Re-determination of R(13C/12C) for Vienna Peedee belemnite (VPDB).

RATIONALE: The isotope ratio for the internationally agreed but virtual zero-point of the carbon isotope-delta scale, Vienna Peedee belemnite (VPDB), plays a critical role in linking carbon isotope delta values to the SI. It is also a quantity used for various data processing procedures including '17O correction', clumped isotope analysis and conversion of carbon isotope delta values into other expressions of isotopic composition. A value for RVPDB(13C/12C) with small uncertainty is therefore desirable to facilitate these procedures. METHODS: The value of RVPDB(13C/12C) was determined by errors-in-variables regression of isotope delta values traceable to VPDB measured by isotope ratio mass spectrometry against isotope ratios traceable to the SI by use of gravimetric mixtures of 12C- and 13C-enriched d-glucose measured by multicollector inductively coupled plasma mass spectrometry. RESULTS: A value of RVPDB(13C/12C) = 0.0111105 ± 0.0000042 (expanded uncertainty, k = 2) was obtained. CONCLUSIONS: The new value for RVPDB(13C/12C) agrees very well with the consensus values calculated from previous measurement results proposed by Kaiser and by ourselves, as well as recent determinations independent of mass spectrometry. The expanded uncertainty of 0.4‰ when expressed as an isotope delta value is a tenfold improvement over the previous best measurement of the isotopic composition of carbon.

Redefinition of the Mole in the Revised International System of Units and the Ongoing Importance of Metrology for Accurate Chemical Measurements.

This Feature highlights the role of metrology, the science of measurement, in maintaining the infrastructure we all rely on for accurate chemical measurements. In particular, the recent change to the definition of the mole, the unit of chemistry, is explained.

Investigation of mass-scale drift effects in the milli-mass range: Influence on high mass resolution mode multicollector-inductively coupled plasma mass spectrometer isotope ratio measurements.

The consequences, possible origins, and prevention of mass-scale drifts in the high mass resolution mode (HR, M/ΔM ≈ 8000) under constant conditions were investigated and simulated in case of a multicollector-inductively coupled plasma mass spectrometer (MC-ICP-MS) using silicon enriched in 28 Si as the main element in this survey. A drifting mass scale strongly impairs the precise and accurate determination of isotope ratios, depending especially on the peak/plateau width. For example, 29 Si+ in Si highly enriched in 28 Si has an extremely small mass plateau width of ΔM ≤ 4 × 10-3 u, compare ΔM(56 Fe+ ) ≈ 18 × 10-3 u, which is to our knowledge one of the smallest plateaus routinely investigated in isotope ratio measurements, thus requiring extreme stability. During warm-up of the double-focusing sector field mass spectrometer, a mass drift up to ΔM/Δt ≥ 0.006 u/hr has been observed. Long-term studies on mass scale stability and simulations concerning fluctuations of the magnetic field B, acceleration voltage Uacc and ESA voltage UESA are reported. A change of one of these quantities of 0.01% induces changes of the mass scale of 6 × 10-3 u, 3 × 10-3 u, and 1 × 10-3 u in the case of B, Uacc , and UESA , respectively. After identifying electrical charging/discharging effects in the mass spectrometer affecting the mass scale stability, the instrument was completely dismantled and carefully reinstalled. Additional stability tests using silicon, strontium, and lead finally yielded a mass drift of ΔM/Δt ≤ 0.001 u/8 h in the case of silicon. This enhanced stability guarantees measurements of isotope ratios on smallest plateaus with lowest uncertainty. The importance of a stable mass scale is pointed out and the relevant quantities of a typical magnetic sector field mass spectrometer are discussed.

Combining Isotope Dilution and Standard Addition-Elemental Analysis in Complex Samples.

A new method combining isotope dilution mass spectrometry (IDMS) and standard addition has been developed to determine the mass fractions w of different elements in complex matrices: (a) silicon in aqueous tetramethylammonium hydroxide (TMAH), (b) sulfur in biodiesel fuel, and (c) iron bound to transferrin in human serum. All measurements were carried out using inductively coupled plasma mass spectrometry (ICP-MS). The method requires the gravimetric preparation of several blends (bi)-each consisting of roughly the same masses (mx,i) of the sample solution (x) and my,i of a spike solution (y) plus different masses (mz,i) of a reference solution (z). Only these masses and the isotope ratios (Rb,i) in the blends and reference and spike solutions have to be measured. The derivation of the underlying equations based on linear regression is presented and compared to a related concept reported by Pagliano and Meija. The uncertainties achievable, e.g., in the case of the Si blank in extremely pure TMAH of urel (w(Si)) = 90% (linear regression method, this work) and urel (w(Si)) = 150% (the method reported by Pagliano and Meija) seem to suggest better applicability of the new method in practical use due to the higher robustness of regression analysis.

Mass Spectrometric Investigation of Silicon Extremely Enriched in (28)Si: From (28)SiF4 (Gas Phase IRMS) to (28)Si Crystals (MC-ICP-MS).

A new generation of silicon crystals even further enriched in (28)Si (x((28)Si) > 0.999 98 mol/mol), recently produced by companies and institutes in Russia within the framework of a project initiated by PTB, were investigated with respect to their isotopic composition and molar mass M(Si). A modified isotope dilution mass spectrometric (IDMS) method treating the silicon as the matrix containing a so-called virtual element (VE) existing of the isotopes (29)Si and (30)Si solely and high resolution multicollector inductively coupled plasma mass spectrometry (MC-ICP-MS) were applied in combination. This method succeeds also when examining the new materials holding merely trace amounts of (29)Si (x((29)Si) ≈ 5 × 10(-6) mol/mol) and (30)Si (x((30)Si) ≈ 7 × 10(-7) mol/mol) extremely difficult to detect with lowest uncertainty. However, there is a need for validating the enrichment in (28)Si already in the precursor material of the final crystals, silicon tetrafluoride (SiF4) gas prior to crystal production. For that purpose, the isotopic composition of selected SiF4 samples was determined using a multicollector magnetic sector field gas-phase isotope ratio mass spectrometer. Contaminations of SiF4 by natural silicon due to storing and during the isotope ratio mass spectrometry (IRMS) measurements were observed and quantified. The respective MC-ICP-MS measurements of the corresponding crystal samples show-in contrast-several advantages compared to gas phase IRMS. M(Si) of the new crystals were determined to some extent with uncertainties urel(M) < 1 × 10(-9). This study presents a clear dependence of the uncertainty urel(M(Si)) on the degree of enrichment in (28)Si. This leads to a reduction of urel(M(Si)) during the past decade by almost 3 orders of magnitude and thus further reduces the uncertainty of the Avogadro constant NA which is one of the preconditions for the redefinition of the SI unit kilogram.

Gravimetric preparation and characterization of primary reference solutions of molybdenum and rhodium.

Gravimetrically prepared mono-elemental reference solutions having a well-known mass fraction of approximately 1 g/kg (or a mass concentration of 1 g/L) define the very basis of virtually all measurements in inorganic analysis. Serving as the starting materials of all standard/calibration solutions, they link virtually all measurements of inorganic analytes (regardless of the method applied) to the purity of the solid materials (high-purity metals or salts) they were prepared from. In case these solid materials are characterized comprehensively with respect to their purity, this link also establishes direct metrological traceability to The International System of Units (SI). This, in turn, ensures the comparability of all results on the highest level achievable. Several national metrology institutes (NMIs) and designated institutes (DIs) have been working for nearly two decades in close cooperation with commercial producers on making an increasing number of traceable reference solutions available. Besides the comprehensive characterization of the solid starting materials, dissolving them both loss-free and completely under strict gravimetric control is a challenging problem in the case of several elements like molybdenum and rhodium. Within the framework of the European Metrology Research Programme (EMRP), in the Joint Research Project (JRP) called SIB09 Primary standards for challenging elements, reference solutions of molybdenum and rhodium were prepared directly from the respective metals with a relative expanded uncertainty associated with the mass fraction of U rel(w) < 0.05 %. To achieve this, a microwave-assisted digestion procedure for Rh and a hotplate digestion procedure for Mo were developed along with highly accurate and precise inductively coupled plasma optical emission spectrometry (ICP OES) and multicollector inductively coupled plasma mass spectrometry (MC-ICP-MS) methods required to assist with the preparation and as dissemination tools.

Improving species-specific IDMS: the advantages of triple IDMS.

Triple isotope dilution mass spectrometry (triple IDMS) has been applied for the first time on protein quantification, especially on transferrin. Transferrin as an acute phase protein is a marker for several inflammation processes in the human body. Therefore, in Germany, the accurate and precise measurement of this important analyte is required. In this work, a new approach to triple IDMS is described and compared to double IDMS. Also, complete uncertainty budgets for both methods were set up to demonstrate the ability of this method to be used as a reference procedure. The relative expanded uncertainty (k=2) for triple IDMS (3.6 %) is smaller than the one for double IDMS (4.0 %). The content of transferrin found in the human serum reference material ERM-DA470k/IFCC ((2.41±0.08) g/kg) with both methods was in good agreement with each other and with the certificate. For triple IDMS ((2.426±0.086) g/kg) and for double IDMS ((2.317±0.092) g/kg), transferrin was determined. Although triple IDMS is a little more time consuming compared to double IDMS, there is the advantage that the isotopic composition of the spike material does not have to be determined. This is very useful especially in case of a marginal isotopic enrichment in the spike or problems with the accurate measurement of the spike isotope ratio.

Reference measurement procedures for the iron saturation in human transferrin based on IDMS and Raman scattering.

Two reference measurement procedures are presented here that allow the determination of the iron saturation in human transferrin, based on different molecular properties. The results, directly derived from the number of ions bound to the protein molecule, are traceable to the SI. Up to now, the iron saturation has only been deduced indirectly from the amount-of-substance ratio of serum iron to transferrin in serum. Interlaboratory tests have shown the need for more accurate methods, as the results from many participant test samples for both parameters do not lie within the acceptable range of deviation given by relevant guidelines when different methods or kits are applied. Using isotope dilution, an HPLC ICP-MS procedure was developed in compliance with the requirements of a primary reference measurement procedure. In this manner, the iron saturation was measured with an associated relative expanded measurement uncertainty of 4%. Based on the results, a straightforward Raman procedure was evolved, which allows the determination of the iron saturation in transferrin with an associated relative expanded uncertainty of 7%.

Silicon isotope ratios affected by sodium-induced broadband interference in high resolution multicollector-ICPMS.

The measurement of isotope ratios of silicon highly enriched in (28)Si ("Si28", x((28)Si) > 99.99%) is influenced by a significant interference (20%) on the (30)Si(+) signal when using a cup configuration of C ((29)Si(+)) and H3 ((30)Si(+)) on a Neptune MC-ICPMS. This interference was observed in silicon solutions with aqueous NaOH (w(NaOH) > 0.001 g/g) and in highly concentrated aqueous NaOH blank solutions (e.g., w(NaOH) = 0.25 g/g) but never in KOH solutions. By redirecting the ions, the interference was detected with all other Faraday cups except the center cup. The interference can be explained by ion scattering induced by the presence of large amounts of sodium. Due to its shielded location, these stray ions were not detected in the center cup. This effect explains an anomalous increase of the abundance of the (30)Si(+) signal in (30)Si/(29)Si isotope ratio measurements made using aqueous NaOH blank solutions with w(NaOH) ≥ 0.001 g/g. For silicon isotopic measurements, it is recommended to use alkaline solutions for sample dissolution and dilution that do not contain sodium. The effects of this interference are extremely important for the experimental determination of the Avogadro constant N(A) using the "silicon sphere approach". It can also have a significant effect on Si isotope analyses in matrices with a naturally high concentration of sodium (e.g., seawater).

Routine internal- and external-quality control data in clinical laboratories for estimating measurement and diagnostic uncertainty using GUM principles.

Healthcare laboratories are increasingly joining into larger laboratory organizations encompassing several physical laboratories. This caters for important new opportunities for re-defining the concept of a 'laboratory' to encompass all laboratories and measurement methods measuring the same measurand for a population of patients. In order to make measurement results, comparable bias should be minimized or eliminated and measurement uncertainty properly evaluated for all methods used for a particular patient population. The measurement as well as diagnostic uncertainty can be evaluated from internal and external quality control results using GUM principles. In this paper the uncertainty evaluations are described in detail using only two main components, within-laboratory reproducibility and uncertainty of the bias component according to a Nordtest guideline. The evaluation is exemplified for the determination of creatinine in serum for a conglomerate of laboratories both expressed in absolute units (µmol/L) and relative (%). An expanded measurement uncertainty of 12 µmol/L associated with concentrations of creatinine below 120 µmol/L and of 10% associated with concentrations above 120 µmol/L was estimated. The diagnostic uncertainty encompasses both measurement uncertainty and biological variation, and can be estimated for a single value and for a difference. This diagnostic uncertainty for the difference for two samples from the same patient was determined to be 14 µmol/L associated with concentrations of creatinine below 100 µmol/L and 14 % associated with concentrations above 100 µmol/L.

Impact of pump flow fluctuations on post column online ID-ICP-MS.

In post column online isotope dilution mass spectrometry (IDMS), the stability of the spike mass flow is a key element. Changes in viscosity or fluctuations in the pump rate of the peristaltic pump may affect the results of post column online IDMS measurements. It was shown by simulating random fluctuations and studying the changes in the resulting integrals of the isotope ratio chromatogram of the sample that even small fluctuations, observable when using peristaltic pumps, can influence the result and especially its uncertainty. The use of a balance to continuously monitor the mass flow of the spike during the measurement which we presented in a previous publication allows now to correct the isotope ratio chromatogram for these fluctuations. Subsequently, the simulated effect was verified experimentally for the determination of Se-Met in the human serum reference material BCR 637, where the corrected mass fraction was plainly closer to the mass fraction obtained by species specific IDMS. Additional attention was paid to the fact that there is a time shift between the observation of the fluctuations in the pump rate and the detection of these fluctuations in the ICP-MS.

Double isotope dilution surface-enhanced Raman scattering as a reference procedure for the quantification of biomarkers in human serum.

Double isotope dilution surface-enhanced Raman scattering (double IDSERS) is qualified as a method for accurate and precise determination of biomarkers in human blood serum. Providing a full evaluation of the measurement uncertainty as well as traceability to a reference material sets the procedure in line with the requirements of a primary ratio method. Data evaluation is based on a partial least squares (PLS) model, whose prediction ability is validated from quantifying the uric acid concentration in both an artificial reference solution and a real human blood serum sample. With the proposed approach, the uric acid serum concentration can be determined with an uncertainty of 1.6% at a confidence level of 95%.