Measuring technique for thermal ionisation mass spectrometry of human tracer kinetic study with stable cerium isotopes

Thermal ionisation mass spectrometry (TIMS) method has been developed for the simultaneous detection of different cerium isotopes in biological samples (i.e., blood and urine) at very low concentrations. The work has been done in the frame of a biokinetic study, where different stable cerium isotopes have been administered orally and intravenously as tracers to the human body.

In order to develop an appropriate detection method for the tracers in the biological samples, an optimum sample preparation technique has been set and adapted to the specific requirements of the analysis technique used, i.e., TIMS. For sample evaporation and ionisation, the double tantalum filament technique showed the best results. The ions produced were simultaneously collected on a secondary electron multiplier so that the isotopic ratios of the cerium isotopes in the biological samples could be measured.

The technique has been optimised for the determination of cerium down to 1 ng loaded on the evaporation filament corresponding to cerium concentrations of down to 1 ng ml^?1 in the blood or urine samples. It has been shown that the technique is reliable in application and enables studies on cerium metabolism and biokinetics in humans without employing radioactive tracers.     

Measuring technique for thermal ionisation mass spectrometry of human tracer kinetic study with stable cerium isotopes

Thermal ionisation mass spectrometry (TIMS) method has been developed for the simultaneous detection of different cerium isotopes in biological samples (i.e., blood and urine) at very low concentrations. The work has been done in the frame of a biokinetic study, where different stable cerium isotopes have been administered orally and intravenously as tracers to the human body. In order to develop an appropriate detection method for the tracers in the biological samples, an optimum sample preparation technique has been set and adapted to the specific requirements of the analysis technique used, i.e., TIMS. For sample evaporation and ionisation, the double tantalum filament technique showed the best results. The ions produced were simultaneously collected on a secondary electron multiplier so that the isotopic ratios of the cerium isotopes in the biological samples could be measured. The technique has been optimised for the determination of cerium down to 1?ng loaded on the evaporation filament corresponding to cerium concentrations of down to 1?ng?ml(-1) in the blood or urine samples. It has been shown that the technique is reliable in application and enables studies on cerium metabolism and biokinetics in humans without employing radioactive tracers.     

金属稳定同位素标记生物分析进展

细胞和组织的很多特定功能都由其在不同的生理条件下的生物分子含量决定,极少数分子的改变就有可能影响细胞生物功能并触发疾病生理过程,因此高灵敏的生物分子检测技术在疾病机理研究和疾病早期诊断方面具有重要作用。金属稳定同位素和放射同位素化学性质相近,借鉴放射同位素标记的成功经验,通过金属稳定同位素标记多组分生物分子,可以用原子质谱高灵敏地检测多组分生物分子。作为灵敏准确的金属元素检测工具,电感耦合等离子体质谱检出限低、基体效应低、线性范围广、同位素谱线分辨率高,因此适用于金属元素标记生物分子检测。金属稳定同位素标记已经被广泛应用到蛋白质、核酸、酶活性、生物小分子、甚至单个细胞的检测中,取得了一些可喜的进展,并展现了广阔未来应用前景。金属稳定同位素标记生物分析方法有三个特性：高灵敏度-大多数金属的稳定同位素有较高的标记灵敏度,并且可以通过纳米材料标记等方法实现信号放大;多组分同时分析-质谱仪同位素谱线高分辨率提供了多组分分析能力;高准确度-同位素稀释法提供了可溯源到SI国际单位制的高准确度检测结果。为了更好的推动相关研究,简要介绍金属稳定同位素标记生物分析的进展,主要内容包括以下几个部分：金属稳定同位素检测工具-无机质谱、金属稳定同位素标记高灵敏度分析、金属稳定同位素标记多组分同时分析、金属稳定同位素标记高准确度分析、金属稳定同位素标记单细胞分析的进展。     

Mass Spectrometric Determination of Transuranium Elements

Abstract

Mass spectrometric techniques are playing a predominant role for the determination of transuranium elements in bulk samples as well as in microparticles. Their applications to liquid and solid samples for the determination of the isotopic composition as well as for the concentration measurements are discussed. The new developments for the characterization of microparticles stemming from different release scenarios of radioactivity are considered. Inductively coupled plasma mass spectrometry and its hyphenation with other techniques for resolving isobaric interferences are presented. The application of glow discharge and laser ablation directly to solid samples is highlighted. Finally, the exploitation of secondary ion mass spectrometry, accelerator mass spectrometry, resonance ionization mass spectrometry, and thermal ionization mass spectrometry for the determination of the isotopic composition of uranium and plutonium in microparticles is illustrated.     

Forensic Studies by EA-IRMS

Abstract

The authenticity of natural and synthetic matter can be checked by measurement of the isotope ratios of C, N and S. Controlled substances like drugs of abuse (cocaine, heroin) and explosives (TNT) or, simply, traces of paint can hold information in their isotope pattern. Total combustion of samples in an elemental analyzer followed by on-line determination of the isotopes of the combustion products (CO², N², SO²) in an isotope ratio mass spectrometer (EA-IRMS) provides high sample throughout with a minimum of sample preparation.     

Elemental Analyzer-Quadrupole MS Coupling—A Low Cost Equipment for the Simultaneous Determination of Carbon/13C and Nitrogen/15N in Isotopically Enriched Soil and Plant Samples

Abstract

Since the end of the 80s elemental analyzer-isotope ratio mass spectrometer connections have been used for the fast, automatic and highly precise determination of carbon and nitrogen content as well as their isotopic composition in one run. But for artificially enriched stable isotopes as tracer in biological processes and since these processes have a high biological variability anyway (e.g. soil processes) the use of these highly precise but also sophisticated and expensive instruments is not required. In this case the use of a quadrupole mass spectrometer connected with an elemental analyzer can offer a low cost alternative. As shown, such coupling is suitable for automatic simultaneous routine analysis of total nitrogen and carbon and their isotopic enrichment (¹⁵N, ¹³C) in plant material and soils. The relative standard deviation for ¹⁵N and ¹³C determination is 2% To meet this precision a careful sample homogenization by grinding is very important. The duration of one measurement is 6–8 min. depending on whether nitrogen alone or both nitrogen and carbon are determined. This enables a high sample throughput.     

Determination of 13CO2/12CO2 Ratio by IRMS and NDIRS

Abstract

Breath tests using ¹³C-labelled substrates require the measurement of ¹³CO₂/¹²CO₂ ratio in breath gas samples. Next to isotope ratio mass spectrometry (IRMS), which is very sensitive but also complex and expensive, alternatively isotope selective nondispersive infrared spectrometry (NDIRS) can be used to determine the ¹³CO₂/¹²CO₂ ratio in expired breath. In this study we compared NDIRS- with IRMS-results to investigate whether the less expensive and very simply to operate NDIRS works as reliable as IRMS. For this purpose we applicated 1-¹³C-Phenylalanine to patients with advanced liver cirrhosis and healthy volunteers and took duplicated breath samples for IRMS and NDIRS at selected time points. Our data show a good correlation between these two methods for a small number of samples as required for simple breath tests. Longer series, where repeated measurements are required on the NDIRS instrument lead to a decreasing correlation. This indicates the superiority of IRMS concerning ¹³CO₂-kinetics over longer time periods.     

Ion Optical Methods - Means to Improve Performance of Mass Spectrometers Designed for Isotopic or Chemical Analysis

Abstract

To improve performances of mass spectrometers dedicated to isotopic or chemical analysis, the methods of the ion optics are to be used. To apply the transfer matrix method of ion optics in mass spectrometer design, the matrix elements of various mass analyzers as Wien filters and crossed field sectors, of energy analyzers as electric prisms, were presented. These elements result from ion trajectory calculations representing solutions of the Euler–Lagrange equations. The basic parameters of an unconventional double focusing mass spectrometer were calculated and compared with those of classical design instruments.     

A new concept for sensitive in situ stable isotope ratio infrared spectroscopy based on sample modulation

Diode-laser absorption spectroscopy finds increasing applications in the emerging field of stable isotope research. To meet the requirements of the water isotopes measurement challenge in environmental research, ways have to be found to cope with the present limitations of spectroscopic systems. In this article, we discuss an approach based on the Stark effect in molecular spectra to reduce the influence of time-dependent, unwanted background structures generally superimposed on the desired signal from the spectral feature under investigation. A road map to high-sensitivity isotopic ratio measurements of water isotopes is presented. On the basis of an Allan Variance analysis of measured data, the detection limits have been calculated as a function of the integration time. To achieve the required optical density of about 6×10^?7 for H₂ ¹⁷O measurements, the duty cycle has to be optimized and the implementation of a sample modulation within an optical multipass cell is a promising approach to increase the stability of spectroscopic instrumentation required for ecosystem research and airborne atmospheric platforms.     

Isotope shifts and hyperfine structure in the transitions of gadolinium

High-resolution resonance ionization mass spectrometry has been used to measure isotope shifts and hyperfine structure in all (J = 2-6) and the transitions of gadolinium (Gd I). Gadolinium atoms in an atomic beam were excited with a tunable single-frequency laser in the wavelength range of 422-429 nm. Resonant excitation was followed by photoionization with the 363.8 nm line of an argon ion laser and resulting ions were mass separated and detected with a quadrupole mass spectrometer. Isotope shifts for all stable gadolinium isotopes in these transitions have been measured for the first time. Additionally, the hyperfine structure constants of the upper states have been derived for the isotopes ^{155, 157} Gd and are compared with previous work. Using prior experimental values for the mean nuclear charge radii, derived from the combination of muonic atoms and electron scattering data, field shift and specific mass shift coefficients for the investigated transitions have been determined and nuclear charge parameters for the minor isotopes ^{152, 154} Gd have been calculated. Received 18 November 1999     

The charge-distribution differences of 209Bi, 208, 207, 206, 204Pb and 205, 203Tl investigated by elastic electron scattering and muonic X-ray data

Elastic electron scattering cross sections and cross-section ratios have been measured for the stable Bi, Pb and T1 isotopes. The data are analysed with the Fourier-Bessel method and the charge-distribution differences of the isotonic and isotopic pairs are presented as well as the Fourier-Bessel coefficients of the seven single nuclei. To improve the accuracy of the results, muonic X-ray data are incorporated into the analysis. The measured Δρ(r) are compared with the simple shell model, where the stretching due to the additional nucleons is taken into account, and with more sophisticated HF calculations.     

On the potential of Raman‐spectroscopy‐based carbonate mass spectrometry

The potential for using Raman spectroscopy to measure stable oxygen isotope ratios (¹⁸O/¹⁶O) in carbonates is evaluated by measuring the Raman spectra and isotope ratios of a suite of 60 synthesized, ¹⁸O‐enriched calcite crystals ranging in composition from natural abundance (0.2 mole‐% ¹⁸O) to 1.2 mole‐% ¹⁸O. We determined the Raman‐inferred isotopic ratios (R_Raman) by fitting curves to the ν₁ symmetric stretching peak at 1086 cm⁻¹ and the smaller satellite peak, associated with the ν₁ stretching mode of singly substituted carbonate groups (C¹⁶O₂¹⁸O) at 1065 cm⁻¹. The ratio of the two peak areas shows a 1:1 correspondence with the ¹⁸O/¹⁶O ratios derived from standard mass spectrometry methods, confirming that the relative intensities of the ν₁ symmetric stretching peaks is a direct measure of the isotopic ratio in the carbonates. The 1‐sigma uncertainties of the R_Raman values of the individual crystals were 0.00079 (384‰ PDB) and 0.00043 (210‰ PDB) for the four‐crystal sample means. This level of uncertainty is much too high to provide significant estimates of natural variability; however, there are multiple prospects for improving the accuracy and precision of the technique. Carbon isotope ratios in carbonates cannot be measured by our approach, but our results highlight the potential of Raman‐based isotope ratio measurement for C and other elements in minerals and organic compounds. Copyright © 2012 John Wiley & Sons, Ltd.     

Mass dependence of calcium isotope fractionations in crown-ether resin chromatography

Benzo 18-crown-6-ether resin was synthesised by the phenol condensation polymerisation process in porous silica beads, of which particle diameter was ca 60μ Calcium adsorption chromatography was performed with the synthesised resin packed in a glass column. The effluent was sampled in fractions, and the isotopic abundance ratios of ⁴²Ca, ⁴³Ca, ⁴⁴Ca, and ⁴⁸Ca against ⁴⁰Ca were measured by a thermo-ionisation mass spectrometer. The enrichment of heavier calcium isotopes was observed at the front boundary of calcium adsorption chromatogram. The mass dependence of mutual separation of calcium isotopes was analysed by using the three-isotope-plots method. The slopes of three-isotope-plots indicate the relative values of mutual separation coefficients for concerned isotopic pairs. The results have shown the normal mass dependence; isotope fractionation is proportional to the reduced mass difference, (M – M′)/MM′, where M and M′ are masses of heavy and light isotope, respectively. The mass dependence clarifies that the isotope fractionations are originated from molecular vibration. The observed separation coefficient ? is 3.1×10^?3 for the pair of ⁴⁰Ca and ⁴⁸Ca. Productivity of enriched ⁴⁸Ca by crown-ether-resin was discussed as the function of the separation coefficient and the height equivalent to the theoretical plate.     

Carbon-13 Kinetic Isotope Effects in the Decarbonylation of Liquid Formic Acid Assisted with Acetic Anhydride

Abstract

We evaluated the use of δ¹⁵N- and δ¹³C-values to monitor the development of food web complexity and biodiversity in a regenerating ecosystem. Therefore a model food chain was established feeding cultivated woodlice (Porcellio dilatatus) on a cellulolytic fungus (Chaetomium globosum) grown on cellulose paper. Two diets of different quality (C:N ratios of 54 vs. 200) with different δ¹⁵N- (1.3‰ vs. 3.1‰) but identical δ¹³C-values caused low and high dietary stress in animals of treatment A and B, respectively. After an incubation time of 7 weeks amount, elemental and isotopic composition of collected faeces and exuviae as well as woodlice and remaining food were determined.

The increase of δ¹⁵N-values of woodlice relative to the diet was 5.7‰ and 2.5‰ in treatments A and B, respectively, whereas δ¹³C-shifts were 1.0‰ and 1.6‰, showing a reverse relationship. Modelling of elemental and isotopic mass balances indicated that faeces recycling explains the unexpected high ¹⁵N-enrichments. Moreover, ¹³C-enrichments were positively correlated to the degree of starvation. Considering the effects of starvation and recycling of faeces, stable isotopes represent a useful tool to elucidate trophic interactions in regenerating food webs.     

Effect of different lipid extraction methods on δ13C of lipid and lipid-free fractions of fish and different fish feeds

For many ecological applications of stable carbon isotope techniques, it is necessary to separate the lipid and lipid-free fractions. The effect of different lipid extraction methods on the isotope signature of the remaining lipid-free matter as well as the lipid fraction was tested. A hot extraction form of the Soxhlet method using petrol-ether was compared with two liquid-liquid extraction methods for lipid determination described by Bligh and Dyer and Smedes. Solid samples of fish and different natural food items were subjected to extraction and the carbon isotope ratios in lipid and lipid-free matter determined by IRMS. All methods were suitable for lipid extraction from all samples analysed here and did not cause biologically relevant differences (>1) in carbon isotopic ratios, except the Bligh and Dyer extraction method using chloroform which caused systematic errors for δ ¹³C when applied to diatoms.     

New Methods for Fully Automated Isotope Ratio Determination from Hydrogen at the Natural Abundance Level

Abstract

A variety of methods for measurement of ²H/¹H from H₂ are evaluated for their ability to be fully automated and for applicability to automated isotopic analysis of water and organic compounds. Equilibration of water with H₂ gas with the aid of a platinum catalyst has been commercialized into a fully automated sample preparation device. A second and newer technique, involving injecting water, methane, or other volatile organic compounds onto hot chromium in a reactor attached to the dual inlet system of a gas isotope ratio mass spectrometer, can be integrated with a conventional GC-autosampler to allow automated analysis of a variety of substrates. Both techniques result in precisions around 1‰ (δ notation) on the VSMOW scale, and are fast and accurate, and with appropriate mass spectrometers require only negligible scaling for the SLAP/VSMOW difference. Several experimental methods which show considerable promise employ “isotope ratio monitoring” (irm) inlet systems, in which a carrier gas is used for transport of H₂ to the mass spectrometer. Any such method has to address the problem of He ions corrupting the measurement of the H₂ ions. One such approach uses a heated palladium membrane for selective introduction of H₂ into the mass spectrometer, and a second involves modifications to the ion optics to control the stray helium ions. Both approaches have significant limitations that must be overcome before irm techniques can be used in routine applications, in particular for measuring hydrogen isotopes from GC effluents (irm-GCMS).     

Penning-trap mass measurements on <Superscript>92, 94-98, 100</Superscript>Mo with JYFLTRAP

Penning-trap measurements on stable ^{92, 94-98, 100}Mo isotopes have been performed with relative accuracy of \(\ensuremath 1\cdot 10^{-8}\) with the JYFLTRAP Penning-trap mass spectrometer by using ⁸⁵Rb as a reference. The Mo isotopes have been found to be about 3keV more bound than given in the Atomic Mass Evaluation 2003 (AME03). The results confirm that the discrepancy between the ISOLTRAP and JYFLTRAP data for ^101-105Cd isotopes was due to an erroneous value in the AME03 for ⁹⁶Mo used as a reference at JYFLTRAP. The measured frequency ratios of Mo isotopes have been used to update mass-excess values of 30 neutron-deficient nuclides measured at JYFLTRAP.     

Isotopic heterogeneity in synthetic and natural silicon carbide

The distribution of both carbon and silicon isotopes in synthetic sublimation growth SiC wafers and in natural SiC grains was studied using secondary ion mass-spectrometry (SIMS). Significant variations in both isotopic ratios were observed which were broadly correlated with the crystalline perfection as documented by Raman microspectroscopy. Domains consisting of 15R (or with its admixture) are, on average, enriched in ¹²C isotope relative to 6H domains, and they also show larger scatter in their observed silicon isotope ratios. We ascribe such heterogeneity to fluctuations of Si/C ratio in the growth medium and it is possible to model the spatial extent of such fluctuations. For the natural SiC grains the isotopic data suggest that they grew under relatively stable conditions, although some of them show significant isotopic zoning.     

Variations of Lead Isotopes and Airborne Particulate Concentrations From the Kozani Basin,West Macedonia,Greece

Abstract

The spread and variation in ²⁰⁶Pb/²⁰⁷Pb ratios make Pb isotopes a powerful tool when it comes to detecting trends in airborne particulates originating mainly from power plants. This study was conducted to determine the source of pollution in Kozani area, an affected industrial area. Lead isotopic ratios of air filters under certain meteorological conditions were compared to Pb isotope analyses sampled from lignite mines, but also to Pb isotope analyses of cultivations in soil originating from the reclamation of old abandoned lignite-mines. The particles taken into consideration have an aerodynamic diameter less than 10 μm (PM10). The measurements were carried out in a central part of the town of Kozani, West Macedonia, for one year observation period. The lead isotope values of air filters and of wheat in the Kozani area are between the values of lignite Pb and of Greek gasoline.     

Ultratrace Determination of Selenium by Hydride Generation–Inductively Coupled Plasma Mass Spectrometry Operated Under Nonrobust Plasma Conditions

A hydride generation–inductively coupled plasma mass spectrometer (HG‐ICPMS) operated at low RF power (720 W) was demonstrated to be suitable for ultra trace determination of Se, which is an element with high ionization potential (IP). ⁷⁸Se analysis free from ³⁸Ar⁴⁰Ar spectral interference was achieved by operating the plasma under a so‐called warm plasma condition (as opposed to traditionally defined hot and cool plasmas). In this warm plasma, there is a sufficient population of energetic Ar⁺ to ensure ionization of Se, while the number of ³⁸Ar⁴⁰Ar ions is at the minimum, due to the dimer's bimodal profile. A detection limit of 1 ng/L was achieved for ⁷⁸Se. Background spectra of warm and hot plasmas were compared. Two types of HG gas–liquid separators were compared. The technique was applied to measure trace amounts of Se in atmospheric samples; namely, cloud water and aerosol particulate. Good agreement was found between HG warm plasma ICPMS and pneumatic micronebulization hot plasma ICPMS for the cloud water samples. The water extract of aerosol particulate typically contained 50–100 ng/L of Se, equivalent to 0.25–0.5 ng/m³ in the atmosphere. Ours appears to be the first report of the use of nonrobust plasma ICPMS for a high‐IP element; the superb accuracy and sensitivity of this technique rival those of other powerful trace analytical methodologies such as HG‐LIF, HG‐LEI, or DRC‐ICPMS. It is conceivable that warm plasma ICPMS is applicable to other elements with high IP.