Analysis of cancer cell lipids using matrix-assisted laser desorption/ionization 15-T Fourier transform ion cyclotron resonance mass spectrometry

A combination of methodologies using the extremely high mass accuracy and resolution of 15-T Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) was introduced for the identification of intact cancer cell phospholipids. Lipids from a malignant glioma cell line were initially analyzed at a resolution of >200,000 and identified by setting the mass tolerance to ±1 mDa using matrix-assisted laser desorption/ionization (MALDI) 15-T FT-ICR MS in positive ion mode. In most cases, a database search of potential lipid candidates using the exact masses of the lipids yielded only one possible chemical composition. Extremely high mass accuracy (<0.1?ppm) was then attained by using previously identified lipids as internal standards. This, combined with an extremely high resolution (>800,000), yielded well-resolved isotopic fine structures allowing for the identification of lipids by MALDI 15-T FT-ICR MS without using tandem mass spectrometric (MS/MS) analysis. Using this method, a total of 38 unique lipids were successfully identified.     

Recent developments in ion detection techniques for Penning trap mass spectrometry at TRIGA-TRAP

The highest precision in the determination of nuclear and atomic masses can be achieved by Penning trap mass spectrometry. The mass value is obtained through a measurement of the cyclotron frequency of the stored charged particle. Two different approaches are used at the Penning trap mass spectrometer TRIGA-TRAP for the mass determination: the destructive Time-Of-Flight Ion Cyclotron Resonance (TOF-ICR) technique and the non-destructive Fourier Transform Ion Cyclotron Resonance (FT-ICR) method. New developments for both techniques are described, which will improve the detection efficiency and the suppression of contaminations in the case of TOF-ICR. The FT-ICR detection systems will allow for the investigation of an incoming ion bunch from a radioactive-beam facility on the one hand, and for the detection of a single singly charged ion in the Penning trap on the other hand.     

Precise mass measurement of a double-stranded 500 base-pair (309 kDa) polymerase chain reaction product by negative ion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry

Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICRMS) has been used to determine the mass of a double-stranded 500 base-pair (bp) polymerase chain reaction (PCR) product with an average theoretical mass of the blunt-ended (i.e. unadenylated) species of 308 859.35 Da. The PCR product was generated from the linearized bacteriophage Lambda genome which is a double-stranded template. Utilization of ethanol precipitation in tandem with a rapid microdialysis step to purify and desalt the PCR product was crucial to obtain a precise mass measurement. The PCR product (0.8 pmol/μL) was electrosprayed from a solution containing 75% acetonitrile, 25 mM piperidine, and 25 mM imidazole and was infused at a rate of 200 nL/min. The average molecular mass and the corresponding precision were determined using the charge-states ranging from 172 to 235 net negative charges. The experimental mass and corresponding precision (reported as the 95% confidence interval of the mean) was 309 406 +/- 27 Da (87 ppm). The mass accuracy was compromised due to the fact that the PCR generates multiple products when using Taq polymerase due to the non-template directed 3'-adenylation. This results in a mixture of three PCR products with nearly identical mass (i.e. blunt-ended, mono-adenylated and di-adenylated) with unknown relative abundances that were not resolved in the spectrum. Thus, the experimental mass will be a weighted average of the three species which, under our experimental conditions, reflects a nearly equal concentration of the mono- and di-adenylated species. This report demonstrates that precise mass measurements of PCR products up to 309 kDa (500 bp) can be routinely obtained by ESI-FTICR requiring low femtomole amounts. Copyright 1999 John Wiley & Sons, Ltd.     

The use of secondary ion mass spectrometry in surface analysis

Secondary ion mass spectrometry (SIMS) is based on the bombardment of solids by ions and subsequent mass analysis of the sputtered ions or of the post-ionized neutrals. Various models have been proposed for the emission of secondary ions from the target. These models can roughly be grouped into two categories: (a) lonization takes place outside the target; the sputtered particles are assumed to leave the target in an excited or super-excited state; ionization can then result from such processes as Auger de-excitation or resonance ionization. (b) Ions are generated inside the target by collision cascades initiated by a primary impinging ion. Experimental data of the element- and matrix-dependent ion yield and estimates of the minimum detectable concentrations are shown as well as the rate of consumption of the target. Methods for efficient use of the sputtered material will be discussed. Examples of the wide range of applications of SIMS for determination of the chemical composition and structure of the surface layer and for imaging of the distribution of elements in the surface are given. The SIMS results are compared with those of Auger and Ion Scattering Spectrometry. The essentially non-destructive method of static SIMS is shown to be a powerful tool for the investigation of the outermost atomic layers of a solid.     

Remote sensing of mass fluxes of trace gases in the boundary layer

The combination of remote sensing methods like Doppler lidar and FTIR offers the possibility to determine mass fluxes of gases remotely. Doppler lidar measures the three-dimensional wind vector in the vicinity of diffuse sources or the velocity of air in a chimney plume if an industrial complex is monitored. FTIR is a multi-component remote sensing method for gas concentrations. The Fourier transformation of an interferogram of a Michelson interferometer within a FTIR system converts the recorded intensity (function of optical path length) to a spectral signal (function of wavenumber). Both information, velocity and concentration, give the mass fluxes of the tracer (gas). A first test was performed at Munich-North power station with FTIR and cw-Doppler lidar. Fluxes of CO₂, CO, NO, and HC1 were determined. The results are in good agreement with the fluxes measured by in-situ instruments of the power station. The method can be used to control industrial complexes from an outside observation site.     

Technical developments for an upgrade of the LEBIT Penning trap mass spectrometry facility for rare isotopes

The LEBIT (Low Energy Beam and Ion Trap) facility is the only Penning trap mass spectrometry (PTMS) facility to utilize rare isotopes produced via fast-beam fragmentation. This technique allows access to practically all elements lighter than uranium, and in particular enables the production of isotopes that are not available or that are difficult to obtain at isotope separation on-line facilities. The preparation of the high-energy rare-isotope beam produced by projectile fragmentation for low-energy PTMS experiments is achieved by gas stopping to slow down and thermalize the fast-beam ions, along with an rf quadrupole cooler and buncher and rf quadrupole ion guides to deliver the beam to the Penning trap. During its first phase of operation LEBIT has been very successful, and new developments are now underway to access rare isotopes even farther from stability, which requires dealing with extremely short lifetimes and low production rates. These developments aim at increasing delivery efficiency, minimizing delivery and measurement time, and maximizing use of available beam time. They include an upgrade to the gas-stopping station, active magnetic field monitoring and stabilization by employing a miniature Penning trap as a magnetometer, the use of stored waveform inverse Fourier transform (SWIFT) to most effectively remove unwanted ions, and charge breeding.     

The use of mass defect in modern mass spectrometry

Mass defect is defined as the difference between a compound's exact mass and its nominal mass. This concept has been increasingly used in mass spectrometry over the years, mainly due to the growing use of high resolution mass spectrometers capable of exact mass measurements in many application areas in analytical and bioanalytical chemistry. This article is meant as an introduction to the different uses of mass defect in applications using modern MS instrumentation. Visualizing complex mass spectra may be simplified with the concept of Kendrick mass by plotting nominal mass as a function of Kendrick mass defect, based on hydrocarbons subunits, as well as slight variations on this theme. Mass defect filtering of complex MS data has been used for selectively detecting compounds of interest, including drugs and their metabolites or endogenous compounds such as peptides and small molecule metabolites. Several strategies have been applied for labeling analytes with reagents containing unique mass defect features, thus shifting molecules into a less noisy area in the mass spectrum, thus increasing their detectability, especially in the area of proteomics. All these concepts will be covered to introduce the interested reader to the plethora of possibilities of mass defect analysis of high resolution mass spectra.     

Fourier analysis on space-like surfaces II. the case of mass ϰ = 0

Fourier transformations of functions or functionals on some space-like surfaces and related subjects are studied with the condition that the mass of particles under consideration is equal to zero. To some extent, the study can be developed nearly along the same lines as in the case where the mass is not equal to zero. At some stage, however, we are obliged to introduce a new type of function space and its dual space, and this enables us to arrive at satisfactory results.     

Secondary ion mass spectrometry for quantitative surface and in-depth analysis of materials

Secondary ion mass spectrometry (SIMS) is a technique based on the sputtering of material surfaces under primary ion bombardment. A fraction of the sputtered ions which largely originate from the top one or two atomic layers of the solid is extracted and passed into a mass spectrometer where they are separated according to their mass-to-charge ratios and subsequently detected. Because the sputter-yields of the individual species, coupled with their ionization probabilities, can be quite high and the mass spectrometers can be built with high efficiencies, the SIMS technique can provide an extremely high degree of surface sensitivity. Using a particular mode like static SIMS where a primary ion current is as low as 10^?11 amp, the erosion rate of the surface can be kept as low as 1 Å per hour and one can obtain the chemical information of the uppermost atomic layer of the target. The other mode like dynamic SIMS where the primary ion current is much higher can be employed for depth profiling of any chemical species within the target matrix, providing a very sensitive tool (～ 1 ppm down to ppb) for quantitative characterization of surfaces, thin films, superlattices, etc. The presence of molecular ions amongst the sputtered species makes this method particularly valuable in the study of molecular surfaces and molecular adsorbates. The range of peak-intensities in a typical SIMS spectrum spans about seven to eight orders of magnitude, showing its enormously high dynamic range; an advantage in addition to high sensitivity and high depth-resolution. Furthermore, the high sensitivity of SIMS to a very small amount of material implies that this technique is adaptable to microscopy, offering its imaging possibilities. By using this possibility in static SIMS or dynamic SIMS mode of analysis, one can obtain a two-dimensional (2D) surface mapping or a three-dimensional (3D) reconstruction of the elemental distribution, respectively within the target matrix. Secondary ion yields for elements can differ from matrix to matrix. These sensitivity variations pose serious limitations in quantifying SIMS data. Various methods like calibration curve approach, implantation standard method, use of relative sensitivity factor, etc. are presently employed for making quantitative SIMS analysis. The formation of secondary ions by ion bombardment of solids is relatively a complex process and theoretical research in this direction continues in understanding this process in general. The present paper briefly reviews the perspective of this subject in the field of materials analysis.     

Mechanism of MCs+ formation in Cs based secondary ion mass spectrometry

Quantitative analysis using MCs⁺ secondary ions has long been impossible because sample loading with Cs could not be controlled adequately. Using recently developed, advanced instrumentation, it can be shown that, at low levels of Cs loading, ionization and formation probabilities of MCs⁺ ions arrive at a constant, maximum level. On the basis of results obtained in three independent studies, involving three vastly different methods of controlling the sample loading with Cs, evidence is provided that MCs⁺ ions are emitted as such, independent of the number of atoms sputtered in the same impact event. Taken together, these findings finally pave the way for quantification of secondary ion signals without matrix effects.     

Optimization of an ion-to-photon detector for large molecules in mass spectrometry

Ion packets can be detected in time-of-flight mass spectrometry by collecting the photons that are produced during the impact of the packets with a scintillator. The photon yield is a function of the ion energy. It was found that post-acceleration of the particles in front of the scintillator was an efficient way of increasing signal intensities. For the same total ion energy, the intensities were larger with post-acceleration than when only increasing the initial ion kinetic energy. A venetian blind dynode, converting the primary ion beam into electrons/secondary ions, was also introduced. Positive or negative secondary particles produced on the dynode surface could be accelerated to the scintillator. Electrons were found to give the highest signals. Intensities similar to those measured with microchannel plates were found. The linearity and onset of saturation of the microchannel plates and the ion-to-photon detector were compared. At optimum operating conditions, the ion-to-photon detector gave around 10 times higher signals than the microchannel plates for heavy ions (150 kDa), with similar mass resolution. Copyright 1999 John Wiley & Sons, Ltd.     

Optimization of a quadrupole ion storage trap as a source for time-of-flight mass spectrometry

Designs of a quadrupole ion trap (QIT) as a source for time-of-flight (TOF) mass spectrometry are evaluated for mass resolution, ion trapping, and laser activation of trapped ions. Comparisons are made with the standard hyperbolic electrode ion trap geometry for TOF mass analysis in both linear and reflectron modes. A parallel-plate design for the QIT is found to give significantly improved TOF mass spectrometer performance. Effects of ion temperature, trapped ion cloud size, mass, and extraction field on mass resolution are investigated in detail by simulation of the TOF peak profiles. Mass resolution (m/Δm) values of several thousand are predicted even at room temperature with moderate extraction fields for the optimized design. The optimized design also allows larger radial ion collection size compared with the hyperbolic ion trap, without compromising the mass resolution. The proposed design of the QIT also improves the ion-laser interaction volume and photon collection efficiency for fluorescence measurements on trapped ions.     

原子核第一激发能的统计规律

原子核的第一激发态能级是所有激发态能级中最重要的一条能级,在一定程度上可直接反映该核素的稳定性。通过对2 125个核素的第一激发态能级纲图进行统计分析,发现传统幻数位置的第一激发能明显高于邻近核素的第一激发能,亦对应于同位素链、同中子素链上原子核第一激发能最大的核素。对于第一激发能较大且明显偏离传统幻数位置的少量核素,发现都具有同质异位素相似态或为裂变核的混合能级,这些给出的值是否是第一激发态,在理论和实验上仍存在一定的不确定性;而对于原子核第一激发能最大的核素,其自旋宇称为2+的最多（高达42%）。对于中重核区内的偶偶核,其第一激发能与价核子N_pN_n关系明显趋于指数的衰减形式。     

Top-down mass spectrometry reveals new sequence variants of the major bovine seminal plasma protein PDC-109

The major protein of bovine seminal plasma, PDC-109, is a 109-residue polypeptide that exists as a polydisperse aggregate under native conditions. The oligomeric state of this aggregate varies with ionic strength and the presence of lipids. Binding of PDC-109 to choline phospholipids on the sperm plasma membrane results in an efflux of cholesterol and choline phospholipids, which is an important step in sperm capacitation. In this study, Fourier transform ion cyclotron resonance mass spectrometry was used to analyze PDC-109 purified from bovine seminal plasma. In addition to the previously known PDC-109 variants, four new sequence variants were identified by top-down mass spectrometry. For example, a protein variant containing point mutations P10L and G14R was identified along with another form having a 14-residue truncation in the N-terminal region. Two other minor variants could also be identified from the affinity-purified PDC-109. These results demonstrate that PDC-109 is naturally produced as a mixture of several protein forms, most of which have not been detected in previous studies. Native mass spectrometry revealed that PDC-109 is exclusively monomeric at low protein concentrations, suggesting that the protein oligomers are weakly bound and can easily be disrupted. Ligand binding to PDC-109 was also investigated, and it was observed that two molecules of O-phosphorylcholine bind to each PDC-109 monomer, consistent with previous reports.     

高分辨质谱用于分析和检测α-硫羰基硫代甲酰胺类化合物

苯乙酮及其衍生物与氯化亚砜反应所得中间产物再与仲胺反应得α－羰基硫代甲酰胺（1a-1f),经硫代得目标物α－硫羰基硫代甲酰胺（2a-2f)。化合物2a-2f含有二个硫羰基,为深红或深绿色晶体,可用作远红外吸收染料、激光Q开关及有机导体等。本文利用英国Micromass公司的OA－TOF高分辨质谱仪对α－硫羰基硫代甲酰胺类化合物的裂解行为进行了详细的研究。结果表明该类化合物容易失去S2分子形成特征的碎片离子M－S2（基峰）,为分析和检测这类化合物提供了一种有效的分析方法。OA－TOF高分辨质谱仪体积小、操作简单、快速,适合于分析纯的α－硫羰基硫代甲酰胺类化合物、检测混合物中及作为反应中间体的这类化合物。     

静态傅里叶变换光谱仪的微阶梯反射镜设计及制作

静态傅里叶变换光谱仪的反射镜采取微阶梯反射镜，使光谱仪可在无需空间驱动装置的前提下实现空域上各级次的同时采样。通过理论研究和对测试数据的对比分析，确定使用楔形玻璃条制作微阶梯反射镜。此方法采用常规光学零件加工工艺制作1个楔形玻璃块和10个楔形玻璃条，然后按序选取楔形玻璃条，并逐一光胶在楔形玻璃块的斜面上，且相邻楔形玻璃条的接触面用紫外胶固连；水平方向反复推动相邻后一个楔形玻璃条直到检测仪器测量出相邻楔形玻璃条的阶梯厚度差达到要求为止；用紫外灯固化紫外胶；重复以上步骤制作出所需台阶数目的微阶梯反射镜。和别的制作方法相比，此方法安全性和可行性高，而且具有一致性、台阶厚度可控特点，可制作出台阶高度误差为0.124 μm、表面粗糙度为12 nm的微阶梯反射镜，达到系统设计要求。     

Analytical laser induced liquid beam desorption mass spectrometry of protonated amino acids and their non-covalently bound aggregates

We have used analytical laser induced liquid beam desorption in combination with high resolution mass spectrometry ( m/Δm≥ 1000) for the study of protonated amino acids (ornithine, citrulline, lysine, arginine) and their non-covalently bound complexes in the gas phase desorbed from water solutions. We report studies in which the desorption mechanism has been investigated. The results imply that biomolecule desorption at our conditions is a single step process involving laser heating of the solvent above its supercritical temperature, a rapid expansion, ion recombination and finally isolation and desorption of only a small fraction of preformed ions and charged aggregates. In addition, we report an investigation of the aqueous solution concentration and pH-dependence of the laser induced desorption of protonated species (monomers and dimers). The experimental findings suggest that the desorption process depends critically upon the proton affinity of the molecules, the concentration of other ions, and of the pH value of the solution. Therefore the ion concentrations measured in the gas phase very likely reflect solution properties (equilibrium concentrations). Arginine self-assembles large non-covalent singly protonated multimers (n = 1...8) when sampled by IR laser induced water beam desorption mass spectrometry. The structures of these aggregates may resemble those of the solid state and may be preformed in solution prior to desorption. A desorption of mixtures of amino acids in water solution enabled us to study (mixed) protonated dimers, one of the various applications of the present technique. Reasons for preferred dimerization - leading to simple cases of molecular recognition - as well as less preferred binding is discussed in terms of the number of specific H-bonds that can be established in the clusters.     

Analysis of furanocoumarins from Yemenite Dorstenia species by liquid chromatography/electrospray tandem mass spectrometry

A series of prevailing prenylated furanocoumarins from leaves of Dorstenia gigas and Dorstenia foetida (Moraceae) were investigated by liquid chromatography/electrospray tandem mass spectrometry. The mass spectral behavior of the furanocoumarins under positive ion electrospray conditions is discussed using both an ion trap and a triple quadrupole system. It is demonstrated that both methods represent valuable tools not only for the rapid classification of this type of compounds, but also with respect to their substitution pattern.     

Depth profiling using secondary ion mass spectrometry and sample current measurements

The features of the method for measuring the total current in the sample circuit in combination with secondary ion mass spectrometry (SIMS) depth profiling of various thin-film structures are discussed in detail. The results on depth profiling of multilayer CrN/AlN coatings magnetron-deposited on the surface of a nickel alloy, titanium dioxide films on stainless steel, and corrosion layers formed on the magnesium alloy surface during the interaction with an ionic liquid are considered. These results give grounds to consider the proposed method for measuring the sample current as an efficient and informative addition to the conventional SIMS.