首页 > 最新文献

Biosensors最新文献

英文 中文
Quantifying Plant Signaling Pathways by Integrating Luminescence-Based Biosensors and Mathematical Modeling 通过整合发光生物传感器和数学建模量化植物信号通路
Pub Date : 2024-08-05 DOI: 10.3390/bios14080378
Shakeel Ahmed, Syed Muhammad Zaigham Abbas Naqvi, Fida Hussain, Muhammad Awais, Yongzhe Ren, Junfeng Wu, Hao Zhang, Yiheng Zang, Jiandong Hu
Plants have evolved intricate signaling pathways, which operate as networks governed by feedback to deal with stressors. Nevertheless, the sophisticated molecular mechanisms underlying these routes still need to be comprehended, and experimental validation poses significant challenges and expenses. Consequently, computational hypothesis evaluation gains prominence in understanding plant signaling dynamics. Biosensors are genetically modified to emit light when exposed to a particular hormone, such as abscisic acid (ABA), enabling quantification. We developed computational models to simulate the relationship between ABA concentrations and bioluminescent sensors utilizing the Hill equation and ordinary differential equations (ODEs), aiding better hypothesis development regarding plant signaling. Based on simulation results, the luminescence intensity was recorded for a concentration of 47.646 RLUs for 1.5 μmol, given the specified parameters and model assumptions. This method enhances our understanding of plant signaling pathways at the cellular level, offering significant benefits to the scientific community in a cost-effective manner. The alignment of these computational predictions with experimental results emphasizes the robustness of our approach, providing a cost-effective means to validate mathematical models empirically. The research intended to correlate the bioluminescence of biosensors with plant signaling and its mathematical models for quantified detection of specific plant hormone ABA.
植物进化出了复杂的信号通路,这些通路作为受反馈控制的网络运行,以应对压力因素。然而,这些途径背后的复杂分子机制仍有待理解,而实验验证也带来了巨大的挑战和费用。因此,计算假说评估在理解植物信号传递动力学方面变得越来越重要。生物传感器经过基因改造,在暴露于特定激素(如脱落酸(ABA))时会发光,从而实现量化。我们开发了计算模型,利用希尔方程和常微分方程(ODEs)模拟 ABA 浓度与生物发光传感器之间的关系,有助于更好地提出有关植物信号传递的假设。根据模拟结果,在指定的参数和模型假设条件下,1.5 μmol 浓度的发光强度为 47.646 RLUs。这种方法增强了我们对细胞水平植物信号通路的了解,以经济高效的方式为科学界带来了巨大收益。这些计算预测与实验结果的吻合强调了我们的方法的稳健性,为通过经验验证数学模型提供了一种经济有效的方法。该研究旨在将生物传感器的生物发光与植物信号传导及其数学模型相关联,以量化检测特定的植物激素 ABA。
{"title":"Quantifying Plant Signaling Pathways by Integrating Luminescence-Based Biosensors and Mathematical Modeling","authors":"Shakeel Ahmed, Syed Muhammad Zaigham Abbas Naqvi, Fida Hussain, Muhammad Awais, Yongzhe Ren, Junfeng Wu, Hao Zhang, Yiheng Zang, Jiandong Hu","doi":"10.3390/bios14080378","DOIUrl":"https://doi.org/10.3390/bios14080378","url":null,"abstract":"Plants have evolved intricate signaling pathways, which operate as networks governed by feedback to deal with stressors. Nevertheless, the sophisticated molecular mechanisms underlying these routes still need to be comprehended, and experimental validation poses significant challenges and expenses. Consequently, computational hypothesis evaluation gains prominence in understanding plant signaling dynamics. Biosensors are genetically modified to emit light when exposed to a particular hormone, such as abscisic acid (ABA), enabling quantification. We developed computational models to simulate the relationship between ABA concentrations and bioluminescent sensors utilizing the Hill equation and ordinary differential equations (ODEs), aiding better hypothesis development regarding plant signaling. Based on simulation results, the luminescence intensity was recorded for a concentration of 47.646 RLUs for 1.5 μmol, given the specified parameters and model assumptions. This method enhances our understanding of plant signaling pathways at the cellular level, offering significant benefits to the scientific community in a cost-effective manner. The alignment of these computational predictions with experimental results emphasizes the robustness of our approach, providing a cost-effective means to validate mathematical models empirically. The research intended to correlate the bioluminescence of biosensors with plant signaling and its mathematical models for quantified detection of specific plant hormone ABA.","PeriodicalId":100185,"journal":{"name":"Biosensors","volume":"80 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141939803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sesame Detection in Food Using DNA-Functionalized Gold Nanoparticles: A Sensitive, Rapid, and Cost-Effective Colorimetric Approach 利用 DNA 功能化金纳米粒子检测食品中的芝麻:灵敏、快速、经济的比色法
Pub Date : 2024-08-03 DOI: 10.3390/bios14080377
Pablo Llano-Suárez, Adrián Sánchez-Visedo, Inmaculada Ortiz-Gómez, María Teresa Fernández-Argüelles, Marta Prado, José Manuel Costa-Fernández, Ana Soldado
Food safety control is a key issue in the food and agriculture industries. For such purposes, developing miniaturized analytical methods is critical for enabling the rapid and sensitive detection of food supplements, allergens, and pollutants. Here, a novel bioanalytical methodology based on DNA-functionalized gold nanoparticles (AuNPs) and colorimetric detection was developed to detect the presence of sesame (a major allergen) through sesame seed DNA as a target, in food samples. The presence of sesame DNA induces controlled nanoparticle aggregation/desegregation, resulting in a color change (from blue to red) proportional to sesame DNA concentration. The incorporation of multicomponent nucleic acid enzymes (MNAzymes) in this strategy has been carried out to perform an isothermal signal amplification strategy to improve the sensitivity of detection. Also, open-source software for color analysis was used to ensure an unbiased visual color-change detection, enhancing detection accuracy and sensitivity and opening the possibility of performing a simple and decentralized analyte detection. The method successfully detected the presence of sesame DNA in sesame seed, sesame oil, olive oil, and sunflower oil. In brief, the developed approach constitutes a simple and affordable alternative to perform a highly sensitive detection of DNA in food without complex methodologies or the requirement of expensive instrumentation.
食品安全控制是食品和农业行业的一个关键问题。为此,开发微型分析方法对于快速灵敏地检测食品添加剂、过敏原和污染物至关重要。在此,我们开发了一种基于 DNA 功能化金纳米粒子(AuNPs)和比色检测的新型生物分析方法,以芝麻种子 DNA 为目标,检测食品样品中是否含有芝麻(一种主要过敏原)。芝麻 DNA 的存在会诱导受控纳米粒子的聚集/解聚,导致颜色变化(从蓝色到红色)与芝麻 DNA 的浓度成正比。在这一策略中加入了多组分核酸酶(MNAzymes),执行等温信号放大策略,以提高检测灵敏度。此外,还使用了开源的颜色分析软件,以确保无偏见的视觉颜色变化检测,从而提高了检测的准确性和灵敏度,为进行简单、分散的分析物检测提供了可能。该方法成功地检测出了芝麻、芝麻油、橄榄油和葵花籽油中芝麻 DNA 的存在。简而言之,所开发的方法是对食品中 DNA 进行高灵敏度检测的一种简单而经济的替代方法,无需复杂的方法或昂贵的仪器。
{"title":"Sesame Detection in Food Using DNA-Functionalized Gold Nanoparticles: A Sensitive, Rapid, and Cost-Effective Colorimetric Approach","authors":"Pablo Llano-Suárez, Adrián Sánchez-Visedo, Inmaculada Ortiz-Gómez, María Teresa Fernández-Argüelles, Marta Prado, José Manuel Costa-Fernández, Ana Soldado","doi":"10.3390/bios14080377","DOIUrl":"https://doi.org/10.3390/bios14080377","url":null,"abstract":"Food safety control is a key issue in the food and agriculture industries. For such purposes, developing miniaturized analytical methods is critical for enabling the rapid and sensitive detection of food supplements, allergens, and pollutants. Here, a novel bioanalytical methodology based on DNA-functionalized gold nanoparticles (AuNPs) and colorimetric detection was developed to detect the presence of sesame (a major allergen) through sesame seed DNA as a target, in food samples. The presence of sesame DNA induces controlled nanoparticle aggregation/desegregation, resulting in a color change (from blue to red) proportional to sesame DNA concentration. The incorporation of multicomponent nucleic acid enzymes (MNAzymes) in this strategy has been carried out to perform an isothermal signal amplification strategy to improve the sensitivity of detection. Also, open-source software for color analysis was used to ensure an unbiased visual color-change detection, enhancing detection accuracy and sensitivity and opening the possibility of performing a simple and decentralized analyte detection. The method successfully detected the presence of sesame DNA in sesame seed, sesame oil, olive oil, and sunflower oil. In brief, the developed approach constitutes a simple and affordable alternative to perform a highly sensitive detection of DNA in food without complex methodologies or the requirement of expensive instrumentation.","PeriodicalId":100185,"journal":{"name":"Biosensors","volume":"133 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141886111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impedance Characteristics of Microfluidic Channels and Integrated Coplanar Parallel Electrodes as Design Parameters for Whole-Channel Analysis in Organ-on-Chip Micro-Systems 微流控通道和集成共面平行电极的阻抗特性是片上器官微系统全通道分析的设计参数
Pub Date : 2024-08-01 DOI: 10.3390/bios14080374
Crystal E. Rapier, Srikanth Jagadeesan, Gad D. Vatine, Hadar Ben-Yoav
Microfluidics have revolutionized cell culture by allowing for precise physical and chemical environmental control. Coupled with electrodes, microfluidic cell culture can be activated or have its changes sensed in real-time. We used our previously developed reliable and stable microfluidic device for cell growth and monitoring to design, fabricate, and characterize a whole-channel impedance-based sensor and used it to systematically assess the electrical and electrochemical influences of microfluidic channel boundaries coupled with varying electrode sizes, distances, coatings, and cell coverage. Our investigation includes both theoretical and experimental approaches to investigate how design parameters and insulating boundary conditions change impedance characteristics. We examined the system with various solutions using a frequency range of 0.5 Hz to 1 MHz and a modulation voltage of 50 mV. The results show that impedance is directly proportional to electrode distance and inversely proportional to electrode coating, area, and channel size. We also demonstrate that electrode spacing is a dominant factor contributing to impedance. In the end, we summarize all the relationships found and comment on the appropriateness of using this system to investigate barrier cells in blood vessel models and organ-on-a-chip devices. This fundamental study can help in the careful design of microfluidic culture constructs and models that require channel geometries and impedance-based biosensing.
微流体技术实现了精确的物理和化学环境控制,为细胞培养带来了革命性的变化。配合电极,微流控细胞培养可以被激活或实时感知其变化。我们利用之前开发的用于细胞生长和监测的可靠、稳定的微流控装置,设计、制造并表征了一种基于全通道阻抗的传感器,并利用它系统地评估了微流控通道边界与不同的电极尺寸、距离、涂层和细胞覆盖面之间的电学和电化学影响。我们的调查包括理论和实验方法,以研究设计参数和绝缘边界条件如何改变阻抗特性。我们使用频率范围为 0.5 Hz 至 1 MHz、调制电压为 50 mV 的各种解决方案对系统进行了研究。结果表明,阻抗与电极间距成正比,与电极涂层、面积和通道大小成反比。我们还证明,电极间距是影响阻抗的主要因素。最后,我们总结了所有发现的关系,并就使用该系统研究血管模型和片上器官设备中的屏障细胞是否合适发表了评论。这项基础研究有助于精心设计需要通道几何形状和基于阻抗的生物传感的微流控培养结构和模型。
{"title":"Impedance Characteristics of Microfluidic Channels and Integrated Coplanar Parallel Electrodes as Design Parameters for Whole-Channel Analysis in Organ-on-Chip Micro-Systems","authors":"Crystal E. Rapier, Srikanth Jagadeesan, Gad D. Vatine, Hadar Ben-Yoav","doi":"10.3390/bios14080374","DOIUrl":"https://doi.org/10.3390/bios14080374","url":null,"abstract":"Microfluidics have revolutionized cell culture by allowing for precise physical and chemical environmental control. Coupled with electrodes, microfluidic cell culture can be activated or have its changes sensed in real-time. We used our previously developed reliable and stable microfluidic device for cell growth and monitoring to design, fabricate, and characterize a whole-channel impedance-based sensor and used it to systematically assess the electrical and electrochemical influences of microfluidic channel boundaries coupled with varying electrode sizes, distances, coatings, and cell coverage. Our investigation includes both theoretical and experimental approaches to investigate how design parameters and insulating boundary conditions change impedance characteristics. We examined the system with various solutions using a frequency range of 0.5 Hz to 1 MHz and a modulation voltage of 50 mV. The results show that impedance is directly proportional to electrode distance and inversely proportional to electrode coating, area, and channel size. We also demonstrate that electrode spacing is a dominant factor contributing to impedance. In the end, we summarize all the relationships found and comment on the appropriateness of using this system to investigate barrier cells in blood vessel models and organ-on-a-chip devices. This fundamental study can help in the careful design of microfluidic culture constructs and models that require channel geometries and impedance-based biosensing.","PeriodicalId":100185,"journal":{"name":"Biosensors","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141886113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fluorogenic RNA-Based Biosensors of Small Molecules: Current Developments, Uses, and Perspectives 基于荧光 RNA 的小分子生物传感器:当前发展、用途和前景
Pub Date : 2024-08-01 DOI: 10.3390/bios14080376
Janine Kehrli, Claire Husser, Michael Ryckelynck
Small molecules are highly relevant targets for detection and quantification. They are also used to diagnose and monitor the progression of disease and infectious processes and track the presence of contaminants. Fluorogenic RNA-based biosensors (FRBs) represent an appealing solution to the problem of detecting these targets. They combine the portability of molecular systems with the sensitivity and multiplexing capacity of fluorescence, as well as the exquisite ligand selectivity of RNA aptamers. In this review, we first present the different sensing and reporting aptamer modules currently available to design an FRB, together with the main methodologies used to discover modules with new specificities. We next introduce and discuss how both modules can be functionally connected prior to exploring the main applications for which FRB have been used. Finally, we conclude by discussing how using alternative nucleotide chemistries may improve FRB properties and further widen their application scope.
小分子是高度相关的检测和量化目标。它们还可用于诊断和监测疾病和传染过程的进展,以及追踪污染物的存在。基于荧光 RNA 的生物传感器(FRB)是检测这些靶标的一个极具吸引力的解决方案。它们结合了分子系统的便携性、荧光的灵敏度和多路复用能力,以及 RNA 类似物的精致配体选择性。在本综述中,我们首先介绍了目前可用于设计 FRB 的不同传感和报告适配体模块,以及用于发现具有新特异性的模块的主要方法。接下来,在探讨 FRB 的主要应用之前,我们将介绍和讨论如何在功能上将这两个模块联系起来。最后,我们将讨论使用替代核苷酸化学物质如何改善 FRB 特性并进一步拓宽其应用范围。
{"title":"Fluorogenic RNA-Based Biosensors of Small Molecules: Current Developments, Uses, and Perspectives","authors":"Janine Kehrli, Claire Husser, Michael Ryckelynck","doi":"10.3390/bios14080376","DOIUrl":"https://doi.org/10.3390/bios14080376","url":null,"abstract":"Small molecules are highly relevant targets for detection and quantification. They are also used to diagnose and monitor the progression of disease and infectious processes and track the presence of contaminants. Fluorogenic RNA-based biosensors (FRBs) represent an appealing solution to the problem of detecting these targets. They combine the portability of molecular systems with the sensitivity and multiplexing capacity of fluorescence, as well as the exquisite ligand selectivity of RNA aptamers. In this review, we first present the different sensing and reporting aptamer modules currently available to design an FRB, together with the main methodologies used to discover modules with new specificities. We next introduce and discuss how both modules can be functionally connected prior to exploring the main applications for which FRB have been used. Finally, we conclude by discussing how using alternative nucleotide chemistries may improve FRB properties and further widen their application scope.","PeriodicalId":100185,"journal":{"name":"Biosensors","volume":"299 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141886114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Recent Advances in Bacterial Detection Using Surface-Enhanced Raman Scattering 利用表面增强拉曼散射检测细菌的最新进展
Pub Date : 2024-08-01 DOI: 10.3390/bios14080375
Manal Hassan, Yiping Zhao, Susu M. Zughaier
Rapid identification of microorganisms with a high sensitivity and selectivity is of great interest in many fields, primarily in clinical diagnosis, environmental monitoring, and the food industry. For over the past decades, a surface-enhanced Raman scattering (SERS)-based detection platform has been extensively used for bacterial detection, and the effort has been extended to clinical, environmental, and food samples. In contrast to other approaches, such as enzyme-linked immunosorbent assays and polymerase chain reaction, SERS exhibits outstanding advantages of rapid detection, being culture-free, low cost, high sensitivity, and lack of water interference. This review aims to cover the development of SERS-based methods for bacterial detection with an emphasis on the source of the signal, techniques used to improve the limit of detection and specificity, and the application of SERS in high-throughput settings and complex samples. The challenges and advancements with the implementation of artificial intelligence (AI) are also discussed.
以高灵敏度和高选择性快速识别微生物在许多领域都具有重大意义,主要是在临床诊断、环境监测和食品工业领域。在过去的几十年里,基于表面增强拉曼散射(SERS)的检测平台已被广泛用于细菌检测,并已扩展到临床、环境和食品样本。与酶联免疫吸附法和聚合酶链反应等其他方法相比,SERS 具有检测速度快、无需培养、成本低、灵敏度高、无水干扰等突出优点。本综述旨在介绍基于 SERS 的细菌检测方法的发展,重点是信号源、用于提高检测限和特异性的技术,以及 SERS 在高通量环境和复杂样品中的应用。此外,还讨论了人工智能(AI)的实施所带来的挑战和进步。
{"title":"Recent Advances in Bacterial Detection Using Surface-Enhanced Raman Scattering","authors":"Manal Hassan, Yiping Zhao, Susu M. Zughaier","doi":"10.3390/bios14080375","DOIUrl":"https://doi.org/10.3390/bios14080375","url":null,"abstract":"Rapid identification of microorganisms with a high sensitivity and selectivity is of great interest in many fields, primarily in clinical diagnosis, environmental monitoring, and the food industry. For over the past decades, a surface-enhanced Raman scattering (SERS)-based detection platform has been extensively used for bacterial detection, and the effort has been extended to clinical, environmental, and food samples. In contrast to other approaches, such as enzyme-linked immunosorbent assays and polymerase chain reaction, SERS exhibits outstanding advantages of rapid detection, being culture-free, low cost, high sensitivity, and lack of water interference. This review aims to cover the development of SERS-based methods for bacterial detection with an emphasis on the source of the signal, techniques used to improve the limit of detection and specificity, and the application of SERS in high-throughput settings and complex samples. The challenges and advancements with the implementation of artificial intelligence (AI) are also discussed.","PeriodicalId":100185,"journal":{"name":"Biosensors","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141886112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Label-Free Surface-Enhanced Raman Spectroscopy with Machine Learning for the Diagnosis of Thyroid Cancer by Using Fine-Needle Aspiration Liquid Samples 利用细针抽吸液样本进行无标记表面增强拉曼光谱与机器学习以诊断甲状腺癌
Pub Date : 2024-07-31 DOI: 10.3390/bios14080372
Lili Gao, Siyi Wu, Puwasit Wongwasuratthakul, Zhou Chen, Wei Cai, Qinyu Li, Linley Li LIN
The incidence of thyroid cancer is increasing worldwide. Fine-needle aspiration (FNA) cytology is widely applied with the use of extracted biological cell samples, but current FNA cytology is labor-intensive, time-consuming, and can lead to the risk of false-negative results. Surface-enhanced Raman spectroscopy (SERS) combined with machine learning algorithms holds promise for cancer diagnosis. In this study, we develop a label-free SERS liquid biopsy method with machine learning for the rapid and accurate diagnosis of thyroid cancer by using thyroid FNA washout fluids. These liquid supernatants are mixed with silver nanoparticle colloids, and dispersed in quartz capillary for SERS measurements to discriminate between healthy and malignant samples. We collect Raman spectra of 36 thyroid FNA samples (18 malignant and 18 benign) and compare four classification models: Principal Component Analysis–Linear Discriminant Analysis (PCA-LDA), Random Forest (RF), Support Vector Machine (SVM), and Convolutional Neural Network (CNN). The results show that the CNN algorithm is the most precise, with a high accuracy of 88.1%, sensitivity of 87.8%, and the area under the receiver operating characteristic curve of 0.953. Our approach is simple, convenient, and cost-effective. This study indicates that label-free SERS liquid biopsy assisted by deep learning models holds great promise for the early detection and screening of thyroid cancer.
甲状腺癌的发病率在全球范围内不断上升。细针穿刺(FNA)细胞学广泛应用于提取生物细胞样本,但目前的 FNA 细胞学耗费大量人力和时间,并可能导致假阴性结果。表面增强拉曼光谱(SERS)与机器学习算法相结合,有望用于癌症诊断。在这项研究中,我们利用甲状腺 FNA 冲洗液开发了一种无标记 SERS 液体活检方法,并将其与机器学习相结合,用于快速准确地诊断甲状腺癌。这些液体上清液与银纳米粒子胶体混合,分散在石英毛细管中进行 SERS 测量,以区分健康样本和恶性样本。我们收集了 36 份甲状腺 FNA 样品(18 份恶性和 18 份良性)的拉曼光谱,并比较了四种分类模型:主成分分析-线性判别分析(PCA-LDA)、随机森林(RF)、支持向量机(SVM)和卷积神经网络(CNN)。结果表明,CNN 算法最为精确,准确率高达 88.1%,灵敏度为 87.8%,接收者工作特征曲线下面积为 0.953。我们的方法简单、方便、经济。这项研究表明,由深度学习模型辅助的无标记 SERS 液体活检在甲状腺癌的早期检测和筛查方面大有可为。
{"title":"Label-Free Surface-Enhanced Raman Spectroscopy with Machine Learning for the Diagnosis of Thyroid Cancer by Using Fine-Needle Aspiration Liquid Samples","authors":"Lili Gao, Siyi Wu, Puwasit Wongwasuratthakul, Zhou Chen, Wei Cai, Qinyu Li, Linley Li LIN","doi":"10.3390/bios14080372","DOIUrl":"https://doi.org/10.3390/bios14080372","url":null,"abstract":"The incidence of thyroid cancer is increasing worldwide. Fine-needle aspiration (FNA) cytology is widely applied with the use of extracted biological cell samples, but current FNA cytology is labor-intensive, time-consuming, and can lead to the risk of false-negative results. Surface-enhanced Raman spectroscopy (SERS) combined with machine learning algorithms holds promise for cancer diagnosis. In this study, we develop a label-free SERS liquid biopsy method with machine learning for the rapid and accurate diagnosis of thyroid cancer by using thyroid FNA washout fluids. These liquid supernatants are mixed with silver nanoparticle colloids, and dispersed in quartz capillary for SERS measurements to discriminate between healthy and malignant samples. We collect Raman spectra of 36 thyroid FNA samples (18 malignant and 18 benign) and compare four classification models: Principal Component Analysis–Linear Discriminant Analysis (PCA-LDA), Random Forest (RF), Support Vector Machine (SVM), and Convolutional Neural Network (CNN). The results show that the CNN algorithm is the most precise, with a high accuracy of 88.1%, sensitivity of 87.8%, and the area under the receiver operating characteristic curve of 0.953. Our approach is simple, convenient, and cost-effective. This study indicates that label-free SERS liquid biopsy assisted by deep learning models holds great promise for the early detection and screening of thyroid cancer.","PeriodicalId":100185,"journal":{"name":"Biosensors","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141864333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fire up Biosensor Technology to Assess the Vitality of Trees after Wildfires 用生物传感器技术评估野火后树木的生命力
Pub Date : 2024-07-31 DOI: 10.3390/bios14080373
Eleftherios Touloupakis, Isabela Calegari Moia, Raffaella Margherita Zampieri, Claudia Cocozza, Niccolò Frassinelli, Enrico Marchi, Cristiano Foderi, Tiziana Di Lorenzo, Negar Rezaie, Valerio Giorgio Muzzini, Maria Laura Traversi, Alessio Giovannelli
The development of tools to quickly identify the fate of damaged trees after a stress event such as a wildfire is of great importance. In this context, an innovative approach to assess irreversible physiological damage in trees could help to support the planning of management decisions for disturbed sites to restore biodiversity, protect the environment and understand the adaptations of ecosystem functionality. The vitality of trees can be estimated by several physiological indicators, such as cambium activity and the amount of starch and soluble sugars, while the accumulation of ethanol in the cambial cells and phloem is considered an alarm sign of cell death. However, their determination requires time-consuming laboratory protocols, making the approach impractical in the field. Biosensors hold considerable promise for substantially advancing this field. The general objective of this review is to define a system for quantifying the plant vitality in forest areas exposed to fire. This review describes recent electrochemical biosensors that can detect plant molecules, focusing on biosensors for glucose, fructose, and ethanol as indicators of tree vitality.
在野火等压力事件发生后,开发可快速识别受损树木命运的工具具有重要意义。在这种情况下,评估树木不可逆转的生理损伤的创新方法有助于支持受干扰地点的管理决策规划,以恢复生物多样性、保护环境并了解生态系统功能的适应性。树木的生命力可以通过一些生理指标来估测,如骨架活性、淀粉和可溶性糖的含量,而骨架细胞和韧皮部乙醇的积累则被认为是细胞死亡的警报信号。然而,测定这些指标需要耗时的实验室规程,因此这种方法在田间并不实用。生物传感器在大幅推动这一领域的发展方面大有可为。本综述的总体目标是确定一个系统,用于量化遭受火灾的林区的植物生命力。本综述介绍了可检测植物分子的最新电化学生物传感器,重点是作为树木生命力指标的葡萄糖、果糖和乙醇生物传感器。
{"title":"Fire up Biosensor Technology to Assess the Vitality of Trees after Wildfires","authors":"Eleftherios Touloupakis, Isabela Calegari Moia, Raffaella Margherita Zampieri, Claudia Cocozza, Niccolò Frassinelli, Enrico Marchi, Cristiano Foderi, Tiziana Di Lorenzo, Negar Rezaie, Valerio Giorgio Muzzini, Maria Laura Traversi, Alessio Giovannelli","doi":"10.3390/bios14080373","DOIUrl":"https://doi.org/10.3390/bios14080373","url":null,"abstract":"The development of tools to quickly identify the fate of damaged trees after a stress event such as a wildfire is of great importance. In this context, an innovative approach to assess irreversible physiological damage in trees could help to support the planning of management decisions for disturbed sites to restore biodiversity, protect the environment and understand the adaptations of ecosystem functionality. The vitality of trees can be estimated by several physiological indicators, such as cambium activity and the amount of starch and soluble sugars, while the accumulation of ethanol in the cambial cells and phloem is considered an alarm sign of cell death. However, their determination requires time-consuming laboratory protocols, making the approach impractical in the field. Biosensors hold considerable promise for substantially advancing this field. The general objective of this review is to define a system for quantifying the plant vitality in forest areas exposed to fire. This review describes recent electrochemical biosensors that can detect plant molecules, focusing on biosensors for glucose, fructose, and ethanol as indicators of tree vitality.","PeriodicalId":100185,"journal":{"name":"Biosensors","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141864335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Brillouin Biosensing of Viscoelasticity across Phase Transitions in Ovine Cornea 布里渊生物传感技术检测绵羊角膜相变过程中的粘弹性
Pub Date : 2024-07-30 DOI: 10.3390/bios14080371
Chingis Kharmyssov, Zhandos Utegulov
Noninvasive in situ monitoring of viscoelastic characteristics of corneal tissue at elevated temperatures is pivotal for mechanical property-informed refractive surgery techniques, including thermokeratoplasty and photorefractive keratectomy, requiring precise thermal modifications of the corneal structure during these surgical procedures. This study harnesses Brillouin light scattering spectroscopy as a biosensing platform to noninvasively probe the viscoelastic properties of ovine corneas across a temperature range of 25–64 °C. By submerging the tissue samples in silicone oil, consistent hydration and immiscibility are maintained, allowing for their accurate sensing of temperature-dependent mechanical behaviors. We identify significant phase transitions in the corneal tissue, particularly beyond 40 °C, likely due to collagen unfolding, marking the beginning of thermal destabilization. A subsequent transition, observed beyond 60 °C, correlates with collagen denaturation. These phase transformations highlight the cornea’s sensitivity to both physiologically reversible and irreversible viscoelastic changes induced by mild to high temperatures. Our findings underscore the potential of the Brillouin biosensing technique for real-time diagnostics of corneal biomechanics during refractive surgeries to attain optimized therapeutic outcomes.
无创原位监测角膜组织在高温下的粘弹性特性,对于以机械特性为依据的屈光手术技术(包括热角膜移植术和光屈光性角膜切除术)至关重要,因为在这些手术过程中需要对角膜结构进行精确的热调节。本研究利用布里渊光散射光谱作为生物传感平台,在 25-64 °C 的温度范围内对绵羊角膜的粘弹性能进行无创探测。通过将组织样本浸没在硅油中,可保持稳定的水合性和不溶性,从而准确感知随温度变化的机械行为。我们在角膜组织中发现了明显的相变,尤其是超过 40 °C时,这可能是由于胶原蛋白展开,标志着热不稳定性的开始。在 60 °C 以上观察到的后续转变与胶原蛋白变性有关。这些相变突显了角膜对轻度到高温诱导的生理可逆和不可逆粘弹性变化的敏感性。我们的研究结果凸显了布里渊生物传感技术在屈光手术过程中实时诊断角膜生物力学以达到最佳治疗效果的潜力。
{"title":"Brillouin Biosensing of Viscoelasticity across Phase Transitions in Ovine Cornea","authors":"Chingis Kharmyssov, Zhandos Utegulov","doi":"10.3390/bios14080371","DOIUrl":"https://doi.org/10.3390/bios14080371","url":null,"abstract":"Noninvasive in situ monitoring of viscoelastic characteristics of corneal tissue at elevated temperatures is pivotal for mechanical property-informed refractive surgery techniques, including thermokeratoplasty and photorefractive keratectomy, requiring precise thermal modifications of the corneal structure during these surgical procedures. This study harnesses Brillouin light scattering spectroscopy as a biosensing platform to noninvasively probe the viscoelastic properties of ovine corneas across a temperature range of 25–64 °C. By submerging the tissue samples in silicone oil, consistent hydration and immiscibility are maintained, allowing for their accurate sensing of temperature-dependent mechanical behaviors. We identify significant phase transitions in the corneal tissue, particularly beyond 40 °C, likely due to collagen unfolding, marking the beginning of thermal destabilization. A subsequent transition, observed beyond 60 °C, correlates with collagen denaturation. These phase transformations highlight the cornea’s sensitivity to both physiologically reversible and irreversible viscoelastic changes induced by mild to high temperatures. Our findings underscore the potential of the Brillouin biosensing technique for real-time diagnostics of corneal biomechanics during refractive surgeries to attain optimized therapeutic outcomes.","PeriodicalId":100185,"journal":{"name":"Biosensors","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141864341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Using AuNPs-DNA Walker with Fluorophores Detects the Hepatitis Virus Rapidly 利用带有荧光团的 AuNPs-DNA Walker 快速检测肝炎病毒
Pub Date : 2024-07-29 DOI: 10.3390/bios14080370
Baining Sun, Chenxiang Zheng, Dun Pan, Leer Shen, Wan Zhang, Xiaohua Chen, Yanqin Wen, Yongyong Shi
Viral hepatitis is a systemic infectious diseases caused by various hepatitis viruses, primarily leading to liver damage. It is widely prevalent worldwide, with hepatitis viruses categorized into five types: hepatitis A, B, C, D, and E, based on their etiology. Currently, the detection of hepatitis viruses relies on methods such as enzyme-linked immunosorbent assay (ELISA), immunoelectron microscopy to observe and identify viral particles, and in situ hybridization to detect viral DNA in tissues. However, these methods have limitations, including low sensitivity, high error rates in results, and potential false negative reactions due to occult serum infection conditions. To address these challenges, we have designed an AuNPs-DNA walker method that uses gold nanoparticles (AuNPs) and complementary DNA strands for detecting viral DNA fragments through a colorimetric assay and fluorescence detection. The DNA walker, attached to gold nanoparticles, comprises a long walking strand with a probe sequence bound and stem-loop structural strands featuring a modified fluorescent molecule at the 3′ end, which contains the DNAzyme structural domain. Upon the addition of virus fragments, the target sequence binds to the probe chains. Subsequently, the long walking strand is released and continuously hybridizes with the stem-loop structural strand. The DNAzyme undergoes hydrolytical cleavage by Mg2+, breaking the stem-loop structural strand into linear single strands. As a result of these structural changes, the negative charge density in the solution decreases, weakening spatial repulsion and rapidly reducing the stability of the DNA walker. This leads to aggregation upon the addition of a high-salt solution, accompanied by a color change. Virus typing can be performed through fluorescence detection. The innovative method can detect DNA/RNA fragments with high specificity for the target sequence, reaching concentrations as low as 1 nM. Overall, our approach offers a more convenient and reliable method for the detection of hepatitis viruses.
病毒性肝炎是由各种肝炎病毒引起的一种全身性传染病,主要导致肝脏损伤。根据病因,肝炎病毒可分为甲型、乙型、丙型、丁型和戊型五种。目前,肝炎病毒的检测主要依靠酶联免疫吸附试验(ELISA)、免疫电子显微镜观察和识别病毒颗粒以及原位杂交检测组织中的病毒 DNA 等方法。然而,这些方法都有其局限性,包括灵敏度低、结果误差率高,以及隐性血清感染条件下可能出现的假阴性反应。为了解决这些难题,我们设计了一种 AuNPs-DNA walker 方法,它使用金纳米粒子(AuNPs)和互补 DNA 链,通过比色法和荧光检测来检测病毒 DNA 片段。附着在金纳米粒子上的 DNA 步行器包括一条结合了探针序列的长步行链和茎环结构链,茎环结构链的 3′端有一个修饰过的荧光分子,其中包含 DNA 酶结构域。加入病毒片段后,目标序列与探针链结合。随后,长游走链被释放出来,并不断与茎环结构链杂交。DNA 酶在 Mg2+ 的作用下发生水解裂解,将茎环结构链分解成线性单链。由于这些结构变化,溶液中的负电荷密度降低,削弱了空间斥力,迅速降低了 DNA 步行器的稳定性。这导致在加入高盐溶液后出现聚集,并伴有颜色变化。通过荧光检测可以进行病毒分型。这种创新方法可以检测 DNA/RNA 片段,对目标序列具有高度特异性,检测浓度可低至 1 nM。总之,我们的方法为检测肝炎病毒提供了一种更方便、更可靠的方法。
{"title":"Using AuNPs-DNA Walker with Fluorophores Detects the Hepatitis Virus Rapidly","authors":"Baining Sun, Chenxiang Zheng, Dun Pan, Leer Shen, Wan Zhang, Xiaohua Chen, Yanqin Wen, Yongyong Shi","doi":"10.3390/bios14080370","DOIUrl":"https://doi.org/10.3390/bios14080370","url":null,"abstract":"Viral hepatitis is a systemic infectious diseases caused by various hepatitis viruses, primarily leading to liver damage. It is widely prevalent worldwide, with hepatitis viruses categorized into five types: hepatitis A, B, C, D, and E, based on their etiology. Currently, the detection of hepatitis viruses relies on methods such as enzyme-linked immunosorbent assay (ELISA), immunoelectron microscopy to observe and identify viral particles, and in situ hybridization to detect viral DNA in tissues. However, these methods have limitations, including low sensitivity, high error rates in results, and potential false negative reactions due to occult serum infection conditions. To address these challenges, we have designed an AuNPs-DNA walker method that uses gold nanoparticles (AuNPs) and complementary DNA strands for detecting viral DNA fragments through a colorimetric assay and fluorescence detection. The DNA walker, attached to gold nanoparticles, comprises a long walking strand with a probe sequence bound and stem-loop structural strands featuring a modified fluorescent molecule at the 3′ end, which contains the DNAzyme structural domain. Upon the addition of virus fragments, the target sequence binds to the probe chains. Subsequently, the long walking strand is released and continuously hybridizes with the stem-loop structural strand. The DNAzyme undergoes hydrolytical cleavage by Mg2+, breaking the stem-loop structural strand into linear single strands. As a result of these structural changes, the negative charge density in the solution decreases, weakening spatial repulsion and rapidly reducing the stability of the DNA walker. This leads to aggregation upon the addition of a high-salt solution, accompanied by a color change. Virus typing can be performed through fluorescence detection. The innovative method can detect DNA/RNA fragments with high specificity for the target sequence, reaching concentrations as low as 1 nM. Overall, our approach offers a more convenient and reliable method for the detection of hepatitis viruses.","PeriodicalId":100185,"journal":{"name":"Biosensors","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141864337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development of a NIR Iridium(III) Complex-Based Probe for the Selective Detection of Iron(II) Ions 开发用于选择性检测铁(II)离子的近红外铱(III)络合物探针
Pub Date : 2024-07-29 DOI: 10.3390/bios14080369
Wanyi Wang, Zixi Zhang, Jingqi Liu, Lingtan Kong, Wanhe Wang, Chung-Hang Leung, Jing Wang
As a commonly used metal ion, iron(II) (Fe2+) ions pose a potential threat to ecosystems and human health. Therefore, it is particularly important to develop analytical techniques for the rapid and accurate detection of Fe2+ ions. However, the development of near-infrared (NIR) luminescence probes with good photostability for Fe2+ ions remain challenging. In this work, we report a novel iridium(III) complex-based luminescence probe for the sensitive and rapid detection of Fe2+ ions in a solution based on an Fe2+-mediated reduction reaction. This probe is capable of sensitively detecting Fe2+ ions with a limit of detection (LOD) of 0.26 μM. Furthermore, this probe shows high photostability, and its luminescence remains stable under 365 nm irradiation over a time period of 30 min. To our knowledge, this is first iridium(III) complex-based NIR probe for the detection of Fe2+ ions. We believe that this work provides a new method for the detection of Fe2+ ions and has great potential for future applications in water quality testing and human monitoring.
作为一种常用的金属离子,铁(II)(Fe2+)离子对生态系统和人类健康构成潜在威胁。因此,开发快速准确检测 Fe2+ 离子的分析技术尤为重要。然而,开发对 Fe2+ 离子具有良好光稳定性的近红外(NIR)发光探针仍然具有挑战性。在这项工作中,我们报告了一种基于铱(III)络合物的新型发光探针,该探针基于 Fe2+ 介导的还原反应,可灵敏、快速地检测溶液中的 Fe2+ 离子。该探针能够灵敏地检测 Fe2+离子,检测限(LOD)为 0.26 μM。此外,该探针还具有很高的光稳定性,在 365 纳米波长的照射下,其发光可在 30 分钟内保持稳定。据我们所知,这是第一个基于铱(III)复合物的近红外探针,用于检测 Fe2+ 离子。我们相信,这项工作为检测 Fe2+ 离子提供了一种新方法,在未来的水质检测和人体监测中具有巨大的应用潜力。
{"title":"Development of a NIR Iridium(III) Complex-Based Probe for the Selective Detection of Iron(II) Ions","authors":"Wanyi Wang, Zixi Zhang, Jingqi Liu, Lingtan Kong, Wanhe Wang, Chung-Hang Leung, Jing Wang","doi":"10.3390/bios14080369","DOIUrl":"https://doi.org/10.3390/bios14080369","url":null,"abstract":"As a commonly used metal ion, iron(II) (Fe2+) ions pose a potential threat to ecosystems and human health. Therefore, it is particularly important to develop analytical techniques for the rapid and accurate detection of Fe2+ ions. However, the development of near-infrared (NIR) luminescence probes with good photostability for Fe2+ ions remain challenging. In this work, we report a novel iridium(III) complex-based luminescence probe for the sensitive and rapid detection of Fe2+ ions in a solution based on an Fe2+-mediated reduction reaction. This probe is capable of sensitively detecting Fe2+ ions with a limit of detection (LOD) of 0.26 μM. Furthermore, this probe shows high photostability, and its luminescence remains stable under 365 nm irradiation over a time period of 30 min. To our knowledge, this is first iridium(III) complex-based NIR probe for the detection of Fe2+ ions. We believe that this work provides a new method for the detection of Fe2+ ions and has great potential for future applications in water quality testing and human monitoring.","PeriodicalId":100185,"journal":{"name":"Biosensors","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141864336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Biosensors
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:481959085
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