all RMs fell within the 95% PIs across all method pairs and were classified as commutable. In contrast, the IFCC approach, with concentration partitioning at 1.0 ng/mL distinguished differences in commutability among the RMs. Serum-based in-house prepared materials were classified as commutable or indeterminate, whereas commercial materials showed multiple indeterminate results and one non-commutable result.</p><p><strong>Conclusion: </strong>Pooled human serum-based in-house prepared materials demonstrated more stable commutability than commercial materials, supporting their use in C-peptide EQA programs.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"122908"},"PeriodicalIF":4.1,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel dual-epitope ELISA reveals heterogeneity of circulating lipoprotein lipase: distinguishing intact LPL from total LPL.","authors":"Takumi Nagasawa, Katsuyuki Nakajima, Takashi Shirakawa, Kazuya Miyashita, Isamu Fukamachi, Akira Tanaka, Jian Wang, Adam D McIntyre, Robert A Hegele, Kiyomi Nakajima, Katsuhiko Tsunekawa, Masami Murakami","doi":"10.1016/j.cca.2026.122896","DOIUrl":"https://doi.org/10.1016/j.cca.2026.122896","url":null,"abstract":"<p><strong>Background: </strong>Conventional immunoassays measure total circulating lipoprotein lipase (LPL) but do not distinguish molecular species retaining both terminal regions. We developed a dual-epitope E LISA that measures LPL simultaneously recognized through defined N- and C-terminal epitopes, operationally termed \"intact LPL.\"</p><p><strong>Methods: </strong>The F1A/R23B ELISA was evaluated using recombinant full-length LPL, analytical validation, immunoblotting, reciprocal immunoprecipitation-immunoblotting, post-heparin kinetics, LPL activity measurements, and ex vivo tetrahydrolipstatin treatment. Clinical analyses included healthy volunteers (n = 19), patients with multifactorial chylomicronemia syndrome (MCS; n = 170), and patients with GPIHBP1 autoantibody syndrome (n = 17).</p><p><strong>Results: </strong>The assay showed a detection limit of 0.01 ng/mL, good dilutional linearity, and intra- and inter-assay coefficients of variation below 7%. An approximately 55-kDa plasma species was recognized through both terminal regions, whereas 30-35-kDa N-terminal-reactive species demonstrated molecular heterogeneity. Intact LPL represented a minority of total LPL immunoreactivity and broadly paralleled LPL activity after heparin administration in two individuals. In healthy participants, intact LPL and the intact-to-total LPL ratio decreased significantly. In MCS, pancreatitis history was associated with higher triglyceride (TG)/intact LPL ratios, although intact LPL alone did not differ significantly. Patients with GPIHBP1 autoantibody syndrome had markedly reduced intact LPL concentrations and intact-to-total LPL ratios.</p><p><strong>Conclusions: </strong>The F1A/R23B ELISA distinguishes an LPL species retaining both antibody-defined terminal regions from conventional total LPL immunoreactivity. These findings demonstrate biochemical heterogeneity of circulating LPL under the specific experimental and clinical conditions examined in this study. Prospective studies are required to establish the incremental clinical value of intact LPL measurement.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"122896"},"PeriodicalIF":4.1,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicle-based diagnosis of Mucormycosis: Candidate biomarkers, analytical challenges, and clinical translation.","authors":"Obaid Afzal, Ali Altharawi, Mubarak A Alamri, Manal A Alossaimi, Abdulmalik S A Altamimi, Alhumaidi Alabbas, Safar M Alqahtani, Surya Nath Pandey, A Rekha, Rajat Sharma","doi":"10.1016/j.cca.2026.122906","DOIUrl":"10.1016/j.cca.2026.122906","url":null,"abstract":"<p><p>Currently, no standard serological test is available for the detection of Mucorales. Mucormycosis is a rapidly progressing angioinvasive infection with a high mortality rate. However, since a diagnostically useful target (1 → 3)-β-D-glucan or Aspergillus galactomannan is not present in Mucorales, a negative result for such targets is a true negative and does not rule out the diagnosis of mucormycosis. PCR detection using PCR for Mucorales can be performed in the early stages, and there is a commercially available quantitative PCR kit in some places, although it is not uniform. Extracellular vesicles (EVs) are membrane-bound particles present in biofluids that play a protective role against the degradation of proteins and nucleic acids and allow for their enrichment prior to measurement. Two studies provided evidence of Mucorales direct culture using extracellular RNA profiles from Rhizopus delemar and proteomic characterization of Mucor lusitanicus EVs, respectively; however, neither resulted in a patient-derived diagnostic test. This structured narrative review separates Mucorales EV direct evidence from extrapolations from other fungi and clinical EV assays. We recommend using a patient-derived discovery workflow involving EV-enriched RNA sequencing, EV-associated DNA analysis, and proteomics, followed by a locked multiplex assay of two or three independent fungal targets. Therefore, molecules from the CotH family, mucoricin, glucoamylase, iron-acquisition factors, and host-response signals should be considered as candidates and should be directly demonstrated within EVs from patients, rather than being considered as known EV markers.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"122906"},"PeriodicalIF":4.1,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ThaCoder: an explainable deep learning framework for thalassemia screening using routine complete blood count: a multi-center validation study.","authors":"Xiaosong Su, Yan Lin, Kouqiong Wang, Yuning Lin, Lin Wu, Xiang Jiang, Yi Shi, Baishen Pan, Beili Wang, Wei Guo, Jiaye Zhou","doi":"10.1016/j.cca.2026.122912","DOIUrl":"https://doi.org/10.1016/j.cca.2026.122912","url":null,"abstract":"<p><strong>Background and aims: </strong>Thalassemia remains a global public health challenge, yet definitive diagnosis via genetic testing is often restricted by high costs and infrastructure requirements. We aimed to develop and externally evaluate an interpretable deep-learning framework using routine complete blood count (CBC) parameters for thalassemia screening.</p><p><strong>Materials and methods: </strong>Using 2317 CBC records from the internal derivation cohort, we implemented a two-stage analytical architecture. First, exploratory factor analysis (EFA) with Varimax rotation reduced nine continuous parameters to three factors, providing a lower-dimensional representation that attenuated multicollinearity among the erythrocyte indices. These latent factors, alongside gender, formed a 4-dimensional feature space that was processed through a deep neural network (DNN) optimized via a two-stage Bayesian-Grid search strategy and out-of-fold threshold selection. The locked model and operating threshold were evaluated without refitting or threshold reselection across four independent external centers (N = 1442).</p><p><strong>Results: </strong>In the internal test set, the model achieved an AUROC of 0.9598 and a specificity of 0.9337. External AUROC ranged from 0.8771 to 0.9439 across the four centers. Sensitivity was 0.8387 overall but was lower for silent α-thalassemia carriers (0.5270, 39/74) than for non-silent α-thalassemia carriers (0.8692, 226/260). SHAP-based interpretability indicated that the model's learned associations are consistent with the microcytic, hypochromic phenotype of thalassemia, with reduced MCV and MCH alongside a raised red-cell count emerging as the dominant drivers of a positive prediction. Health economic simulations suggest this algorithmic triage could reduce genetic-testing referrals and associated costs by approximately 76% in a preliminary 10%-prevalence illustration, although a subset of milder carriers is missed at the chosen threshold and the estimate is not a formal economic evaluation.</p><p><strong>Conclusions: </strong>By integrating statistical feature engineering with deep learning, this framework provides a CBC-based pre-genetic-testing risk-stratification (triage) approach. The locked model and operating threshold were evaluated without refitting in four external centers, with between-center heterogeneity quantified, although absolute risk estimates require site-specific recalibration.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"122912"},"PeriodicalIF":4.1,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 1 diabetes metabolomics and multi-omics: Current applications, limitations, and future directions - A narrative review.","authors":"Husam Eldin Elhag Abugabr Elhag, Haya Al-Sulaiti","doi":"10.1016/j.cca.2026.122900","DOIUrl":"10.1016/j.cca.2026.122900","url":null,"abstract":"<p><p>Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by immune-mediated destruction of pancreatic β-cells, resulting in absolute insulin deficiency and lifelong dependence on exogenous insulin. This disease, if not treated, leads to acute and chronic complications affecting the cardiovascular, renal, and retinal systems and introduces significant psychosocial burdens. But even with advances in insulin therapy, optimal glycemic control remains difficult to achieve. T1DM progression spans from autoantibody seroconversion to overt diabetes, accompanied by dynamic metabolic perturbations, contributing to β-cell dysfunction. These metabolic alterations correlate with glycemic markers and provide integrated signatures of gene-environment interactions and disease heterogeneity. Therefore, metabolomics has emerged as a promising approach for identifying metabolic dysregulation associated with T1DM, with some studies reporting metabolite alterations detectable before clinical onset or autoantibody positivity; targeted and untargeted approaches enable comprehensive profiling of disease-associated metabolic pathways, although these findings largely reflect associations from observational cohorts rather than validated early-detection tools. Here, the analysis of biofluids with advanced platforms such as UPLC-MS and NMR provides high-resolution insights into systemic metabolism, supporting the discovery of candidate biomarkers that may, pending further validation, contribute to earlier diagnosis and precision medicine strategies in T1DM. Even though current metabolomic studies have substantially improved the classification of metabolic alterations associated with T1DM, the field still necessitates clarification of causal mechanisms, standardization of methodologies, validation of findings across diverse populations, and integration of metabolomics with other omics platforms in robust longitudinal designs. These gaps highlight a clear necessity of moving beyond descriptive profiling toward systematically standardized and validated metabolomic markers embedded within multi-omics and longitudinal frameworks.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"122900"},"PeriodicalIF":4.1,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating citrullinated proteins as candidate liquid biopsy analytes in cancer.","authors":"Asma B Omer, Shakir Saleem, Ruqaiyah Khan, A Rekha, Rashmi Bhavasar","doi":"10.1016/j.cca.2026.122904","DOIUrl":"https://doi.org/10.1016/j.cca.2026.122904","url":null,"abstract":"<p><p>This review outlines the functions of circulating citrullinated histone H3 (CitH3), citrullinated and matrix metalloproteinase-degraded vimentin (VICM), peptidylarginine deiminase 4 (PAD4), and related proteoforms in oncology and discusses their suitability as analytes in liquid biopsies. Evidence in the serum and plasma is different from that in the tissue, bone marrow, in vitro, or preclinical evidence. Special emphasis has been placed on the following techniques: serum and plasma-based enzyme-linked immunosorbent assay (ELISA), liquid chromatography - tandem mass spectrometry (LC-MS/MS), targeted proteomics, and biosensors. Evidence is best established for CitH3, but the biology of neutrophil extracellular traps (NETs) and their reported associations are context- and assay-dependent, with nucleosomal assays and assays of free histones/free peptides measuring distinct pools of analytes. However, for some cancers, these analytes have preliminary prognostic and treatment-response-monitoring value, but there is a lack of evidence for their clinical use in cancer diagnosis, patient stratification, or minimal residual disease (MRD) monitoring. Assay heterogeneity, matrix effects, lack of certified reference materials, limited inter-platform comparability and harmonization, lack of external quality assessment (EQA), and lack of validated clinical cut-offs hinder clinical implementation. Key preanalytical requirements include preanalytical control, harmonization of assays, assessment of the commutability of reference materials, calibrators, control materials, and EQA materials, and compliance with the International Organization for Standardization (ISO) 15,189 and the In Vitro Diagnostic Regulation (IVDR). At present, citrullinated proteins should be considered as research use/early translational analytes, and not as clinically reportable oncology biomarkers.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"122904"},"PeriodicalIF":4.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optical biosensors for cancer diagnosis and monitoring.","authors":"Heru Agung Saputra, Md Ali Zaber Sahin, Yeni Wahyuni Hartati","doi":"10.1016/j.cca.2026.122895","DOIUrl":"10.1016/j.cca.2026.122895","url":null,"abstract":"<p><p>Cancer is driven by complex genetic and epigenetic alterations that promote uncontrolled cellular proliferation, invasion, and metastasis. Despite substantial advances in oncology, conventional diagnostic approaches remain constrained by invasiveness, cost, limited sensitivity, and limited capacity to detect malignancies at early stages. Optical biosensors have emerged as promising platforms for sensitive, rapid, and non- or minimally invasive cancer biomarker detection, offering opportunities for real-time, label-free analysis of biofluids. These systems integrate highly selective biorecognition elements with optical transducers that interrogate molecular interactions. Recent advances in nanomaterials and nanophotonic architectures have further improved analytical sensitivity, while artificial intelligence (AI) and machine-learning approaches enable multiplexed biomarker profiling, pattern recognition, and increasingly precise diagnostic interpretation. This review critically presents the fundamental principles, sensor configurations, and applications of optical biosensors for cancer detection and monitoring, with particular emphasis on technological advances that underpin sensitivity, specificity, multiplexing, and clinical translation. The review also discusses key barriers to widespread implementation, including reproducibility, scalability, biofluid complexity, and standardization. Emerging directions, including quantum-enhanced sensing, advanced nanophotonics, and AI-driven analytics, are evaluated in the context of next-generation precision diagnostics. By integrating photonics, molecular biology, nanotechnology, and bioengineering, optical biosensors have strong potential to enable earlier, non-invasive or minimally invasive, patient-centric cancer detection and contribute to more effective precision oncology.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"122895"},"PeriodicalIF":4.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}