Methods in mass spectrometry using collision gas as an ion source

Abstract

Mass spectrometry methods, the method comprising the following steps: a. Generating an ion beam from an ICP ion source; b. Guiding the ion beam into a collision cell, c. Introducing a charge-neutral analyte gas into the collision cell through a gas inlet on the collision cell; d. Generation of ions from the analyte gas in the collision cell by means of collisions between the analyte gas and the ion beam; e. Sending generated ions from the collision cell to a mass spectrometry analyzer; and f. Analyzing the mass of the emitted ions of the ionized analyte gas, which includes determining an isotopic abundance or isotopic ratio of the ions in the mass analyzer; wherein the method comprises: adjusting the energy of the ion beam to fragment at least a fraction of the analyte gas to form at least one ionized atomic or molecular fragment of the analyte gas, sending the formed ionized atomic or molecular fragment to the mass analyzer and analyzing the fragment for its mass.

Description

Field of invention

[0001] The invention relates to a mass spectrometer, in particular an inductively coupled plasma mass spectrometer (ICP-MS), and its uses for determining atomic or molecular species present in samples. The invention further relates to mass spectrometry methods. Introduction

[0002] Mass spectrometry is an analytical method for the qualitative and quantitative determination of molecular species present in samples, based on the mass / charge ratio and the abundance of gaseous ions.

[0003] In inductively coupled plasma mass spectrometry (ICP-MS), atomic species can be measured with high sensitivity and precision at concentrations as low as 1 in 10 15in relation to a background that does not have a disturbing influence. In ICP-MS, the sample to be analyzed is ionized with an inductively coupled plasma (ICP) and then separated and quantitatively determined in a mass analyzer.

[0004] Precise and accurate isotope ratio measurements often represent the only way to gain deeper insights into scientific questions that cannot be answered by other analytical techniques. Multi-collector ICP-MS is an established method for accurate isotope ratio analysis with high precision. Applications of ICP-MS can be found in the fields of geochronology, geochemistry, cosmochemistry, biogeochemistry, environmental science, and the life sciences. However, elemental and molecular interference in the mass spectrometer can limit the achievable precision and accuracy of the analysis.

[0005] These interferences can be present in the sample material itself or be generated during sample preparation from a contamination source, such as the chemicals used, sample containers, or through fractionation during sample cleanup. Contaminating species can also be generated in the ion source or the mass spectrometer.

[0006] To achieve accurate isotope ratio measurements with high precision, extensive physical and chemical sample preparation is often employed to obtain clean samples free from potential interferences and impurities that could adversely affect the mass spectrum. Typical analyte concentrations in the sample material used in isotope ratio ICP-MS are in the parts-per-billion range. The analyte of interest may also be concentrated in small inclusions or crystals within a heterogeneous sample material, such as rock samples.

[0007] Extensive quality control measures are often integrated into sample preparation to ensure that the preparation process itself does not alter the isotopic ratio of the sample material. Each sample preparation step carries the potential for introducing impurities and / or causing isotopic fractionation of the analytes to be extracted from the original sample material—which could be, for example, a rock, a crystal, soil, a dust particle, a liquid, and / or organic matter. Even when all these steps are performed with great care, the possibility of contamination, incomplete separation, and mass-spectrum interference remains.

[0008] Ideally, one would want to eliminate the chemical sample preparation step entirely. Furthermore, chemical sample preparation is impossible when a laser is used to directly ablate the sample and flush the ablated material into the ICP source. In these cases, there is no chemical separation of the desired analyte from the sample matrix, and all specificity must be derived from the mass analyzer and the sample introduction system within the mass analyzer. Specificity describes the ability of an analyzer to unambiguously identify and detect a particular species in a sample. One way to achieve specificity in a mass spectrometer is to ensure that the mass resolution M / (ΔM) of the mass analyzer is high enough to distinguish one species from another, where ΔM is the mass difference between the species and M is the mass of the species of interest.This requires very high mass resolution for isobaric interferences with species of the same nominal mass. In sector-field mass spectrometers, high mass resolution necessitates the use of very narrow entrance slits into the mass analyzer, and the small entrance slit significantly reduces the transmission and thus the sensitivity of the mass analyzer. Consequently, this approach becomes impractical in cases where very high mass resolution is required. This poses a particular challenge for mass spectrometry instruments, for which there are currently only limited technical solutions.

[0009] The inductively coupled plasma (ICP) ion source is a highly efficient ion source for elemental and isotopic analysis using mass spectrometry. This analytical method can detect elements in concentrations in the very low range, down to a fraction in 10 15(parts per quadrillion, ppq) on undisturbed isotopes with low background activity. The method involves ionizing the sample to be analyzed with an inductively coupled plasma and subsequently using a mass spectrometer to separate and quantify the ions thus generated.

[0010] By ionizing a gas, usually argon, in an electromagnetic coil to create a high-energy mixture of argon atoms, free electrons, and argon ions, a plasma is generated in which the temperature is high enough to cause the atomization and ionization of the sample. The generated ions are introduced, via one or more pressure reduction stages, into a mass analyzer, which is usually a quadrupole analyzer, a magnetic sector analyzer, or a time-of-flight analyzer.

[0011] A description of ICP mass spectrometers can be found in the articles A Beginner's Guide to ICP-MS by Robert Thomas (SPECTROSCOPY 16(4)-18(2), April 2001-February 2003), the disclosure of which is hereby incorporated in its entirety by reference (however, in case of contradictions between statements in the incorporated reference and statements in the present application, the present application shall prevail).

[0012] A known design of a multi-collector (MC) ICPMS instrument is the NEPTUNE™ or NEPTUNE Plus™, as described in brochures and operating manuals of Thermo Scientific™, the disclosures of which are hereby incorporated in their entirety by reference (however, in case of contradictions between statements in the incorporated reference and statements in the present application, the present application shall prevail).

[0013] High-precision mass analyzers enable high mass resolution for the separation of element ions from molecular species that inevitably form to some extent within the ICP source (e.g., OH). + , NO + , CO + , CO2 + , ArO + , ArN + , ArAr + , etc.) and interfere with the elemental ions. Certain elements are known for their relatively poor detection limits in ICP-MS. These are predominantly those negatively affected by artifacts or spectral interferences generated by ions originating from the plasma gas, matrix components, or the solvent used to dissolve the samples. Examples include, but are not limited to... 40 Ar 18 Q for determining 56 Fe, 38 ArH for the determination of 30 K, 40 Ar for the determination of 40 Approximately, 40 Ar 40 Ar for the determination of 80 See, 40 Ar35 Cl for the determination of 75 As, 40 Ar 12 C for the determination of 52 Cr and 35 Cl 16 O for the determination of 51 V.

[0014] Using a high-mass-resolution magnetic sector multicollector mass spectrometer, the molecular species can be separated along the focal plane of the mass spectrometer, allowing only the elemental ions to be detected, while molecular interferences are discriminated against at the detector slit (see Weyer & Schwieters, International Journal of Mass Spectrometry, Vol. 226, No. 3, May 2003, incorporated into this document by reference). This method works well for interferences where the relative mass difference between the analyte and the interference is in the range of (M / ΔM) < 2,000 - 10,000 (M: mass of the analyte, ΔM: mass difference between analyte and interference).

[0015] A sector mass spectrometer with high mass resolution typically results in reduced ion optical transmission to the mass analyzer. This is because the high mass resolution necessitates a narrower entrance slit and smaller apertures to minimize second- and third-order angular aberrations downstream in the ion beam path from the entrance slit to the detector. In the particular case where the sample volume is limited or the analyte concentration in a sample is low, the reduced sensitivity in high-mass-resolution mode poses a significant problem. It directly leads to lower analytical accuracy due to the poorer counting statistics resulting from the effectively reduced transmission through the sector field analyzer.Therefore, high mass resolution is generally not a practical solution for eliminating interference and achieving specificity in cases where the mass resolution performance of the mass spectrometer would be sufficient to distinguish the interference.

[0016] There are other applications where isobaric interference of element ions cannot be avoided by sample preparation and where a mass resolution of >> 10,000 would be required to separate the interfering species. One example is the analysis of 40 Ca with argon-based plasma. There is strong interference of elemental 40 Ar + on 40 Approx + The mass resolution required to separate the two species would be >193,000, which is considerably larger than the value achievable by a magnetic sector field analyzer.

[0017] One solution to this problem is collision cell technology (ICP-CCT), which comprises a collision / reaction cell located between the ion source but upstream of the analyzer. This collision cell offers an additional means of achieving specificity for analysis. Instead of mass resolution, it uses chemical reactions to distinguish between interfering species. A collision gas, such as helium or hydrogen, is introduced into this cell, which typically includes a multipole antenna operating in a radio frequency mode to focus the ions. The collision gas collides with and reacts with the ions in the cell to convert interfering ions into non-interfering species.

[0018] A collision cell can be used to remove unwanted artifact ions from an elemental mass spectrum. The use of a collision cell is described, for example, in documents EP 0 813 228 A1, WO 97 / 25737 A1, and US 5 049 739 A, all of which are incorporated into this document by reference. A collision cell is essentially a gas-tight enclosure through which the ions are passed. It is placed between the ion source and the main mass analyzer. A target gas (molecular and / or atomic) is introduced into the collision cell with the aim of promoting collisions between ions and the neutral gas molecules or atoms. A collision cell can be a passive cell, as disclosed in US 5 049 739 A, or the ions can be trapped in the cell by means of an ion optic, for example a multipole driven by alternating voltages or a combination of alternating and direct voltages, as in EP 0 813 228 A1.This allows the collision cell to be configured to pass ions with minimal losses, even when the cell is operated at a pressure high enough to ensure numerous collisions between the ions and the gas molecules.

[0019] For example, the use of a collision cell, in which approximately 2% H2 is added to the helium gas in the cell, neutralizes 40 Ar + -ions through low-energy collisions of the 40 Ar + with the H2 gas and a resonant charge transfer of an electron from the H2 gas to neutralize the 40 Ar + -ions (see Tanner, Baranov & Bandura, 2002, Spectrochimica Acta Part B: Atomic Spectroscopy, 57:1361-1452, incorporated into this document by reference). This charge transfer mechanism is extraordinarily selective and efficiently neutralizes argon ions, thus distinguishing 40 Ar + -ions of40 Approx + . Such effects are sometimes referred to as chemical resolution (Tanner & Holland, 2001, in: Plasma Source Mass Spectrometry: The New Millennium, Publisher: Royal Soc of Chem), in comparison to mass resolution in a mass spectrometer.

[0020] In addition to charge transfer reactions, other mechanisms within the collision cell can be employed to reduce interference using different collision gases or mixtures of collision gases. These mechanisms include: kinetic energy differentiation due to collisions within the collision cell (e.g., Hattendorf & Guenther, 2004, J. Analytical Atomic Spectroscopy 19:600, incorporated into this document by reference); fragmentation of molecular species within the collision cell (see Koppenaal, D., W., Eiden, G., C. and Barinaga, C., J., (2004), Collision and reaction cells in atomic mass spectrometry: development, status, and applications, Journal of Analytical Atomic Spectroscopy, Vol. 19, pp. 561-570, incorporated into this document by reference); and / or mass displacement reactions within the collision cell.With this range of ICP-CCT tools, one can get closer to the goal of detection specificity through direct sample analysis with significantly reduced sample preparation, but there are still analytical problems and interferences that cannot be solved by incorporating a collision cell into a mass spectrometer.

[0021] By carefully monitoring the conditions in the collision cell, it is possible to efficiently pass through the desired ions. This is possible because the desired ions—those that are part of the mass spectrum to be analyzed—are generally monatomic and singly positively charged, meaning they have lost an electron. If such an ion collides with a neutral gas atom or molecule, the ion will retain its positive charge unless the initial ionization potential of the gas is low enough for an electron to be transferred to the ion, thus neutralizing it. Therefore, gases with high ionization potentials are ideal target gases. Conversely, it is possible to remove artifact ions while continuing to efficiently pass through the desired ions. For example, the artifact ions can be molecular ions such as ArO₂. + or Ar2 +These are far less stable than atomic ions. In a collision with a neutral gas atom or molecule, a molecular ion can dissociate, forming a new ion with a lower mass and one or more neutral fragments. Furthermore, the collision cross-section for collisions involving a molecular ion tends to be larger than that for an atomic ion. This was demonstrated by Douglas (Canadian Journal Spectroscopy, 1989, Vol. 34(2), pp. 36–49), referenced in this document. Another possibility is to utilize reactive collisions. Eiden et al. (Journal of Analytical Atomic Spectrometry, Vol. 11, pp. 317–322, 1996) used hydrogen to atomize many molecular ions and also argon. + to eliminate, while monatomic analyte ions remain largely unaffected.

[0022] US Patent 2012 / 0003748 A1 describes a system and methods for generating reagent ions and productions for use in a mass spectrometry system. A microwave or radio frequency (RF) energy source ionizes particles of a reagent vapor to form reagent ions. The reagent ions enter a chamber, such as a drift chamber, to interact with a liquid sample. An electric field guides the reagent ions and facilitates their interaction with the liquid sample to form productions. The reagent ions and productions then exit the chamber under the influence of an electric field and are detected by a mass spectrometer module.

[0023] US Patent 2013 / 0264475 A1 discloses the selective ionization of a sample diluted in air at atmospheric or near-atmospheric pressure in several steps. First, components of the air and / or other gases are ionized to generate reactive ions. The reactive ions are then filtered using a radio frequency filter to obtain selected reactive ions. Subsequently, the selected reactive ions react with sample molecules of the sample to be analyzed in a charge transfer process. Depending on the properties of the sample molecules, the filter can select some reactive ions for entry into the sample zone and completely block others, thus controlling the ion chemistry and charge transfer yield in the sample zone.

[0024] GB 2 541 384 A discloses a mass spectrometer comprising an ion source, a collision cell, a mass analyzer and a detector, wherein the collision cell has an axial electric field that enhances the transfer of ions through the collision cell.

[0025] US 2016 / 0189948 A1 describes a device for analyzing a sample gas, comprising an ion source for generating primary ions, a reaction chamber into which the primary ions generated in the ion source and the sample gas to be analyzed can be fed to form product ions by chemical ionization of components of the sample gas, and an analyzer / detector unit for determining different types of ions. Summary

[0026] The present invention introduces novel mass spectrometry methods in which an analyte gas is ionized within a collision cell by collisions with an ion beam, which is preferably intense, and the ions of the ionized analyte gas are subsequently passed through a mass analyzer for mass analysis. The ion beam used for this purpose can be mass-selected by the use of mass filters, as further described in this document. The novel methods presented in this document offer a new operating mode for mass spectrometers with various applications, e.g., for structure elucidation, site-specific isotope analysis, and others.

[0027] The invention provides a modified method for isotope ratio mass spectrometry, wherein sample ions are reacted in a collision cell with a charge-neutral reaction gas introduced therein, thereby generating an adduct ion species which is mass-analyzed, and the mass spectrum is compared with the isotope mass spectrum of the reaction gas itself, which is ionized with an ion beam. Thus, the isotopic abundance and / or the isotopic ratio of the sample ions can be determined and corrected by the measured isotopic ratio of the reaction gas.

[0028] The present invention provides a method of mass spectrometry, wherein the method comprises the following steps: a. Generating an ion beam from an ion source, which is conveniently an ICP ion source; b. Guiding the ion beam into a collision cell, c. Introducing a charge-neutral analyte gas into the collision cell through a gas inlet on the collision cell; d. Generation of ions from the analyte gas in the collision cell by means of collisions between the analyte gas and the ion beam; e. Sending generated ions from the collision cell to a mass spectrometry analyzer; and f. Analyzing the mass of the ions of the ionized analyte gas passed through, which includes determining an isotopic abundance or isotopic ratio of the ions in the mass analyzer; wherein the method comprises: adjusting the energy of the ion beam to fragment at least a fraction of the analyte gas to form at least one ionized atomic or molecular fragment of the analyte gas, sending the formed ionized atomic or molecular fragment to the mass analyzer and analyzing the fragment for its mass.

[0029] As described in more detail below, the analyte gas can be a reactant gas that can be used for a mass-shift reaction with sample ions in a separate isotope ratio experiment to resolve the sample ions in a mass spectrum and determine their isotopic ratio. By analyzing the mass of the reactant gas and preferably determining its isotopic abundance and / or ratio, a corrected isotopic ratio for the sample ions from the mass-shift experiment can be obtained.

[0030] It follows that the ion beam is preferably and expediently generated by an inductively coupled plasma (ICP) ion source by introducing a plasma-generating gas into a plasma torch, wherein plasma is generated in the torch and ions are extracted from the plasma to form the ion beam. In some embodiments, the ion beam essentially comprises ions of the plasma-generating gas, wherein in other embodiments the ion beam alternatively or additionally comprises ions other than ions of the plasma-generating gas, these other ions being introduced by the plasma.

[0031] The plasma-generating gas is expediently selected from one or more gases conventionally used to generate plasma in an ICP, such as, but not limited to, argon, neon, helium, nitrogen, and oxygen. The ion beam may include ions of the plasma-generating gas. In certain embodiments, the ion beam comprises at least one of 36 Ar + , 36 Ar + , 40 Ar + and 40 Ar2 + selected ion species. In a preferred embodiment, the ion beam comprises 40 Ar + -ions.

[0032] In embodiments where the ion beam comprises ions other than those of the plasma-generating gas, the method may advantageously include introducing a solution or gas containing a target species into the plasma, thereby generating the ions of the target species. In some of these embodiments, the ion beam may essentially comprise ions of the target species. This may be advantageously achieved by filtering the selected target species ions according to their mass. The target species may preferably be an element, and the target species ions elemental ions.

[0033] Thus, in some embodiments, the ion beam essentially comprises element ions. In some of these embodiments and other embodiments, the ion beam comprises element ions of a single element species filtered by mass.

[0034] The ion beam captured in the collision cell is preferably configured and controlled to a desired and useful intensity, such as a beam intensity between 10 pA and 100 nA, with the upper end of this range (10–100 nA) being preferred. Such currents can be generated using a plasma ion source, such as an argon plasma ion source. The energy of the ion beam is preferably in the energy range of approximately 0 to approximately 250 eV, and more preferably in the range of approximately 5 eV, or from approximately 10 eV to approximately 250 eV, or to approximately 200 eV, or to approximately 100 eV, for example, approximately 50 eV. It follows that in some useful embodiments, the energy of the ion beam is controllable, for example, by using an accelerator electrode upstream of the collision cell.

[0035] As mentioned above, ions from the ion source can be mass-selected before entering the collision cell. This is conveniently done using a mass filter positioned between the ion source and the collision cell.

[0036] The collision cell, sometimes also called a reaction cell, can comprise a chamber having at least one gas inlet. The chamber can further comprise an ion inlet for introducing ions into the chamber and an ion outlet through which ions are passed to a downstream mass analyzer. The collision cell can have any suitable shape and size. In certain embodiments, the collision cell comprises at least one chamber including at least one ion guide.

[0037] In general, the collision cell preferably includes at least one gas inlet for supplying the charge-neutral analyte gas, collision gas, or reaction gas into the cell. One, two, or more gases can be supplied to the cell through a single gas inlet. Alternatively, the cell can include two or more gas inlets, each for supplying two or more gases. In some embodiments, the introduced gas can be used to cool the ion beam in the collision cell. By cooling the ion beam, the collision gas can preferably reduce both the absolute kinetic energy of the ions in the ion beam and the energy distribution of the ions. The gas inlet can further include or be in fluid communication with a gas flow controller for regulating the gas flow into the collision cell. The gas flow controller can, for example, be a mass flow controller.

[0038] The collision cell can be a passive cell, as disclosed in US 5,049,739 A, the entire contents of which are hereby incorporated by reference, or the ions can be trapped in the cell by means of an ion optic, for example, a multipole driven by AC voltages or a combination of AC and DC voltages, as in EP 0 813 228 A1, the entire contents of which are hereby incorporated by reference. This allows the collision cell to be configured to pass ions with minimal losses, even when the cell is operated at a pressure high enough to ensure numerous collisions between the ions and the gas molecules. The collision cell can comprise at least one quadrupole, at least one hexapole, or at least one octupole. Preferably, the multipole is operated only in an RF (radio frequency) mode, i.e.,There is no mass selection in the collision cell; instead, the multipole has the effect of focusing the ions within the cell.

[0039] The collision cell can be linear, and the axis of the ion beam through the cell can also be linear. However, the collision cell can also be non-linear, for example, if it is provided as a curved multipole array. Accordingly, the axis of the collision cell can be linear, curved, or non-linear. The axis can also be partially linear and partially non-linear. The collision cell can comprise a parallel, straight multipole, or it can comprise a curved multipole. The curved multipole can be provided as a multipole such as a quadrupole, in which the distance between the rods decreases from the entrance and exit of the collision cell toward the center of the cell.

[0040] The quadrupole can be a three-dimensional quadrupole or a two-dimensional, i.e., linear, quadrupole. The rods of the multipole can be round rods or hyperbolic rods. In some embodiments, the multipole is a flatapole, in which the rods are flat, i.e., the rods have at least one flat surface.

[0041] Preferably, the collision cell is arranged upstream of the mass analyzer of the mass spectrometer. The collision cell can be arranged between a mass filter arranged upstream and a mass analyzer arranged downstream.

[0042] The mass filter can be a mass filter comprising electrodes supplied with a combination of RF and DC voltages in a mass / charge (m / z) filter mode, and supplied with an essentially exclusively RF voltage in a non-filtering mode. In other words, the non-filtering mode is preferably an exclusively RF mode. In this mode, ions of all mass / charge ratios are stable within the mass filter and are consequently passed through it. It is possible to apply a small DC voltage to the electrodes in addition to the RF voltage during the pass-through mode. Preferably, the DC / RF voltage ratio in the non-filtering mode is 0.0 (i.e., exclusively RF, no DC voltage), or not more than 0.001, or not more than 0.01, or not more than 0.05, or not more than 0.1. Preferably, the DC / RF ratio is 0.0.

[0043] Preferably, the mass filter is a multipole filter. The electrodes of the mass filter are therefore preferably the rods of a multipole mass filter. The multipole can be a quadrupole, a hexapole, or an octupole. Preferably, the multipole is a quadrupole. The quadrupole can be a three-dimensional quadrupole or it can be a two-dimensional, i.e., linear, quadrupole. Preferably, the quadrupole is a linear quadrupole mass filter. The rods of the multipole can be round rods or they can be hyperbolic rods. During mass selection by the mass filter, a mass window with a width of approximately 2 amu (1 amu = 1.6605 × 10⁻⁶) can be achieved. -27 kg) or less, such as preferably of approximately 1 amu or less, and more preferably of approximately 0.7 amu.

[0044] In certain embodiments, the quadrupole mass filter integrates the RF-only pre- and post-filter sections into the quadrupole arrangement to achieve high transmission at the quadrupole input and to better control the ion beam phase volume at the quadrupole output.

[0045] By adjusting the energy of the ion beam, it is possible to select an energy level that leads to the fragmentation of at least a portion of the analyte gas, forming at least one ionized atomic or molecular fragment species of the analyte gas. The resulting fragment species is then conveniently passed to the mass analyzer and analyzed for its mass. It follows that the energy of the ion beam can be conveniently adjusted to favor the formation of a desired ionized fragment of the analyte gas.

[0046] The foregoing features enable the specific analysis of one or more organic compounds introduced as analyte gas and analyzed for their mass using the aforementioned methods. The methods can be used in isotope measurements, e.g., isotope ratio measurements, such as site-specific isotope ratio measurements, and an organic compound to be analyzed may also include carbon and hydrogen, one or more of the elements oxygen, nitrogen, sulfur, halogens, and phosphorus. In some embodiments, the one or more organic compounds may be selected, among others, from the group consisting of: hydrocarbons, substituted hydrocarbons, proteins, lipids, carbohydrates, and nucleic acids.

[0047] It is understood that the method is useful in embodiments where the analyte gas comprises a reaction gas used to fill the collision cell in a separate isotope ratio experiment, in order to react with the sample ions introduced into the collision cell from the ion source. For example, the reaction gas can be used to react with sample ions to form adduct ion species, and the isotopic abundance and / or isotopic ratio of these adduct ions can subsequently be determined in the mass analyzer. For example, the sample ions may exhibit isobaric interference, which prevents an accurate isotopic ratio determination of their ions. Using the reaction gas can avoid the interference by reacting with the sample ions but hardly or not at all with the isobaric interference ions. The adduct ions are thus free from interference.This is particularly useful when used with the mass filter, allowing the mass filter to select a mass window that permits the transfer of ions with the mass / charge ratio of the sample ions, but not with the mass / charge ratio of the adduct ions (i.e., it does not allow the transfer of interfering ions that could disrupt the mass spectrum of the adduct ions formed in the collision cell). In a separate experiment (measurement), the isotopic abundance of the reaction gas itself can be determined, i.e., by including the ionization of the reaction gas in the collision cell using the ion beam. Thus, by comparing these obtained data, it is possible to determine the isotopic abundance or isotopic ratio of the sample ions with improved accuracy. This is especially useful when the direct isotopic abundance of the sample ions is disrupted by interfering species.

[0048] It follows from the foregoing that the analyte gas in the processes disclosed in this document can be essentially any substance or mixture of substances that can be introduced into the collision cell in gaseous form. This includes, among others, substances such as helium, hydrogen, oxygen, nitrogen, ammonia, methane, ethane, propane, isobutane, n-butane, carbon dioxide, nitric oxide, nitrogen dioxide, nitrous oxide, diborane, and / or sulfur dioxide, or mixtures of any two or more of these substances. The substance can be introduced, for example, by means of an adjustable leakage valve or by other means known to those skilled in the art. In still further embodiments, species that are not gaseous under normal conditions can be converted into a gas for introduction into the collision cell, for example, by using a gas chromatograph coupled to an inlet valve, such as a suitable transfer line.Accordingly, a wide range of substances and compounds can be introduced by various means known to those skilled in the art and used as analyte gas / reaction gas and introduced into the collision cell, and this substance or compound can (i) be directly and accurately analyzed with the mass analyzer to obtain, for example, isotope ratios and isotope profiles, and (ii) be reacted with the sample ions to form product species, such as, among others, adduct species.

[0049] As explained above, it is useful in many applications to be able to determine the isotopic abundance or isotopic ratio of the ionized analyte gas in the mass analyzer. The methods of the invention are applicable to several different mass analyzers, including, but not limited to, magnetic sector mass analyzers, including single-collector and multi-collector sector mass analyzers, quadrupole mass analyzers, time-of-flight (TOF) mass analyzers, ion trap mass analyzers, and electrostatic trap mass analyzers, including electrostatic orbital traps such as the Orbitrap™.

[0050] In another aspect based on the foregoing descriptions, the invention provides a method of isotope ratio mass spectrometry, wherein the method comprises the following steps: a. Determining the isotopic abundance and / or isotopic ratio of sample ions by - Introducing the sample ions into a collision cell; - Providing at least one reaction gas in the collision cell to react with the sample ions; - Reacting the sample ions with the reaction gas in the collision cell to generate at least one chemical adduct ion species from the reaction of the sample ions and the reaction gas; and - Determining the isotopic abundance and / or isotopic ratio of the sample ions by analyzing the mass of the chemical adduct ion species; b. Determining an isotopic abundance and / or an isotopic ratio of the reaction gas according to the described method, wherein the analyte gas is a reaction gas; and by c. Adjusting / correcting the determination of the isotopic abundance and / or ratio of the sample ions from step a based on the isotopic abundance and / or ratio of the reaction gas determined in step b.

[0051] The reaction gas referred to in this process is preferably selected from one or more of the gases mentioned above with respect to analyte gases, such as, but not limited to, helium, hydrogen, oxygen, nitrogen, ammonia, methane, ethane, propane, isobutane, n-butane, carbon dioxide, nitric oxide, nitrogen dioxide, nitrous oxide, diborane, and / or sulfur dioxide. The process preferably generates the at least one reaction gas ion species in the collision cell that is free of sample ions (i.e., the ion beam does not contain the sample ions when used to ionize the reaction gas). Determining the isotopic abundance and / or ratio of the reaction gas (the preceding ‘step b’) can be performed before or after determining the isotopic abundance and / or ratio of the sample ions. This means that steps a. and b. can be performed in any order, i.e., step a. followed by step b., or step b. followed by step a.

[0052] It is understood that it is advantageous to generate the sample ions in the preceding method in an ICP as described above. In some embodiments, it is particularly advantageous that the ion beam for ionizing the reaction gas is generated from the same ICP source as the sample ions. Thus, in some embodiments, the ion beam is generated by introducing a plasma-generating gas into a plasma torch, and the ion beam essentially comprises ions of the plasma-generating gas. In certain embodiments, the plasma-generating gas is argon gas.

[0053] The aforementioned method may further include mass filtering of an ion beam containing the sample ions and / or an ion beam free of sample ions before passing the sample ions and / or the ion beam through the collision cell. The method may also include selecting the energy of an ion beam containing the sample ions and / or the ion beam free of sample ions before passing the sample ions and / or the ion beam through the collision cell. For example, the sample ions may exhibit isobaric interference (the extent of which may be unknown) that prevents accurate determination of the isotopic ratios of their ions. Using the reaction gas can avoid the interference by allowing the reaction gas to react with the sample ions but hardly or not at all with the isobaric interference ions. The adduct ions are thus free from interference.This is particularly useful when used with the mass filtration step, allowing the mass filter to select a mass window that permits the transfer of ions with the mass / charge ratio of the sample ions, but not with the mass / charge ratio of the adduct ions (i.e., it does not allow the transfer of interfering ions that could disrupt the mass spectrum of the adduct ions formed in the collision cell). When used to ionize the reaction gas, mass filtration of the ion beam can select a mass / charge ratio or range that includes ions of the plasma-generating gas, e.g., argon ions, especially its most abundant isotopes. 40 Ar +The mass filtering can select a mass window width of approximately 2 amu or less, such as preferably approximately 1 amu or less, and more preferably approximately 0.7 amu. In this way, an intense ion beam can be selected and introduced into the collision cell to ionize the reaction gas.

[0054] An inductively coupled plasma (ICP) source is a plasma source to which energy is supplied by electric currents generated by electromagnetic induction, i.e., by time-varying magnetic fields. The inductively coupled plasma (ICP) source can be any such source known to those skilled in the art. For example, the ICP source comprises a plasma torch consisting of three concentric tubes, which may be made of quartz, for instance. The ICP source can further include a spiral electrode which, when a time-varying electric current is applied to it, will generate a time-varying magnetic field. The ICP source can be designed to operate with any suitable plasma-generating gas, such as argon gas. Brief description of the drawings

[0055] Those skilled in the art will understand that the drawings described below are for illustrative purposes only. The drawings are not intended to limit the scope of the teachings presented here in any way. Fig. Figure 1 shows an inductively coupled plasma (ICP) source according to the invention, with two alternative configurations for introducing the reaction gas into the ICP source. Fig. Figure 2 shows a sample introduction system consisting of an atomizer and a spray chamber for introducing an aerosol into the ICP source. Two alternative configurations for introducing a reactive species into the sample introduction system are shown. Fig. Figure 3 shows a schematic representation of a mass spectrometer that can be used with the invention, highlighting the collision cell and the mass filter arranged upstream of the process. Description of the different designs

[0056] The exemplary embodiments of the invention are described below with reference to the figures. These examples are intended to provide a more thorough understanding of the invention without limiting its scope.

[0057] The following description outlines a sequence of steps. The person skilled in the art will recognize that, unless the context requires it, the order of the steps is not critical to the resulting configuration and its effect. Furthermore, it will be apparent to the person skilled in the art that, regardless of the order of the steps, there may be a time delay between some or all of the described steps.

[0058] It should be understood that the invention applies to the mass analysis of materials in general, such as gases, liquids, solids, particles, and aerosols. Therefore, the sample analyzed in the system is generally variable.

[0059] An inductively coupled plasma (ICP) source 10 according to the invention is used in Fig.Figure 1 shows an exemplary ICP source comprising three concentric tubes 11, 12, 13, typically made of quartz, and a charging coil 21. As is known in the art, plasma gas can be introduced into the inner tube 11 via the sample inlet 14, into the middle tube 12 via an auxiliary gas inlet 17 and an auxiliary gas line 15, and / or into the outer tube 13 via a cooling gas line 18. The charging coil 21 couples a very intense RF field into the argon gas stream (auxiliary gas and cooling gas). Due to the high energy (and an initial ignition to form seed electrons), a plasma is generated and maintained at temperatures typically in the range of > 8000 °C.

[0060] A sample is typically introduced into a plasma gas, such as argon, through the sample inlet 14. The sample can be an aerosol generated by means of an atomizer and a spray chamber, as further described in Fig. Figure 2 illustrates. Optionally, another gas species to be ionized can be introduced into the ICP source along with the sample through the sample inlet 14, or alternatively or additionally through optional inlets 16, 19 on the auxiliary gas inlet line 15 and / or the cooling gas inlet line 18.

[0061] The sample can be introduced into a sample introduction system such as a spray chamber arrangement 30, as shown in Fig. Figure 2 illustrates the arrangement. It comprises an atomizer 31, which has a sample inlet 32, and an atomizer gas inlet 34, which will typically be identical to the plasma gas (such as argon). An optional inlet 33 can be provided at the atomizer gas inlet, which can be used to supply an additional gas mixed with the atomizer gas to the atomizer.

[0062] The atomizer supplies a sample spray to the spray chamber 37, which has an outlet 36 and a discharge 38 that feeds the sample inlet 14 of the ICP source 10. The spray chamber can optionally also have a gas inlet 35, which can be used to supply additional gas to the spray chamber, where it will mix with the sample aerosol and be supplied to the ICP source through the discharge 38.

[0063] Therefore, alternative embodiments for supplying sample gas to the spray chamber arrangement are possible. These embodiments can be used alternatively, or they can be used in combination.

[0064] The ions generated in the plasma enter the mass spectrometer via an interface comprising one or more cones 22.

[0065] In Fig.Figure 3 shows a mass spectrometer that can be used to put the invention into practice. Downstream of the ICP source 10 is a quadrupole mass filter 60. The mass filter can be used to selectively pass ions of interest, or ions within a mass range of interest, through to the collision cell for subsequent mass analysis in the downstream mass analyzer. Alternatively, the mass filter can be used to selectively pass the intense ion beam from the ICP source through to ionize the gas in the collision cell.

[0066] The collision cell 40 captures ions that are passed through the mass filter 60 located upstream of the process. The collision cell also has a gas inlet 41 for receiving charge-neutral collision / reaction gas that reacts with the ions in the collision cell. For example, the arriving ions can be ions from the Ar + The ion beam is generated in the ICP source and selectively passed through the upstream mass filter 60. The ion beam can ionize the charge-neutral collision gas (e.g., oxygen), and the mass of the resulting collision / reaction gas ions can be analyzed in the downstream mass analyzer.

[0067] Alternatively, the gas inlet 41 can be used to supply the analyte gas into the collision cell, which is then energized within the collision cell by the incoming ion beam (e.g., the Ar). +-ion ​​beam) can be ionized and / or fragmented. The ions and / or ionized fragments of the analyte thus generated can be analyzed for their mass in the mass analyzer 50 located downstream of the process. This means that the incoming ion beam is used to ionize the charge-neutral analyte for the subsequent mass analysis.

[0068] The ions generated in the collision cell are then directed to a mass analyzer 50 located downstream of the process, where their mass is analyzed. In principle, the mass analyzer can be any suitable mass analyzer, such as a single- or dual-sector mass analyzer (e.g., a dual-sector multicollector), a quadrupole mass analyzer, an ion trap mass analyzer, a time-of-flight mass analyzer, or an electrostatic trap mass analyzer, including an Orbitrap mass analyzer.

[0069] The following non-limiting examples provide exemplary descriptions of certain analytical advantages of the present invention. Example 1

[0070] This experiment is designed to determine titanium (Ti) isotope abundances in a sample containing titanium and chromium (Cr). Of particular interest is the abundance of 50 Ti isotopes. In this example, the sample is introduced directly into the ICP ion source via laser ablation, so there is no way to separate Ti from Cr before analysis, and all the specificity in the analysis must be achieved in the mass spectrometer. This is problematic because the 50 Ti isotope isobaric interference with 50 Cr contains values ​​that need to be resolved or corrected to allow for an accurate determination of 50 To reach Ti.

[0071] The experiment comprises two parts: first, the mass filter is used to introduce a specific mass range into the collision cell; second, oxygen gas is introduced into the collision cell to form TiO₂ adduct ions in a mass-shift reaction; and third, the adduct ions are analyzed for their mass to determine the isotopic abundance of 50 Ti and / or a ratio of 50 to determine Ti with another Ti isotope. In the second part, the mass filter is adjusted so that only the intensive 40 The argon ion beam from the plasma ion source can enter the collision cell. Oxygen gas is introduced into the collision cell under the same conditions as in the first part of the experiment. The intensive 40The argon beam undergoes charge exchange reactions with neutral O₂ gas, leading to the ionization and dissociation of the O₂ gas. The resulting oxygen ions then leave the collision cell and can be subjected to mass analysis for their isotopic ratio. The known isotopic ratio of oxygen gas can then be used to more accurately compensate for the presence of minor isotope oxides that will be present in the first experiment. Details of the experiment

[0072] For the first part, the sample is introduced into the instrument's Ar plasma ion source using laser ablation to extract Ti + - and Cr + to generate -ions. Since Cr isotopes cause isobaric interference with the target- 50Since the species contain Ti isotopes, these must be separated in the mass spectrometer. Subsequently, the chemical resolution achievable with the collision cell is used, and oxygen gas is introduced into the collision cell. The selective reactivity of the different elements to separate Ti + preferably away from the interfering Cr + to move is used by extracting the sample-Ti + and O2 gas TiO + is formed. Since this reaction is many times more efficient for TiO₂ + compared to CrO +If this is the case, the Ti species can be successfully separated from Cr in the mass spectrum. The resulting TiO species formed in the collision cell is now present at masses 62-66 in the copper and zinc spectrum, and this can be measured in the mass analyzer located downstream of the process. To avoid the need for a complicated correction for the potential presence of copper and zinc in the sample, it is expedient to use the mass filter located upstream of the collision cell to pass through only a selected mass range. In this example, we assume that we have a mass window of ±10 centered on 50 They have Ti. This allows all isotopes of Ti and Cr to pass through, but essentially prevents copper or zinc from passing through into the collision cell. Thus, the adduct TiO₂ produced in the cell +-ions in the copper and zinc mass range can be measured, but if copper and zinc are not present in the sample, they will not pass through the first mass filter. Thus, the 50 Ti abundance and the Ti isotope ratio in the sample can be determined without interference from Cr.

[0073] The second part allows for a more precise evaluation of the 50 Ti abundance in the sample is determined by taking into account the presence of minor oxide isotopes by determining the isotopic composition of the reaction gas (oxygen). During the conversion of Ti + -ions in TiO + While the collision cell can effectively separate Ti ions from Cr in the sample, the oxide conversion system generates further isobaric interferences from the presence of TiO₂. + -Species consisting of the minor oxygen isotopes 17 O and 18 have formed O, e.g. 48 Ti 18 O, that isobaric to the target-50 Ti 16 O is. These interferences can only be present in small amounts, e.g., makes 18 O only accounts for ~0.2% of the total oxygen, but if a major Ti isotope / minor oxygen pair interferes with a Ti isotope / major oxygen pair, this contribution can be significant enough to lead to an inaccuracy in the Ti isotope measurement. For example, 48 Ti 18 O approximately 3% to mass 66 for 50 Ti 16 Contribute to the measured beam.

[0074] Corrections to these interferences can be made by monitoring an undisturbed secondary isotope oxide such as e.g. 50 Ti 18O at mass 68 and corrections based on reference isotope ratios for oxygen are performed. However, for the highest accuracy in determining Ti isotope abundances and ratios, it would be desirable to characterize the isotopic composition of the oxygen gas supplied to the collision cell. This could be achieved through a separate offline analysis of the gas, but it would also be useful to know whether the introduction into and exit from the collision cell causes isotopic fractionation of the gas. To measure this, oxygen is first introduced into the collision cell under identical conditions as for the Ti isotope ratio analysis. The mass filter positioned upstream of the collision cell is then adjusted so that only the dominant 40 Ar ions are introduced from the plasma into the collision cell. 40The Ar ion has a higher ionization potential than the O2 molecule and undergoes a charge exchange with the molecule, converting O2 into O + The oxygen ions dissociate and ionize. They then exit the collision cell, and the isotopic composition of the oxygen gas can be analyzed in the main mass analyzer. This determination of the isotopic ratio of the oxygen reaction gas can subsequently be used to compensate for the contribution of the minor oxide species to the Ti isotopic ratio measurements performed in Part 1 of the experiment. This method has advantages over using the reference ratio for the reaction gas isotopic ratio because it allows for the correction of any fractionation in the isotopic composition that may occur when the reaction gas is introduced into the cell or when the molecular adduct ion leaves the reaction cell.

[0075] The atomic and molecular species considered in this example are listed in Table 1 below. Table 1. Atomic and molecular species considered in Example 1. mass 46 47 48 49 50 51 52 species 46 Of 47 Of 48 Of 49 Of 50 Of 50 V 51V 50 Cr 52 Cr mass 62 63 64 65 66 67 68 species 160 46 Of 16 SHE 47 Of 16 SHE 48 Of 16 SHE 49 Of 16 SHE 50 Of 16 SHE 17 O 46 Of 17 SHE 47 Of 17 SHE 48 Of 17 SHE 49 Of 17 SHE 50 Of 17 SHE 18 O 46 Of 18 SHE 47 Of 18 SHE 48 Of 18 SHE 49 Of 18 SHE 50 Of 18 SHE

[0076] For example, it can be seen that an undisturbed measurement of the 46 Ti 16 O-species is possible at mass 62. The frequency (intensity) measured at mass 63 consists mainly of 47 Ti 16 O with a small contribution from 46 Ti 17 O. From the isotope measurement of the oxygen reaction gas, the ratio 16 O: 17 O is known, and therefore the frequency of 46 Ti 17 O from the measured frequency of the undisturbed 46 Ti 16 O can be determined. Since the frequency of 46 Ti 17 Once O is determined, the corrected frequency of 47 Ti 16O can be determined from the mass 63 measurement, and thus the corrected isotope ratio can be calculated. 47 Ti: 46 Ti can be obtained. This method can be applied to the other mass measurements to obtain corrected isotopic ratios of other Ti isotopes. Example 2

[0077] This experiment was designed to determine the site-specific isotopic composition of carbon isotopes in a propane molecule. In this experiment, ions are generated in the ICP ion source and extracted from the plasma. The first mass filter is used to remove only the 40 Ar +The process involves selecting an intense ion beam and directing it into the collision cell. Propane analyte gas is introduced through the gas inlet of the collision cell. Propane is a saturated alkane molecule with a chain of three carbon atoms. The ion energy of the incident beam is increased by means of an accelerator electrode positioned in front of the collision cell. 40 Ar + The -ion interacts with the propane molecule, leading to fragmentation and ionization of the molecule along the C1-C2 bond. Thus, the charge-neutral propane molecule with three carbon and eight hydrogen atoms is split into two fragments – one with one carbon and three hydrogen atoms, and a second with two carbon and five hydrogen atoms.

[0078] These molecular ion fragments then leave the collision cell and can be analyzed for their mass by the second mass analyzer. The strength of this technique lies in the fact that by monitoring both the masses (15) 12 CH3) and 16 ( 13 CH3), as well as 24 ( 12 C2H3) and 25 ( 13 C 13 CH3) can determine the isotopic composition of the position-specific carbon in the propane molecule, i.e., one can determine the carbon isotopic composition of the C1 carbon atom and the C 2-3 -determine carbon clusters. If the incoming 40 Ar + If this can be used to cause further fragmentation of the propane molecule in the collision cell, and if a sufficient mass resolution (m / Δm ~3500) can be achieved in the second mass analyzer, then one can even decide to use the masses 14 ( 12 CH2) and 15 ( 13CH2) for the isotopic composition of the C2 carbon atom simultaneously with the 15 ( 12 CH3) and 16 ( 13 CH3) to monitor the isotopic composition of C1.

[0079] For the purposes of their use in this document, including the claims, singular forms of terms are to be interpreted as including the plural form, and vice versa, unless the context suggests otherwise. Thus, it should be noted that the singular forms "ein / einer / eine / eines" and "der / die / das" include plural forms unless the context clearly indicates otherwise.

[0080] Throughout the entire description and claims, the terms “comprise”, “include”, “feature” and “contain” and their variants are to be understood as meaning “including, but not limited to”, and are not intended to exclude other components.

[0081] The present invention also covers the exact terms, features, values ​​and bandwidths, etc., if these terms, features, values ​​and bandwidths, etc., are used in conjunction with terms such as approximately, about, generally, essentially, mainly, at least, etc. (i.e., "about 3" also covers "exactly 3", or "essentially constant" also covers "exactly constant").

[0082] The term "at least one" is to be understood as meaning "one or more" and therefore includes both embodiments comprising one or more components. Furthermore, dependent claims that refer to independent claims describing features with "at least one" have the same meaning whether the feature is designated as "the" or "the at least one".

[0083] All steps described in the specification can be performed in any order or simultaneously, unless the context clearly suggests otherwise.

[0084] All features and / or steps disclosed in the specification can be combined in any combination, except for combinations in which at least some of the features and / or steps are mutually exclusive. In particular, the preferred features of the invention apply to all aspects of the invention and can be used in any combination.

Claims

[1] A method of mass spectrometry, the method comprising the following steps: a. generating an ion beam from an ICP ion source; b. guiding the ion beam into a collision cell, c. Introducing a charge-neutral analyte gas into the collision cell through a gas inlet on the collision cell; d. generating ions from the analyte gas in the collision cell by means of collisions between the analyte gas and the ion beam; e. Sending generated ions from the collision cell into a mass spectrometry analyzer; and f. Analyzing the mass of the transmitted ions of the ionized analyte gas, which includes determining an isotopic abundance or isotopic ratio of the ions in the mass analyzer; the method comprising: adjusting the energy of the ion beam to fragment at least a portion of the analyte gas to form at least one ionized atomic or molecular fragment of the analyte gas, sending the formed ionized atomic or molecular fragment to the mass analyzer, and analyzing the fragment for its mass. [2] A method according to any one of the preceding claims, wherein the ion beam essentially comprises ions of the plasma-generating gas. [3] A method according to the preceding claim, wherein the plasma-generating gas comprises a species selected from argon, neon, helium, nitrogen and oxygen. [4] The method of claim 1, further comprising introducing a solution or gas comprising a target element into the plasma, thereby generating ions of the target element, wherein the ion beam substantially comprises ions of the target element. [5] A method according to any one of the preceding claims, wherein the ion beam comprises essentially elemental ions. [6] A method according to any preceding claim, wherein the ion beam comprises substantially mass-filtered elemental ions of a single elemental species. [7] A method according to any preceding claim, further comprising mass selecting ions of the ion beam (m / z) to enter the collision cell by means of a mass filter arranged between the ion source and the collision cell. [8] The method of claim 7, wherein the mass filter is a quadrupole mass filter. [9] The method of claim 7, wherein the step of mass selecting comprises setting a mass window of approximately 2 amu (1 amu = 1.6605 × 10 -27 kg) or less, and preferably about 1 amu or less, and more preferably about 0.7 amu. [10] Method according to one of the preceding claims, wherein the energy of the ion beam received in the collision cell is in the range of 0 to 250 eV and preferably in the range of 10 eV to 200 eV. [11] A method according to the preceding claim, which comprises adjusting the energy of the ion beam to promote the formation of a desired ionized fragment of the analyte gas. [12] Method according to at least one preceding claim, wherein the at least one analyte gas comprises at least one organic compound whose mass is to be analyzed. [13] A process according to the preceding claim, wherein the at least one organic compound comprises the elements carbon, hydrogen and optionally at least one of oxygen, nitrogen, sulfur, halogen and phosphorus. [14] The method according to the preceding claim, wherein the at least one organic compound is selected from the group consisting of: Hydrocarbons, substituted hydrocarbons, proteins, carbohydrates, lipids and nucleic acids. [15] A method according to any preceding claim, wherein the analyte gas comprises a reaction gas and the method further comprises determining an isotopic abundance and / or ratio of sample ions by: - Introducing the sample ions into a collision cell; - Providing at least one reaction gas in the collision cell to react with the sample ions; - reacting the sample ions with the reaction gas in the collision cell to produce at least one chemical adduct ion species from the reaction of the sample ions and the reaction gas; and - Determining an isotopic abundance and / or an isotopic ratio of the sample ions by analyzing the mass of the chemical adduct ion species. [16] Method according to one of the preceding claims, wherein the at least one analyte gas comprises a substance selected from helium, hydrogen, oxygen, nitrogen, ammonia, methane, ethane, propane, isobutane, n-butane, carbon dioxide, nitrogen oxide, nitrogen dioxide, nitrous oxide, diborane and / or sulfur dioxide. [17] A method according to any preceding claim, wherein the mass analyzer is selected from a sector mass analyzer and a quadrupole mass analyzer. [18] A method according to any preceding claim, wherein the mass analyzer is a multi-collector sector mass analyzer. [19] A method according to any one of the preceding claims, wherein the collision cell comprises at least one chamber comprising at least one ion guide. [20] Isotope ratio mass spectrometry method comprising the following steps: a. Determining an isotopic abundance and / or ratio of sample ions by - Introducing the sample ions into a collision cell; - Providing at least one reaction gas in the collision cell to react with the sample ions; - reacting the sample ions with the reaction gas in the collision cell to produce at least one chemical adduct ion species from the reaction of the sample ions and the reaction gas; and - Determining an isotopic abundance and / or an isotopic ratio of the sample ions by analyzing the mass of the chemical adduct ion species; b. Determining an isotopic abundance and / or an isotopic ratio of the reaction gas according to the method of any one of claims 1 to 19, wherein the analyte gas is the reaction gas; and c. Adjusting / correcting the determination of the isotopic abundance and / or ratio of the sample ions from step (a) based on the isotopic abundance and / or ratio of the reaction gas determined in step (b). [21] The method of claim 20, wherein determining the isotopic abundance and / or ratio of the reaction gas is carried out before determining the isotopic abundance of the sample ions. [22] A method according to claim 20 or claim 21, wherein the sample ions are generated in an inductively coupled plasma (ICP) source. [23] The method of claim 22, wherein the ion beam is generated in the same inductively coupled plasma (ICP) source as the sample ions. [24] A method according to any one of claims 20 to 22, wherein the ion beam is generated by introducing a plasma-generating gas into a plasma torch such that the ion beam substantially comprises ions of the plasma-generating gas. [25] A method according to any one of claims 21 to 24, further comprising mass filtering the ion beam prior to sending the ion beam into the collision cell. [26] A method according to any one of claims 21 to 25, further comprising selecting the energy of the ion beam prior to sending the ion beam into the collision cell.

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