ACCELERATOR MASS SPECTROMETRY METHOD

20180277347 ยท 2018-09-27

    Inventors

    Cpc classification

    International classification

    Abstract

    Accelerator mass spectrometry methods for analyzing a sample are provided. In an embodiment, the method includes measuring with an accelerator mass spectrometry system, an isotope of a first element and an isotope of a second element, wherein the measurement of the second element is used for normalizing the measurement of the first element.

    Claims

    1. An accelerator mass spectrometry method for analyzing a sample, comprising measuring with an accelerator mass spectrometry system an isotope of a first element and an isotope of a second element, wherein the measurement of the second element is used for normalizing the measurement of the first element.

    2. The method according to claim 1, wherein the method is for determining the quantity and/or concentration of the first element in the sample, and comprises providing the sample, analyzing a part of the sample with accelerator mass spectrometry with sequential injection of ions of an isotope of the first element and ions of an isotope of the second element into the accelerator, thereby measuring said ions separately, and wherein said normalization involves using a ratio of a value derived from the result of the measurement of ions of an isotope of the first element to a value derived from the result of the measurement of ions of an isotope of the second element to calculate said quantity and/or concentration.

    3. The method according to claim 1, wherein said first element is fluorine and said second element is chlorine.

    4. The method according to claim 3, wherein said accelerator mass spectroscopy system comprises a tandem accelerator and an injector for sequentially injecting selected ions into the accelerator, and the method comprises sequentially selecting masses corresponding to .sup.19F.sub.2.sup. or .sup.19F.sup. and .sup.35Cl.sup. with said injector.

    5. The method according to claim 4, wherein said method comprises sequentially selecting masses corresponding to .sup.19F.sub.2.sup. and .sup.35Cl.sup. with said injector, and wherein the accelerator is configured for producing F.sup.+ and Cl.sup.2+.

    6. The method according to claim 1, wherein a stable first isotope of said first element is measured, and wherein said second element is more abundant than said first element in the sample.

    7. The method according to claim 1, wherein said sample comprises a biological sample.

    8. The method according to claim 1, wherein said sample comprises one or more selected from the group consisting of urine, faeces, blood, plasma, serum, tissue, saliva, exhaled air, and milk.

    9. The method according to claim 1, wherein a sample is obtained from an organism which during a time period has been exposed to a substance or to which a substance has been administered during a time period, wherein the sample is obtained from said organism at a pre-determined and/or measured time after said time period.

    10. The method according to claim 1, wherein said sample is obtained in a mass balance study from a subject to which a dose of a test compound has been administered.

    11. The method according to claim 10, wherein said sample comprises said test compound and/or metabolites of said test compound.

    12. The method according to claim 10, wherein molecules of said test compound comprise a fluorine atom covalently bound to a carbon atom.

    13. The method according to claim 1, wherein the method comprises separating ions of said first and second element upstream of the detector for ions of at last the first element.

    14. The method according to claim 1, the first element is platina and the second element is gold.

    15. The method according to claim 7, wherein the biological sample is a physiological sample or excretion sample or is at least in part derived thereof.

    16. The method according to claim 1, wherein the method is for determining the quantity and/or concentration of the first element in the sample, and comprises providing the sample, analyzing the sample with accelerator mass spectrometry with sequential injection of ions of an isotope of the first element and ions of an isotope of the second element into the accelerator, thereby measuring said ions separately, and wherein said normalization involves using a ratio of a value derived from the result of the measurement of ions of an isotope of the first element to a value derived from the result of the measurement of ions of an isotope of the second element to calculate said quantity and/or concentration.

    Description

    EXAMPLE 1

    [0065] The AMS comprises several units, including the low energy end (including the ion source), the accelerator and the high energy end (including the gas phase ionisation detector). Generally, the settings may vary, for example depending on the selection of the ions.

    [0066] At the low energy end the negatively charged dimer of F was selected for transmission through the bouncer injector (.sup.19F.sub.2.sup.). After the accelerator positively charged F (F.sup.+) ions are selected. Regarding the counter ion; Cl.sup. was selected at the low energy side, and Cl.sup.2+ at the high energy side of the AMS.

    [0067] Example Instrumental Settings

    [0068] Ionizer: 18 A; Cesium temperature: 60 C; Target voltage: 7 kV; Extraction voltage: 28 kV; Terminal voltage: 600 kV; Stripper gas pressure: 2 20-2 mbar; Detector gas pressure: 7 mbar; ESA voltage: 40 kV; Bouncer Injector: 84 A; Analyzing magnet: 214 A; Time for Cl: 100 s; Time for F: 10 ms

    [0069] The following experiment has been performed:

    [0070] A solution of 1.10.sup.7 g/mL CaF was prepared in methanol and mixed with a 10 mg/mL solution of LiCl (prepared in methanol). To each sample silver (Ag) was added, and the targets for the AMS were pressed. The silver provides for more material for pressing and for conduction during the ionisation process in the AMS source. The results are shown in FIG. 1 and table 1. This example demonstrates F/Cl calibration with AMS. Good results were obtained even for concentrations lower than 100 pg F/ml, in particular a linear correlation between F/Cl isotope ratio and F concentration was achieved.

    [0071] In FIG. 1, H11-36 is the number of the example. The line shows the linear interpolation with y=8.56E-14x1.70E-12 and R.sup.2=0.984. The diamonds show the experimental results.

    [0072] Table 1, note (1): the samples are mixed with 0.25 mg LiCl/mg Au. When using only a 1 mg/mL LiCl solution the same ratio would be measurable if the F concentration would also drop by a factor 10. Thus the concentration of F in pg/mL that can be quantified would also be a factor 10 lower. The amount of Cl that will be sufficient to generate a stable current on the Faraday cups (after the analysing magnet) is not yet determined for the example AMS, however it is expected that it can be lower than the 0.25 mg LiCl/mg Ag that is currently used.

    TABLE-US-00001 TABLE 1 L CaF pg F/mL solution that can be (1 .Math. 10.sup.7 Measured quantified mg Ag g/mL) pg F/mL ratio (1) Sample 1 1 40 19800 1.12174E10 1980 Sample 2 1 20 9900 6.09813E11 990 Sample 3 1 10 4500 1.69919E11 450 Sample 4 1 4 500 8.12944E12 50 Sample 5 1 2 250 6.06532E12 25 Sample 6 1 0 0 2.3481E12 0