Reliable and non‐destructive Raman analysis to determine the urea concentration in a cream formulation

We present a reliable and nondestructive analytical method for the determination of urea concentration in a pharmaceutical cream formulation using Raman spectroscopy. A pharmaceutical cream is a highly viscous emulsion; therefore, its composition and physical mixing could be inhomogeneous on a microscopic scale. The local environment around the urea could vary, which could influence the molecular vibrations of the urea molecule. As expected, when Raman spectra were collected by focusing the laser onto a tiny area (∼2–3 µm), the position of the urea band at 1003 cm⁻¹ varied as a result of the microscopic inhomogeneity within the sample. Therefore, acquisition of Raman spectra representative of the entire sample rather than a localized portion of it is very important for the analysis of pharmaceutical creams. Based on the preliminary Raman mapping results of a urea cream, a sample area of at least 750 × 750 µm should be covered for reliable quantitative analysis. In this study, we used a wide‐area illumination scheme capable of covering a sample area of 28.3 mm² for Raman spectral collection in order to ensure a reliable representative sample. In addition, to simplify the measurements, Raman spectra of urea creams in plastic bottles were directly collected without further sampling, and partial least squares regression was used for quantitative analysis. The urea concentrations were accurately determined despite the spectral collection being performed through plastic bottles. Copyright © 2010 John Wiley & Sons, Ltd.     

Comparison of molecular images as defined by Raman spectra between normal mucosa and squamous cell carcinoma in the oral cavity

Raman spectroscopy has been effectively applied to clinically differentiate normal and cancerous mucosal tissues. Micro‐Raman spectroscopy provides a tool to better understand the molecular basis for the Raman clinical signal. The objective of the current study was to utilize micro‐Raman spectroscopy to define the molecular/spectral differences between normal and abnormal squamous cell carcinoma (SCC) in oral mucosa (in vitro). Understanding this may help in identifying unique spectra or may be useful for in vivo application of this technology. Micro‐Raman (confocal) spectroscopy was used to obtain molecular images of normal and SCC cells of human oral mucosa. Four fresh flashed‐frozen tumor and four matched normal tongue specimens were studied. The spectra covered a wavenumber range from 300 to 4000 cm⁻¹ with a spectral resolution of 8 cm⁻¹ and a spatial resolution of 1.0 µm. The cells were located within thin sections of tongue mucosa biopsies. The excitation wavelength of 515 nm was used. We were able to obtain Raman images with rich information about the spectroscopic and structural features within the cytoplasm, cell membrane, and cell nuclei. Significant spectral differences were observed between the Raman images of normal and malignant squamous cells. The heterogeneity of tumor cells within the abnormal tissue was also demonstrated. Spectral differences demonstrated between both tissue types have provided important information regarding the origins of specific signals within the cells of each tissue type. In our search for specific spectral biomarkers, we believe that a cell surface protein, greatly upregulated in SCC cells, was discovered at 1583 cm⁻¹. Copyright © 2010 John Wiley & Sons, Ltd.     

Proton µ‐PIXE mapping,AFM imaging and size statistics of mineral granules in a dental composite

We applied proton microbeam particle‐induced X‐ray emission (µ‐PIXE) for mapping Ca, Zr, Ba and Yb, and atomic force microscopy (AFM) for imaging the surface landscape of a dental composite which releases Ca²⁺ and F^? for the protection of hard dental tissues. Three areas ～250 × 250 µm² located ～0.5–2 mm apart on a smooth surface specimen were mapped with 3.1 MeV protons focused to a ～3.0 µm spot and at ～3.9 µm pixel size sampling. The maps evidenced particles with diameters of 3.2–32 µm (Ca), 20–60 µm (Zr), ≤ 4 µm (Ba) and 10–50 µm (Yb). Cross‐section area histograms of Ca‐rich particles fitted with 2–6 Poisson functions revealed a polydisperse size distribution and substantial differences from an area to another, possibly implying large local variations of Ca²⁺ released in the hard tissue near a dental filling of a few millimeters in diameter. Such imbalances may lead to low local Ca²⁺ protection of the dental tissue, favoring the onset of secondary caries. Similarly, AFM images showed high zone‐dependent differences in the distributions of grains with apparent diameters of 1–4 µm, plausibly recognized as Ca‐ and Ba‐containing particles. In a simple model based on demineralization data, lateral diffusion of Ca²⁺ between adjacent domains containing high‐ and low‐area Ca‐rich grains is described by exponential concentration gradients. These gradients may generate appreciable electromotive forces, which may enhance electrochemically the local tissue demineralization. Similar effects are to be expected in the protective action of F^? ions released from microgranules of YbF₃ and of Ba fluoroaluminosilicate glass. Copyright © 2010 John Wiley & Sons, Ltd.     

Raman spectroscopy and security applications: the detection of explosives and precursors on clothing

This study describes the application of confocal Raman microscopy to the detection and identification of explosives and their precursors in situ on undyed natural and synthetic fibres and coloured textile specimens. Raman spectra were obtained from explosives particles trapped between the fibres of the specimens. The explosives pentaerythritol tetranitrate (PETN), trinitrotoluene (TNT), and ammonium nitrate as well as the explosives precursors hexamethylenetetraamine (HMTA) and pentaerythritol were used in this study. Raman spectra were collected from explosives particles with maximum dimensions in the range 5–10 µm. Despite the presence of spectral bands arising from the natural and synthetic polymers and dyed textiles, the explosive substances could be identified by their characteristic Raman bands. Furthermore, Raman spectra were obtained from explosives particles trapped between highly fluorescent clothing fibres. Raman spectra of the explosive and explosive precursor substances on dyed and undyed clothing substrates were readily obtained in situ within 90 s without sample preparation and with no alteration of the evidential material. Copyright © 2009 John Wiley & Sons, Ltd.     

肺正常组织与癌变组织的表面增强拉曼光谱

采用共焦显微拉曼光谱进行肺正常组织与癌变组织的表面增强拉曼光谱测试,拉曼位移测试范围为300～1700cm-1 。根据得到的肺正常和癌变组织的表面增强拉曼光谱,对比分析了两者的特点与差异。选取蛋白质主链构象中构象不灵敏的CH₂弯曲振动在1454cm-1的谱线为内标,发现相比肺正常组织,癌变组织蛋白质主链中酰胺Ⅲ和酰胺Ⅰ谱带的有序构象明显减少,对α螺旋和无规则卷曲的损伤比较严重,β回折几乎消失,而骨架C—N,C—C伸缩振动却出现了与前2个谱带截然相反的状况,有序构象显著增加,蛋白质侧链构象变化与主链相比则相对复杂;DNA的骨架磷酸基团、脱氧核糖、磷酸-脱氧核糖和碱基的含量总体呈增加趋势;RNA的情况与DNA类似;磷脂的链内纵向有序性参数明显下降。     

On‐and off‐site Raman study of rock‐shelter paintings at world‐heritage site of Bhimbetka

Rock‐shelter paintings of Bhimbetka world‐heritage site near Bhopal, India have been investigated using a portable Raman spectrometer. These paintings in the rock shelters belong to periods starting from pre‐historic to the 19th century AD (Gond period). In addition, tiny fragments of pigments (100–200 µm in size) extracted from some of the artworks were also studied in laboratory using a micro‐Raman spectrometer and analyzed using energy‐dispersive X‐ray analysis for elemental composition. Based on the Raman spectra and the elemental analysis mineral‐based pigments such as calcite, gypsum, hematite, whewellite, and goethite could be identified. A comparison of the spectra recorded on‐site using a light‐weight portable spectrometer with those using laboratory equipment is also made and discussed. Copyright © 2012 John Wiley & Sons, Ltd.     

人体肿瘤组织的拉曼光谱相关系数成像

运用逐点扫描(Scanning)采谱技术,测量了人体乳腺肿瘤组织的阵列拉曼光谱集(Mapping);利用自编的软件,分析和计算了该谱集与参考谱DNA、细胞质等拉曼谱的相关系数;并将其映射为灰度值,构建了点阵的相关系数成像。结果表明,相关系数成像较好地反映了参考谱所代表的生化成分的分布;DNA谱与组织中其他成分谱的相关性很小,因此DNA谱的相关系数成像能够直接地反映成像区域DNA的分布,可信度尤其高。该研究结果为进一步研究乳腺肿瘤的拉曼诊断方法奠定了一定基础。     

High‐energy X‐ray diffraction using the Pixium 4700 flat‐panel detector

The Pixium 4700 detector represents a significant step forward in detector technology for high‐energy X‐ray diffraction. The detector design is based on digital flat‐panel technology, combining an amorphous Si panel with a CsI scintillator. The detector has a useful pixel array of 1910 × 2480 pixels with a pixel size of 154 µm × 154 µm, and thus it covers an effective area of 294 mm × 379 mm. Designed for medical imaging, the detector has good efficiency at high X‐ray energies. Furthermore, it is capable of acquiring sequences of images at 7.5 frames per second in full image mode, and up to 60 frames per second in binned region of interest modes. Here, the basic properties of this detector applied to high‐energy X‐ray diffraction are presented. Quantitative comparisons with a widespread high‐energy detector, the MAR345 image plate scanner, are shown. Other properties of the Pixium 4700 detector, including a narrow point‐spread function and distortion‐free image, allows for the acquisition of high‐quality diffraction data at high X‐ray energies. In addition, high frame rates and shutterless operation open new experimental possibilities. Also provided are the necessary data for the correction of images collected using the Pixium 4700 for diffraction purposes.     

Improvement of spatial resolution of µ‐XRF by using a thin metal filter

An improvement of spatial resolution of µ‐XRF by using a thin metal filter was investigated. The size of the x‐ray beam focused by the polycapillary x‐ray lens depended on the energy of the characteristic x‐rays. Original spot sizes at the focal point were 48 µm for CrKα, 41 µm for NiKα, and 28 µm for MoKα, respectively. To make the x‐ray beam size small, Ti? Cu thin foil was placed between the output of the lens and the focal point as a metal filter to reduce the continuous x‐rays. Finally, the x‐ray microbeam size was improved to 30 µm by applying a filter. Clear 2D mapping images of Cr, Fe, and Ni in 300‐mesh stainless steel could be obtained by applying this filter. Copyright © 2008 John Wiley & Sons, Ltd.     

Fast mapping of inhomogeneities in the popular metallic perovskite Nb:SrTiO3 by confocal Raman microscopy

Confocal Raman microscopy was applied in order to investigate the homogeneity of donor doping in Nb:SrTiO₃ single crystals. Measurements of local Raman spectra revealed a systematic relation between the intensity of the Raman signal and the donor content of the crystals. We successfully elaborated a correspondence between the electronic structure and the intensity of the Raman lines using a crystal with macroscopic inhomogeneity as a demonstration sample. By mapping the distribution of the intensity of the Raman signal, we identified a characteristic inhomogeneous structure related to the presence of clusters with sizes of 5 µm to 20 µm, indicating inhomogeneous donor distribution caused by flaws introduced during crystal growth. Hence, we propose confocal Raman microscopy as a convenient technique for investigating the homogeneity and quality of doped perovskite surfaces, which are needed for various technological applications. (© 2014 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)     

A comprehensive spectroscopic study of synthetic Fe2+, Fe3+, Mg2+ and Al3+ copiapite by Raman,XRD, LIBS,MIR and vis–NIR

The identification of iron sulfates on Mars by the Mars Exploration Rovers (MERs) and the Mars Reconnaissance Orbiter emphasized the importance of studying iron sulfates in laboratory simulation experiments. The copiapite group of minerals was suggested as one of the potential iron sulfates occurring on the surface and subsurface on Mars, so it is meaningful to study their spectroscopic features, especially the spectral changes caused by cation substitutions. Four copiapite samples with cation substitutions (Fe³⁺, Al³⁺, Fe²⁺, Mg²⁺) were synthesized in our laboratory. Their identities were confirmed by powder X‐ray diffraction (XRD). Spectroscopic characterizations by Raman, mid‐IR, vis‐NIR and laser‐induced‐breakdown spectroscopy (LIBS) were conducted on those synthetic copiapite samples, as these technologies are being (and will be) used in current (and future) missions to Mars. We have found a systematic ν₁peak shift in the Raman spectra of the copiapite samples with cation substitutions, a consistent atomic ratio detection by LIBS, a set of systematic XRD line shifts representing structural change caused by the cation substitutions and a weakening of selection rules in mid‐IR spectra caused by the low site symmetry of (SO₄)²⁻ in the copiapite structures. The near‐infrared (NIR) spectra of the trivalent copiapite species show two strong diagnostic water features near 1.4 and 1.9 µm, with two additional bands near 2.0 µm. In the vis‐NIR spectra, the position of an electronic band shifts from 0.85 µm for ferricopiapite to 0.866 µm for copiapite, and this shift suggests the appearance of a Fe²⁺ electronic transition band near 0.9 µm. Copyright © 2010 John Wiley & Sons, Ltd.     

人胚胎干细胞与急性早幼粒细胞白血病细胞的拉曼光谱特征研究

急性早幼粒细胞白血病(APL)属于急性髓系白血病(AML),是FAB分型中的M3亚型。部分APL患者形成早幼粒细胞白血病/维甲酸受体融合基因,即PML-RARα融合基因。在内外界多种因素的共同作用下,早幼粒细胞白血病发病。胚胎干细胞(ESCs)具有多向分化的能力,在一定诱导条件下, ESCs可以向造血系统分化。早幼粒细胞位于ESCs分化下游,为粒系分化阶段的一种细胞。探索一种非标记的技术方法鉴别不同分化阶段造血细胞具有重要的科研和实践意义。拉曼光谱技术可用于多种类型疾病的鉴别诊断研究,近年来应用前景愈加广阔。实验研究人胚胎干细胞系(ES)、急性早幼粒细胞白血病细胞系(NB4)和急性早幼粒细胞白血病患者(M3)白血病细胞的拉曼光谱特征,建立拉曼光谱非标记鉴别不同分化阶段白血病的方法,为临床实验研究提供基础。分别收集胚胎干细胞系(ES)、急性早幼粒细胞白血病细胞系(NB4)和4例M3患者白血病细胞,使用Horiba Xplora拉曼光谱仪获取拉曼光谱,每组或每例患者采集25~30个白血病细胞光谱。结合应用主成分分析法(PCA)、判别函数分析(DFA)、系统聚类分析和偏最小二乘判别分析(PLS-DA),对三类细胞的光谱进行分析并建立模型,进而对三类细胞进行鉴别,应用交互验证法对模型进行验证。同时结合细胞超微结构分析三种细胞的拉曼光谱特征。M3, NB4和ES细胞的拉曼光谱差别显著,主要表现为M3和NB4细胞光谱中对应核酸、蛋白质及脂类物质的谱峰明显高于ES细胞,其生物学机制包含了APL与PI3K/Akt/mTOR通路的密切关系。PI3K/Akt/mTOR通路在急性早幼粒细胞白血病细胞中存在异常激活,影响白血病细胞的生物大分子代谢;鉴别建模的总体分类准确率达100%(181/181),交互验证的分类准确率达98.9%(179/181),表明鉴别模型预测能力良好。拉曼光谱分析显示M3细胞和NB4细胞增殖代谢明显高于ES细胞,根据PCA-DFA、聚类分析及PLS-DA建立的拉曼光谱鉴别模型能够准确区分3种不同分化阶段白血病相关细胞,其结果与电镜结果相符。     

Monitoring of the growth of microcrystalline silicon by plasma‐enhanced chemical vapor deposition using in‐situ Raman spectroscopy

Raman spectra of microcrystalline silicon layers have been recorded in‐situ during growth. The spectra have been collected under realistic conditions for solar cell deposition. To enable these measurements an electrode with an optical feed through has been developed. By using a metallic grid to shield the feed through it is possible to achieve homogeneous deposition of µc‐Si:H at a sufficient optical transmission. In‐situ Raman measurements were carried out during the deposition of a layer with an intentionally introduced gradient in crystallinity that was seen in‐situ as well in reference measurements performed on the same layer ex‐situ. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

人乳腺癌组织阵列拉曼谱的模型成像研究

测量了人体乳腺管正常上皮组织及浸润性导管癌组织的阵列(Mapping)拉曼谱;利用作者前期建立的人体乳腺组织拉曼光谱模型,拟合了这些阵列谱,并将得到的归一化的拟合系数映射为灰度值,构建了乳腺组织的阵列拉曼谱模型成像。结果表明,这种模型成像具有较为明确的意义,尤其是细胞质、DNA、细胞间质基谱的拟合系数成像,较为清晰地呈现肌动蛋白、DNA及胶原的空间分布特征以及组织形态结构。与相关系数成像比较,模型成像给出了相似的结果。但模型成像对生化物质含量更敏感,成像分辨率更高。模型成像还显示癌变组织中细胞核明显增大、与细胞质相对比例明显增高,并为发展乳腺肿瘤拉曼诊断方法提供实验依据。     

The Fourier Raman spectra of HiPCO single-wall carbon nanotubes under high pressure

The Raman spectra of single-wall carbon semiconducting nanotubes of the HiPCO type were investigated upon excitation at 1.06 μm at pressures up to 3 GPa. A method of purification of the initial material from iron is proposed and the diffraction patterns of purified nanotubes are considered. The diameters and chiralities of the nanotubes manifesting themselves in the spectra are determined. Pressure dependences of the frequencies are obtained and the Gruneisen parameters and their relationship with interatomic interactions in nanotubes are discussed. Original Russian Text ? V.D. Blank, V.A. Ivdenko, A.S. Lobach, B.N. Mavrin, N.R. Serebryanaya, 2006, published in Optika i Spektroskopiya, 2006, Vol. 100, No. 2, pp. 282–289.     

Ultrasonication and hydrothermal assisted synthesis of cloud-like zinc molybdate nanospheres for enhanced detection of flutamide

Ultrasonication is one of the emerging probes for nanoparticles synthesis as well as promoting the material property by treasuring the precious time during a chemical reaction. In this present work, we successfully designed a cloud-like α-ZnMoO₄ nanospheres (ZMNS) using ultrasound assistance (bath sonication with the power of 60 W and frequency of 37/80 kHz) hydrothermal method for catalyzing the effective electrochemical determination of anti-androgen drug candidate flutamide (FLT). The crystallinity and phase purity were investigated using powder X-ray diffractometric analysis. The FTIR and Raman spectra information were compared to detect the possible bonding in ZMNS. The texture and surface morphology were studied using Field emission scanning electron microscope and High-resolution Transmission electron microscope images. The presence of the elements (Zn, Mo and O) and the absence of any other impurities were monitored and confirmed using EDAX analysis. The fabrication of ZMNS modified GCE was performed carefully. Additionally, the ZMNS modified glassy carbon electrode (GCE) exhibits superior electrocatalytic activity by means of higher cathodic peak current towards the detection of FLT. The fashioned electrode attained two wide linear response ranges (0.1 to 73 µM; 111 to 1026 µM) with a lower detection limit of about 33 nM correspondingly. Furthermore, the fabricated sensor displayed excellent sensitivity of 1.095 µA µM⁻¹ cm⁻² and good selectivity for FLT sensing even in the existence of similar interfering compounds and biomolecules. Along with that, the designed sensor executed noticeable reproducibility, repeatability, and enduring stability.     

Approximate chemical analysis of volcanic glasses using Raman spectroscopy

The effect of chemical composition on the Raman spectra of a series of natural calcalkaline silicate glasses has been quantified by performing electron microprobe analyses and obtaining Raman spectra on glassy filaments (~450 µm) derived from a magma mingling experiment. The results provide a robust compositionally‐dependent database for the Raman spectra of natural silicate glasses along the calcalkaline series. An empirical model based on both the acquired Raman spectra and an ideal mixing equation between calcalkaline basaltic and rhyolitic end‐members is constructed enabling the estimation of the chemical composition and degree of polymerization of silicate glasses using Raman spectra. The model is relatively insensitive to acquisition conditions and has been validated using the MPI‐DING geochemical standard glasses 1 as well as further samples. The methods and model developed here offer several advantages compared with other analytical and spectroscopic methods such as infrared spectroscopy, X‐ray fluorescence spectroscopy, electron and ion microprobe analyses, inasmuch as Raman spectroscopy can be performed with a high spatial resolution (1 µm²) without the need for any sample preparation as a nondestructive technique. This study represents an advance in efforts to provide the first database of Raman spectra for natural silicate glasses and yields a new approach for the treatment of Raman spectra, which allows us to extract approximate information about the chemical composition of natural silicate glasses using Raman spectroscopy. We anticipate its application in handheld in situ terrestrial field studies of silicate glasses under extreme conditions (e.g. extraterrestrial and submarine environments). © 2015 The Authors Journal of Raman Spectroscopy Published by John Wiley & Sons Ltd     

Comparison of connective tissue invaded by Lewis lung carcinoma to healthy connective tissue by means of micro‐Raman spectroscopy

We have measured the micro‐Raman spectra of mouse tissues invaded by Lewis lung carcinoma (LLC). We have also carried out categorical principal component analysis (CATPCA) on the acquired spectra. The results indicate that the tumor tissues can be well discriminated from normal tissues by the first two principal components extracted from the spectra. Furthermore, we have found that the concentrations of nucleic acids and lipids/fatty acids in the tumor are considerably higher than those in the normal tissue, whereas the collagen concentration is lower. These differences can be detected and characterized by Raman images using the 788 cm⁻¹ DNA/RNA band and the 1301 cm⁻¹ lipid/fatty acid band. Copyright © 2009 John Wiley & Sons, Ltd.     

The changing biochemical composition and organisation of the murine oocyte and early embryo as revealed by Raman spectroscopic mapping

Despite an exponential uptake in recent years of assisted reproductive techniques, such as in vitro fertilisation, much is still not fully understood about the biochemical modifications that take place during the development and maturation of the egg and embryo. As such, in order to improve the efficiency of these techniques, furthering our understanding of the processes that underpin oocyte and embryo development is necessary. Raman spectroscopic mapping as a technique enables the investigation of biochemical variation within intact cells without the need for labelling. Here, Raman maps of fixed immature and mature oocytes along with early stage embryos were collected using 785 nm excitation and a step size of 2 µm. The results were analysed using both univariate and multivariate techniques. It was found that significant macromolecular accumulation took place during oocyte maturation, while a decrease in total lipid content consistent with the formation of new cellular membranes is observed upon embryo cleavage. Furthermore, an observed asymmetrical localisation of macromolecules in the mature oocyte may indicate the existence of cytoplasmic polarisation, a phenomenon that has been observed in the eggs of lower organisms. As such, these results indicate that Raman spectroscopic mapping may present an alternative analytical tool for investigating the biochemistry of egg and embryo development. In particular, these results indicate that temporal Raman analysis may help to reveal the existence of cytoplasmic polarisation in the murine egg. Copyright © 2011 John Wiley & Sons, Ltd.     

扬子克拉通西部砂矿型金刚石的CL和FTIR光谱分析及在金刚石生长速率研究中的意义

鉴于当前人们在有效重建天然金刚石的生长过程等中所遇到的困难,如果能在微观层面上详细分析金刚石的生长过程,高度关注金刚石的生长速度,就可以为人们探讨金刚石的生长过程、分析其深部科学意义提供更为精准的科学线索。基于此,以扬子克拉通西部沅水流域砂矿型金刚石为研究对象,从微区研究的角度,采用CL光谱分析金刚石的生长环带,界定其生长微区;再利用FTIR光谱研究不同生长微区的生长时间;最后,利用生长微区的长度除以微区的生长时间,计算出不同微区的生长速度,进而分析其意义。样品的CL和FTIR光谱研究结果表明,该金刚石既发育早期生长环带,也发育后期再生长环带,其中早期生长环带为规则的平直带,环带总体呈阶梯状,大部分边缘呈不规则锯齿状;金刚石样品为IaAB型,氮总量介于47.88~321.89 μg·g-1,其最低结晶温度为1 490 K,不同部位在地幔中的停留时间不尽相同,且停留的时间最大介于0.264~4.6 Ga;金刚石样品不同生长环带之间的生长速率存在较大差异,介于9.26~5 218.18 μm·Ga-1。同时,样品的生长并不是各向均匀生长,而是具有一定优先取向。