Uncertainty Modeling and the Double Spikes

Uncertainty evaluation is often perceived as a passive (a posteriori) part of the analysis process. The double-spike method of isotope ratio calibration, however, has demonstrated that uncertainty evaluation is an active research tool and the results obtained this way are significant in steering the entire field of mass bias correction. 

It is known that the random error magnification in isotope dilution depends largely on the composition and the amount of the admixed isotopic spike (see also 

Chapter 8). The same is true for the results from the double-spike method. Finding the optimal isotopic composition of the spike, however, has proved to be a challenge. 

It can be shown that this type of conclusion, that is, that the uncertainty of isotope amount ratios depends on the denominator isotope, is a result of ignoring the correlations between the isotopic signals and their ratios [27[. 

Virtually all published uncertainty evaluations of mass spectrometric methods assume independent ion currents or isotope amount ratios for all simultaneously measured isotopes [62, 63]. It is unclear why this paradigm has received such widespread acceptance. Isotopic signals in mass spectrometry are always correlated, provided that they are well above the background noise. The method of internal standardization is made possible precisely because mass spectrometric signals are correlated. 

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