Optical biosensors

光学生物传感器
  • 文章类型: Journal Article
    背景:由于低成本等优点,光纤传感器已用于检测葡萄糖,小尺寸,操作方便等。苯基硼酸是一种常用的葡萄糖检测受体,然而苯基硼酸基再生光纤传感器通常是累积再生,再生再生传感器已从文献中缺失。
    结果:在这项工作中,而不是使用苯基硼酸,我们通过在苯基硼酸的另一端引入含羧基的短链,然后在过度倾斜的光纤光栅(Ex-TFG)表面共价键合BPOA,合成了琥珀酰氨基苯硼酸分子(BPOA)。这为可再生再生提供了非常稳定的平台,再生缓冲液也得到了优化。所提出的可再生再生方法相对于常规累积再生方法(R2=0.9718,4.9pm/mM)表现出更高的线性和灵敏度(R2=0.9992,8pm/mM)。发现BPOA和葡萄糖之间的结合亲和力在140个结合/释放循环中几乎是恒定的,具有小于0.3%的相对标准偏差的变化。
    结论:所提出的装置的再生和无标记传感能力为无标记糖检测和基于光纤传感器的可穿戴葡萄糖监测装置的开发提供了理论基础。
    BACKGROUND: Optical fiber sensors have been used to detect glucose owing to advantages such as low cost, small size, and ease of operation etc. phenylboronic acid is one of the commonly used receptors for glucose detection, however phenylboronic acid based regenerative optical fiber sensors are commonly cumulative regeneration, renewable regeneration sensor has been missing from the literature.
    RESULTS: In this work, instead of using phenylboronic acid, we synthesized succinylaminobenzenoboronic acid molecule (BPOA) by introducing a short chain containing carboxyl group at the other end of phenylboronic acid then covalently bonded BPOA on the surface of excessively tilted fiber grating (Ex-TFG). This provides a very stable platform for renewable regeneration and the regenerative buffer was also optimized. The proposed renewable regeneration method exhibited higher linearity and sensitivity (R2 = 0.9992, 8 pm/mM) in relative to the conventional cumulative regeneration method (R2 = 0.9718, 4.9 pm/mM). The binding affinity between BPOA and glucose was found to be almost constant over 140 bind/release cycles with a variation of less than 0.3 % relative standard deviation.
    CONCLUSIONS: The regenerative and label-free sensing capacity of the proposed device provides a theoretical foundation for label-free saccharide detection and the development of wearable glucose monitoring devices based on fiber optic sensors.
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  • 文章类型: Journal Article
    水产养殖有望在解决可持续地为不断增长的世界人口提供健康和营养食物的挑战方面发挥至关重要的作用。病原体暴发是该部门的主要风险,所以早期发现和及时反应是至关重要的。这可以通过监测水产养殖设施中的病原体水平来实现。本文介绍了一种基于氮化硅波导技术的集成有源元件的光子生物传感平台,可用于此类应用。与最先进的技术相比,当前系统在光子集成电路(PIC)的小型化和用于有源组件的混合集成以及用于材料选择性化学和生物表面改性的晶片级工艺的开发方面提出了改进。此外,开发了将PIC集成到微流体盒中的可扩展工艺,以及一个原型台式读出仪器。三种细菌性水产养殖病原体(沙门纳气单胞菌,沙门氏菌阴道球菌,选择鲁氏耶尔森氏菌)进行测定开发。确定了DNA生物标志物,设计相应的引物-探针组,并开发了qPCR测定。还使用混合PIC平台检测了气单胞菌的生物标志物。这是在混合PIC平台上首次成功的生物传感演示。
    Aquaculture is expected to play a vital role in solving the challenge of sustainably providing the growing world population with healthy and nutritious food. Pathogen outbreaks are a major risk for the sector, so early detection and a timely response are crucial. This can be enabled by monitoring the pathogen levels in aquaculture facilities. This paper describes a photonic biosensing platform based on silicon nitride waveguide technology with integrated active components, which could be used for such applications. Compared to the state of the art, the current system presents improvements in terms of miniaturization of the Photonic Integrated Circuit (PIC) and the development of wafer-level processes for hybrid integration of active components and for material-selective chemical and biological surface modification. Furthermore, scalable processes for integrating the PIC in a microfluidic cartridge were developed, as well as a prototype desktop readout instrument. Three bacterial aquaculture pathogens (Aeromonas salmonicida, Vagococcus salmoninarum, and Yersinia ruckeri) were selected for assay development. DNA biomarkers were identified, corresponding primer-probe sets designed, and qPCR assays developed. The biomarker for Aeromonas was also detected using the hybrid PIC platform. This is the first successful demonstration of biosensing on the hybrid PIC platform.
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  • 文章类型: Journal Article
    生物传感器用于生物分子的特异性和灵敏检测。在传统方法中,将可疑的靶分子与选定的捕获分子结合,并通过额外的标记来指示成功的结合,以实现光学读出。该标记需要针对应用定制的附加处理步骤。虽然存在许多无标签相互作用测定,它们经常在检测特性上妥协。在这种情况下,我们介绍了一种新型的衍射生物传感器,包括衍射生物传感器芯片和相关联的光学读取器组件。这个创新的系统可以捕获整个化验,以无标记的方式检测各种类型的分子,并以单一的方式呈现结果,全面的形象。评估生物传感器的适用性,用于直接检测人血浆中的病毒DNA和蛋白质。研究不同的抗原。在我们的实验中,我们实现了4.2pg/mm²的检测极限,这与其他无标签光学生物传感器相当。该方法的简单性和鲁棒性使其成为推进生物传感技术的令人信服的选择。这项工作有助于开发成像衍射生物传感器,具有在分子相互作用分析中多种应用的潜力。
    Biosensors are used for the specific and sensitive detection of biomolecules. In conventional approaches, the suspected target molecules are bound to selected capture molecules and successful binding is indicated by additional labelling to enable optical readout. This labelling requires additional processing steps tailored to the application. While numerous label-free interaction assays exist, they often compromise on detection characteristics. In this context, we introduce a novel diffractometric biosensor, comprising a diffractive biosensor chip and an associated optical reader assembly. This innovative system can capture an entire assay, detecting various types of molecules in a label-free manner and present the results within in a single, comprehensive image. The applicability of the biosensor is assessed for the detection of viral DNA as well as proteins directly in human plasma, investigating different antigens. In our experiments, we achieve a detection limit of 4.2 pg/mm², which is comparable to other label-free optical biosensors. The simplicity and robustness of the method make it a compelling option for advancing biosensing technologies. This work contributes to the development of an imaging diffractometric biosensor with the potential for multiple applications in molecular interaction analysis.
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  • 文章类型: Journal Article
    铜绿假单胞菌是一种机会性革兰氏阴性细菌,仍然是普遍的临床和环境挑战。群体感应(QS)分子是确定铜绿假单胞菌存在的有效生物标志物。本研究旨在开发一种使用方便的,使用分别封装在藻酸盐-聚-L-赖氨酸(藻酸盐-PLL)微珠中的铜绿假单胞菌报道分子的全细胞生物传感器,以特异性检测细菌自身诱导物的存在。PLL增强的微珠是使用两步法制备的,该两步法涉及离子交联并随后用PLL薄层涂覆。在已知的阳离子清除剂(柠檬酸钠)存在下,藻酸盐-PLL珠显示出良好的稳定性,这通常限制了海藻酸钙的广泛应用。在含有合成自诱导物的培养基中,例如N-(3-氧代十二烷酰基)高丝氨酸内酯(3-氧代-C12-HSL)和N-丁酰基-L-高丝氨酸内酯(C4-HSL),或野生铜绿假单胞菌(PAO1)的浮游无细胞上清液或流动细胞生物膜流出物-包封的细菌能够剂量依赖性地检测这些QS分子的存在。制备的生物报告珠在4和-80°C下的延长储存期间保持稳定,并且准备用于现场感测而不需要回收。概念证明,基于光纤的,和这里开发的全细胞生物传感器证明了基于特定QS分子的封装的生物报道分子用于细菌检测的实用性。
    Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that remains a prevalent clinical and environmental challenge. Quorum-sensing (QS) molecules are effective biomarkers in pinpointing the presence of P. aeruginosa. This study aimed to develop a convenient-to-use, whole-cell biosensor using P. aeruginosa reporters individually encapsulated within alginate-poly-L-lysine (alginate-PLL) microbeads to specifically detect the presence of bacterial autoinducers. The PLL-reinforced microbeads were prepared using a two-step method involving ionic cross-linking and subsequent coating with thin layers of PLL. The alginate-PLL beads showed good stability in the presence of a known cation scavenger (sodium citrate), which typically limits the widespread applications of calcium alginate. In media containing synthetic autoinducers-such as N-(3-oxo dodecanoyl) homoserine lactone (3-oxo-C12-HSL) and N-butanoyl-L-homoserine lactone (C4-HSL), or the cell-free supernatants of planktonic or the flow-cell biofilm effluent of wild P. aeruginosa (PAO1)-the encapsulated bacteria enabled a dose-dependent detection of the presence of these QS molecules. The prepared bioreporter beads remained stable during prolonged storage at 4 and -80 °C and were ready for on-the-spot sensing without the need for recovery. The proof-of-concept, optical fiber-based, and whole-cell biosensor developed here demonstrates the practicality of the encapsulated bioreporter for bacterial detection based on specific QS molecules.
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  • 文章类型: Journal Article
    在不懈追求创新的癌症诊断工具的过程中,这篇综述通过先进的光学生物传感技术阐明了细胞外囊泡(EV)及其生物分子货物检测的前沿领域,主要强调了它们在癌症诊断中的意义。从纳米材料的复杂领域到表面等离子体共振的精度,我们在这里研究光学生物传感器的不同领域,强调它们在癌症诊断中的特定应用。探索和了解电动汽车的细节,我们提出了增强和混合信号的创新应用,超越极限,以更高的敏感性和特异性来增强我们的感知和区分能力。我们对癌症诊断的特别关注强调了光学生物传感器在早期检测和个性化医疗中的变革潜力。这篇综述旨在帮助指导研究人员,临床医生,和爱好者进入迷人的领域,在那里光线与细胞秘密相遇,在癌症诊断中创造创新机会。
    In the relentless pursuit of innovative diagnostic tools for cancer, this review illuminates the cutting-edge realm of extracellular vesicles (EVs) and their biomolecular cargo detection through advanced optical biosensing techniques with a primary emphasis on their significance in cancer diagnosis. From the sophisticated domain of nanomaterials to the precision of surface plasmon resonance, we herein examine the diverse universe of optical biosensors, emphasizing their specified applications in cancer diagnosis. Exploring and understanding the details of EVs, we present innovative applications of enhancing and blending signals, going beyond the limits to sharpen our ability to sense and distinguish with greater sensitivity and specificity. Our special focus on cancer diagnosis underscores the transformative potential of optical biosensors in early detection and personalized medicine. This review aims to help guide researchers, clinicians, and enthusiasts into the captivating domain where light meets cellular secrets, creating innovative opportunities in cancer diagnostics.
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  • 文章类型: Journal Article
    单壁碳纳米管(SWNT)具有强且稳定的近红外(nIR)荧光,可用于选择性检测目标分析物,即使在单分子水平上,通过改变它们的荧光强度或发射峰值波长。SWNT已被用作用于检测多种分析物的NIR光学传感器。然而,高成本,长制造时间,和较差的分布限制了将SWNT传感器固定在固体基材上的当前方法。最近,我们小组报告了一种高荧光产量的SWNT固定方案,长寿,荧光分布,和传感器响应,不幸的是,这个过程需要5天才能完成。在这里,我们报告了一种改进的方法来固定SWNT传感器,只需要2天,并导致更高的荧光强度,同时保持高水平的SWNT分布。我们对原始和新的合成方法进行了表面形态和化学成分测试,并比较了传感器的响应速率。这种将SWNT传感器连接到平台的新方法的开发允许在短短2天内创建传感系统,而不会牺牲原始传感器的有利特性。5天平台
    Single-walled carbon nanotubes (SWNT) have a strong and stable near-infrared (nIR) fluorescence that can be used to selectively detect target analytes, even at the single molecule level, through changes in either their fluorescence intensity or emission peak wavelength. SWNTs have been employed as NIR optical sensors for detecting a variety of analytes. However, high costs, long fabrication times, and poor distributions limit the current methods for immobilizing SWNT sensors on solid substrates. Recently, our group reported a protocol for SWNT immobilization with high fluorescence yield, longevity, fluorescence distribution, and sensor response, unfortunately this process takes 5 days to complete. Herein we report an improved method to immobilize SWNT sensors that only takes 2 days and results in higher fluorescence intensity while maintaining a high level of SWNT distribution. We performed surface morphology and chemical composition tests on the original and new synthesis methods and compared the sensor response rates. The development of this new method of attaching SWNT sensors to a platform allows for creation of a sensing system in just 2 days without sacrificing the advantageous characteristics of the original, 5-day platforms.
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  • 文章类型: Journal Article
    在这项研究中,我们报道了一种新型高灵敏度基于强度的表面等离子体共振成像(SPRi)生物传感器的成功开发及其在检测分子相互作用中的应用。通过优化激发波长并采用波分复用(WDM)算法,该系统可以根据样品的初始折射率确定最佳激发波长,而无需调整入射角。实验结果表明,该系统的折射率分辨率达到1.77×10-6RIU。此外,它可以获得初始折射率在1.333至1.370RIU范围内的样品的最佳激发波长,并精确监测0.0037RIU范围内的变化,而无需调整入射角。此外,我们的新SPRi技术实现了高通量生物分子结合过程的实时检测,能够分析动力学参数。这项研究有望促进更精确的SPRi分子相互作用分析技术的发展。
    In this study, we report the successful development of a novel high-sensitivity intensity-based Surface Plasmon Resonance imaging (SPRi) biosensor and its application for detecting molecular interactions. By optimizing the excitation wavelength and employing a wavelength division multiplexing (WDM) algorithm, the system can determine the optimal excitation wavelength based on the initial refractive index of the sample without adjusting the incidence angle. The experimental results demonstrate that the refractive index resolution of the system reaches 1.77×10-6 RIU. Moreover, it can obtain the optimal excitation wavelength for samples with an initial refractive index in the range of 1.333 to 1.370 RIU and accurately monitor variations within the range of 0.0037 RIU without adjusting the incidence angle. Additionally, our new SPRi technique realized real-time detection of high-throughput biomolecular binding processes, enabling analysis of kinetic parameters. This research is expected to advance the development of more accurate SPRi technologies for molecular interaction analysis.
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  • 文章类型: Journal Article
    近年来,纳米科学和材料设计的进步促进了用于癌症诊断和生物分子感测的即时护理设备的创建。外泌体(EXO)促进生物活性分子在局部和远处微环境中的癌细胞和不同细胞之间的转移,从而促进癌症进展和转移。具体来说,源自癌症的EXO可能作为早期癌症检测的生物标志物起作用,这是由于它们作为有效载荷在起源的癌细胞内运输的遗传或信号改变。已经证实,EXO在身体分泌物中稳定地循环,并且包含指示肿瘤进展的各种信息。然而,由于其纳米级性质和高度异质性,获取有关EXO的分子信息和相互作用提出了重大的技术挑战。比色法,表面等离子体共振(SPR),荧光,和拉曼散射是用于量化癌症外泌体生物标志物的光学技术的例子,包括脂类,蛋白质,RNA,和DNA。许多光学活性纳米粒子(NP),主要是基于碳的,无机,有机,和复合材料基纳米材料,已用于生物传感技术。纳米材料表现出的特殊物理性质,包括碳NPs,贵金属NP,和磁性NP,促进了用于检测源自肿瘤的EXO的光学纳米生物传感器的开发的重大进展。在总结了生物发生之后,生物学功能,和已知EXO的生物标志物值,本文提供了当前正在调查的检测方法的更新。总之,我们提出了一些用于检测EXO的光学生物传感器的潜在增强,利用各种NP材料,如硅NP,氧化石墨烯(GO),金属NP,和量子点(QD)。
    The advancement of nanoscience and material design in recent times has facilitated the creation of point-of-care devices for cancer diagnosis and biomolecule sensing. Exosomes (EXOs) facilitate the transfer of bioactive molecules between cancer cells and diverse cells in the local and distant microenvironments, thereby contributing to cancer progression and metastasis. Specifically, EXOs derived from cancer are likely to function as biomarkers for early cancer detection due to the genetic or signaling alterations they transport as payload within the cancer cells of origin. It has been verified that EXOs circulate steadily in bodily secretions and contain a variety of information that indicates the progression of the tumor. However, acquiring molecular information and interactions regarding EXOs has presented significant technical challenges due to their nanoscale nature and high heterogeneity. Colorimetry, surface plasmon resonance (SPR), fluorescence, and Raman scattering are examples of optical techniques utilized to quantify cancer exosomal biomarkers, including lipids, proteins, RNA, and DNA. Many optically active nanoparticles (NPs), predominantly carbon-based, inorganic, organic, and composite-based nanomaterials, have been employed in biosensing technology. The exceptional physical properties exhibited by nanomaterials, including carbon NPs, noble metal NPs, and magnetic NPs, have facilitated significant progress in the development of optical nanobiosensors intended for the detection of EXOs originating from tumors. Following a summary of the biogenesis, biological functions, and biomarker value of known EXOs, this article provides an update on the detection methodologies currently under investigation. In conclusion, we propose some potential enhancements to optical biosensors utilized in detecting EXO, utilizing various NP materials such as silicon NPs, graphene oxide (GO), metal NPs, and quantum dots (QDs).
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  • 文章类型: Journal Article
    在过去的40年里,光学生物传感器采用了至少三种不同的系统架构,从“样本输入-应答输出”系统到将光学生物传感器完全嵌入到样本中,再到将识别模块嵌入样本中,并从样本外部光学询问识别模块。这篇趋势文章概述了这三种系统体系结构的演变,并讨论了如何应用每种体系结构来解决各种应用程序的测量挑战。第四个生物传感器系统架构,一个“自主”生物传感器,它“将用户带出循环”,同时检测目标分析物并响应测量,目前正在开发应用,最初包括环境清理和“智能疗法”。“就像许多其他技术领域的情况一样,观察优雅的进一步发展和应用将是非常有趣的,更简单的(光学)生物传感器系统,以满足明天的测量需求。
    Optical biosensors have employed at least three distinct system architectures over the last 40 years, moving from \"sample in-answer out\" systems to completely embedding the optical biosensor into the sample to embedding the recognition module in the sample and optically interrogating the recognition module from outside of the sample. This trends article provides an overview of the evolution of these three system architectures and discusses how each architecture has been applied to solve the measurement challenges of a wide variety of applications. A fourth biosensor system architecture, that of an \"autonomous\" biosensor which \"takes the user out of the loop\" while both detecting target analytes and responding to that measurement, is currently under development for applications initially including environmental cleanup and \"smart therapeutics.\" As is the case in many other areas of technology, it will be profoundly interesting to observe the further development and application of elegant, simpler (optical) biosensor systems to address tomorrow\'s measurement needs.
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  • 文章类型: Journal Article
    小分子天然化合物在生物医学中越来越受欢迎,因为它们容易获得广泛的结构多样性,并且在几个案例研究中证明了它们的健康益处。现在,使用少量样品以无标记和自动化的方式对分子量低于100Da的小分子进行亲和力测量已成为可能,并在本工作中进行了综述。我们还突出了新颖的无标签设置,具有出色的时间分辨率,这对于生物分子和活细胞的动力学测量很重要。我们总结了如何从细胞动力学信号的深入分析中获得分子尺度的亲和力数据。与传统测量不同,无标签生物传感器使这种测量成为可能,即使没有分离感兴趣的特定细胞受体。在整个审查过程中,我们认为表没食子儿茶素没食子酸酯(EGCG)是一个典型的化合物。EGCG,在绿茶中发现的儿茶素,是一种公认的抗炎和抗癌剂。它在许多研究中经历了广泛的检验,它通常依赖于基于荧光的方法来探索其对健康和肿瘤细胞的影响。总结的研究主题从与蛋白质和生物膜的分子相互作用到EGCG存在下新型仿生界面上细胞粘附和运动的动力学。虽然小分子对活细胞和生物分子的直接影响在文献中使用传统的生物学测量方法进行了相对较好的研究,这篇综述还强调了这些分子通过改变其纳米环境对细胞的间接影响。此外,我们强调了新型高通量无标记技术在小分子测量中的重要性,在一个实验中促进分子尺度相互作用和细胞过程的研究。这一进步为探索更复杂的多组分模型打开了大门,这些模型以前超出了传统测定法的范围。
    Small molecule natural compounds are gaining popularity in biomedicine due to their easy access to wide structural diversity and their proven health benefits in several case studies. Affinity measurements of small molecules below 100 Da molecular weight in a label-free and automatized manner using small amounts of samples have now become a possibility and reviewed in the present work. We also highlight novel label-free setups with excellent time resolution, which is important for kinetic measurements of biomolecules and living cells. We summarize how molecular-scale affinity data can be obtained from the in-depth analysis of cellular kinetic signals. Unlike traditional measurements, label-free biosensors have made such measurements possible, even without the isolation of specific cellular receptors of interest. Throughout this review, we consider epigallocatechin gallate (EGCG) as an exemplary compound. EGCG, a catechin found in green tea, is a well-established anti-inflammatory and anti-cancer agent. It has undergone extensive examination in numerous studies, which typically rely on fluorescent-based methods to explore its effects on both healthy and tumor cells. The summarized research topics range from molecular interactions with proteins and biological films to the kinetics of cellular adhesion and movement on novel biomimetic interfaces in the presence of EGCG. While the direct impact of small molecules on living cells and biomolecules is relatively well investigated in the literature using traditional biological measurements, this review also highlights the indirect influence of these molecules on the cells by modifying their nano-environment. Moreover, we underscore the significance of novel high-throughput label-free techniques in small molecular measurements, facilitating the investigation of both molecular-scale interactions and cellular processes in one single experiment. This advancement opens the door to exploring more complex multicomponent models that were previously beyond the reach of traditional assays.
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