Extraction of hidden information of ToF‐SIMS data using different multivariate analyses

Time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) is a powerful tool for determining surface information of complex systems such as polymers and biological materials. However, the interpretation of ToF‐SIMS raw data is often difficult. Multivariate analysis has become effective methods for the interpretation of ToF‐SIMS data. Some of multivariate analysis methods such as principal component analysis and multivariate curve resolution are useful for simplifying ToF‐SIMS data consisting of many components to that explained by a smaller number of components. In this study, the ToF‐SIMS data of four layers of three polymers was analyzed using these analysis methods. The information acquired by using each method was compared in terms of the spatial distribution of the polymers and identification. Moreover, in order to investigate the influence of surface contamination, the ToF‐SIMS data before and after Ar cluster ion beam sputtering was compared. As a result, materials in the sample of multiple components, including unknown contaminants, were distinguished. Copyright © 2014 John Wiley & Sons, Ltd.     

表面残留有机沾污物的TOF－SIMS及XPS研究

飞行时间次级离子质谱（ＴＯＦ－ＳＩＭＳ）结合Ｘ射线光电子能谱（ＸＰＳ）分析了用化学方法清洗后、银片上残留的未知的有机物。结果显示，有机沾污物主要是一些含１８～３０碳原子、碳链饱和度很高的酮类和酯类化合物；个别有机物可能是硬脂酰胺。这种结构特点使有机物中的Ｃ＝Ｏ基团易于采取氧原子指向基体表面的取向，通过带部分负电荷的氧原子与金属基体镜像力的作用而增强粘附。ＴＯＦ－ＳＩＭＳ二维离子像显示有机沾污物在银片表面上呈极稀薄的均匀分布。     

Olfactory Stimulation Successfully Modulates the Neurochemical,Biochemical and Behavioral Phenotypes of the Visceral Pain

Visceral pain (VP) is the organ-derived nociception in which increased inflammatory reaction and exaggerated activation of the central nucleus of the amygdala (CeA) may contribute to this deficiency. Considering the amygdala also serves as the integration center for olfaction, the present study aimed to determine whether olfactory stimulation (OS) would effectively depress over-activation and inflammatory reaction in CeA, and successfully relieve VP-induced abnormalities. Adult rats subjected to intraperitoneal injection of acetic acid inhaled lavender essential oil for 2 or 4 h. The potential benefits of OS were determined by measuring the pro-inflammatory cytokine level, intracellular potassium and the upstream small-conductance calcium-activated potassium (SK) channel expression, together with detecting the stress transmitters that participated in the modulation of CeA activity. Results indicated that in VP rats, strong potassium intensity, reduced SK channel protein level, and increased corticotropin-releasing factor, c-fos, and substance P immuno-reactivities were detected in CeA. Enhanced CeA activation corresponded well with increased inflammatory reaction and decreased locomotion, respectively. However, in rats subjected to VP and received OS, all above parameters were significantly returned to normal levels with higher change detected in treating OS of 4h. As OS successfully depresses inflammation and CeA over-activation, application of OS may serve as an alternative and effective strategy to efficiently relieve VP-induced deficiency.     

Inverse velocities of sputtered monatomic ions: Systematics and quantification

The emission of secondary ions of about fifteen different elements, sputtered from Ti-base metal specimens, has been studied by SIMS. Both positive and negative ion yields have been measured at different exit energies up to ca 350 eV. It is found that when the logarithm of ionizability is plotted versus the inverse of the exit velocity, each element suggests a straight line behavior at energies above ca 20 eV. The gradient of the straight line is related to the respective 1st ionization potential (for positive ions) or electron affinity (negative ions). This behavior gives considerable support to the premises of modern theory of ionization in sputtering. Furthermore, the straight line plots for different elements are seen to converge as exit velocity increases; the intercepts at zero inverse velocity are found to be proportional to the respective element concentrations. This in principle offers a means of quantification in elemental analysis by SIMS, a method that does not require any external standards. The usefulness of the new method is demonstrated for ten elements sputtered from two specified titanium-base alloy standards from NIST.Dedicated to Professor Dr. rer. nat. Dr. h.c. Hubertus Nickel on the occasion of his 65th birthday     

A pseudotargeted method based on sequential window acquisition of all theoretical spectra mass spectrometry acquisition and its application in quality assessment of traditional Chinese medicine preparation-Yuanhu Zhitong tablet

Quality control plays a key role in the application of Chinese materia medica, especially in the preparation of traditional Chinese medicine. A pseudotargeted analysis method using an ultra-high-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry that was operated in the sequential window acquisition of all theoretical spectra mode was proposed to explore the chemical markers of traditional Chinese medicine preparation. Full-scan-based untargeted analysis was applied to extract the target ions. After data preprocessing, 302 target ions were extracted and used for the subsequent sequential window acquisition of all theoretical spectra analyses. The established sequential window acquisition of all theoretical spectra-based pseudotargeted approaches exhibited good repeatability and a wide linear range. The established method was successfully applied to discover analytical markers for the Yuanhu Zhitong tablet. After multivariate statistical analysis, 94 potential markers were identified. Ten markers were annotated by matching accurate m/z and product ion information obtained from previous reports. It is clearly indicated that the pseudotargeted analysis could make a great contribution to the quality assessment of traditional Chinese medicine preparation as a newly emerging technique.     

Hidden information in principal component analysis of ToF‐SIMS data: On the use of correlation loadings for the identification of significant signals and structure elucidation

In this paper, an improved approach to interpret results of principal component analysis (PCA) of time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) spectra is presented. Signals are typically observed in different intensity ranges in a single ToF‐SIMS spectrum due to different sensitivity factors and surface concentrations. This can complicate the PCA interpretation, because loadings are reported to be strongly affected by these intensity changes. In contrast, it is shown here that correlation loadings are unaffected by these differences. In particular, correlation loadings were successfully used to identify signals with relatively low intensity but high significance. These signals may be overlooked when only loadings are used. This is particularly true in failure analysis, where ToF‐SIMS is used to screen for initially unknown signals that may be relevant for the characteristics/failure of a product. As a model study, the concept was applied to investigate ageing of Li‐ion batteries by ToF‐SIMS. In this data set, the significance of impurities that affect the quality of Li‐ion batteries was identified only by correlation loadings, whereas the loadings were found to overestimate the influence of other matrix signals. In addition, correlation loadings aid in the chemical identification and helped to successfully assign unknown peaks.     

Three dimensional ultra trace analysis of materials

We have developed a new imaging system for secondary ion mass spectrometry, including a new interface to control all functional units of the CAMECA IMS 3f instrument, especially the high voltage channel plate. Use of a 386 PC (HP Vectra RS-25) made a new 20-bit magnetic field control, a new counting board with higher dynamic range and a new sample position unit possible. A double channel plate enables us to detect single ions with a sensitive CCD camera.An Imaging Technology 151 image processor digitizes and accumulates camera data. During summation the image processor detects the brightest and darkest pixel in the channel plate picture, thus channel plate high voltage may be dynamically controlled according to the intensity of the secondary ion signal. This results in fully automatic measurement of unknown samples with large variations in the lateral and depth concentration of elements. A dynamic range for measurement of secondary ion intensities of 10⁸ can be achieved.Software written in C controls the image processor, the channel plate high voltage and all other parts of the instrument, and has a user friendly interactive interface. To visualise multidimensional data (three dimensional distribution of more than one element) a software package was written which allows to correlate elemental distributions.     

Classification of secondary ion mass spectrometry (SIMS) micrographs to characterize chemical phases

This work demonstrates the potential of multivariate image analysis methods in the extraction of useful, problem dependent information from SIMS images. Specific algorithms have been developed to classify SIMS micrographs manually as well as automatically. A feature selection has been achieved by means of principal component analysis with a subsequent image classification.As an application example for these improved digital image processing tools chemical phases within a soldered industrial metal sample have been identified. This is of highly practical value as it was assumed that during the soldering process inhomogeneities occur along the joint site which cause a cracking of the brazed material under mechanical strain conditions.     

Probing the surface chemical structure of some novel poly(ortho esters) prepared with N-methyl and N-phenyl ethanolamine by time-of-flight secondary ion mass spectrometry (ToF-SIMS)

The surface chemical structures of a series of novel poly(ortho ester) homopolymer and copolymer films prepared using N-methyl- and N-phenyl-ethanolamine (MDE and PDE) have been investigated using time-of-flight secondary ion mass spectrometry (ToF-SIMS). Systematic fragmentation patterns were observed within the ToF-SIMS spectra up to m/z = 1600, which were readily interpreted in terms of the polymer structures. Cations were detected which could be assigned to structures arising from the diols, the ortho ester species and diads, triads etc. of the monomer, from both the homopolymer and the random portion of the copolymer chains. The analysis of the proposed ion structures suggested two major mechanisms of fragmentation based on the cleavage of the ortho ester bonds involving either the exocyclic or the endocyclic alkoxy group. The Tof-SIMS peak area ratios for ions diagnostic of the diols and the ortho ester species reflected the bulk copolymer composition in a semi-quantitative fashion. The observation of such relationships for high mass cations (up to m/z = 500) is particularly noteworthy and has not been reported previously. These studies allow a dramatic insight into the surface chemical structure of these poly(ortho esters), information which has formed the foundation of current investigations on the mechanisms of the acid-catalysed surface degradation of these polymers.     

Real-Time Distinguishing of the Xylene Isomers Using Photoionization and Dissociation Mass Spectra Obtained by Femtosecond Laser Mass Spectrometry (FLMS)

Abstract

Distinguishing chemicals and improvement on analytical methods has a direct impact on modern chemical analysis. In this work, the dissociative ionization of xylene isomers was investigated using a femtosecond laser mass spectrometry (FLMS) method with a custom-built linear time-of-flight (TOF) instrument. Laser beams at 800?nm and 400?nm were used and intensity-dependent analysis of the obtained mass spectra was performed using principal component analysis (PCA) to distinguish the xylene isomers, which give identical mass spectra in appearance that cannot be distinguished using normal mass spectrometry methods. The results show that there is a statistically highly significant difference between the xylene isomers for two principal components (1 ? α?>?99.99%) and minimal information loss (<5%) took place during the PCA procedure. Also, the use of the k-medoid clustering method showed that the isomers may be distinguished in real-time for a wide range of ionization laser pulse powers with approximately 99% accuracy. The results suggest that real-time isomer analysis by the FLMS method is suitable for mass spectral identification applications. The FLMS method has been shown to be an important alternative to other mass spectrometric methods that use different ionization mechanisms.     

基于液相色谱-质谱联用技术的肺癌细胞代谢组学分析

通过高效液相色谱-四极杆飞行时间质谱(HPLC-Q-TOF/MS)分别对肺癌细胞与正常细胞的极性与非极性代谢物进行指纹图谱分析,进一步应用偏最小二乘判别分析(PLS-DA)对代谢组学数据进行多维统计分析。研究结果显示,与正常细胞相比,肿瘤细胞存在异常的蛋白质、脂肪酸、磷脂代谢,并发现31种对分类有显著贡献的代谢小分子物质。通过本研究,建立了基于液相色谱-质谱联用技术的肺癌细胞代谢组学分析方法,发现了肺癌潜在疾病标记物,可为肺癌分子标记物的发现及其早期诊断提供新思路和新方法。     

Multi-ion quantitative mass spectrometry by orthogonal projection method with periodic signal of electrostatic ion beam trap

In this article, orthogonal projection method (OPM) is introduced which could perform multi-ion quantitative MS with signal of electrostatic ion beam trap (EIBT), and its application has been demonstrated by numerical modeling. To acquire periodic current signal, a model of EIBT with cylindrical-detector is set up to simulate ions' oscillatory motion. Whereafter, OPM is introduced and applied for quantitative MS with sampling time being as short as 200 μs. Comparing with fast Fourier transform (FFT), the MS acquired by OPM is characterized by a more readable spectrum, a much shortened sampling time and the ability to do quantitative analysis. Within the optimum sampling time range, quantitative MS could be performed with accuracy of over 90%. It is found that the lower limit and the upper limit of the optimum sampling time range are all proportional to M(3/2)/δM and its relation is specified by linear regression. Aided by the results of FFT, OPM is applied to a compound tested signal induced by three kinds of ions. It shows that OPM could be performed respectively to each kind of ions without interference from other component of the signal. The resolving power acquired by OPM is about 75 000 with sampling time as short as 10 ms, and the quantitative result that acquired is quite accurate.     

Glass of the past: The degradation and deterioration of medieval glass artifacts

Medieval artifacts made of glass are at a serious disadvantage concerning the chemical stability compared with ancient or common modern glasses. The total amount of silica and other network formers such as alumina is very low and potassium instead of sodium was introduced into the silicate structure by using local raw material. By means of scanning electron microscopy (SEM), secondary ion mass spectrometry (SIMS) and nuclear reaction analysis (NRA) a weathering mechanism governed by an ion exchange process could be determined for medieval glass paintings exposed to the ambient air for centuries. Additionally, the leached glass surface of medieval hollow glass artifacts found in a well and exposed to moist earth show a brown discoloring due to the oxidation of Mn(II) to Mn(IV) oxide. That process can be converted by a treatment of the glass objects in an aqueous hydrazine solution.     

Diagnosis of gastric endoscopic biopsies using attenuated total reflectance (ATR) Fourier transform infrared (FT-IR) spectroscopy with entropy weight local-hyperplane k-nearest neighbor based on frequency domain information (EWHFI)

Fourier transform infrared spectroscopy (FT-IR) is an effective diagnostic tool for the characterization of biological molecules that may provide uninvasive, rapid detection of gastric cancer in vivo in the future. FT-IR spectra were obtained from 103 endoscopic biopsy gastric tissue samples that included 20 healthy, 35 chronic atrophic gastritis, 29 chronic superficial gastritis, and 19 gastric cancerous samples. A new approach using entropy weight local-hyperplane k-nearest neighbor based on frequency domain information (EWHFI) is proposed that improves and extends the adaptive weight local-hyperplane k-nearest neighbor (AWHK) approach. EWHFI combines the AWHK algorithm with the fine Fourier transform information in the frequency domain to effectively distinguish similar pathological states. The experimental results show that EWHFI enhances the accuracy, sensitivity, and specificity for the diagnosis of early gastric cancer. The average results of the random classification showed that the EWHFI classifiers for differentiating gastric cancerous, chronic atrophic gastritis, chronic superficial gastritis, and healthy tissues were 95.1%, 86.4%, 88.3%, and 99%, respectively.     

Influence of Basicity on the Formation of Cluster Ions/Adduct Ions for Organic Ammonium Halides by Positive Secondary Ion Mass Spectrometry

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Discrimination of isomers and isobars by varying the reduced-field across drift tube in proton-transfer-reaction mass spectrometry (PTR-MS)

Proton-transfer-reaction mass spectrometry (PTR-MS) is a powerful technique for the real time trace gas analysis of volatile organic compounds (VOCs). However, quadrupole mass spectrometer (MS) used in PTR-MS has a relatively low mass resolution and is therefore not suitable for differentiating isobars. Furthermore, because of the lack of chemical separation before analysis, isomers can not be identified, either. In the present study, by varying the reduced-field E/N in the reaction chamber with a range of 50–180 Td in PTR-MS, we studied the product ion distribution (PID) of three sets of isobars/isomers, i.e. n-propanol/iso-propanol/acetic acid, propanal/acetone and four structural isomers of butyl alcohol. The profiles of the reduced-field dependence (PFD) of the PID under the chosen E/N-values show obvious differences which can be used to discriminate between these isobars/isomers thus enabling the titled method. Noticeably, we have observed that even the isomers, in the case of four structural isomers of butyl alcohol, which show little difference with each other at high reduced-field, can be discriminated easily at low reduced-field. Finally, two examples for the application of this method are discussed: (1) cyclohexanone was identified to be a major compound in the headspace of medical infusion sets; and (2) the differentiation and quantification of propanal and acetone in three synthetic mixtures with different ratios. This study presents a potential method to distinguish and quantify isobars/isomers conveniently in practical applications of PTR-MS analysis without additional instrumental configurations.     

Characterization of the Chemical Profile of Euphorbia Species from Turkey by Gas Chromatography–Mass Spectrometry (GC-MS), Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS), and Liquid Chromatography–Ion Trap–Time-of-Flight–Mass Spectrometry (LC-IT-TOF-MS) and Chemometric Analysis†

The Euphorbiaceae family comprises of about 300 genera and 5000 species primarily distributed in America and tropical Africa. The Euphorbia genus is represented by 105 species and locally named as “Sütle?en” and “Xa?îl” in Turkey. The present study aimed to determine the chemical constituents of E. aleppica, E. eriophora, E. macroclada, E. grisophylla, E. seguieriana subsp. seguieriana, E. craspedia, E. denticulata, E. falcata, and E. fistulosa, and classify them by utilizing the chemometric techniques of principal component analysis (PCA) and hierarchical cluster analysis (HCA). Linoleic acid, 17-tetratriacontane, palmitic acid, and hexatriacontane were the major fatty acids from the gas chromatography–mass spectrometry (GC/MS) analyses. Characterization of 268 constituents of the studied species was achieved by liquid chromatography–ion trap–time-of-flight–mass spectrometry (LC-IT-TOF-MS). Furthermore, a new liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantitative determination of 11 compounds (quinic acid, protocatechuic acid, rutin, hesperidin, eugenol, p-coumaric acid, piceatannol, scopoletin, dl-kavain, chrysophanic acid, and resiniferatoxin) in these species. The developed method was validated for the linearity, limit of detection, limit of quantification, repeatability, and recovery.     

Quantification of fructo-oligosaccharides based on the evaluation of oligomer ratios using an artificial neural network

The application of an internal standard in quantitative analysis is desirable in order to correct for variations in sample preparation and instrumental response. In mass spectrometry of organic compounds, the internal standard is preferably labelled with a stable isotope, such as ¹⁸O, ¹⁵N or ¹³C. In this study, a method for the quantification of fructo-oligosaccharides using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI TOF MS) was proposed and tested on raftilose, a partially hydrolysed inulin with a degree of polymeration 2-7. A tetraoligosaccharide nystose, which is chemically identical to the raftilose tetramer, was used as an internal standard rather than an isotope-labelled analyte. Two mathematical approaches used for data processing, conventional calculations and artificial neural networks (ANN), were compared. The conventional data processing relies on the assumption that a constant oligomer dispersion profile will change after the addition of the internal standard and some simple numerical calculations. On the other hand, ANN was found to compensate for a non-linear MALDI response and variations in the oligomer dispersion profile with raftilose concentration. As a result, the application of ANN led to lower quantification errors and excellent day-to-day repeatability compared to the conventional data analysis. The developed method is feasible for MS quantification of raftilose in the range of 10-750 pg with errors below 7%. The content of raftilose was determined in dietary cream; application can be extended to other similar polymers. It should be stressed that no special optimisation of the MALDI process was carried out. A common MALDI matrix and sample preparation were used and only the basic parameters, such as sampling and laser energy, were optimised prior to quantification.     

Ultrasound‐assisted oxidation of tungsten in oxygen plasma: the early stages of the oxide film growth

The effect of ultrasonic vibrations applied in situ on the formation of W–WO interface during the exposure of a pure tungsten foil to a low‐temperature oxygen plasma is investigated by photoelectron spectroscopy (XPS) and time‐of‐flight secondary ion mass spectrometry (TOF‐SIMS). The tungsten surface was exposed to oxygen plasma at different time intervals and the evolution of the interface formation was studied by angle‐resolved XPS. We show that oxidation without ultrasonic vibrations leads to the formation of a thin oxide film whose growth kinetics is governed by an island growth mechanism. On the other hand, oxide growth in the presence of ultrasonic treatment (UST) appears to follow a layer‐by‐layer growth mode with a distinctly sharper W–WO interface. TOF‐SIMS analysis in this case revealed a reduced amount of water bonded in the film, which suggests an increase in the film's packing density. Copyright © 2006 John Wiley & Sons, Ltd.     

Chemical profiling and quantification of multiple components in Jin-Gu-Lian capsule using a multivariate data processing approach based on UHPLC-Orbitrap Exploris 240 MS and UHPLC-MS/MS

The Jin-Gu-Lian capsule, a Chinese Miao herbal compound, is widely used to treat rheumatoid arthritis. In this study, a rapid, selective, and sensitive UHPLC-Orbitrap Exploris 240 MS method was developed to analyze the chemical composition of Jin-Gu-Lian capsules. A total of 88 compounds were identified, including 23 flavonoids, 23 organic acids, 14 phenylpropanoids, 12 phenols, eight alkaloids, four terpenes, three quinones, and one ketone. Among these, 21 compounds were clearly detected based on a comparison with reference standards and selected as quality control markers. Thereafter, these compounds were simultaneously determined in the Jin-Gu-Lian capsules. The established method was successfully validated and applied for the simultaneous determination of 21 biologically active compounds in Jin-Gu-Lian capsules of 27 sample batches. Quantitative data of the analytes were analyzed using multivariate statistical analysis to determine the quality of the Jin-Gu-Lian capsules. Four compounds (JGLC6 [salidroside], JGLC8 [chlorogenic acid], JGLC12 [liriodendrin], JGLC19 [quercetin]) were identified as chemical markers for quality control of Jin-Gu-Lian capsules. Altogether, the established method was validated as a novel and efficient tool, that can be used for rapid analysis of Jin-Gu-Lian capsules. Accordingly, this study serves as a reference for scientific research on traditional Chinese and ethnic medicine.