Accuracy in isotope ratio

Merritt, D. A. and J. M. Hayes (1994) Factors controlling precision and accuracy in isotope-ratio-monitoring mass spectrometiy. Analyt Chem. 66, 2336-47. 

Table 13.2 Precision and accuracy in isotope ratio measurement of toxic metals by GC-MS ...

The advantages and limitations of these mass spectrometers are the same as described earlier. ICPMS has a very high throughput compared to TIMS, and the MC-ICPMS has quite similar accuracy in isotopic ratio measurements and sensitivity as the SIMS and TIMS methods. 

Heumann, K. G., Gallus, S. M., Radlinger, G., and Vogl, J. (1998) Precision and accuracy in isotope ratio measurements by plasma source mass spectrometry. J. Anal. At. Spectrom., 13, 1001. 

The measurements that have been made at Rochester and the experience that has been gathered over the years on the operation of sputter ion sources [38] indicate that an analytical tool of unprecedented sensitivity and accuracy for isotopic ratio determinations can be constructed by coupling SIMS technology with the new accelerator technique. The only difference in principle between the experiments that have been conducted to date and the technique as it would be applied in secondary ion mass spectrometry is that the primary beam of cesium would be focussed to a fine probe of pm dimensions rather than the spot diameters of approximately 1 mm that have been used to date. 

Corrections for instrumentally-produced mass fractionation that preserve natural mass dependent fractionation can be approached in one of two ways a double-spike method, which allows for rigorous calculation of instrumental mass fractionation (e.g., Dodson 1963 Compston and Oversby 1969 Eugster et al. 1969 Gale 1970 Hamelin et al. 1985 Galer 1999 see section Double-spike analysis ), or an empirical adjustment, based on comparison with isotopic analysis of standards (Dixon et al. 1993 Taylor et al. 1992 1993). The empirical approach assumes that standards and samples fractionate to the same degree during isotopic analysis, requiring carefully controlled analysis conditions. Such approaches are commonly used for Pb isotope work. However, it is important to stress that the precision and accuracy of isotope ratios determined on unknown samples may be very difficult to evaluate because each filament load in a TIMS analysis is different. 

An analytical procedure has been proposed for precise uranium isotope ratio measurements in a thin uranium layer on a biological surface by LA-ICP-MS using a cooled laser ablation chamber.125 One drop of uranium isotope standard reference materials NIST, 350, NIST 930, of our isotopic laboratory standard CCLU 500 (20p.l, U concentration 200 ng 1) and of uranium with natural isotopic pattern were deposited on the leaf surface and analyzed by LA-ICP-MS at well defined laser crater diameters of 10, 15, 25 and 50 p.m. A precision for measurements of isotope ratios in the range of 2.1-1.0% for 235U/238U in selected isotope standards was observed whereby the precision and the accuracy of isotope ratios compared to the non-cooled laser ablation chamber was improved.125... 

In order to overcome, or at least minimise, such drawbacks we can resort to the use of chemometric techniques (which will be presented in the following chapters of this book), such as multivariate experimental design and optimisation and multivariate regression methods, that offer great possibilities for simplifying the sometimes complex calibrations, enhancing the precision and accuracy of isotope ratio measurements and/or reducing problems due to spectral overlaps. 

As the precision of the ICP-MS isotope ratio is poor compared with the precision using TIMS, the range of applications for ICP-MS have traditionally been limited to measuring induced changes in the isotopic composition of a target element (for example, to calibrate by means of isotope dilution). However, the introduction of multicollector ICP-MS systems to enhance precision and accuracy in isotopic analysis opened up novel applications. 

Accuracy of isotope ratio measurement is critically dependent on having the instrument properly calibrated and following correct analytical protocol. Mass bias is present to some degree in all thermal ionization analyses, and a lot of ingenuity has been invested in mitigating its effect. Mass bias arises from a... 

Matrix effects (termed instrumental mass bias) also present problems in isotope ratio analysis as the measured isotope ratio is almost always light isotope enriched relative to the accepted ratio, and the degree of this enrichment depends on the matrix composition. Although mass bias variations between different mineral compositions are relatively minor for most elements (a few percentage points at most), the high accuracy required in isotope analysis (often 1% or better) demands careful calibration. For isotope ratio measurements in essentially isochemical... 

Figure 1.11. The effect of sample size and isotope abundance on the accuracy of isotope ratio measurements in GC-MS using a quadrupole instrument and computer data system. The curves are based on numerous separate studies (reproduced from reference [110])...

Detector saturation can effect both quantitative and qualitative data analysis, and each of these effects should be appreciated. The effect on sample quanti-tation is intuitive, where for instance a twofold increase in sample concentration produces a less than twofold increase in response. This will cause a flattening of calibration curves at higher concentrations. For API techniques, source saturation (or ion suppression) is another source of response saturation independent of detector saturation. Detector saturation can also effect qualitative measurements such as mass accuracy and isotope ratio calculations. In the former, when a mass spectral peak that has some finite resolution stalls to saturate the detector the peak-top calculations that provide the m/ measurement of the peak will become ambiguous. Likewise, it is possible that as one isotope of an ion starts to saturate the detector, adjacent isotopes in the distribution will still provide a linear response. The result of this is that incorrect isotope ratios will be obtained. Changes in relative isotope ratios of individual spectra across a chromatographic peak is an indicator of possible detector saturation. 

In Earth sciences, the relative differences in isotopic ratios between a sample and a standard are mostly used for reporting stable isotope abundances and variations. The reason is that the absolute value of an isotopic ratio is difficult to determine with sufficient accuracy for geochemical applications. The reporting notation employed is the 5-value, defined as... 

There are also a few limitations of GC-MS. The problems encountered previously by several investigators have been the poor precision and accuracy of isotope ratio data, the memory effect during the sequential analysis of samples with different isotope ratios, and the lack of suitable chelating agents. In addition, the contributions of the different isotopes of C, N, S, etc., present in the chelating agent need to be accounted for, particularly when studying the enrichments in different samples followed by tracer administration (intravenous or oral). 

Besides suppression of sensitivity caused by solutions with high ionic strength [11,12], high salt concentrations also affected the accuracy of isotope ratio determinations, possibly due to greater losses of the lower-mass uranium isotopes as a result of ion-ion repulsions in the ion beam known as the space-charge effect. While this may not be much of an issue for water analyses, the application of these principles to the accurate determination of uranium isotope ratios in urine imphes that either one needs to attempt a close matrix match for every sample or sample preparation should include the elimination of as many neutral and ionic compounds as possible within the constraints of minimal sample preparation complexity. 

In order to perform the isotope ratio experiment correctly it is necessary to compensate for a number of biases in the instrumentation. Mass spectrometers and their associated ion optics do not transmit ions of different mass equally. In other words, if an elemental solution composed of two isotopes with an exactly 1 1 molar ratio is analyzed using ICP-MS, then a 1 1 isotopic ratio will not necessarily be observed. This so-called mass bias will differ depending on mass, and even very small mass-biases can have deleterious effects on the accuracy of isotope ratio determinations, so a correction must always be made using an isotopic standard of known composition, as shown in Equation (173) ... 

Over the past decade, awareness has grown significantly that isotopic analysis by ICP-MS is full of potential sources of bias that need to be controlled carefully to generate not only precise but also accurate data. Whereas in the early days the speed advantage of ICP-MS over TIMS in isotope ratio measurements has been emphasized has been emphasized because it permits direct analysis of digested samples, this advantage has now mostly vanished. Because of much better control of spectral and non-spectral interferences, it is now common practice in ICP-MS as in TIMS to separate the element chemically from the matrix when high analytical accuracy is of concern. This does not equalize the two... 

In this equation the index al represents the interfered isotope of the element a while the index p 1 represents the interfering isotope of element p. /fpi/pa represents the measured isotope amount ratio P l/p2, where P2 is a non-interfered isotope of element p. Since the interference is present, this ratio cannot be accurately measured in the sample and therefore has to be replaced with a value derived from an alternative source. Most ICP-MS instruments simply replace the ratio I3i/I32 by the reported lUPAC ratio value. ° They do not consider mass discrimination effects, despite the fact that equation (4.1) only deals with measured intensities, which are intrinsically affected by mass discrimination. For measurements requiring higher accuracy, especially isotope ratio measurements, this fact has to be taken into account and the interference correction has to be modified accordingly. 

Moens and co-workers used the fluoride transfer reaction frommethyl fluoride to Sr+ (resulting in the formation of SrF+) to separate the strontium isotope pattern from a rubidium-containing background matrix, with the aim of making Rb-interference free isotope ratio measurements of strontium. However, it has been proposed that mass discrimination effects due to the ion-molecule reaction can alter the experimentally determined isotope pattern, thereby degrading the accuracy of isotope ratio measurements made using this approach. Consider the reaction... 

Isotopic dilution analysis is widely used to determine the amounts of trace elements in a wide range of samples. The technique involves the addition to any sample of a known quantity (a spike) of an isotope of the element to be analyzed. By measuring isotope ratios in the sample before and after addition of the spike, the amount of the trace element can be determined with high accuracy. The method is described more fully in Figure 48.13. 

Accurate, precise isotope ratio measurements are important in a wide variety of applications, including dating, examination of environmental samples, and studies on drug metabolism. The degree of accuracy and precision required necessitates the use of special isotope mass spectrometers, which mostly use thermal ionization or inductively coupled plasma ionization, often together with multiple ion collectors. 

Instability in the flame leads to varying efficiencies in ion formation within the plasma (varying plasma temperature) and, therefore, to variations in measured isotope ratios (lack of accuracy). 

If solid samples are vaporized quickly, then the sample enters the flame as a small plug and the elements must be measured over a short period of time. This mode is useful for high sensitivity because the entire sample passes through the flame in a short time. (The abundances of ions appear as a sharp peak on the output.) If samples are introduced continuously, then ultimate sensitivity may be reduced, but isotope ratios can be determined continuously to provide high accuracy. 

Accurate, precise isotope ratio measurements are used in a variety of applications including dating of artifacts or rocks, studies on drug metabolism, and investigations of environmental issues. Special mass spectrometers are needed for such accuracy and precision. 

---