Biosensors and Bioelectronics最新文献

Synergistic optimization strategies for the development of multienzymatic cascade system-based electrochemical biosensors with enhanced performance

IF 10.7 1区生物学

Biosensors and Bioelectronics Pub Date : 2025-02-02 DOI: 10.1016/j.bios.2025.117222

Yuzhuo Zhu , Zhaoming Cheng , Xueqi Wang , Chuanjun Zhang , Xuwen Li , Yanxue Wei , Jiajia Wang , Yuxin Fang , Yi Wang , Di Zhang

{"title":"Synergistic optimization strategies for the development of multienzymatic cascade system-based electrochemical biosensors with enhanced performance","authors":"Yuzhuo Zhu , Zhaoming Cheng , Xueqi Wang , Chuanjun Zhang , Xuwen Li , Yanxue Wei , Jiajia Wang , Yuxin Fang , Yi Wang , Di Zhang","doi":"10.1016/j.bios.2025.117222","DOIUrl":"10.1016/j.bios.2025.117222","url":null,"abstract":"<div><div>Multienzymatic cascade system (MCS) strategies have been a topic of growing interest in the electrochemical biosensor research field owing to their many advantages. By combining two or more enzymes in an appropriate manner, MCS approaches can extend the range of detection for particular analytes while improving the overall efficiency of biocatalytic cascade reactions. Compared with mono-enzyme biosensors, the integration of MCS and electrochemical biosensor platforms is inherently more challenging owing to the increased complexity of the resultant system. In recent years, substantial progress in the development of MCS-based electrochemical biosensors with enhanced analytical performance has been made. This review provides an overview of the types of MCS strategies and their biosensor applications, together with a summary of synergistic optimization approaches that can help improve key parameters including sensitivity, selectivity, and stability when designing MCS-based electrochemical biosensors. These discussions include examples of published biosensor platforms (2016–2024) while also surveying key advances in associated research areas including redox mediators/enzyme co-immobilization, enzyme engineering, multienzyme spatial regulation, enzyme-nanozyme integration and others. Lastly, a brief overview of current challenges and future perspectives pertaining to MCS-based electrochemical biosensor design is provided.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"274 ","pages":"Article 117222"},"PeriodicalIF":10.7,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143170905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Detection of brain metastases from blood using Brain nanoMET sensor: Extracellular vesicles as a dynamic marker for metastatic brain tumors 利用脑纳米MET传感器从血液中检测脑转移瘤：细胞外囊泡作为转移性脑肿瘤的动态标记物。

IF 10.7 1区生物学

Biosensors and Bioelectronics Pub Date : 2025-02-01 DOI: 10.1016/j.bios.2024.116968

Srilakshmi Premachandran , Ishita Shreshtha , Krishnan Venkatakrishnan , Sunit Das , Bo Tan

{"title":"Detection of brain metastases from blood using Brain nanoMET sensor: Extracellular vesicles as a dynamic marker for metastatic brain tumors","authors":"Srilakshmi Premachandran , Ishita Shreshtha , Krishnan Venkatakrishnan , Sunit Das , Bo Tan","doi":"10.1016/j.bios.2024.116968","DOIUrl":"10.1016/j.bios.2024.116968","url":null,"abstract":"<div><div>Brain metastases account for a significant number of cancer-related deaths with poor prognosis and limited treatment options. Current diagnostic methods have limitations in resolution, sensitivity, inability to differentiate between primary and metastatic brain tumors, and invasiveness. Liquid biopsy is a promising non-invasive alternative; however, current approaches have shown limited efficacy for diagnosing brain metastases due to biomarker instability and low levels of detectable tumor-specific biomarkers. This study introduces an innovative liquid biopsy technique using extracellular vesicles (EVs) as a biomarker for brain metastases, employing the Brain nanoMET sensor. The sensor was fabricated through an ultrashort femtosecond laser ablation process and provides excellent surface-enhanced Raman Scattering functionality. We developed an in vitro model of metastatic tumors to understand the tumor microenvironment and secretomes influencing brain metastases from breast and lung cancers. Molecular profiling of EVs derived from brain-seeking metastatic tumors revealed unique, brain-specific signatures, which were also validated in the peripheral circulation of brain metastasis patients. Compared to primary brain tumor EVs, we also observed an upregulation of PD-L1 marker in the metastatic EVs. A machine learning model trained on these EV molecular profiles achieved 97% sensitivity in differentiating metastatic brain cancer from primary brain cancer, with 94% accuracy in predicting the primary tissue of origin for breast metastasis and 100% accuracy for lung metastasis. The results from this pilot validation suggest that this technique holds significant potential for improving metastasis diagnosis and targeted treatment strategies for brain metastases, addressing a critical unmet need in neuro-oncology.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"269 ","pages":"Article 116968"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Functionalized cascaded tapered optical fiber sensor for simultaneous detection of dengue II E and SARS-CoV-2 S proteins.

IF 10.7 1区生物学

Biosensors and Bioelectronics Pub Date : 2025-02-01 DOI: 10.1016/j.bios.2025.117200

Nurul Nadiah Zulkeflee, Yasmin Mustapha Kamil, Syamsiah Mashohor, Muhammad Hafiz Abu Bakar

{"title":"Functionalized cascaded tapered optical fiber sensor for simultaneous detection of dengue II E and SARS-CoV-2 S proteins.","authors":"Nurul Nadiah Zulkeflee, Yasmin Mustapha Kamil, Syamsiah Mashohor, Muhammad Hafiz Abu Bakar","doi":"10.1016/j.bios.2025.117200","DOIUrl":"https://doi.org/10.1016/j.bios.2025.117200","url":null,"abstract":"<p><p>This work demonstrates a label-free dual-sensing biosensor utilizing cascaded single-mode tapered fiber (SMTF) for the concurrent detection of Dengue II envelope (E) and SARS-CoV-2 spike (S) proteins. Two fiber tapers of different dimensions were employed in-line, with each taper functionalized with specific complementary antibodies to the targeted antigens. The cascaded interferometric effect yielded composite spectral output that exhibited discrete response toward localized refractive index changes due to binding of antigens and antibodies. Consistent red shifts were observed with increasing concentration of the targeted analyte, which led to sensitivity values of 6.91 nm/nM for SMTF1 and 9.96 nm/nM for SMTF2, with a detection limit of 0.1 pM. This dual-sensing platform demonstrates high sensitivity and specificity, rapid response times, and the potential for integration into portable diagnostic devices, presenting it as a promising tool for point-of-care diagnostics and simultaneous detection of multiple disease biomarkers.</p>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":" ","pages":"117200"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bivariate tracking of NIR phototherapeutic probe that illuminates the deterioration process of NAFLD-HCC 对照亮非酒精性脂肪肝-肝癌恶化过程的近红外光疗探针进行双变量追踪。

IF 10.7 1区生物学

Biosensors and Bioelectronics Pub Date : 2025-02-01 DOI: 10.1016/j.bios.2024.116967

Jialu Yang , Huimin Xu , Yijun Zhao , Pengju Sun , Yuanyuan Li , Ting Chen , Yanmei Zhou

{"title":"Bivariate tracking of NIR phototherapeutic probe that illuminates the deterioration process of NAFLD-HCC","authors":"Jialu Yang , Huimin Xu , Yijun Zhao , Pengju Sun , Yuanyuan Li , Ting Chen , Yanmei Zhou","doi":"10.1016/j.bios.2024.116967","DOIUrl":"10.1016/j.bios.2024.116967","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD) has evolved to become a major cause of hepatocellular carcinoma (HCC). Visualization of NAFLD-HCC deterioration process imaging is essential to understand the underlying pathophysiological processes. However, currently relevant probes with short emission wavelengths, univariate and the inability to achieve theranostics functionality have encountered obstacles in further evaluating the NAFLD-HCC process. Here, we present a carboxylesterase (CE)-activated NIR fluorescent probe (<strong>BODJ</strong>) which has lipid droplets (LDs)-targeting ability and emits at a wavelength of 858 nm with a fluorescence quantum yield of 19.06%. CE-activated <strong>BODJ</strong> was used as a visual tool to successfully visualize both NAFLD deterioration processes and HCC in situ based on changes in the average number of LDs and the associated fluorescence intensity fluctuations. Imaging results showed that changes associated with CE and LDs in the modelled cells varied during the transition from nonalcoholic fatty liver to nonalcoholic steatohepatitis and later progression to HCC, highlighting the close association between bivariate and disease. We also demonstrate that <strong>BODJ</strong> has photodynamic (PDT) and photothermal therapy (PTT) capabilities, allowing image-guided dual phototherapy to damage HCC in situ. This NIR probe, which takes advantage of bivariate to track the deterioration process that illuminates NAFLD-HCC and has dual phototherapy capabilities, provides new ideas for the design of probes related to the diagnosis and treatment of hepatic metabolic diseases.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"269 ","pages":"Article 116967"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intelligent molecular cleavage and dual-signal relay amplification ratiometric strategy for high-sensitivity analysis and dynamic monitoring of exosomal RNA in glioma

IF 10.7 1区生物学

Biosensors and Bioelectronics Pub Date : 2025-01-31 DOI: 10.1016/j.bios.2025.117205

Xiankai Niu , Yiqun Guo , Na Li , Siyu Li , Yilei Yu , Jianwei Jiao , Yuna Guo

{"title":"Intelligent molecular cleavage and dual-signal relay amplification ratiometric strategy for high-sensitivity analysis and dynamic monitoring of exosomal RNA in glioma","authors":"Xiankai Niu , Yiqun Guo , Na Li , Siyu Li , Yilei Yu , Jianwei Jiao , Yuna Guo","doi":"10.1016/j.bios.2025.117205","DOIUrl":"10.1016/j.bios.2025.117205","url":null,"abstract":"<div><div>Exosomal RNA has emerged as a promising biomarker for glioblastoma (GBM) due to its exceptional stability in biofluids and strong correlation with tumor progression. In this study, we present an innovative intelligent molecular cleavage and dual-signal relay amplification-based ratiometric (ISR) strategy for high-sensitivity monitoring and dynamic analysis of exosomal RNA in glioma. The core mechanism is based on a hollow duplex structure that effectively prevents premature cleavage by duplex-specific nuclease (DSN), ensuring both the accuracy and stability of the detection system. Upon the introduction of the target microRNA (miRNA), one strand of the hollow duplex is displaced, forming a miRNA-DNA duplex that serves as a substrate for DSN, initiating target recycling and signal amplification. This dynamic process, coupled with dual-signal relay amplification, significantly enhances both sensitivity and stability, even at low miRNA concentrations. Our ratiometric approach substantially improves detection accuracy by comparing dual signal outputs. We further demonstrate the capability of real-time tracking of exosomal RNA dynamics, enabling precise monitoring of miRNA fluctuations over time. The practical applicability of our ISR strategy was validated by accurately detecting exosomal miRNA levels in clinical serum samples from glioblastoma patients, distinguishing them from healthy controls with high precision. Our method represents a significant advancement in early cancer detection and disease monitoring, with broad implications for precision medicine and the development of point-of-care diagnostic tools. Looking ahead, the ISR strategy holds great potential for monitoring a wide range of diseases, offering new opportunities for personalized diagnostics and therapeutic strategies.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"274 ","pages":"Article 117205"},"PeriodicalIF":10.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143171472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ViPER: A visual bipolar electrochemical biosensor based on isothermal addition of a universal tag for detection of SARS-CoV-2.

IF 10.7 1区生物学

Biosensors and Bioelectronics Pub Date : 2025-01-31 DOI: 10.1016/j.bios.2025.117199

Seyedeh Malahat Shadman, Reyhaneh Tavakoli-Koopaei, Masoud A Mehrgardi, Fatemeh Javadi-Zarnaghi

{"title":"ViPER: A visual bipolar electrochemical biosensor based on isothermal addition of a universal tag for detection of SARS-CoV-2.","authors":"Seyedeh Malahat Shadman, Reyhaneh Tavakoli-Koopaei, Masoud A Mehrgardi, Fatemeh Javadi-Zarnaghi","doi":"10.1016/j.bios.2025.117199","DOIUrl":"https://doi.org/10.1016/j.bios.2025.117199","url":null,"abstract":"<p><p>Emergence of recent pandemics/endemics e.g. COVID-19 and Dengue fever, demonstrated the necessity of development of strategies for swift adaptation of present biosensor for detection of the new emerging pathogens. However, development of a biosensor for a new target is time- and labor-consuming. In this study, we aimed to integrate the primer exchange reaction (PER), an isothermal technique that extends an initiator DNA with a user-defined single-stranded DNA tail, with bipolar electrochemistry. This integration led to the development of a universal biosensor, termed ViPER. We demonstrated the utility of the developed system to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic RNA as a model. The genomic RNA was reverse transcribed to a short cDNA and was tailed with a universal tag, consequently, the tagged cDNA was applied to an electrochemiluminescence integrated bipolar electrochemical biosensor (BPE-ECL). ECL signals were recorded using a digital camera and analyzed by ImageJ. The platform demonstrated a linear response over a wide dynamic range of 10<sup>-7</sup>-10<sup>-17</sup> M for the target nucleic acid with a detection limit of 2.31 × 10<sup>-17</sup> M for synthetic targets. The biosensor could also successfully discriminate between biological RNA samples from infected and non-infected individuals. This study introduces the potential of DNA-based visual biosensors for detecting single-stranded RNAs in low-equipped environments, and it holds promises for further development of an ultrasensitive method for various human RNA-based viral pathogens. Moreover, we can design a platform with a predetermined DNA probe sequence for a vast variety of different targets, simply by changing the PER input.</p>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":" ","pages":"117199"},"PeriodicalIF":10.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to "Recent advances in implantable sensors and electronics using printable materials for advanced healthcare" [Biosens. Bioelectron. 257 (2024) 116302].

IF 10.7 1区生物学

Biosensors and Bioelectronics Pub Date : 2025-01-30 DOI: 10.1016/j.bios.2025.117191

Seunghyeb Ban, Haran Lee, Jiehao Chen, Hee-Seok Kim, Yuhang Hu, Seong J Cho, Woon-Hong Yeo

引用次数: 0

Cu2+-encapsulated DNA nanosphere and filter enable sensitive and rapid analysis of miRNA-155

IF 10.7 1区生物学

Biosensors and Bioelectronics Pub Date : 2025-01-28 DOI: 10.1016/j.bios.2025.117203

Weijing Liu , Yue Wang , Wu Peng , Xianghu Zeng , Pengjun Jiang , Wei Xiao , Jie Chen , Piaopiao Chen

{"title":"Cu2+-encapsulated DNA nanosphere and filter enable sensitive and rapid analysis of miRNA-155","authors":"Weijing Liu , Yue Wang , Wu Peng , Xianghu Zeng , Pengjun Jiang , Wei Xiao , Jie Chen , Piaopiao Chen","doi":"10.1016/j.bios.2025.117203","DOIUrl":"10.1016/j.bios.2025.117203","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) are critical regulators of gene expression, with aberrant levels linked to diseases such as breast cancer. Notably, they are challenging to detect due to their low abundance in complex sample matrices. In this study, a Cu<sup>2</sup><sup>⁺</sup>-encapsulated DNA nanosphere system capable of homogeneous, enzyme-free, one-pot detection of microRNA-155 (miRNA-155) in human plasma was developed. The system employed self-assembled DNA nanospheres loaded with copper ions as specific recognizers, coupled with a filter membrane-assisted reaction to separate free-Cu<sup>2+</sup> from residual components. Moreover, dual quantum dots (QDs) were utilized for signal output, using competitive binding to enhance sensitivity for detecting ultra-low and subtle changes in miRNA levels in complex samples. The method achieved an excellent detection performance, with a limit of detection (LOD) at the low-aM level. Additionally, it demonstrated high specificity in distinguishing between different miRNAs and single nucleotide polymorphisms (SNPs). Validation using 38 clinical plasma samples achieved over 95% accuracy in identifying breast cancer patients, demonstrating 100% sensitivity and approximately 90% clinical consistency compared to imaging, pathology, and quantitative real-time polymerase chain reaction (qRT-PCR). The method required minimal sample pre-treatment and was completed within 1 h. Overall, the developed method offers a reliable tool for breast cancer diagnosis and establishes a mode for extending its application to other biomarkers in the clinical setting.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"274 ","pages":"Article 117203"},"PeriodicalIF":10.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Green and cost-effective voltammetric assay based on activated glassy carbon electrode for determination of the plant growth regulator methyl jasmonate 基于活性玻璃碳电极的绿色经济型伏安测定法，用于测定植物生长调节剂茉莉酸甲酯。

IF 10.7 1区生物学

Biosensors and Bioelectronics Pub Date : 2025-01-28 DOI: 10.1016/j.bios.2025.117217

Katarzyna Tyszczuk-Rotko , Katarzyna Staniec , Agnieszka Hanaka

{"title":"Green and cost-effective voltammetric assay based on activated glassy carbon electrode for determination of the plant growth regulator methyl jasmonate","authors":"Katarzyna Tyszczuk-Rotko , Katarzyna Staniec , Agnieszka Hanaka","doi":"10.1016/j.bios.2025.117217","DOIUrl":"10.1016/j.bios.2025.117217","url":null,"abstract":"<div><div>A green, cost-effective, and efficient square-wave voltammetric (SWV) assay based on an electrochemically activated glassy carbon electrode (aGCE) for the determination of the plant growth regulator methyl jasmonate (MeJA) was developed. The activation was performed by anodization in 0.1 mol L<sup>−1</sup> NaOH by 5 cyclic voltammetric measurements in the potential range of 0–2 V at a scan rate of 100 mV s<sup>−1</sup>. Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and X-ray photoelectron spectroscopy (XPS) were applied to analyze the difference between the bare GCE and the aGCE in terms of their electrochemical properties. The functionalization of the GCE surface by oxygen-containing groups not only creates new active sites but also improves electron transfer dynamics and electrocatalytic activity. The SWV procedure displays a wide linear response from 0.1 to 50.0 μmol L<sup>−1</sup>, a low LOD = 0.027 μmol L<sup>−1</sup>, and LOQ = 0.097 μmol L<sup>−1</sup>. The aGCE was successfully applied to MeJA analysis in <em>Phaseolus coccineus</em> leaf extracts.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"274 ","pages":"Article 117217"},"PeriodicalIF":10.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Construction of a hierarchical DNA circuit for single-molecule profiling of locus-specific N6-methyladenosine-MALAT1 in clinical tissues

IF 10.7 1区生物学

Biosensors and Bioelectronics Pub Date : 2025-01-28 DOI: 10.1016/j.bios.2025.117198

Qian Liu, Bao-mei Zhou, Li-juan Wang, Chun-yang Zhang

{"title":"Construction of a hierarchical DNA circuit for single-molecule profiling of locus-specific N6-methyladenosine-MALAT1 in clinical tissues","authors":"Qian Liu, Bao-mei Zhou, Li-juan Wang, Chun-yang Zhang","doi":"10.1016/j.bios.2025.117198","DOIUrl":"10.1016/j.bios.2025.117198","url":null,"abstract":"<div><div><em>N</em><sup>6</sup>-methyladenosine (m<sup>6</sup>A) is the most important internal methylation in eukaryotic RNAs, and it is critically implicated in diverse RNA metabolisms for cancer development. Because epigenetic modifications do not interfere with Watson-Crick base pairing and m<sup>6</sup>A modification is not susceptible to chemical decorations, standard hybridization-based techniques cannot be applied for sensing m<sup>6</sup>A in RNAs. Consequently, the development of new methods for accurate and sensitive profiling of locus-specific m<sup>6</sup>A in RNAs remains a great challenge. Herein, we demonstrate for the first time the construction of a hierarchical DNA circuit for single-molecule profiling of locus-specific m<sup>6</sup>A-metastasis-associated lung adenocarcinoma transcript 1 (m<sup>6</sup>A-MALAT1) in clinical tissues. Taking advantage of high discrimination of VMC10-DNAzyme between m<sup>6</sup>A and A, exponential efficiency of hierarchical DNA circuit, and ultrahigh signal-to-noise ratio of single-molecule detection, this nanodevice exhibits attomolar sensitivity with a limit of detection (LOD) of 1.8 aM for m<sup>6</sup>A-MALAT1 <em>in vitro</em> and a dynamic range of 7 orders of magnitude. Moreover, it can discriminate 0.001% m<sup>6</sup>A-MALAT1 from excess A-MALAT1, quantify m<sup>6</sup>A-MALAT1 in diverse cancer cells at single-cell level, distinguish m<sup>6</sup>A-MALAT1 expressions in breast cancer patients and healthy individuals, and monitor cellular m<sup>6</sup>A-MALAT1 for gene therapy, offering a promising platform for epitranscriptomic research and clinical diagnostics.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"274 ","pages":"Article 117198"},"PeriodicalIF":10.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0