首页 > 最新文献

Biosensors-Basel最新文献

英文 中文
Nanoaggregate-Based Innovative Electrochemiluminescence Sensors for Foodborne Contaminant Analysis. 基于纳米聚合体的新型电化学发光传感器用于食源性污染物分析。
IF 5.6 3区 工程技术 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2025-12-22 DOI: 10.3390/bios16010006
Tingting Han, Jinyang Zhuang, Yueling Lu, Jianhong Xu, Jun-Jie Zhu

The pervasive presence of foodborne contaminants in foods poses a significant global threat, contributing to various foodborne diseases and food safety issues. Therefore, developing rapid, sensitive, and universal detection methods for them is essential to ensure public health and food safety. Electrochemiluminescence (ECL) sensors, particularly those incorporating innovative nanoaggregates, have been widely used to detect related contaminant residues in foodstuffs owing to their superior sensitivity and low background signals. This review summarizes recent advances in nanoaggregate-based novel ECL sensors for detecting a wide range of contaminants, with emphasis on their fundamentals and representative applications. This area has not yet been comprehensively covered in the existing literature. The current challenges and emerging trends for next-generation ECL sensors based on nanoaggregates in food safety monitoring are also discussed.

食品中普遍存在的食源性污染物构成了重大的全球威胁,导致各种食源性疾病和食品安全问题。因此,开发快速、灵敏、通用的检测方法对保障公众健康和食品安全至关重要。电化学发光(ECL)传感器,特别是那些包含创新纳米聚集体的传感器,由于其优越的灵敏度和低背景信号,已广泛用于检测食品中相关污染物残留。本文综述了基于纳米聚集体的新型ECL传感器的最新进展,重点介绍了它们的基本原理和代表性应用。这一领域在现有文献中尚未得到全面的论述。本文还讨论了基于纳米聚集体的下一代ECL传感器在食品安全监测中的当前挑战和新兴趋势。
{"title":"Nanoaggregate-Based Innovative Electrochemiluminescence Sensors for Foodborne Contaminant Analysis.","authors":"Tingting Han, Jinyang Zhuang, Yueling Lu, Jianhong Xu, Jun-Jie Zhu","doi":"10.3390/bios16010006","DOIUrl":"10.3390/bios16010006","url":null,"abstract":"<p><p>The pervasive presence of foodborne contaminants in foods poses a significant global threat, contributing to various foodborne diseases and food safety issues. Therefore, developing rapid, sensitive, and universal detection methods for them is essential to ensure public health and food safety. Electrochemiluminescence (ECL) sensors, particularly those incorporating innovative nanoaggregates, have been widely used to detect related contaminant residues in foodstuffs owing to their superior sensitivity and low background signals. This review summarizes recent advances in nanoaggregate-based novel ECL sensors for detecting a wide range of contaminants, with emphasis on their fundamentals and representative applications. This area has not yet been comprehensively covered in the existing literature. The current challenges and emerging trends for next-generation ECL sensors based on nanoaggregates in food safety monitoring are also discussed.</p>","PeriodicalId":48608,"journal":{"name":"Biosensors-Basel","volume":"16 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12838546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146054524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Wearable Ultrasound Sensing System for Soft Tissue Stiffness Detection: A Feasibility Study. 一种用于软组织刚度检测的可穿戴超声传感系统的可行性研究。
IF 5.6 3区 工程技术 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2025-12-22 DOI: 10.3390/bios16010009
Guangshuai Bao, Tongyi Xu, Xiaoyu Li, Bo Meng

Manual palpation serves as a conventional clinical method for assessing soft tissue stiffness; however, its results are susceptible to subjective factors and exhibit limited reliability. To achieve objective evaluation of pathological tissue stiffness, this study utilizes ultrasonic transducers to measure the time-of-flight (ToF) difference in ultrasound signals in silicone samples and ex vivo animal tissues under specific pressure gradients. A correlation model between the ToF difference and tissue stiffness was established, thereby enabling the detection of tissue stiffness. Based on this methodology, a wearable sensing system incorporating ultrasonic transducers was developed. The system applies fixed gradient pressure to human tissues via a pneumatic control unit and detects the corresponding ToF difference, allowing real-time monitoring of stiffness variations in the biceps brachii and thigh during relaxation and contraction, in the forearm during gripping and release actions, as well as in simulated lesions. This study provides a quantitative technological framework for wearable tissue stiffness monitoring, and its objective measurement characteristics offer support for clinical diagnostic decision-making.

手动触诊是评估软组织硬度的常规临床方法;然而,其结果易受主观因素影响,可靠性有限。为了客观评价病理组织刚度,本研究利用超声换能器测量硅胶样品和离体动物组织中超声信号在特定压力梯度下的飞行时间(ToF)差异。建立ToF差与组织刚度的相关模型,从而实现组织刚度的检测。基于该方法,开发了一种结合超声换能器的可穿戴传感系统。该系统通过气动控制单元对人体组织施加固定梯度压力,并检测相应的ToF差异,从而实时监测肱二头肌和大腿在放松和收缩过程中的刚度变化,以及前臂在抓握和释放动作中的刚度变化,以及模拟病变。本研究为可穿戴组织刚度监测提供了定量技术框架,其客观测量特性为临床诊断决策提供支持。
{"title":"A Wearable Ultrasound Sensing System for Soft Tissue Stiffness Detection: A Feasibility Study.","authors":"Guangshuai Bao, Tongyi Xu, Xiaoyu Li, Bo Meng","doi":"10.3390/bios16010009","DOIUrl":"10.3390/bios16010009","url":null,"abstract":"<p><p>Manual palpation serves as a conventional clinical method for assessing soft tissue stiffness; however, its results are susceptible to subjective factors and exhibit limited reliability. To achieve objective evaluation of pathological tissue stiffness, this study utilizes ultrasonic transducers to measure the time-of-flight (ToF) difference in ultrasound signals in silicone samples and ex vivo animal tissues under specific pressure gradients. A correlation model between the ToF difference and tissue stiffness was established, thereby enabling the detection of tissue stiffness. Based on this methodology, a wearable sensing system incorporating ultrasonic transducers was developed. The system applies fixed gradient pressure to human tissues via a pneumatic control unit and detects the corresponding ToF difference, allowing real-time monitoring of stiffness variations in the biceps brachii and thigh during relaxation and contraction, in the forearm during gripping and release actions, as well as in simulated lesions. This study provides a quantitative technological framework for wearable tissue stiffness monitoring, and its objective measurement characteristics offer support for clinical diagnostic decision-making.</p>","PeriodicalId":48608,"journal":{"name":"Biosensors-Basel","volume":"16 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12838826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146054422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrated Microfluidic Giant Magnetoresistance (GMR) Biosensor Platform for Magnetoresistive Immunoassay of Myoglobin. 用于肌红蛋白磁阻免疫分析的集成微流控巨磁阻(GMR)生物传感器平台。
IF 5.6 3区 工程技术 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2025-12-22 DOI: 10.3390/bios16010008
Yikai Wang, Huaiyu Wang, Yunyun Zhang, Shuhui Cui, Fei Hu, Bo'an Li

Acute myocardial infarction (AMI) is a rapidly progressing cardiovascular condition associated with high mortality. Myoglobin is an early biomarker of AMI; however, its detection using conventional methods is limited by complex workflows and low resistance to interference. In this study, we developed an integrated myoglobin detection platform that combined magneto-immunoassay with microfluidic technology. A giant magnetoresistance (GMR) sensor was fabricated using micro-electro-mechanical systems (MEMS). The designed microfluidic chip integrated sample pretreatment, immunoreaction, and magnetic signal capture functionalities. Its built-in GMR sensor, labeled with magnetic nanoparticles, directly converted the "antigen-antibody" biochemical signal into detectable magnetoresistance changes, thereby enabling the indirect detection of myoglobin. A magneto-immunoassay analysis system consisted of a fluidic drive, magnetic field control, and data acquisition functions. Various key parameters were optimized, including EDC/NHS concentration, antibody concentration, and magnetic bead size. Under the optimal conditions and using 1 μm magnetic beads as labels and an external detection magnetic field of 60 Oe, the platform successfully detected myoglobin at 75 ng/mL with ∆MR ≥ 0.202%. Specificity tests demonstrated that the platform had high specificity for myoglobin and could effectively distinguish myoglobin from bovine serum albumin (BSA) and troponin I. This study presents a rapid, accurate myoglobin detection platform that can be applied for the early diagnosis of AMI.

急性心肌梗死(AMI)是一种进展迅速的心血管疾病,死亡率高。肌红蛋白是急性心肌梗死的早期生物标志物;然而,传统的检测方法受到复杂的工作流程和低抗干扰性的限制。在这项研究中,我们开发了一个将磁免疫分析与微流体技术相结合的肌红蛋白检测平台。利用微机电系统(MEMS)制作了巨磁阻(GMR)传感器。所设计的微流控芯片集成了样品预处理、免疫反应和磁信号捕获功能。其内置的GMR传感器,用磁性纳米颗粒标记,直接将“抗原-抗体”生化信号转化为可检测的磁电阻变化,从而能够间接检测肌红蛋白。磁免疫分析系统由流体驱动、磁场控制和数据采集功能组成。对EDC/NHS浓度、抗体浓度、磁珠大小等关键参数进行优化。在最优条件下,以1 μm磁珠为标记,外检测磁场为60 Oe,成功检测出75 ng/mL的肌红蛋白,∆MR≥0.202%。特异性试验表明,该平台对肌红蛋白具有较高的特异性,可有效区分肌红蛋白与牛血清白蛋白(BSA)、肌钙蛋白i。本研究为AMI早期诊断提供了一种快速、准确的肌红蛋白检测平台。
{"title":"Integrated Microfluidic Giant Magnetoresistance (GMR) Biosensor Platform for Magnetoresistive Immunoassay of Myoglobin.","authors":"Yikai Wang, Huaiyu Wang, Yunyun Zhang, Shuhui Cui, Fei Hu, Bo'an Li","doi":"10.3390/bios16010008","DOIUrl":"10.3390/bios16010008","url":null,"abstract":"<p><p>Acute myocardial infarction (AMI) is a rapidly progressing cardiovascular condition associated with high mortality. Myoglobin is an early biomarker of AMI; however, its detection using conventional methods is limited by complex workflows and low resistance to interference. In this study, we developed an integrated myoglobin detection platform that combined magneto-immunoassay with microfluidic technology. A giant magnetoresistance (GMR) sensor was fabricated using micro-electro-mechanical systems (MEMS). The designed microfluidic chip integrated sample pretreatment, immunoreaction, and magnetic signal capture functionalities. Its built-in GMR sensor, labeled with magnetic nanoparticles, directly converted the \"antigen-antibody\" biochemical signal into detectable magnetoresistance changes, thereby enabling the indirect detection of myoglobin. A magneto-immunoassay analysis system consisted of a fluidic drive, magnetic field control, and data acquisition functions. Various key parameters were optimized, including EDC/NHS concentration, antibody concentration, and magnetic bead size. Under the optimal conditions and using 1 μm magnetic beads as labels and an external detection magnetic field of 60 Oe, the platform successfully detected myoglobin at 75 ng/mL with ∆MR ≥ 0.202%. Specificity tests demonstrated that the platform had high specificity for myoglobin and could effectively distinguish myoglobin from bovine serum albumin (BSA) and troponin I. This study presents a rapid, accurate myoglobin detection platform that can be applied for the early diagnosis of AMI.</p>","PeriodicalId":48608,"journal":{"name":"Biosensors-Basel","volume":"16 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12838720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146054514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ultra-High-Frequency-Dielectrophoresis Microfluidic Biosensor to Detect the Transformation Potential of Extracellular Vesicles Derived from Cancer Stem Cells. 超高频双向电泳微流控生物传感器检测肿瘤干细胞胞外囊泡转化潜能。
IF 5.6 3区 工程技术 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2025-12-19 DOI: 10.3390/bios16010002
Elodie Barthout, Elisa Lambert, Stéphanie Durand, Céline Hervieu, Léa Ikhlef, Sofiane Saada, Rémi Manczak, Julie Pannequin, Arnaud Pothier, Claire Dalmay, Fabrice Lalloué, Muriel Mathonnet, Barbara Bessette

Cancer stem cells (CSCs) remain challenging to isolate and characterize because of their plastic phenotype. To overcome this issue, we used a microfluidic lab-on-a-chip analysis approach based on ultra-high frequency dielectophoresis (UHF-DEP) to measure the dielectrophoretic signature of colorectal cancer cells. We demonstrated that CSCs exhibit a distinct and lower frequency signature than differentiated cancer cells. Extracellular vesicles (EVs) released by tumor cells are implicated in tumor progression and metastasis. As CSC-derived EVs carry a more aggressive cargo, we hypothesized that treating differentiated colorectal cancer cells with these vesicles might affect their phenotype which would be detected by our lab on a chip. Indeed, the dielectrophoretic signature of cells treated with those EVs was altered in comparison to untreated cells, even in cases where no detectable biological changes were observed. Compared to conventional approaches using biomarkers to characterize CSCs, this UHF-DEP lab on a chip is a label-free method providing rapid and relevant results. Such a method could be useful in the clinic for the early detection of CSCs in the tumor mass, as well as for monitoring CSC-derived EVs in the bloodstream in order to study responses to therapy and prevent relapses.

肿瘤干细胞(CSCs)由于其可塑性表型,其分离和表征仍然具有挑战性。为了克服这一问题,我们采用了一种基于超高频电介质(UHF-DEP)的微流控芯片实验室分析方法来测量结直肠癌细胞的电介质特征。我们证明了csc比分化的癌细胞表现出明显的低频率特征。肿瘤细胞释放的细胞外囊泡(EVs)与肿瘤的进展和转移有关。由于csc衍生的ev携带更具侵略性的货物,我们假设用这些囊泡治疗分化的结直肠癌细胞可能会影响其表型,这将由我们的实验室在芯片上检测到。事实上,与未处理的细胞相比,使用这些ev处理的细胞的介电泳特征发生了改变,即使在没有观察到可检测到的生物学变化的情况下也是如此。与使用生物标志物表征CSCs的传统方法相比,这种芯片上的UHF-DEP实验室是一种无标签的方法,可提供快速和相关的结果。这种方法可用于临床早期检测肿瘤肿块中的csc,以及监测血液中csc衍生的ev,以研究对治疗的反应并防止复发。
{"title":"Ultra-High-Frequency-Dielectrophoresis Microfluidic Biosensor to Detect the Transformation Potential of Extracellular Vesicles Derived from Cancer Stem Cells.","authors":"Elodie Barthout, Elisa Lambert, Stéphanie Durand, Céline Hervieu, Léa Ikhlef, Sofiane Saada, Rémi Manczak, Julie Pannequin, Arnaud Pothier, Claire Dalmay, Fabrice Lalloué, Muriel Mathonnet, Barbara Bessette","doi":"10.3390/bios16010002","DOIUrl":"10.3390/bios16010002","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) remain challenging to isolate and characterize because of their plastic phenotype. To overcome this issue, we used a microfluidic lab-on-a-chip analysis approach based on ultra-high frequency dielectophoresis (UHF-DEP) to measure the dielectrophoretic signature of colorectal cancer cells. We demonstrated that CSCs exhibit a distinct and lower frequency signature than differentiated cancer cells. Extracellular vesicles (EVs) released by tumor cells are implicated in tumor progression and metastasis. As CSC-derived EVs carry a more aggressive cargo, we hypothesized that treating differentiated colorectal cancer cells with these vesicles might affect their phenotype which would be detected by our lab on a chip. Indeed, the dielectrophoretic signature of cells treated with those EVs was altered in comparison to untreated cells, even in cases where no detectable biological changes were observed. Compared to conventional approaches using biomarkers to characterize CSCs, this UHF-DEP lab on a chip is a label-free method providing rapid and relevant results. Such a method could be useful in the clinic for the early detection of CSCs in the tumor mass, as well as for monitoring CSC-derived EVs in the bloodstream in order to study responses to therapy and prevent relapses.</p>","PeriodicalId":48608,"journal":{"name":"Biosensors-Basel","volume":"16 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12838799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146054511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biosensors for Detection of Labile Heme in Biological Samples. 用于检测生物样品中不稳定血红素的生物传感器。
IF 5.6 3区 工程技术 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2025-12-19 DOI: 10.3390/bios16010004
Krysta Dobill, Delphine Lechardeur, Jasmina Vidic

Heme, a protoporphyrin IX iron complex, functions as an essential prosthetic group in hemoglobin and myoglobin, mediating oxygen storage and transport. Additionally, heme serves as a critical cofactor in various enzymes such as cytochrome c, enabling electron transfer within the mitochondrial respiratory chain. Unlike protein-bound heme, free or labile heme exhibits cytotoxic, pro-oxidant, and pro-inflammatory properties. Elevated levels of free heme are associated with various pathophysiological conditions, including hemolytic disorders such as sickle cell disease, malaria, and sepsis. In this review, we introduce the physiological roles of heme and its involvement in human health and disease. We also examine the mechanisms of heme sensing and regulation in bacterial cells. A variety of analytical methods have been developed to detect and quantify heme, enabling differentiation between protein-bound and free forms. These tools are discussed in the context of their applications in studying cellular heme regulation and their use in monitoring pathological conditions in humans. In particular, we describe examples of biosensors employing bacterial heme sensor proteins as recognition elements.

血红素是一种原卟啉IX铁复合物,在血红蛋白和肌红蛋白中起着重要的修复基团作用,介导氧的储存和运输。此外,血红素作为细胞色素c等多种酶的关键辅助因子,使线粒体呼吸链内的电子转移成为可能。与蛋白结合血红素不同,游离血红素或不稳定血红素具有细胞毒性、促氧化和促炎症特性。游离血红素水平升高与各种病理生理状况有关,包括溶血性疾病,如镰状细胞病、疟疾和败血症。本文就血红素的生理作用及其在人体健康和疾病中的作用作一综述。我们还研究了细菌细胞中血红素感知和调节的机制。各种分析方法已经发展到检测和定量血红素,使区分蛋白结合和自由形式。这些工具在研究细胞血红素调节及其在监测人类病理状况中的应用的背景下进行了讨论。特别地,我们描述了使用细菌血红素传感器蛋白作为识别元件的生物传感器的例子。
{"title":"Biosensors for Detection of Labile Heme in Biological Samples.","authors":"Krysta Dobill, Delphine Lechardeur, Jasmina Vidic","doi":"10.3390/bios16010004","DOIUrl":"10.3390/bios16010004","url":null,"abstract":"<p><p>Heme, a protoporphyrin IX iron complex, functions as an essential prosthetic group in hemoglobin and myoglobin, mediating oxygen storage and transport. Additionally, heme serves as a critical cofactor in various enzymes such as cytochrome c, enabling electron transfer within the mitochondrial respiratory chain. Unlike protein-bound heme, free or labile heme exhibits cytotoxic, pro-oxidant, and pro-inflammatory properties. Elevated levels of free heme are associated with various pathophysiological conditions, including hemolytic disorders such as sickle cell disease, malaria, and sepsis. In this review, we introduce the physiological roles of heme and its involvement in human health and disease. We also examine the mechanisms of heme sensing and regulation in bacterial cells. A variety of analytical methods have been developed to detect and quantify heme, enabling differentiation between protein-bound and free forms. These tools are discussed in the context of their applications in studying cellular heme regulation and their use in monitoring pathological conditions in humans. In particular, we describe examples of biosensors employing bacterial heme sensor proteins as recognition elements.</p>","PeriodicalId":48608,"journal":{"name":"Biosensors-Basel","volume":"16 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12839281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146054400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Detection of Structural Changes in G-Quadruplex-Forming DNA Oligonucleotides via DNA Methylation Based on Luminol Chemiluminescence Catalyzed by Myoglobin. 基于肌红蛋白催化鲁米诺化学发光的DNA甲基化检测g -四聚体形成DNA寡核苷酸结构变化。
IF 5.6 3区 工程技术 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2025-12-19 DOI: 10.3390/bios16010001
Shintaro Inaba, Haruka Kawai, Mizuki Tomizawa, Daimei Miura, Kaori Tsukakoshi, Kazunori Ikebukuro

A novel, label-free chemiluminescence sensing platform for CpG methylation was developed, leveraging the G-quadruplex (G4) structural sensitivity of G4-protein interactions to eliminate bisulfite conversion. This sensing system is based on the enhancement of luminol chemiluminescence generated from myoglobin upon binding to the G4-forming DNA. At the core of this biosensor is the G4-structure-dependent modulation of the peroxidase-like activity generating luminol chemiluminescence of myoglobin. The structural change by CpG methylation within the G4-forming sequence of the B cell lymphoma 2 (BCL2) gene promoter altered its binding to myoglobin, transducing the methylation state into a measurable signal catalyzed by myoglobin. This principle was validated in a practical assay using immobilized probes to capture the target DNA for methylation analysis. This system demonstrated the capability to distinguish methylation differences of 50% when the target DNA concentration was over 25 nM. Versatility was further confirmed using the sequence from the dopamine receptor D2 (DRD2) gene promoter, where the methylation similarly induced distinct topological and functional changes. This is the first study to directly link the epigenetic state of a G4-forming DNA sequence to a protein-mediated enzymatic output, offering a framework for simple, rapid, and highly adaptable biosensors for research and clinical applications.

开发了一种新的、无标记的CpG甲基化化学发光传感平台,利用G4蛋白相互作用的g -四重体(G4)结构敏感性来消除亚硫酸氢盐转化。该传感系统基于肌红蛋白与g4形成DNA结合后产生的发光氨化学发光增强。该生物传感器的核心是g4结构依赖性调节过氧化物酶样活性,产生肌红蛋白的发光化学发光。B细胞淋巴瘤2 (BCL2)基因启动子g4形成序列中CpG甲基化的结构变化改变了其与肌红蛋白的结合,将甲基化状态转化为肌红蛋白催化的可测量信号。这一原理在实际分析中得到验证,使用固定化探针捕获目标DNA进行甲基化分析。当目标DNA浓度大于25 nM时,该系统能够区分50%的甲基化差异。使用多巴胺受体D2 (DRD2)基因启动子的序列进一步证实了多功能性,其中甲基化类似地诱导了不同的拓扑和功能变化。这是第一个将g4形成DNA序列的表观遗传状态与蛋白质介导的酶输出直接联系起来的研究,为研究和临床应用提供了一个简单、快速、高适应性的生物传感器框架。
{"title":"Detection of Structural Changes in G-Quadruplex-Forming DNA Oligonucleotides via DNA Methylation Based on Luminol Chemiluminescence Catalyzed by Myoglobin.","authors":"Shintaro Inaba, Haruka Kawai, Mizuki Tomizawa, Daimei Miura, Kaori Tsukakoshi, Kazunori Ikebukuro","doi":"10.3390/bios16010001","DOIUrl":"10.3390/bios16010001","url":null,"abstract":"<p><p>A novel, label-free chemiluminescence sensing platform for CpG methylation was developed, leveraging the G-quadruplex (G4) structural sensitivity of G4-protein interactions to eliminate bisulfite conversion. This sensing system is based on the enhancement of luminol chemiluminescence generated from myoglobin upon binding to the G4-forming DNA. At the core of this biosensor is the G4-structure-dependent modulation of the peroxidase-like activity generating luminol chemiluminescence of myoglobin. The structural change by CpG methylation within the G4-forming sequence of the B cell lymphoma 2 (BCL2) gene promoter altered its binding to myoglobin, transducing the methylation state into a measurable signal catalyzed by myoglobin. This principle was validated in a practical assay using immobilized probes to capture the target DNA for methylation analysis. This system demonstrated the capability to distinguish methylation differences of 50% when the target DNA concentration was over 25 nM. Versatility was further confirmed using the sequence from the dopamine receptor D2 (DRD2) gene promoter, where the methylation similarly induced distinct topological and functional changes. This is the first study to directly link the epigenetic state of a G4-forming DNA sequence to a protein-mediated enzymatic output, offering a framework for simple, rapid, and highly adaptable biosensors for research and clinical applications.</p>","PeriodicalId":48608,"journal":{"name":"Biosensors-Basel","volume":"16 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12838553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146054563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
When Droplets Can "Think": Intelligent Testing in Digital Microfluidic Chips. 当液滴可以“思考”:数字微流控芯片的智能测试。
IF 5.6 3区 工程技术 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2025-12-19 DOI: 10.3390/bios16010003
Zhijie Luo, Shaoxin Li, Wufa Long, Rui Chen, Jianhua Zheng

Digital microfluidic biochips (DMFBs) find extensive applications in biochemical experiments, medical diagnostics, and safety-critical domains, with their reliability dependent on efficient online testing technologies. However, traditional random search algorithms suffer from slow convergence and susceptibility to local optima under complex fluidic constraints. This paper proposes a hybrid optimization method based on priority strategy and an improved sparrow search algorithm for DMFB online test path planning. At the algorithmic level, the improved sparrow search algorithm incorporates three main components: tent chaotic mapping for population initialization, cosine adaptive weights together with Elite Opposition-based Learning (EOBL) to balance global exploration and local exploitation, and a Gaussian perturbation mechanism for fine-grained refinement of promising solutions. Concurrently, this paper proposes an intelligent rescue strategy that integrates global graph-theoretic pathfinding, local greedy heuristics, and space-time constraint verification to establish a closed-loop decision-making system. The experimental results show that the proposed algorithm is efficient. On the standard 7 × 7-15 × 15 DMFB benchmark chips, the shortest offline test path length obtained by the algorithm is equal to the length of the Euler path, indicating that, for these regular layouts, the shortest test path has reached the known optimal value. In both offline and online testing, the shortest paths found by the proposed method are better than or equal to those of existing mainstream algorithms. In particular, for the 15 × 15 chip under online testing, the proposed method reduces the path length from 543 and 471 to 446 compared with the IPSO and IACA algorithms, respectively, and reduces the standard deviation by 53.14% and 39.4% compared with IGWO in offline and online testing.

数字微流控生物芯片(dmfb)在生化实验、医学诊断和安全关键领域得到广泛应用,其可靠性依赖于高效的在线测试技术。然而,在复杂流体约束下,传统的随机搜索算法存在收敛速度慢、易出现局部最优的问题。针对DMFB在线测试路径规划问题,提出了一种基于优先级策略和改进麻雀搜索算法的混合优化方法。在算法层面,改进的麻雀搜索算法包含三个主要组成部分:用于种群初始化的tent混沌映射,余弦自适应权重以及基于精英对立的学习(EOBL)来平衡全局探索和局部开发,以及用于细粒度细化有希望的解决方案的高斯扰动机制。同时,提出了一种集成全局图论寻路、局部贪婪启发式和时空约束验证的智能救援策略,构建闭环决策系统。实验结果表明,该算法是有效的。在标准的7 × 7-15 × 15 DMFB基准芯片上,算法得到的最短离线测试路径长度等于欧拉路径的长度,说明对于这些规则布局,最短测试路径已经达到已知的最优值。在离线和在线测试中,所提方法找到的最短路径都优于或等于现有主流算法。特别是对于在线测试的15 × 15芯片,与IPSO和IACA算法相比,本文方法将路径长度分别从543和471减少到446,与IGWO算法相比,离线和在线测试的标准差分别降低了53.14%和39.4%。
{"title":"When Droplets Can \"Think\": Intelligent Testing in Digital Microfluidic Chips.","authors":"Zhijie Luo, Shaoxin Li, Wufa Long, Rui Chen, Jianhua Zheng","doi":"10.3390/bios16010003","DOIUrl":"10.3390/bios16010003","url":null,"abstract":"<p><p>Digital microfluidic biochips (DMFBs) find extensive applications in biochemical experiments, medical diagnostics, and safety-critical domains, with their reliability dependent on efficient online testing technologies. However, traditional random search algorithms suffer from slow convergence and susceptibility to local optima under complex fluidic constraints. This paper proposes a hybrid optimization method based on priority strategy and an improved sparrow search algorithm for DMFB online test path planning. At the algorithmic level, the improved sparrow search algorithm incorporates three main components: tent chaotic mapping for population initialization, cosine adaptive weights together with Elite Opposition-based Learning (EOBL) to balance global exploration and local exploitation, and a Gaussian perturbation mechanism for fine-grained refinement of promising solutions. Concurrently, this paper proposes an intelligent rescue strategy that integrates global graph-theoretic pathfinding, local greedy heuristics, and space-time constraint verification to establish a closed-loop decision-making system. The experimental results show that the proposed algorithm is efficient. On the standard 7 × 7-15 × 15 DMFB benchmark chips, the shortest offline test path length obtained by the algorithm is equal to the length of the Euler path, indicating that, for these regular layouts, the shortest test path has reached the known optimal value. In both offline and online testing, the shortest paths found by the proposed method are better than or equal to those of existing mainstream algorithms. In particular, for the 15 × 15 chip under online testing, the proposed method reduces the path length from 543 and 471 to 446 compared with the IPSO and IACA algorithms, respectively, and reduces the standard deviation by 53.14% and 39.4% compared with IGWO in offline and online testing.</p>","PeriodicalId":48608,"journal":{"name":"Biosensors-Basel","volume":"16 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12838844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146054663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advanced Immunoassays and Biosensing: From Design to Development. 先进的免疫测定和生物传感:从设计到开发。
IF 5.6 3区 工程技术 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2025-12-18 DOI: 10.3390/bios15120822
Dongyang Li, Xu Wang, Juan Pablo Salvador

Over the past decade, the field of immunoassays and biosensing has undergone remarkable expansion, driven by the urgent demand for sensitive, rapid, and reliable detection technologies across biomedical, environmental, and food safety applications [...].

在过去的十年中,免疫测定和生物传感领域经历了显着的扩张,这是由于对生物医学,环境和食品安全应用中敏感,快速和可靠的检测技术的迫切需求[…]。
{"title":"Advanced Immunoassays and Biosensing: From Design to Development.","authors":"Dongyang Li, Xu Wang, Juan Pablo Salvador","doi":"10.3390/bios15120822","DOIUrl":"10.3390/bios15120822","url":null,"abstract":"<p><p>Over the past decade, the field of immunoassays and biosensing has undergone remarkable expansion, driven by the urgent demand for sensitive, rapid, and reliable detection technologies across biomedical, environmental, and food safety applications [...].</p>","PeriodicalId":48608,"journal":{"name":"Biosensors-Basel","volume":"15 12","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12730626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145821553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comprehensive Review on DNA Hydrogels and DNA Origami-Enabled Wearable and Implantable Biosensors. DNA水凝胶和DNA折纸可穿戴和可植入生物传感器综述。
IF 5.6 3区 工程技术 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2025-12-18 DOI: 10.3390/bios15120819
Man Li, Joonho Bae

DNA nanoparticles have emerged as potent platforms for wearable and implantable biosensors owing to their molecular programmability, biocompatibility, and structural precision. This study delineates two principal categories of DNA-based sensing materials, DNA hydrogels and DNA origami, and encapsulates their fabrication methodologies, sensing mechanisms, and applications at the device level. DNA hydrogels serve as pliable, aqueous signal transduction mediums exhibiting stimulus-responsive characteristics, facilitating applications such as sweat-based cytokine detection with limits of detection as low as pg·mL-1 and microneedle-integrated hydrogels for femtomolar miRNA sensing. DNA origami offers nanometer-scale spatial precision that improves electrochemical, optical, and plasmonic biosensing, as shown by origami-facilitated luminous nucleic acid detection and ultrasensitive circulating tumor DNA assays with fM-level sensitivity. Emerging integration technologies, such as flexible electronics, microfluidics, and wireless readout, are examined, alongside prospective developments in AI-assisted DNA design and materials produced from synthetic biology. This study offers a thorough and practical viewpoint on the progression of DNA nanotechnology for next-generation wearable and implantable biosensing devices.

由于其分子可编程性、生物相容性和结构精度,DNA纳米颗粒已成为可穿戴和可植入生物传感器的有力平台。本研究描述了DNA传感材料的两个主要类别,DNA水凝胶和DNA折纸,并概括了它们的制造方法、传感机制和在设备层面的应用。DNA水凝胶是一种柔软的水性信号转导介质,具有刺激响应特性,有利于基于汗液的细胞因子检测(检测限低至pg·mL-1)和微针集成水凝胶(用于飞分子miRNA传感)等应用。DNA折纸提供了纳米尺度的空间精度,提高了电化学、光学和等离子体生物传感,如折纸促进的发光核酸检测和超灵敏的循环肿瘤DNA检测,具有微米级的灵敏度。新兴的集成技术,如柔性电子、微流体和无线读出,以及人工智能辅助DNA设计和合成生物学生产材料的前景发展进行了研究。本研究为下一代可穿戴和植入式生物传感装置的DNA纳米技术的发展提供了一个全面和实用的观点。
{"title":"Comprehensive Review on DNA Hydrogels and DNA Origami-Enabled Wearable and Implantable Biosensors.","authors":"Man Li, Joonho Bae","doi":"10.3390/bios15120819","DOIUrl":"10.3390/bios15120819","url":null,"abstract":"<p><p>DNA nanoparticles have emerged as potent platforms for wearable and implantable biosensors owing to their molecular programmability, biocompatibility, and structural precision. This study delineates two principal categories of DNA-based sensing materials, DNA hydrogels and DNA origami, and encapsulates their fabrication methodologies, sensing mechanisms, and applications at the device level. DNA hydrogels serve as pliable, aqueous signal transduction mediums exhibiting stimulus-responsive characteristics, facilitating applications such as sweat-based cytokine detection with limits of detection as low as pg·mL<sup>-1</sup> and microneedle-integrated hydrogels for femtomolar miRNA sensing. DNA origami offers nanometer-scale spatial precision that improves electrochemical, optical, and plasmonic biosensing, as shown by origami-facilitated luminous nucleic acid detection and ultrasensitive circulating tumor DNA assays with fM-level sensitivity. Emerging integration technologies, such as flexible electronics, microfluidics, and wireless readout, are examined, alongside prospective developments in AI-assisted DNA design and materials produced from synthetic biology. This study offers a thorough and practical viewpoint on the progression of DNA nanotechnology for next-generation wearable and implantable biosensing devices.</p>","PeriodicalId":48608,"journal":{"name":"Biosensors-Basel","volume":"15 12","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12730752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145821592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rapid Visual Detection of Mycoplasma Hominis Using an RPA-CRISPR/Cas12a Assay. RPA-CRISPR/Cas12a快速检测人支原体
IF 5.6 3区 工程技术 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2025-12-18 DOI: 10.3390/bios15120821
Jie Chen, Shutao Liu, Sunyi Chen, Jingwen Mai, Maiwula Abudukadi, Yao Chen, Jie Lu, Guanglei Li, Chenchen Ge

Mycoplasma hominis (MH) is a prevalent opportunistic pathogen that is strongly associated with a wide range of urogenital tract infections and severe adverse pregnancy outcomes in clinical settings. Current MH detection methods, including microbial culture and qPCR, are time-consuming and rely on complex equipment, making them unsuitable for scenarios requiring rapid or simplified testing. In this study, we developed a visual readout biosensing platform by synergistically integrating recombinase polymerase amplification (RPA), CRISPR/Cas12a-mediated target nucleic acid recognition, and lateral flow biosensors for the rapid, sensitive, and specific identification of MH. The assay specifically targets the MH-specific 16S rRNA gene, achieving a limit of detection as low as 2 copies/reaction of recombinant plasmid containing the target gene with a total assay time of 60 min. Critical reaction parameters, including Cas12a-crRNA molar ratio, volume of RPA amplicon input, and Cas12a cleavage time, were systematically optimized to maximize the biosensor's response efficiency and detection reliability. The platform exhibited exceptional specificity, with no cross-reactivity observed against common co-occurring urogenital pathogens, and effectively minimized aerosol contamination risks via a rigorous decontamination workflow. Furthermore, this work represents the first documented implementation of a contamination-control protocol for an MH-specific CRISPR-LFA assay. Notably, testing results from 18 clinical samples demonstrated the high specificity of this assay, highlighting its promising potential for clinical application.

人支原体(MH)是一种流行的机会性病原体,在临床环境中与广泛的泌尿生殖道感染和严重的不良妊娠结局密切相关。目前的MH检测方法,包括微生物培养和qPCR,耗时且依赖于复杂的设备,不适合需要快速或简化检测的场景。在本研究中,我们将重组酶聚合酶扩增(RPA)、CRISPR/ cas12a介导的靶核酸识别和侧流生物传感器协同整合,开发了一种视觉读取生物传感平台,用于MH的快速、敏感和特异性鉴定。该检测方法专门针对MH特异性16S rRNA基因,检测限低至2拷贝/反应,总检测时间为60 min。系统优化Cas12a- crrna摩尔比、RPA扩增子输入量、Cas12a裂解时间等关键反应参数,最大限度提高生物传感器的响应效率和检测可靠性。该平台表现出特殊的特异性,对常见的泌尿生殖系统共同发生的病原体没有交叉反应,并通过严格的去污工作流程有效地将气溶胶污染风险降至最低。此外,这项工作代表了首次记录的mh特异性CRISPR-LFA检测污染控制方案的实施。值得注意的是,来自18个临床样本的测试结果显示了该检测方法的高特异性,突出了其临床应用的潜力。
{"title":"Rapid Visual Detection of Mycoplasma Hominis Using an RPA-CRISPR/Cas12a Assay.","authors":"Jie Chen, Shutao Liu, Sunyi Chen, Jingwen Mai, Maiwula Abudukadi, Yao Chen, Jie Lu, Guanglei Li, Chenchen Ge","doi":"10.3390/bios15120821","DOIUrl":"10.3390/bios15120821","url":null,"abstract":"<p><p>Mycoplasma hominis (MH) is a prevalent opportunistic pathogen that is strongly associated with a wide range of urogenital tract infections and severe adverse pregnancy outcomes in clinical settings. Current MH detection methods, including microbial culture and qPCR, are time-consuming and rely on complex equipment, making them unsuitable for scenarios requiring rapid or simplified testing. In this study, we developed a visual readout biosensing platform by synergistically integrating recombinase polymerase amplification (RPA), CRISPR/Cas12a-mediated target nucleic acid recognition, and lateral flow biosensors for the rapid, sensitive, and specific identification of MH. The assay specifically targets the MH-specific 16S rRNA gene, achieving a limit of detection as low as 2 copies/reaction of recombinant plasmid containing the target gene with a total assay time of 60 min. Critical reaction parameters, including Cas12a-crRNA molar ratio, volume of RPA amplicon input, and Cas12a cleavage time, were systematically optimized to maximize the biosensor's response efficiency and detection reliability. The platform exhibited exceptional specificity, with no cross-reactivity observed against common co-occurring urogenital pathogens, and effectively minimized aerosol contamination risks via a rigorous decontamination workflow. Furthermore, this work represents the first documented implementation of a contamination-control protocol for an MH-specific CRISPR-LFA assay. Notably, testing results from 18 clinical samples demonstrated the high specificity of this assay, highlighting its promising potential for clinical application.</p>","PeriodicalId":48608,"journal":{"name":"Biosensors-Basel","volume":"15 12","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12730632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145821604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Biosensors-Basel
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1