SERS光谱技术在人体体液研究中的应用

SERS光谱技术具有高检测灵敏度和高特异性的优点,广泛应用于生物组织,细胞及生物分子的研究,表现出极大的应用潜力。本文首先介绍了拉曼及SERS光谱技术的原理,综述了SERS光谱技术在人体体液分析检测的研究概况,特别介绍了本课题组针对血液、精液、尿液开展的研究工作,最后简要讨论SERS光谱技术的发展前景。     

基于纳米信号标签的表面增强拉曼散射在病原菌检测中的应用

表面增强拉曼散射(surface-enhanced Raman scattering,SERS)技术由于其灵敏度高、检测速度快、高特异性和无损等优点,在病原菌检测领域受到了广泛的关注。主要总结了近年来基于纳米信号标签的SERS方法在检测病原菌领域中的研究进展,并介绍了多功能SERS检测平台的构建及在病原菌检测中的应用。最后,对SERS这一技术作为实时、高效和可靠的病原菌检测工具的未来发展进行了展望。     

胃癌血清的表面增强拉曼光谱研究

表面增强拉曼光谱技术在癌症诊断领域已经有了广泛的研究和应用,本文利用金纳米溶胶为增强基底,采用便携式近红外拉曼光谱系统,对89例胃癌患者及正常人血清样本进行了SERS光谱探测。结果表明,血清的特征峰主要归属于氨基酸,其次是核酸、糖类及脂类。相比于正常人血清SERS光谱,胃癌血清中归属于核酸的特征峰强度都较高,大部分归属于蛋白质的特征峰强度较低,与医学研究结论相符。说明SERS技术可以有效地反映胃癌患者和正常人血清的差异,为后期SERS技术快速诊断胃癌提供了实验基础。     

鼻咽癌细胞组织与血液的SERS光谱研究进展

基于表面增强拉曼光谱(SERS)技术对于人体细胞组织与血液的检测和研究,SERS光谱技术能够发现正常组织与病变组织的差异性,为医学临床上实现癌症的早期诊断提供了科学依据。由于鼻咽癌不具有明显的病变特征、病灶的位置难以通过常规医学手段检测。因此利用SERS光谱技术,应用于鼻咽癌细胞组织与血液的研究,可提高鼻咽癌患者的生存率。对鼻咽癌细胞组织与血液SERS光谱分析和诊断的探索研究,有助于SERS光谱技术发展成为一种在生物医学领域中的分析检测手段,在医学临床诊断上具有潜在的应用前景。     

疏水性SERS基底检测应用研究进展

本文简要介绍了表面增强拉曼散射(SERS)的拉曼信号增强原理,常规SERS增强基底的研究应用进展;同时介绍了疏水性基底的定义及优势,并重点综述了疏水性SERS基底的分类及研究应用的进展;最后展望了疏水性SERS基底的研究方向和发展趋势。疏水性SERS基底的发展将有望为今后开展面向超低浓度的生化物质检测以及基于人体体液的疾病的灵敏、客观检测诊断提供新方法和新思路。     

SERS标记方法在生化分析中的应用

表面增强拉曼散射(SERS)标记方法结合现代生物标记方法与SERS光谱技术,使吸附到金或银等贵金属表面的标记分子的拉曼信号显著增强,并将其作为标记示踪信号,具有生物兼容性好、灵敏度高、分子特征性强和快速简便等优点,已成为新颖的标记示踪技术的研究热点之一。本文综述近年来SERS标记技术应用于基因分析、蛋白质检测、微生物检测、肿瘤靶向和小分子物质的最新进展,着重介绍蛋白质和小分子物质的检测,并展望了今后的发展方向。     

单克隆抗体及其交联物在肿瘤诊治中的应用

B淋巴细胞杂交瘤技术问世以来在肿瘤领域中已有广泛的应用。各种抗肿瘤单克隆抗体(MoAb)已用于肿瘤的血清学检测、组织病理分型、定位诊断及导向治疗。血清学检测的主要意义在于监视病情、判定预后及预报复发,在早诊方而迄今尚无突出进展。     

表面增强拉曼光谱在DNA检测中的应用

随着光学技术的发展,表面增强拉曼光谱(SERS)作为一种新兴的技术被逐渐应用于生物医学领域。SERS波谱作为一种振动波谱,能够反应被测物质的内部信息,具有指纹识别特征;具备高灵敏度、高效能的特点,且能实现复合样本的同时测定;带标记的SERS技术能进一步提高SERS检测的特异性。目前SERS技术已被广泛用于体内外DNA、蛋白分子的检测,为生物分子的分析检测提供了一种崭新、高效的手段。     

表面增强拉曼光谱技术在外泌体检测中的研究进展

外泌体是一种含有蛋白质、核酸和脂质等物质的小囊泡,与细胞间通信和肿瘤微环境的调节有关,因而成为一种新兴的无创早期癌症诊断标志物.目前用于外泌体分析的技术较复杂,并且耗时久、成本高.近年来,表面增强拉曼光谱(SERS)技术由于其灵敏度高、样品制备简单、快速无损等优点,在生物医学领域表现出了巨大的应用潜力.本文首先简要介绍...     

细胞形态相关技术在血液系统肿瘤中的应用

细胞形态学检验是一门传统的血液病实验诊断技术,方便快捷,实用性强。细胞形态是病理诊断最直观的依据,但现行的普通光学显微镜镜检技术已不能完全满足血液肿瘤精准诊断的需求。如何开发研究或完善相关技术,最大发挥形态学的优势是值得探讨和研究的问题。系统阐述了细胞形态相关技术在血液系统肿瘤的早期诊断、疗效及预后评估及疾病复发等方面的应用研究进展,相信细胞形态相关技术必将为血液系统肿瘤的诊疗带来新的机遇。     

Parasitological aspects of Schistosoma haematobium (Iran) infection in the American opossum (Didelphis marsupialis L.)

Parasitological studies on 25 American opossums (Didelphis marsupialis) exposed to 1000 cercariae each of S. haematobium (Iran) have indicated a host-parasite situation and general parasitological conditions which show this marsupial to be a satisfactory host for experimental schistosomiasis. The return of schistosomes in relation to cercarial exposure was not excessively high, but there were egg deposits in the major visceral organs. Varied macroscopic pathology due to egg deposits in different organs was demonstrated as well as a potential for urinary bladder involvement, including tumor formation. Even though the precise nature of tumor pathology is not yet known, availability of the host, a good host-parasite compatability, and a low death rate in infected hosts favor this mammal as a model for experimental schistosomiasis haematobia.     

In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags

We describe biocompatible and nontoxic nanoparticles for in vivo tumor targeting and detection based on pegylated gold nanoparticles and surface-enhanced Raman scattering (SERS). Colloidal gold has been safely used to treat rheumatoid arthritis for 50 years, and has recently been found to amplify the efficiency of Raman scattering by 14-15 orders of magnitude. Here we show that large optical enhancements can be achieved under in vivo conditions for tumor detection in live animals. An important finding is that small-molecule Raman reporters such as organic dyes were not displaced but were stabilized by thiol-modified polyethylene glycols. These pegylated SERS nanoparticles were considerably brighter than semiconductor quantum dots with light emission in the near-infrared window. When conjugated to tumor-targeting ligands such as single-chain variable fragment (ScFv) antibodies, the conjugated nanoparticles were able to target tumor biomarkers such as epidermal growth factor receptors on human cancer cells and in xenograft tumor models.     

Single cell analysis using surface enhanced Raman scattering (SERS) tags

Fluorescence is a mainstay of bioanalytical methods, offering sensitive and quantitative reporting, often in multiplexed or multiparameter assays. Perhaps the best example of the latter is flow cytometry, where instruments equipped with multiple lasers and detectors allow measurement of 15 or more different fluorophores simultaneously, but increases beyond this number are limited by the relatively broad emission spectra. Surface enhanced Raman scattering (SERS) from metal nanoparticles can produce signal intensities that rival fluorescence, but with narrower spectral features that allow a greater degree of multiplexing. We are developing nanoparticle SERS tags as well as Raman flow cytometers for multiparameter single cell analysis of suspension or adherent cells. SERS tags are based on plasmonically active nanoparticles (gold nanorods) whose plasmon resonance can be tuned to give optimal SERS signals at a desired excitation wavelength. Raman resonant compounds are adsorbed on the nanoparticles to confer a unique spectral fingerprint on each SERS tag, which are then encapsulated in a polymer coating for conjugation to antibodies or other targeting molecules. Raman flow cytometry employs a high resolution spectral flow cytometer capable of measuring the complete SERS spectra, as well as conventional flow cytometry measurements, from thousands of individual cells per minute. Automated spectral unmixing algorithms extract the contributions of each SERS tag from each cell to generate high content, multiparameter single cell population data. SERS-based cytometry is a powerful complement to conventional fluorescence-based cytometry. The narrow spectral features of the SERS signal enables more distinct probes to be measured in a smaller region of the optical spectrum with a single laser and detector, allowing for higher levels of multiplexing and multiparameter analysis.     

Tapered Fiber Probe Modified by Ag Nanoparticles for SERS Detection

A tapered optical fiber fabricated by a simple chemical etching method and modified with Ag nanoparticles (AgNPs) by chemical deposition was evaluated for surface-enhanced Raman scattering (SERS). The fiber probe was used for SERS measurements in both direct and remote scattering modes, yielding desired performance in both scattering configurations. The state of the obtained AgNPs made a significant contribution to the high sensitivity of SERS to Rhodamine 6G (R6G) molecules (down to a concentration of 10^?7 M), and the substrate had an analyst enhancement factor (AEF) on the order of ～10⁸. Meanwhile, the SERS intensity during the evaporation process was investigated, showing a good stability at the later stage of the evaporation process. The fiber SERS probes demonstrated good reproducibility with the average relative standard deviation (RSD) values being less than 0.2 for the major Raman peaks.     

Single base extension reaction-based surface enhanced Raman spectroscopy for DNA methylation assay

DNA methylation is a key diagnostic maker for genetic disease, cancer progression and pharmcogenomics. So far various techniques have been developed for DNA methylation assay, but most of them are laborious and time-consuming. Here we develop a simple and highly sensitive DNA methylation assay based on single base extension reaction and surface enhanced Raman spectroscopy (SERS). In the presence of methylated DNA, gold nanoparticle-modified capture probe can couple with a cyanine 5-deoxyribonucleoside triphosphate (cy5-dGTP) through single base extension reaction, and generates a high SERS signal after further addition of gold nanoparticles to increase the local electromagnetic field. While in the presence of unmethylated DNA, gold nanoparticle-modified capture probe cannot couple with cy5-dGTP due to the presence of a mismatch base, and no SERS signal is observed. This single base extension reaction-based SERS can determine methylated DNA with a detection limit of 3 pM, and can even distinguish as low as 1% methylation level in tumor suppressor gene CDKN2/p16/MTS1 (p16) from the mixtures. Notably, the sensitivity of this assay has improved by 5 orders of magnitude as compared to reported gold nanoparticle-based colorimetric assay, and by 2 orders of magnitude as compared to microarray-based methylation-sensitive single nucleotide primer extension assay (Ms-SNuPE). This method might be further applied to detect the methylation status in tumor-linked genes for cancer diagnosis.     

Silver Nanoparticle Arrays on a DVD-Derived Template: An easy&cheap SERS Substrate

Commercially available digital versatile discs (DVDs) contain a silver-coated spiral distribution of rectangular-shaped grooves (AgDVD): for the first time, they have been used to produce surface-enhanced Raman scattering (SERS) substrates by electrochemical deposition of silver nanoparticles (AgNPs@AgDVD). The overall procedure only requires cheap and widely available materials and can be easily accomplished. Scanning electron microscopy images of AgNPs@AgDVD revealed that small AgNPs (average diameter about 15 nm) are present within the valleys of AgDVD, whereas over the ridges, the AgNPs are bigger, more densely packed and with a dendrite-like morphology somewhere. The SERS properties of these substrates have been studied in terms of the enhancement factor (EF), point-to-point reproducibility and sample-to-sample repeatability. It turned out that high SERS EF and good reproducibility requirements are both fulfilled. As for repeatability, remarkably better results than typical literature values have been achieved. Such an easy&cheap preparation along with efficient SERS properties make DVD-derived SERS substrates very good candidates for the development of convenient and disposable sensing platforms.     

Transgenic mice harboring SV40 t-antigen genes develop characteristic brain tumors

A high percentage of transgenic mice developing from eggs microinjected with plasmids containing the SV40 early region genes and a metallothionein fusion gene develop tumors within the choroid plexus. A line of mice has been established in which nearly every affected animal succumbs to this brain tumor. Thymic hypertrophy and kidney pathology are also observed in some mice. SV40 T-antigen mRNA and protein are readily detected in affected tissues; however, SV40 T-antigen gene expression is barely detectable in unaffected tissues or in susceptible tissues prior to overt pathology, suggesting that tumorigenesis depends upon activation of the SV40 genes. Comparison of DNA from tumor tissue (or cell lines derived from tumors) with DNA from unaffected tissues reveals structural rearrangements as well as changes in DNA methylation of the foreign DNA. The SV40 genes are frequently amplified in tumor tissue, which further indicates that their expression is intimately involved in tumorigenesis in transgenic mice.     

Surface-Enhanced Raman Scattering from Individual Au Nanoparticles on Au Films

We investigated the effect of optical thick metal films on the surface-enhanced Raman scattering (SERS) activity of individual Au nanoparticle (NP) monomers and dimers. The film presence is revealed to be positive for the SERS activity of individual NP monomers, while it is not always positive for the electromagnetic enhancement at hot spots for SERS of the dimer, which is explained well by our numerical simulations. The polarized SERS signals from the NP dimer are elucidated well in terms of the plasmon hybridization of the dimer. SERS contributions both from individual NP surfaces and the junction between the NP and its supporting substrate were discussed as well.     

Density functional theory and surface enhanced Raman spectroscopy characterization of novel platinum drugs

There is considerable interest in the development of novel platinum-based anticancer drugs that overcome the disadvantages associated with the widely used drug cisplatin, which are its inactivity against some types of tumors and its toxic side effects. In this study we show the suitability of normal Raman spectroscopy (NRS) and surface enhanced Raman spectroscopy (SERS), assisted by density functional theoretical (DFT) calculations, for the characterization of Pt complexes. The Pt complexes studied include the established drugs cisplatin and carboplatin, as well as five novel Pt complexes with anticancer activity. DFT calculations at the B3LYP/LanL2DZ level are a good prediction of the experimental NRS spectra of small and medium sized Pt complexes. The use of SERS allows the investigation of Pt complexes at physiological concentrations, and the binding strengths of the different ligands can be determined. The formation of positively charged hydrolysis products may be necessary for SERS activity. The exiting group in the hydrolysis reaction can be identified.