Isotope ratio mass spectrometry instrumentation

The purpose of this paper was to briefly describe fundamentals of isotope ratio mass spectrometry (IRMS), review the analytical systems currently available both for traditional dual-inlet (DI-IRMS) and the newer continuous-flow (CF-IRMS) and describe the specialized instruments that are in general use for isotopic measurements. 

Abstract In this chapter we discuss practical techniques and instrumentation used in experimental measurements of kinetic and equilibrium isotope effects. After describing methods to determine IE s on rate constants, brief treatments of mass spectrometry and isotope ratio mass spectrometry, NMR measurements of isotope effects, the use of radio-isotopes, techniques to determine vapor pressure and other equilibrium IE s, and IE s in small angle neutron scattering are presented. 

To avoid the kind of problems which trouble whole-molecule mass spectrometry it is better to use instrumentation especially designed for high precision measurements of isotope ratios isotope-ratio mass spectrometry (IRMS). 

More recently, enantiomer ratios have been used as evidence of adulteration in natural foods and essential oils. If the enantiomer distribution of achiral component of a natural food does not agree with that of a questionable sample, then adulteration can be suspected. Chiral GC analysis alone may not provide adequate evidence of adulteration, so it is often used in conjunction with other instrumental methods to completely authenticate the source of a natural food. These methods include isotope ratio mass spectrometry (IRMS), which determines an overall 13C/12C ratio (Mosandl, 1995), and site-specific natural isotope fractionation measured by nuclear magnetic resonance spectroscopy (SNIF-NMR), which determines a 2H/ H ratio at different sites in a molecule (Martin et al 1993), which have largely replaced more traditional analytical methods using GC, GC-MS, and HPLC. 

The main application of the instrument will be for tracer kinetic and pharmacological measurements in biomedical studies. Essentially, C IRMS is an alternative technique to C Isotope Ratio Mass Spectrometry ( C IRMS), which is widely accepted within the biomedical community. C IRMS is at least 1(X)-1000 times more sensitive than C IRMS. This allows, for example, that the kinetics of C-labelled enzymes, aminoacids or carcinogens can be studied in the human body at levels that are comparable to actual environmental exposure. 

Samples may be analysed automatically, where the instrument takes full control of all aspects of the measurement, or manually where sensitive operations, such as raising the sample temperature and identifying the sample ion beam are controlled by the analyst. An extensive description of modern isotope ratio mass spectrometry is given by Habfast (31). 

Brenna JT. High-precision gas isotope ratio mass spectrometry recent advances in instrumentation and biomedical applications. Acc Chem Res 1994 27 340-346. 

This chapter provides an overview of mass spectrometer function and operation. It describes specific instrument types with demonstrated or potential application for measuring radionuclides and surveys the application of these instruments to radionuclide detection. Finally, it discusses the circumstances under which use of mass spectrometers is advantageous, the type of mass spectrometer used for each purpose, and the conditions of sample preparation, introduction and analysis. Its perspective is from a national laboratory active in environmental and non-proliferation monitoring. It emphasizes isotope ratio measurements, but mass spectrometric measurements also provide isotope mass information. Several recent books describe elemental and isotope ratio mass spectrometry in far greater detail than is presented here (Barshick et al., 2000 De Laeter, 2001 Montaser, 1998 Nelms, 2005 Platzner, 1997 Tuniz et al., 1998). High-resolution mass spectrometry forms the basis of the mass scale used for elemental and isotopic masses (Coplen, 2001), but this application of MS falls outside the scope of this chapter. 

Gas-isotope-ratio mass spectrometry is used to measure the and O abundances in the H2 and CO2 samples, respectively. The instrumentation is known as gas-isotope-ratio mass spectrometry because all samples entering the ion source of the mass spectrometer must be in gaseous forms such as H2 for abundance measurements and CO2 for abundance measurements. Upon entry into the ion source of the mass spectrometer, the H2 or the CO2 gas is ionized by electrons to form positively charged ions of and for H2 or and C 0 for CO2. Because of the difference in ionic masses between these positively charged ions, they are separated into two ion beams through a magnetic field. The amounts of H and in the H2 or and in the CO2 are directly proportional to the amplified ion beam intensities of the and or C 02 ... 

CF-IRMS Continuous flow-isotope ratio mass spectrometry. A procedure that uses an instrument that is capable of repeatedly and rapidly measuring the masses of selected gases (e.g., carbon dioxide, hydrogen, nitrogen) delivered in a continuous gas stream from another instrument, such as an elemental analyzer or a gas chromatograph, to determine their isotopic compositions. 

The book concentrates on the most common instruments nsed in chemical, environmental, biological, and medical research. Less frequently encountered forms of mass spectrometry are not addressed, such as inductively coupled plasma mass spectrometry (ICP-MS) isotope ratio mass spectrometry (IRMS), accelerator mass spectrometry (AMS), proton transfer reaction mass spectrometry (PTRMS), and single-particle laser ablation time-of-flight mass spectrometry (SPLAT). 

Mass spectrometric approaches are also very useful for the measurement of stable isotopes in drug metabolism studies. The application of MS to the quantitative measurement of stable isotope has been limited due to the high cost and sophistication of the instruments necessary for stable isotope enrichment studies. Nonetheless, recent improvements in instrument design and performance, as well as computer software for instrument control, data acquisition, and analysis, have increased the sensitivity and reliability of stable isotopic enrichment studies. These new MS instruments, including continuous-flow isotope ratio mass spectrometry (CF-IRMS) and HPLC-chemical reaction interface mass spectrometry (HPLC-CRIMS) are increasingly less expensive, easier to operate, and accessible for mass balance/ metabolite identification studies with stable isotopes. 

Isotope-ratio mass spectrometry is used to determine the relative isotopic abundances of major and trace elements. Mass spectrometric methods are able to measure the relative concentrations of both radioactive and stable isotopes with a precision and accuracy of better than 0.001%. To achieve measurements of this quality, isotope-ratio MS relies almost exclusively on magnetic-sector instruments operated in temperature-controlled laboratories (Becker and Dietze 2000). 

FIGURE 15.5 Diagram showing the main sections of an IRMS instrument (based on a ThermoFinnigan DELTAp XP instrument [28]). Reprinted from Benson, S., Lennard, C., Maynard, P, Roux, C. (2006) Forensic applications of isotope ratio mass spectrometry—a review. Forensic Sci. Int, 157(1), 1-22, with permission from Elsevier [1]. 

Liquid Chromatography While GC-IRMS instruments were commercialized in 1998, the interface allowing liquid chromatography-isotope ratio mass spectrometry (LC-IRMS) coupling was not commercially available until 2004 [38]. Godin et al. [39] provide a schematic overview of an LC instrument interfaced... 

Isotopic abundances can be determined with isotope ratio mass spectrometry (IRMS), an instrument described in Chapter 5. To analyze the stable isotope ratios of carbon and oxygen, the instrumental procedure incorporates a conversion of all organic carbon to CO2, followed by the introduction of that compound into the mass spectrometer. The fragments of interest have amu s of 44 ( 2)/ 45 ( C 2 and and 46 ( 2c 0 D, and 2c 02). ... 

In the early days of mass spectrometry, research was focused on gas source isotope ratio mass spectrometry (IRMS) or thermal ionization mass spectrometry (TIMS), with as the main aim the determination of the isotopic composition and molar masses of the elements. Since the 1940s, isotope ratio measurements have also been used for the determination of isotope ratios involving a radiogenic nuclide and for quantitative element determination via isotope dilution (see also Chapter 8). The age of the solar system and the Earth were also of particular interest within isotope ratio science. With the establishment and improvement of TIMS instrumentation, the awareness of the importance of precision and accuracy and the need to be able to reproduce a result in another laboratory grew, while... 

The steady-state operation of the ICP source is beneficial for the correction of instrumental mass bias by standard-sample bracketing, where the raw (measured and uncorrected) isotope ratio data of a sample are referenced to the results obtained for an isotopic standard, which is preferentially analyzed before and after each sample [27, 35]. This technique is similar to the standardization method commonly used in gas source isotope ratio mass spectrometry. To account best for drifts in instrumental mass bias, which can be particularly severe for light elements such as Li and B, data collection often utilizes multiple but short analytical measurements for samples that are each bracketed by standard analyses. Switching between samples and standards can be very rapid, if long washout protocols are not required, and mass spectrometric measurements of about 5 min or less have been used to optimize the precision of Li and Mg isotope ratio measurements by MC-ICP-MS [111, 112]. 

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