表面等离子体共振生物传感器及其应用

表面等离子体共振(Surface Plasmon Resonance,SPR)生物传感器在检测生物分子特异性结合方面具有的高灵敏度、免标记及检测快速等优点,使其在过去的20年中在生命科学、医药科学、食品安全等领域取得了快速发展。本文对SPR生物传感器进行了简要介绍,并着重对其在生命科学、医药学、环境分析、食品安全等领域的应用进行了综述,最后对该领域的研究前景进行了展望。     

光电化学型半导体生物传感器

光电化学型半导体生物传感器是一种利用半导体的光电特性来检测与光生电流或光生电压相关的待测物质浓度及生化过程参数的分析新技术。随着新兴半导体功能材料及相关加工技术的不断涌现,光电化学型半导体生物传感器已在微型化、集成化、多点及多参数测量方面显现出优势、有望在复杂体系中实现在线高灵敏、快速测定,在生物、医药、环境监测、食品等领域显示出广阔的应用前景。本文主要介绍了光电化学型半导体传感器的基本原理、特点及近几年的研究进展,并对其发展前景做了展望。     

液晶生物传感及其在微流控细胞分析中的应用

液晶(LC)生物传感器是基于LC对界面性质变化的高灵敏响应及其固有的光学各向异性发展起来的一种技术,在生物样品的检测分析方面展现出了非凡的应用价值。通过修饰刺激响应性分子,LC界面可以灵敏地响应待测生物分析物的存在,并诱导界面LC分子发生取向改变,而界面上LC分子的短程相互作用引起LC相本体分子的取向改变,在偏光显微镜(POM)下可见LC显示出不同的光学织构。因此,LC传感器无需对待测物进行标记,凭借其简单的光学检测仪器,容易将分子事件转化为可视化光学信号输出,具有简单、灵敏、高效、快速、廉价等优点,在生物检测分析领域得到了广泛应用。该文综述了近年来液晶生物传感器在检测分析生物小分子、生物大分子以及生物有机体等方面的研究进展,特别提到了液晶生物传感器引入微流控芯片用于细胞分析的新兴领域的发展与挑战。目前,液晶生物传感已经成功地应用于界面现象复杂多样的细胞分析,未来就其在模拟细胞微环境下的传感设计和适用性还需进行更加深入的研究。     

单个等离子体纳米颗粒在生化分析和生物成像中的应用

等离子体纳米颗粒（PNPs）因其独特的物理、化学、光学和生物学特性而被广泛地应用于材料科学、生物学和医药学等研究领域。PNPs的光学性质是可以通过改变其组成、形状和大小来进行调控的,所以利用可控合成的方式能够筛选出适合的光散射探针。在单分子水平上实时研究PNPs的动态行为对于理解细胞及活体组织的生命活动机制、制备功能型纳米材料和开发新型化学生物传感器等有着重要的意义。基于传统的暗场显微镜（DFM）,通过对光源、检测器及其它光学元件的择优组装和调试,我们开发出了一系列具有高灵敏度、高时空分辨率和高通量的等离子体光散射成像技术,并将其应用于单分子检测、多颗粒传感、单细胞成像以及生物过程示踪等领域。基于具有光学各向异性的PNPs,我们还研制出了活细胞三维扫描成像系统和超连续激光光片成像与高速毛细管电泳联用系统,推进了单分子光谱方面的研究。本文将总结近十年来本课题组在PNP单颗粒分析及成像中的工作,并为该领域未来的发展提出一些新的思路。     

基于能量转移机理的水溶性荧光共轭聚合物体系的设计制备及应用

水溶性共轭聚合物由于具有优异的光学性能,如强大的光捕获能力和独特的分子线效应,在化学、生物和医疗领域都有良好的应用前景。共轭聚合物受光激发后,所产生的激子可以沿着长程共轭的π骨架自由迁移,在分子骨架的任何位点都可以转移给能量受体,从而实现高效的能量传递。因此,水溶性共轭聚合物适合于构建各种能量传递体系,从而实现荧光信号放大、多色发光、活性氧产生效率提高等光学性能的优化。本文简述了基于水溶性共轭聚合物构建能量转移体系的原理和方法,总结了其在生物传感、生物成像、光动力杀菌和光动力抗癌等领域的应用,最后对水溶性共轭聚合物存在的主要问题以及未来的发展方向进行了分析和展望。     

含偶氮苯光学活性侧基聚合物研究进展

综述了含偶氮苯光学活性侧基聚合物近年来的发展概况 ,介绍了多种聚合体系的类型。由于偶氮苯光于活性侧基的存在 ,使得这些聚合物具有光致变色性、非线性光学活性、光学各向异性等光学性能 ,在光信息存储材料、非线性光学材料、液晶材料、光电子器件、生物分子活性光调控、纳米技术等诸多领域都有广泛的应用。     

氧化石墨烯荧光传感器

氧化石墨烯因其独特的光学、表面、机械、电学及热学性质在诸多领域都具有良好的应用前景。利用氧化石墨烯能够有效猝灭荧光体(染料分子、量子点及上转换纳米材料)荧光的特性,结合相关生物分析技术,相继开发了各种荧光传感器。本文综述近年来氧化石墨烯荧光传感器的基本原理及研究进展,主要讨论氧化石墨烯荧光传感器在重金属离子、DNA、蛋白质及生物小分子的分析应用,并对该领域的应用前景进行了展望。     

金属钯／铂卟啉室温Lin光探针在生物医学领域的应用研究

钯（Ⅱ）／铂（Ⅱ）卟啉络合物在室温下发射长寿命（ms)、长波长的Lin光，这些特点使其在生物分析方面成为有用的探针。本文综述了该探针在Lin光免疫标记、肿瘤诊断、DNA测定、生物传感器及其它方面的研究进展。引用文献43篇。     

聚合物纳米光诊疗剂的制备与应用新进展

共轭聚合物纳米颗粒是由π-共轭有机聚合物组成的尺寸在1~100nm范围内的新型有机纳米材料。与传统的有机小分子、半导体量子点和无机纳米材料相比,聚合物纳米颗粒具有光学性质特殊、结构多样、表面易修饰和生物相容性好等优点,因而被广泛应用于生物成像、传感与检测、载药和治疗等领域。本文主要围绕聚合物纳米颗粒的制备方法、性质结构和生物相容性等方面,重点介绍了聚合物纳米颗粒作为光诊疗剂在荧光成像、光声成像,以及光动力和光热治疗领域的研究进展,并对聚合物纳米颗粒的发展前景和未来面临的挑战进行了探讨。     

半导体共轭聚合物光学探针的设计及在自发光成像和光声成像中的应用

光学成像因其无侵袭性、高时空分辨率和高灵敏度在生物医学领域得到迅速发展.光学成像中自发光成像包括化学发光成像和长余辉成像不需实时光激发,避免了自发荧光的影响,可以得到较高的灵敏度和信噪比.光声成像则是将光信号通过热膨胀转化为声信号,避免了光散射的影响,具有较高的组织穿透深度.本文针对半导体共轭聚合物光学探针在自发光成像和光声成像技术中的应用进行综述,重点介绍了半导体共轭聚合物光学探针用于增强自发光成像、光声成像的信号强度的设计策略,以及响应型光声探针的设计原理.阐述了通过降低光学探针与发光底物之间的能隙等策略增强自发光成像信号强度,通过淬灭荧光或加速热扩散等策略放大光声信号,以及通过特异性生物分子识别或相互作用激活的响应型光声探针的具体研究成果.最后,对半导体共轭聚合物光学探针在光学成像领域存在的挑战和前景进行了展望.     

An advanced biosensor for the prediction of estrogenic effects of endocrine-disrupting chemicals on the estrogen receptor alpha

A label-free and time-resolved biosensor based on reflectometric interference spectroscopy (RIfS) has been developed to evaluate the agonistic or antagonistic effects of potential ligands with unknown behavior. The biosensor utilizes the specific interaction between the estrogen receptor alpha (ER alpha) and short specific peptides. The unique feature of these peptides allows the investigation of the behavior of ligands and the discrimination between the agonistic and antagonistic effects caused by conformational changes of the receptor. Thus, this developed biosensor allows not only the differentiation between ligands and nonligands of a receptor, but also the potential of these ligands to influence conformational changes in the receptor, leading to activation or inhibition of the receptor-dependent pathways. Owing to the robustness of the direct optical detection principle used, the biosensor is applicable to complex biological matrices, even crude cell extracts. Moreover, the reliability of the biosensor, including regeneration steps when performing subsequent measurements, has been verified.     

Potential of label-free detection in high-content-screening applications

The classical approach of high-content screening (HCS) is based on multiplexed, functional cell-based screening and combines several analytical technologies that have been used before separately to achieve a better level of automation (scale-up) and higher throughput. New HCS methods will help to overcome the bottlenecks, e.g. in the present development chain for lead structures for the pharmaceutical industry or during the identification and validation process of new biomarkers. In addition, there is a strong need in analytical and bioanalytical chemistry for functional high-content assays which can be provided by different hyphenated techniques. This review discusses the potential of a label-free optical biosensor based on reflectometric interference spectroscopy (RIfS) as a bridging technology for different HCS approaches. Technical requirements of RIfS are critically assessed by means of selected applications and compared to the performance characteristics of surface plasmon resonance (SPR) which is currently the leading technology in the area of label-free optical biosensors.     

Label-free biosensing with lipid-functionalized gold nanorods

The fabrication of a label-free mass spectrometry and optical detection-based biosensor platform for the detection of low-abundance lipophilic analytes in complex mixtures is described. The biosensor consists of a lipid layer partially tethered to the surface of a gold nanorod. The effectiveness of the biosensor is demonstrated for the label-free detection of a lipophilic drug in aqueous solution and a lipopeptide in serum.     

非标记光反射干涉生物传感器及其检测模型的构建

构建了基于反射光干涉生物传感器检测系统,用原子力学显微镜对传感单元的表面进行了表征,对检测系统传感单元进行优化,以人IgG和抗人IgG为模型建立了反射光干涉生物传感器的应用模型。结果表明:应用甩膜法构建的传感单元具有较平整的表面,以二氧化钛为干涉增强层的传感单元具有低背景信号,检测光学厚度信号与检测浓度之间具有很好的线性相关性。建立的非标记检测系统在环境、食品安全检测、药物筛选及生物材料等多方面具有广阔的应用前景。     

Label-free detection of C-reactive protein using reflectometric interference spectroscopy-based sensing system

Reflectometric interference spectroscopy (RIfS) is a label-free, time-resolved technique, and suitable for detecting antibody–antigen interaction. This work describes a continuous flow biosensor for C-reactive protein (CRP), involving an effective immobilization method of a monoclonal antibody against CRP (anti-CRP) to achieve highly sensitive RIfS-based detection of CRP. The silicon nitride-coated silicon chip (SiN chip) for the RIfS sensing was first treated with trimethylsilylchloride (TMS), followed by UV-light irradiation to in situ generation of homogeneous silanols on the surface. Following amination by 3-aminopropyltriethoxysilane, carboxymethyldextran (CMD) was grafted, and subsequently, protein A was immobilized to create the oriented anti-CRP surface. The immobilization process of protein A and anti-CRP was monitored with the RIfS system by consecutive injections of an amine coupling reagent, protein A and anti-CRP, respectively, to confirm the progress of each step in real time. The sensitivity was enhanced when all of the processes were adopted, suggesting that the oriented immobilization of anti-CRP via protein A that was coupled with the grafted CMD on the aminated surface of TMS-treated SiN chip. The feasibility of the present sensing system was demonstrated on the detection of CRP, where the silicon-based inexpensive chips and the simple optical setup were employed. It can be applied to other target molecules in various fields of life science as a substitute of surface plasmon resonance-based expensive sensors.     

Label-free detection of biomolecular interaction by optical sensors

Since the first label-free optical biosensor was commercialized in 1990 a rising number of publications have demonstrated the benefits of direct biomolecular interaction analysis (BIA) for biology and biochemistry. This article first gives an overview of the historical development of different transducer principles used for the detection of BIA. Subsequently, the four major parts of a biosensor system: transducer, sample handling, surface/immobilization chemistry and test formats/data evaluation will be discussed, with a main focus on the test formats and data evaluation. The intention of this review is to present an introduction to the field and to point out the difficulties most frequently encountered.     

Chemical surface modifications for the development of silicon-based label-free integrated optical (IO) biosensors: A review

Increasing interest has been paid to label-free biosensors in recent years. Among them, refractive index (RI) optical biosensors enable high density and the chip-scale integration of optical components. This makes them more appealing to help develop lab-on-a-chip devices. Today, many RI integrated optical (IO) devices are made using silicon-based materials. A key issue in their development is the biofunctionalization of sensing surfaces because they provide a specific, sensitive response to the analyte of interest. This review critically discusses the biofunctionalization procedures, assay formats and characterization techniques employed in setting up IO biosensors. In addition, it provides the most relevant results obtained from using these devices for real sample biosensing. Finally, an overview of the most promising future developments in the fields of chemical surface modification and capture agent attachment for IO biosensors follows.