中科院力学所建成纳米检测光学测试系统

“纳米检测光学测试系统”由光谱椭偏仪（Spec Ellipsometer）和近场光学显微镜（SNOM）组成,前者以相敏和光谱的优势为二维纳米材料、多层纳米介质和生物分子膜层的定量光谱分析提供了高灵敏和高精度的检测手段;后者的光探针提供了表征纳米尺度微观光学性质和无扰动探测柔性生物分子及其相互作用的能力,两者的有机结合提供了一种跨尺度光学检测平台。     

金属纳米结构的表面等离子体光学研究获得系列进展

金属纳米结构的表面等离子体光学在光催化、纳米集成光子学、光学传感、生物标记、医学成像、太阳能电池,以及表面增强拉曼光谱（SERS）等领域有广泛的应用前景,这些功能和金属纳米结构与光相互作用时产生的表面等离子体共振密切相关。最近,中科院物理研究所光物理实验室李志远研究组,     

荧光探针在细胞成像领域的研究进展

荧光成像技术是生物医学领域的重要研究手段,可对目标分子进行原位实时的监测,且这种方法具有无损伤、高特异性和高灵敏度,以及能在细胞水平获得更高的分辨率等优势。近年来,荧光材料在离子分子识别、医学诊断、生物分子检测以及生物成像等领域显示出了重要的应用价值,因此受到越来越多的化学和材料工作者的重视。综述了碳纳米材料、半导体量子点、稀土金属、有机荧光小分子、聚合物荧光纳米颗粒几种常见不同类型的荧光探针材料在细胞成像领域的应用,介绍了其发射波长、荧光量子产率、生物相容性、光稳定性、细胞毒性以及遗传毒性等特性。设计并合成发射波长较长、Stokes位移大、生物相容性好、光稳定性好、廉价的荧光探针将是荧光成像技术的主要研究方向。     

分子动力学模拟及其在表面工程中的应用现状

分子动力学模拟是一种通过经典力学建立分子体系模型,利用数值求解分子体系运动方程,对分子和分子体系结构与性质进行研究的计算机模拟方法。分子动力学作为一种应用非常广泛的分子模拟技术,在物理、化学、生物、材料、医学等各种牵涉到微观世界的学科中,都起到了非常重要的作用。目前,分子动力学已被应用于模拟表面工程中表面涂层的沉积过程及其性质、表面改性过程、薄膜应力状态以及表面裂纹的萌生与扩展等方面。综述了分子动力学模拟技术的发展,介绍了分子动力学的基本原理及算法、原子间势函数的选取以及边界条件的选取,并且综述了分子动力学模拟技术在表面工程中的应用及其进一步的研究方向。     

橡胶纳米复合材料计算机模拟研究进展与挑战

总结了作者课题组采用分子动力学模拟研究橡胶纳米复合材料目前取得的主要进展,包括不同几何形状的纳米颗粒在橡胶基体中的分散机理、颗粒与橡胶分子链间的界面结合(聚合物玻璃化层是否存在)、颗粒对应力应变增强机理、碳纳米弹簧的引入对橡胶粘弹性的调控以及橡胶纳米复合材料非线性行为(Payne效应)产生的机理。模拟结果表明,存在一个最佳界面相互作用与接枝密度以实现纳米颗粒均匀分散;对于片状颗粒,在类似氢键界面相互作用时,存在聚合物玻璃化层。静态力学增强来自于两个方面:一是颗粒诱导分子链取向与排列,二是分子链吸附临近颗粒形成桥链在大变形下的有限链伸长。同时发现,碳纳米弹簧的加入会明显降低复合材料的滞后损失,并且得出纳米颗粒直接接触聚集与由分子链同时吸附多个颗粒成网对Payne效应非线性行为均有贡献。这些基础问题的澄清,将为制备动静态力学性能兼顾的橡胶纳米复合材料提供重要科学依据与理论指导,进而实现我国轮胎制品的高性能化与绿色化。最后针对橡胶纳米复合材料多层次多尺度结构与性能关系,简要评述了计算机模拟研究存在的挑战。     

低对称性SiO2/Ag核壳复合纳米结构的银镜反应制备及表面增强拉曼散射活性研究

利用银镜反应在自组装的SiO2纳米粒子单层膜上制备了低对称性的SiO2/Ag核壳复合纳米结构.通过透射电镜(TEM)、扫描电镜(SEM)和紫外-可见分光光度计(UV-Vis)对核壳复合纳米结构的表面形貌和光学性质进行了表征.以亚甲基蓝作为探针分子,研究了低对称性SiO2/Ag核壳复合纳米结构的表面增强拉曼散射(SERS)活性.     

纳米金与生物分子的相互作用及生物传感检测

系统地分析了纳米金与生物分子的相互作用,并从光学比色分析、荧光分析、电化学检测、质量变化检测等几个方面入手,详细介绍了纳米金在DNA检测领域中的应用。     

N-异丙基丙烯酰胺类纳米水凝胶在生物识别中的研究进展

智能型纳米水凝胶是一种内部为三维网络结构且能稳定分散在水中形成胶体体系,粒径在1～1 000 nm,能感知外界环境刺激,并对其进行响应的新型高分子材料。其中具有温敏性的N-异丙基丙烯酰胺类纳米水凝胶是目前水凝胶研究的热点之一,它会随着外界温度的改变而发生体积相转变,凭借其良好的生物相容性和灵敏的温度响应性,在给药系统、蛋白质分离、医学诊断、生物传感器、生物材料等生物医学领域受到了广泛的关注。结合本课题组近年来的相关工作,主要综述了基于N-异丙基丙烯酰胺类纳米水凝胶微球在蛋白识别、药物输送与释放、DNA分离等生物识别中的应用研究和发展前景。     

掺杂型ZnS纳米晶的发光性质及其在生物检测方面的研究进展

主要围绕ZnS纳米晶的制备、掺杂和表面修饰剂所引起的光学性质以及生物分子检测等问题展开了一系列的讨论。由于纳米晶体表面晶面的定向生长,控制着纳米晶形貌的变化,因此综述了多种制备纳米晶的方法。系统总结了对纳米晶进行掺杂而引起了本征发射波长的变化,并对其进行表面修饰从而达到改变其荧光性质的目的。国内外研究表明,对纳米晶进行表面修饰,可以利用表面修饰制备出量子产率高,易于生物分子偶联的水溶性的掺杂型ZnS纳米晶,因此可在生物标记、示踪、检测等多个领域发挥重要的作用,为在生物医学领域中的应用奠定基础,最后展望了ZnS纳米晶未来的发展前景。     

纳米银SERS的应用研究进展

文章对表面增强拉曼散射效应进行了简要介绍,同时对近几年来国内对于纳米银表面增强拉曼散射在生物分子、染料、医学及分析检测等方面的应用研究进行了简要的概括和展望。     

Recent Advances in 2D Inorganic Nanomaterials for SERS Sensing

Surface‐enhanced Raman spectroscopy is a powerful and sensitive analytical tool that has found application in chemical and biomolecule analysis and environmental monitoring. Since its discovery in the early 1970s, a variety of materials ranging from noble metals to nanostructured materials have been employed as surface enhanced Raman scattering (SERS) substrates. In recent years, 2D inorganic materials have found wide use in the development of SERS‐based chemical sensors owing to their unique thickness dependent physico‐chemical properties with enhanced chemical‐based charge‐transfer processes. Here, recent advances in the application of various 2D inorganic nanomaterials, including graphene, boron nitride, semiconducting metal oxides, and transition metal chalcogenides, in chemical detection via SERS are presented. The background of the SERS concept, including its basic theory and sensing mechanism, along with the salient features of different nanomaterials used as substrates in SERS, extending from monometallic nanoparticles to nanometal oxides, is comprehensively discussed. The importance of 2D inorganic nanomaterials in SERS enhancement, along with their application toward chemical detection, is explained in detail with suitable examples and illustrations. In conclusion, some guidelines are presented for the development of this promising field in the future.     

Diverse bio-sensing and therapeutic applications of plasmon enhanced nanostructures

Substantial advancements have been observed over the years in the research and development of Localized Surface Plasmon Resonance (LSPR). A variety of current and future applications involving anisotropic plasmonic nanoparticles include biosensors, photothermal therapies, photocatalysis, and various other fields. Amongst various other applications, plasmonic enhancements are deployed in Surface Enhanced Raman Spectroscopy (SERS) mediated bio-sensing, absorption spectroscopy based analyte quantification, and fluorescence spectroscopy-based biomolecular detection up to femtomolar level and even on the level of single molecules. LSPR based healthcare diagnostics and therapeutics have grown much faster than expected, with an increased number of published original research articles and reviews. Despite the extensive literature available, a comprehensive review with a focused emphasis on recent advances in the field of plasmonic particle anisotropy, plasmonic nanostructure, plasmonic coupling mediated enhanced LSPR intensity and their diverse applications in biosensing is needed. This article focuses on LSPR properties of anisotropic nanostructures like spherical gold nanoparticles (AuNP), gold nanorod (AuNR), gold nanostar (AuNs), gold nanorattles (AuNRT), gold nanoholes (AuNH), dimeric nanostructures and their role in plasmonic enhancements for targeted biosensing and therapeutic research. The contemporary state of the art biosensing development around SERS has also been discussed. A detailed literature analysis of recent development in micro-surgery, photothermal tumor killing, biosensor development for detection up to single molecule level, high-efficiency drug delivery are covered in this article. Furthermore, recent and advanced technologies including Spatially Offset Raman Spectroscopy (SORS), Surface Enhanced Resonance Raman Spectroscopy (SERRS), and Surface Enhanced Spatially Offset Raman Spectroscopy (SESORS) are presented citing their importance in biosensing. We complement this review article with relevant theoretical frameworks to understand finer nuances within the literature that is discussed.     

Isotope edited internal standard method for quantitative surface-enhanced Raman spectroscopy

A new isotope edited internal standard (IEIS) method for quantitative surface-enhanced Raman spectroscopy (SERS) is demonstrated using rhodamine 6G (R6G-d0) and rhodamine 6G (R6G-d4) edited with deuterium. The reproducibility and accuracy of the IEIS method is investigated both under optical resonance (SERRS) and nonresonance (SERS) conditions. A batch-to-batch concentration measurement reproducibility of better than 3% is demonstrated over a concentration range of 200 pM-2 microM with up to a factor of 3 difference between the concentration of the analyte and its IEIS. The superior performance of the IEIS method is further illustrated by comparing results obtained using absolute SERS/SERRS intensity calibration (with no internal standard) or using adenine (rather than R6G-d4) as an internal standard for R6G concentration quantization. Potential biomedical gene expression and comparative proteomic applications of the IEIS method are discussed.     

Split‐GFP: SERS Enhancers in Plasmonic Nanocluster Probes

The assembly of plasmonic metal nanoparticles into hot spot surface‐enhanced Raman scattering (SERS) nanocluster probes is a powerful, yet challenging approach for ultrasensitive biosensing. Scaffolding strategies based on self‐complementary peptides and proteins are of increasing interest for these assemblies, but the electronic and the photonic properties of such hybrid nanoclusters remain difficult to predict and optimize. Here, split‐green fluorescence protein (sGFP) fragments are used as molecular glue and the GFP chromophore is used as a Raman reporter to assemble a variety of gold nanoparticle (AuNP) clusters and explore their plasmonic properties by numerical modeling. It is shown that GFP seeding of plasmonic nanogaps in AuNP/GFP hybrid nanoclusters increases near‐field dipolar couplings between AuNPs and provides SERS enhancement factors above 10⁸. Among the different nanoclusters studied, AuNP/GFP chains allow near‐infrared SERS detection of the GFP chromophore imidazolinone/exocyclic C?C vibrational mode with theoretical enhancement factors of 10⁸–10⁹. For larger AuNP/GFP assemblies, the presence of non‐GFP seeded nanogaps between tightly packed nanoparticles reduces near‐field enhancements at Raman active hot spots, indicating that excessive clustering can decrease SERS amplifications. This study provides rationales to optimize the controlled assembly of hot spot SERS nanoprobes for remote biosensing using Raman reporters that act as molecular glue between plasmonic nanoparticles.     

Nanostructured Ag platforms as biosensors of nucleobase chains

Nanostructured Ag platforms have been obtained by simple chemical procedure and characterized by AFM (atomic force microscopy) measurements, for use in biosensing by means of SERS (surface-enhanced Raman scattering) spectroscopy. The SERS efficiency of these substrates has been verified by microRaman measurements on small RNA chains with different nucleobase content, showing sensitivity near attomole level. It is our opinion that these metal substrates may be widely used as appropriate sensors for detecting biomolecules in many applications concerning medical diagnostics, pharmacological research and nanomaterials technology.     

Single-molecule detection using surface-enhanced resonance Raman scattering and Langmuir-Blodgett monolayers

The Langmuir-Blodgett (LB) technique has been used to obtain spatially resolved surface-enhanced resonance Raman scattering (SERRS) spectra of single dye molecules dispersed in the matrix of a fatty acid. The experimental results presented here mimic the original electrochemical surface-enhanced Raman scattering (SERS) work where the background bulk water did not interfere with the detection of the SERS signal of molecules adsorbed onto the rough silver electrode. LB monolayers of the dye in fatty acid have been fabricated on silver island films with a concentration, in average, of one probe molecule per micrometer square. The properties of single-molecule spectroscopy were investigated using micro-Raman including mapping and global images. Blinking of the SERRS signal was also observed.     

Sensitive carbohydrate detection using surface enhanced Raman tagging

Glycomic analysis is an increasingly important field in biological and biomedical research as glycosylation is one of the most important protein post-translational modifications. We have developed a new technique to detect carbohydrates using surface enhanced Raman spectroscopy (SERS) by designing and applying a Rhodamine B derivative as the SERS tag. Using a reductive amination reaction, the Rhodamine-based tag (RT) was successfully conjugated to three model carbohydrates (glucose, lactose, and glucuronic acid). SERS detection limits obtained with a 633 nm HeNe laser were ～1 nM in concentration for all the RT-carbohydrate conjugates and ～10 fmol in total sample consumption. The dynamic range of the SERS method is about 4 orders of magnitude, spanning from 1 nM to 5 μM. Ratiometric SERS quantification using isotope-substituted SERS internal references allows comparative quantifications of carbohydrates labeled with RT and deuterium/hydrogen substituted RT tags, respectively. In addition to enhancing the SERS detection of the tagged carbohydrates, the Rhodamine tagging facilitates fluorescence and mass spectrometric detection of carbohydrates. Current fluorescence sensitivity of RT-carbohydrates is ～3 nM in concentration while the mass spectrometry (MS) sensitivity is about 1 fmol, achieved with a linear ion trap electrospray ionization (ESI)-MS instrument. Potential applications that take advantage of the high SERS, fluorescence, and MS sensitivity of this SERS tagging strategy are discussed for practical glycomic analysis where carbohydrates may be quantified with a fluorescence and SERS technique and then identified with ESI-MS techniques.     

Plasmon‐Driven Selective Reductions Revealed by Tip‐Enhanced Raman Spectroscopy

We successfully realized in‐situ monitoring plasmon‐driven selective reduction of 2,4‐dinitrobenzenethiol to 2,2′‐diamino‐dimercaptoazobenzene, revealed by high vacuum tip‐enhanced Raman spectroscopy (HV‐TERS). The HV‐TER spectra revealed that the 2‐nitro and the 4‐nitro of 2,4‐DNBT were selectively reduced to the 2‐amine and the –N = N– bond of 2,2′‐diamino‐dimercaptoazobenzene (2,2′DA‐DMAB). Raman‐active and IR‐active modes as well as Fermi resonance were simultaneously observed in HV‐TERS, which demonstrated the advantages of HV‐TERS over SERS, since only Raman‐active modes were observed in SERS. The intensities of molecular IR‐active modes can be manipulated by the distance between tip and substrate in the near field, due to different dependences of the plasmon gradient and plasmon intensity over the distance of nano gap. Our results in HV‐TERS are in‐situ “complete‐vibration modes” spectral analysis, which significantly extend the application of HV‐TERS in the field of ultrasensitive spectral analysis on the nano scale.     

Quantitative characterization of individual microdroplets using surface-enhanced resonance Raman scattering spectroscopy

Surface-enhanced resonance Raman scattering (SERRS) spectroscopy is a highly sensitive optical technique capable of detecting multiple analytes rapidly and simultaneously. There is significant interest in SERRS detection in micro- and nanotechnologies, as it can be used to detect extremely low analyte concentrations in small volumes of fluids, particularly in microfluidic systems. There is also rapidly growing interest in the field of microdroplets, which promises to offer the analyst many potential advantages over existing technologies for both design and control of microfluidic assays. While there have been rapid advances in both fields in recent years, the literature on SERRS-based detection of individual microdroplets remains lacking. In this paper, we demonstrate the ability to quantitatively detect multiple variable analyte concentrations from within individual microdroplets in real time using SERRS spectroscopy. We also demonstrate the use of a programmable pump control algorithm to generate concentration gradients across a chain of droplets.     

Composite‐Scattering Plasmonic Nanoprobes for Label‐Free,Quantitative Biomolecular Sensing

Biosensing based on localized surface plasmon resonance (LSPR) relies on concentrating light to a nanometeric spot and leads to a highly enhanced electromagnetic field near the metal nanostructure. Here, a design of plasmonic nanostructures based on rationally structured metal–dielectric combinations is presented, called composite scattering probes (CSPs), to generate an integrated multimodal biosensing platform featuring LSPR and surface‐enhanced Raman spectroscopy (SERS). Specifically, CSP configurations are proposed, which have several prominent resonance peaks enabling higher tunability and sensitivity for self‐referenced multiplexed analyte sensing. Using electron‐beam evaporation and thermal dewetting, large‐area, uniform, and tunable CSPs are fabricated, which are suitable for label‐free LSPR and SERS measurements. The CSP prototypes are used to demonstrate refractive index sensing and molecular analysis using albumin as a model analyte. By using partial least squares on recorded absorption profiles, differentiation of subtle changes in refractive index (as low as 0.001) in the CSP milieu is demonstrated. Additionally, CSPs facilitate complementary untargeted plasmon‐enhanced Raman measurements from the sample's compositional contributors. With further refinement, it is envisioned that the method may lead to a sensitive, versatile, and tunable platform for quantitative concentration determination and molecular fingerprinting, particularly where limited a priori information of the sample is available.