几种常见纳米材料构建的光学传感体系在生化分析中的应用

近年来生物传感新体系的出现,极大地推动了生物医学、分析、环境等研究领域的发展.由于纳米材料具有一些独特的理化性质,常作为载体材料、信号分子等被广泛应用于构建光学生物传感体系.主要介绍了基于金纳米粒子、石墨烯、碳纳米管、量子点、硅纳米粒子几种常见纳米材料构建的光学传感体系及其在生化分析中的应用.分析讨论了这些体系的原理和实际应用,并展望了其研究和应用前景.     

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。     

聚集诱导发光高分子在光学诊疗应用中的研究进展

高分子因其优异的光学特性、良好的生物相容性和分子结构易于调控等优势,在光学诊疗领域表现出巨大应用潜力.然而,传统荧光分子的聚集导致荧光淬灭现象限制了其生物应用.聚集诱导发光(AIE)分子因其聚集态高效发光的优势而备受关注.本文从AIE高分子的构建出发,重点介绍了D-A型共轭聚合物的构建策略、构-效关系以及相对于小分子的性能和应用优势,并从生物成像、肿瘤诊疗和抗菌三个方面总结了AIE高分子在光学诊疗领域的最新研究进展.生物成像方面主要总结了NIR-Ⅱ区AIE高分子在深部组织高分辨率荧光成像中的应用;肿瘤诊疗方面主要介绍了AIE高分子在光动力治疗、光热治疗及联合治疗中的应用;以及介绍了AIE高分子在细菌感染光动力治疗中的应用.最后对AIE高分子在光学诊疗领域的未来发展前景进行了展望.     

量子点在生物体系中的光学应用

量子点（QDs）与传统染料分子相比,具有量子产率高、光学漂白低、稳定性强、尺寸可调等独特的光学特性.通过与荧光、电化学发光、荧光共振能量转移、循环伏安、差分脉冲伏安以及方波伏安等光电化学技术的联用,使得量子点在DNA、蛋白质、酶等生物分子,细胞以及活体成像中的应用越来越广.本综述简单介绍了量子点的特性及制备方法,重点讨论了其在生物体系中光学检测DNA、蛋白质及酶等生物分子,细胞分析以及活体成像中的应用,并展望了其在未来生命分析中的研究趋势与前景.     

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.     

基于核酸探针的光学传感方法和细胞成像研究

许多疾病的特征在于各种生物分子表现出的异常活性,这些物质通常在细胞内外显示过表达现象,因此对其灵敏靶向识别可以提供诊断和治疗效用。由于基因诊疗和化学传感技术的发展,用于灵敏检测细胞内外生物化学物质的核酸探针突显优势。核酸探针可以在稳定进入细胞的同时,特异性地结合目标物质,通过光学方法检测或通过成像技术标识出来。本文综述了采用光学传感方法和成像技术,基于核酸探针检测生物分子的新进展。根据检测对象进行分类,概括分析了几个代表性体系:核酸序列、蛋白质和酶、化学物质和物理化学条件,并详细阐述其关键设计原理、灵敏度及样品检测等结果,同时指出了各类核酸探针的优缺点。     

基于金纳米粒子的光学生物传感方法研究进展

光学生物传感是以产生各种光学信号为检测基础的一种微量分析技术,具有操作简便、检测成本低、抗干扰能力强及可实现原位检测等优点,在临床诊断、药物分析、环境监测等领域显示出广阔的应用前景。作为纳米材料重要成员之一的金纳米粒子(AuNPs),因其独特的光学性质被广泛用于光学生物传感方法的构建。该文综述了近年来基于金纳米粒子的光学生物传感方法在分析检测中的研究进展,提出了实际应用中可能存在的问题并对未来发展趋势进行展望。     

多肽超分子手性自组装与应用

多肽分子作为一类重要的生物手性小分子,能够通过分子自组装形成包括纳米螺旋、纳米管、手性凝胶等在内的有着独特生物效应和光学活性的手性纳米材料。这类材料具有易于功能化修饰的优点,在化学、生物、医药、材料科学等领域有着广泛应用,成功对多肽手性自组装结构进行精准多级调控,是进一步实现其功能化应用的基础。本文重点介绍了多肽分子氨基酸序列组成与构型等内部因素,以及溶液pH、溶剂、添加剂等外界因素对多肽分子手性自组装行为的影响,并归纳得出其关键作用机制;同时,还介绍了多肽手性自组装材料在手性催化、手性检测、模板合成、手性光学等领域的应用。     

三维光学断层技术在活体成像中的应用

三维光学断层成像(Three Dimensional Optical Tomography Imaging)是以光学探针标记的分子或细胞为成像源,在外部光源的激发下产生发射光,通过测量组织边界处的光强,结合光子在组织中的传播模型,来重建出组织内部发射光分布图像以及组织光学参数。三维光学断层成像能够提供目标物在生物体内的分布信息,克服平面成像的局限性。因此,在肿瘤检测、基因表达、蛋白质分子检测、揭示机体功能变化等方面有着很大的应用潜力。本文总结了光学相干断层成像(Optical Coherence Tomography,OCT)、荧光分子断层成像(Fluorescent Molecular Tomography,FMT)、生物自发光断层成像(Bioluminescence Tomography,BLT)、切伦科夫荧光断层成像(Cerenkov Luminescence Tomography,CLT)等三维光学断层活体成像技术的新进展,分析了其在实际应用中所面临的技术挑战并探讨了相应的解决方案。     

人工分子机器:分子尺度运动的精准化与可视化

分子机器在自然界至关重要,其在生物过程中执行了大量复杂的功能,从而实现不同尺度的动态行为调控.受生物系统的启发,科学家致力于研究人工分子机器在分子尺度下的精准构筑和定向运动,并通过层级组装实现信号传递和功能放大,从而推动动态智能材料的设计发展.但如何利用新方法精准构筑复杂的人工分子机器,如何将分子尺度的运动动态进行“可视化”,以及如何在生命科学研究中发挥其功能,一直是分子机器领域的研究热点.本文基于本课题组的工作,系统介绍了人工分子机器在分子尺度的精准结构构筑、信号输出以及其在跨膜运输方面的研究.最后总结了该领域在多尺度精细化和功能化方面的挑战,并展望了分子机器在宏观智能材料领域的发展前景.     

Optical chemical biosensors for high-throughput screening of drugs

Optical biosensors have been commercially available since the early 1990s, and have been used extensively in many areas of research in the life sciences. Optical biosensors developed for drug analysis generally exploit the high selectivity of the antigen-antibody and drug-protein interaction. Optical biosensors can be made based on optical diffraction or electro-chemiluminescence. High-throughput screening, (HTS) which includes automated preparation of a large number of samples and then screening of their properties in multi-well plates, improves the efficiency of research in many scientific areas, e.g., catalyst screening, food processing, chemical synthesis, drug discovery, absorption, distribution, metabolism, and excretion and toxicological and cell based screening. The three most common detection techniques used in HTS are UV-VIS absorbance, fluorescence and luminescence. In this review, we summarize some recent trends and developments in the construction of optical chemical biosensors used in high-throughput screening of drugs. Also, we have included environmental, biological and other medical applications of biosensors.     

Anti-epidermal growth factor receptor (anti-EGFR) antibody conjugated fluorescent nanoparticles probe for breast cancer imaging

Fluorescent nanoparticles (FNs) with unique optical properties may be useful as biosensors in living cancer cell imaging and cancer targeting. In this study, anti-EGFR antibody conjugated fluorescent nanoparticles (FNs) (anti-EGFR antibody conjugated FNs) probe was used to detect breast cancer cells. FNs with excellent character such as non-toxicity and photostability were first synthesized with a simple, cost-effective and environmentally friendly modified Stőber synthesis method, and then successfully modified with anti-EGFR antibody. This kind of fluorescence probe based on the anti-EGFR antibody conjugated FNs has been used to detect breast cancer cells with fluorescence microscopy imaging technology. The experimental results demonstrate that the anti-EGFR antibody conjugated FNs can effectively recognize breast cancer cells and exhibited good sensitivity and exceptional photostability, which would provide a novel way for the diagnosis and curative effect observation of breast cancer cells and offer a new method in detecting EGFR.     

Anti-Her-2 monoclonal antibody conjugated polymer fluorescent nanoparticles probe for ovarian cancer imaging

Fluorescent nanoparticles (FNPs) with unique optical properties may be useful as biosensors in living cancer cell imaging and cancer targeting. A novel kind of polymer fluorescent nanoparticles (PFNPs) was synthesized and its application for ovarian cancer imaging with fluorescence microscopy imaging technology was presented in this study. The PFNPs were synthesized with precipitation polymerization by using methacrylic acid (MAA) as monomer, trimethylolpropane trimethacrylate (Trim) as cross-linker, azobisisobutyronitrile (AIBN) as radical initiator and butyl rhodamine B (BTRB) as fluorescent dye. And the fluorescent dye was embedded into the three-dimensional network of the polymer when the polymer was produced. With this method the PFNPs can be prepared easily. And then the PFNPs were successfully modified with anti-Her-2 monoclonal antibody. The fluorescence probe based on anti-Her-2 monoclonal antibody conjugated PFNPs has been used to detect ovarian cancer cells with fluorescence microscopy imaging technology. The experimental results demonstrate that the anti-Her-2 monoclonal antibody conjugated PFNPs can effectively recognize ovarian cancer cells and exhibit good sensitivity and exceptional photostability, which would provide a novel way for the diagnosis and curative effect observation of ovarian cancer cells.     

Development of Cell-Based Olfactory Biosensors

The olfactory system is responsible for the discrimination and identification of myriad odorant molecules at very low concentrations. On the basis of the gene super family encoding olfactory receptors, it has led to the rapid development of cell based olfactory biosensors. Attempts are currently made not only to imitate the mechanism of the biological nose but also to utilize some of its sensor molecules as functional unities in olfactory biosensors. Recently, the development of olfactory biosensors has achieved rapid advances by using protein molecules and cells, even biological organs as functional elements, that is, odorant binding proteins (OBPs) and olfactory receptors (ORs) at the molecular level, cell based gene engineered cells or olfactory receptor neurons (ORNs), and mammalian olfactory organs. With using the living cells expressing olfactory signal proteins as sensing elements, the cell based biosensors have a naturally evolved selectivity to odorant molecules. Furthermore, the biosensors also have the capacity to respond to odorant in a physiologically relevant manner. In this paper, we briefly introduce the molecular basis of olfaction and summarize the cell based olfactory biosensors.     

Switchable 'on-off-on' electrochemical technique for direct detection of survivin mRNA in living cells

Survivin is a new member of apoptosis inhibition protein in cells which can promote cell proliferation and inhibit apoptosis through karyokinesis. Survivin mRNA in cells has become an important biomarker for early and accurate cancer diagnostics. Here, a switchable electrochemical sensor for survivin mRNA in living cells has been designed, which is based on the changes of electron transfer efficiency between ferrocene at the end of DNA and the electrode surface after reaction with survivin mRNA. The method was then used to study populations of individual cells with different levels of mRNA. Based on the different current changes, it was possible to evaluate different cell populations and cell status on the basis of the amount of mRNA levels in cells. This strategy may provide a new direction in the fabrication of high-performance electrochemical biosensors for the detection of biomolecules in living cells.     

Optical biosensors based on Prussian Blue films

Optical biosensing schemes based on enzymatically modified inorganic/organic transparent films predominately composed of Prussian Blue are demonstrated. The composite film, which is non-electrochemically deposited on a non-conducting support. is used as an optical transducer for flow-through biosensors based on hydrolases and oxidases. Urease and glucose oxidase are utilized as model enzymes. Action of the urea biosensor is based on optical pH sensitivity of Prussian Blue indicator. The glucose biosensor is acting as first-generation optical biosensor based on in situ generated Prussian White transducer for hydrogen peroxide. These simple, single-pass transmission optical biosensors exhibit sensitivity in the millimolar range of concentration. The biosensors are very stable owing to presence of a poly(pyrrolylbenzoic acid) network in the composite material. This organic polymer plays a dual role as a binding agent for inorganic material and as a functionalized support for strong covalent immobilization of enzyme molecules.     

Recent advances in nucleic acid amplification-based optical biosensors for disease diagnosisEI北大核心CSCD

Optical biosensors have been widely used in the detection of biomarkers due to their advantages of simple operationquick responsehigh sensitivity and visualization. When constructing optical biosensors nucleic acid amplification technology can be used to improve the analytical performance of optical biosensor which can further realize the highly sensitive detection of biomarkers and provide more accurate information for disease diagnosis. In this reviewrecent advances in nucleic acid amplification-based optical biosensors for disease diagnosis were reviewed the possible problems may exist in practical applications and future development trends were proposed. © 2022, Youke Publishing Co.,Ltd. All rights reserved.     

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。     

碳纳米管在电化学和光化学纳米生物传感器中的应用

碳纳米管(CNTs)因具有独特的物理化学及电化学性质,如较大的比表面积、较强的电子转移能力和良好的吸附性能等而引起人们的广泛关注.碳纳米管可以通过物理吸附、静电或疏水作用等非共价结合方式或共价连接方式固定生物大分子(如蛋白质、DNA、抗体等),有效地促进生物大分子与电极间直接、快速的电子转移,可应用于多种电化学生物传感器中.碳纳米管本身在近红外光区具有独特的荧光和拉曼光谱,可以利用多种光谱手段对多种生物分子实现定量检测,因此近年来碳纳米管在光化学生物传感器中的应用也逐渐受到了研究者的重视.本文对碳纳米管在电化学和光化学生物传感器中的应用进行了简要综述和展望.     

A vertically aligned carbon nanotube-based impedance sensing biosensor for rapid and high sensitive detection of cancer cells

A novel vertically aligned carbon nanotube based electrical cell impedance sensing biosensor (CNT-ECIS) was demonstrated for the first time as a more rapid, sensitive and specific device for the detection of cancer cells. This biosensor is based on the fast entrapment of cancer cells on vertically aligned carbon nanotube arrays and leads to mechanical and electrical interactions between CNT tips and entrapped cell membranes, changing the impedance of the biosensor. CNT-ECIS was fabricated through a photolithography process on Ni/SiO(2)/Si layers. Carbon nanotube arrays have been grown on 9 nm thick patterned Ni microelectrodes by DC-PECVD. SW48 colon cancer cells were passed over the surface of CNT covered electrodes to be specifically entrapped on elastic nanotube beams. CNT arrays act as both adhesive and conductive agents and impedance changes occurred as fast as 30 s (for whole entrapment and signaling processes). CNT-ECIS detected the cancer cells with the concentration as low as 4000 cells cm(-2) on its surface and a sensitivity of 1.7 × 10(-3)Ω cm(2). Time and cell efficiency factor (TEF and CEF) parameters were defined which describe the sensor's rapidness and resolution, respectively. TEF and CEF of CNT-ECIS were much higher than other cell based electrical biosensors which are compared in this paper.