The use of Raman spectroscopy to differentiate between different prostatic adenocarcinoma cell lines

Raman spectroscopy (RS) is an optical technique that provides an objective method of pathological diagnosis based on the molecular composition of tissue. Studies have shown that the technique can accurately identify and grade prostatic adenocarcinoma (CaP) in vitro. This study aimed to determine whether RS was able to differentiate between CaP cell lines of varying degrees of biological aggressiveness. Raman spectra were measured from two well-differentiated, androgen-sensitive cell lines (LNCaP and PCa 2b) and two poorly differentiated, androgen-insensitive cell lines (DU145 and PC 3). Principal component analysis was used to study the molecular differences that exist between cell lines and, in conjunction with linear discriminant analysis, was applied to 200 spectra to construct a diagnostic algorithm capable of differentiating between the different cell lines. The algorithm was able to identify the cell line of each individual cell with an overall sensitivity of 98% and a specificity of 99%. The results further demonstrate the ability of RS to differentiate between CaP samples of varying biological aggressiveness. RS shows promise for application in the diagnosis and grading of CaP in clinical practise as well as providing molecular information on CaP samples in a research setting.     

Evaluation of the Microcrystallinity of a Drug Substance,Indomethacin, in a Pharmaceutical Model Tablet by Chemometric FT-Raman Spectroscopy

Purpose To establish a chemometric method for the precise evaluation of the microcrystallinity of indomethacin (IMC) in a pharmaceutical model tablet, based on FT-Raman spectroscopy.Methods Standard sample powders of homogeneous mixtures of amorphous and crystalline IMC were prepared in various proportions. A calibration model for the crystallinity of IMC was constructed by partial least-square (PLS) analysis based on the multiplicative scatter correction (MSC) + second-derivative transformed Raman spectra. A calibration model for the crystallinity of IMC in a model pharmaceutical product (IMC/mannitol = 1:9 wt/wt) was also constructed using homogeneous standard sample powders of various degrees of crystallinity of IMC.Results This technique was validated to detect to 2% an amorphous or crystalline material in IMC contained in the model product (0.2% of the total mass of the tablet). Using this technique, not only pressure-induced amorphization but also the difference in microcrystallinity of IMC at the surface and interior of a model product tablet was elucidated after compaction of the tablet.Conclusions The established technique is ideally suited for precise quantification of microanalysis of drug substances and drug products, particularly at the surface and interior of the tablet.     

A Spectroscopic Investigation of Losartan Polymorphs

Losartan, an antihypertensive agent in clinical development, was found to exist in two enantiotropic polymorphic forms, a low-temperature stable form (Form I) and a high-temperature stable form (Form II), the temperatures at which they are stable being related to the transition temperature. X-ray powder diffraction patterns indicated differences in the crystal packing of the two forms. The vibrational data from infrared and Raman spectroscopy suggested a subtle change in molecular conformation and crystal packing in the two forms. Solid-state ¹³C NMR data of the polymorphs concurred with the vibrational data and indicated that, while the observed line widths reflect no major changes in crystallinity, signal multiplicities and chemical shifts do reflect differences in molecular packing in the respective unit cells. Thus, in the absence of crystal-lographic data, useful structural information could be derived from spectroscopic results to identify each of the crystalline forms.     

Carbonate in Struvite Stone Detected in Raman Spectra Compared with Infrared Spectra and X-Ray Diffraction

Background : In regard to identify the compositions of urinary stones, the infrared spectra is a contemporary routine method. However, it is difficult to detect the absorption of carbonate in struvite stone by infrared spectra, because NH₄ absorption of magnesium ammonium phosphate overlaps CO₃ absorption of carbonate at 1420–1435 cm^?1. With the purpose of demonstrating the existence of carbonate in struvite stones, the analysis of these stones by means of Raman spectra has been tried. Methods : Forty urinary stones, the chemical compositions of which were previously determined by infrared spectroscopy, were submitted to Raman spectrum analysis, and subsequently to analysis by x-ray diffraction. Results : Thirty of 40 urinary stones were found to be composed of struvite and of mixed struvite-calcium oxalate by infrared analysis. Twelve of these stones were shown to have Raman spectra of magnesium ammonium phosphate, and the other stones to have spectra of apatite. By x-ray diffraction magnesium ammonium phosphate crystals were detected in 25 of these struvite stones and hydroxyl-apatite in another 3, and 2 cases were undeterminable. For other components, such as calcium oxalate, uric acid and cystine, the analytical results of infrared spectra coincided with those of Raman spectra and x-ray diffraction. Carbonate was detected in only a part of one struvite stone by Raman spectra. Conclusions : Above-mentioned results may indicate that carbonate is only a minor component of urinary stones. Therefore, most of 1420–1435 cm^?1bands on the infrared spectra of struvite stones do not indicate CO₃ absorption of carbonate, but NH₄ absorption of magnesium ammonium phosphate.     

Analysis of near-infrared Raman spectroscopy as a new technique for a transcutaneous non-invasive diagnosis of blood components

. Near-infrared Raman spectroscopy can be a new technique for physical evaluations, allowing the measurement of lactic acid concentrations, in blood or muscles, during the physical activity in a transcutaneous non-invasive way. Lactic acid accumulation in the human body is one of the factors that leads to fatigue and therefore it should be continually monitored during physical training. Our proposal is to use Raman spectroscopy to monitor the lactic acid present in an athlete without interrupting his exercise for sample collection. The experimental set-up for Raman spectroscopy comprised a near infrared laser at 830 nm, a Kaiser f/1.8 spectrometer and a liquid nitrogen cooled CCD detector. The radiation from the exciting laser is blocked in the collecting system by Kaiser holographic filters. A personal computer controls the entire system, saving and processing the Raman spectra. Experiments were undertaken to verify the presence of lactic acid in the Raman spectra of solutions of lactic acid in human serum and in blood from a Wistar rat. After these two experiments, another was developed in vivo in a Wistar rat, injecting intraperitoneally 1 ml of a 0.12 mol/l lactic acid aqueous solution. An optical fibre catheter touching the skin of the rat groin, over the ileac vein collected the Raman signal. The presence of lactic acid was detected inside a live organism, in a transcutaneous non-invasive way. The minimum lactic acid concentration that the equipment can detect was also studied. An experiment was undertaken for that purpose, in which the laser illuminated directly a quartz cuvette containing solutions with decreasing lactic acid concentrations up to values near to the physiological level in the human body. The results indicated that the technique can be suitable for the physical evaluation of athletes. Paper received 12 May 2000; accepted after revision 29 June 2000.     

基于表面增强拉曼检测技术的唾液检测研究

拉曼光谱可以表征化学物质的分子结构特性,表面增强拉曼检测方法采用纳米技术使原有的光谱强度提高了(4~10)个数量级,在痕量化学物质快速检测方面显示出巨大的潜力。本文介绍了表面增强拉曼检测技术所用的设备和检测方法,并报告了将表面增强拉曼光谱检测技术应用于吸毒者的鉴别,检测了29例吸毒者的唾液,与健康人的样本进行了对比分析,发现吸毒者唾液的拉曼光谱在1030cm-1具有明显的特异性。     

PS/MWNT复合材料界面上的化学反应性

利用悬浮聚合法制备了可溶于甲苯的聚苯乙烯／多壁碳纳米管（PS／MWNT）复合材料，通过透射电镜观察到MWNT完全或部分被PS包裹。拉曼光谱分析表明，复合材料中MWNT的两个特征峰D峰和G峰的位置均发生了红移，且D峰的强度及ID／IG值也较MWNT明显增大。凝胶渗透色谱测得复合材料的分子量相对于纯PS的分子量有较大幅度提高。同时比较共混法与悬浮聚合法制得的复合材料在甲苯中的溶解性。可以认为悬浮聚合法制备复合材料的过程中，MWNT参与了PS的聚合反应，与PS形成了化学键从而完全或部分地被PS包裹。     

PAT tools for the control of co-extrusion implants manufacturing process

Hot melt extrusion is a novel pharmaceutical manufacturing process technique. In this study, we identified four Critical Quality Attributes (CQAs) of the implant manufacturing process by hot melt extrusion: the implant diameter, the quantity of the Active Pharmaceutical Ingredient (API), the homogeneity distribution of API and the thickness of the membrane. We controlled the implant diameter and the quantity of API in-line with a laser measurement, NIR and Raman spectroscopy, respectively. These two different spectroscopic techniques provided comparable results. In fact, the RMSEC and RMSECV were very close in each PAT technique but NIR spectroscopy was easier to use and less sensitive to external changes. For the control of the homogeneity of API distribution and the thickness of the membrane, we used successfully Raman spectroscopy imaging. These PAT tools help reducing analysis time.     

Carbon nanotubes as optical biomedical sensors

Biosensors are important tools in biomedical research. Moreover, they are becoming an essential part of modern healthcare. In the future, biosensor development will become even more crucial due to the demand for personalized-medicine, point-of care devices and cheaper diagnostic tools. Substantial advances in sensor technology are often fueled by the advent of new materials. Therefore, nanomaterials have motivated a large body of research and such materials have been implemented into biosensor devices. Among these new materials carbon nanotubes (CNTs) are especially promising building blocks for biosensors due to their unique electronic and optical properties. Carbon nanotubes are rolled-up cylinders of carbon monolayers (graphene). They can be chemically modified in such a way that biologically relevant molecules can be detected with high sensitivity and selectivity. In this review article we will discuss how carbon nanotubes can be used to create biosensors. We review the latest advancements of optical carbon nanotube based biosensors with a special focus on near-infrared (NIR)-fluorescence, Raman-scattering and fluorescence quenching.