Methods in mass spectrometry using collision gas as ion source

Abstract

A mass spectrometry method comprising steps of generating an ion beam from an ion source; directing the ion beam into a collision cell; introducing into the collision cell through a gas inlet on the collision cell a charge-neutral analyte gas or reaction gas; ionizing the analyte gas or reaction gas in the collision cell by means of collisions between the analyte gas or reaction gas and the ion beam; transmitting ions from the ionized analyte gas or reaction gas from the collision cell into a mass analyzer; and mass analyzing the transmitted ions of the ionized analyte or reaction gas. The methods can be applied in isotope ratio mass spectrometry to determine the isotope abundance or isotope ratio of a reaction gas used in mass shift reactions between the gas and sample ions, to determine a corrected isotope abundance or ratio of the sample ions.

Claims

1. A method of isotope ratio mass spectrometry, comprising: a. determining an isotope 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 generate at least one chemical adduct ion species resulting from the reaction of the sample ions and the reaction gas; and determining an isotope abundance and/or isotope ratio of the sample ions by mass analysis of the chemical adduct ion species; b. determining an isotope abundance and/or isotope ratio of the reaction gas, by ionizing the reaction gas in the collision cell by means of an ion beam, so as to generate at least one reaction gas ion species in the collision cell that is free of sample ions; and determining the isotope abundance and/or isotope ratio of the at least one reaction gas by mass analysis of the at least one reaction gas ion species; and c. adjusting/correcting the determination of the isotope abundance and/or ratio of the sample ions from step (a) based on the isotope abundance and/or ratio of the reaction gas determined in step (b).

2. The method of claim 1, wherein the determining of the isotope abundance and/or ratio of the reaction gas is performed before determining the isotope abundance of the sample ions.

3. The method of claim 2, further comprising mass filtering an ion beam comprising the sample ions and/or an ion beam that is free of sample ions prior to transmitting the sample ions and/or the ion beam into the collision cell.

4. The method of claim 2, further comprising selecting the energy of an ion beam comprising the sample ions and/or the ion beam that is free of sample ions prior to transmitting the sample ions and/or the ion beam into the collision cell.

5. The method of claim 1, wherein the sample ions are generated in an inductively coupled plasma (ICP) source.

6. The method of claim 5, wherein the ion beam is generated in the same inductively coupled plasma (ICP) source as the sample ions.

7. The method of claim 1, wherein the ion beam is generated by streaming a plasma generating gas into a plasma torch such that the ion beam substantially comprises ions of the plasma generating gas.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The skilled person will understand that the drawings, described below, are for illustration purposes only. The drawings are not intended to limit the scope of the present teachings in any way.

(2) FIG. 1 shows an Inductively Coupled Plasma (ICP) source in accordance with the invention, indicating two alternate configurations for introduction of reaction gas into the ICP source

(3) FIG. 2 shows a sample introduction system that consists of a nebulizer and a spray chamber, for introducing an aerosol into the ICP source. Two alternate configurations for introducing a reactive species into the sample introduction system are indicated.

(4) FIG. 3 shows schematic illustration of a mass spectrometer that can be used with the invention, highlighting the collision cell and upstream mass filter.

DESCRIPTION OF VARIOUS EMBODIMENTS

(5) In the following, exemplary embodiments of the invention will be described, referring to the figures. These examples are provided to provide further understanding of the invention, without limiting its scope.

(6) In the following description, a series of steps are described. The skilled person will appreciate that unless required by the context, the order of steps is not critical for the resulting configuration and its effect. Further, it will be apparent to the skilled person that irrespective of the order of steps, the presence or absence of time delay between steps, can be present between some or all of the described steps.

(7) It should be appreciated that the invention is applicable for mass analysis of materials in general, such as gases, liquids, solids, particles and aerosols. In general, therefore, the sample that is being analyzed in the system will be variable.

(8) An Inductively Coupled Plasma (ICP) source 10 in accordance with the invention is shown in FIG. 1. The ICP source exemplified contains three concentric tubes 11, 12, 13 which are typically made from quartz, and a load coil 21. As known in the art, plasma gas can be introduced through the sample inlet 14 into the inner tube 11, an auxiliary gas inlet 17 via an auxiliary gas line 15 into the middle tube 12 and/or a cooling gas inlet 20 via a cooling gas line 18 into the outer tube 13. The load coil 21 couples a very intense RF field into the argon gas flow (auxiliary gas and cooling gas). As a result of the high amount of energy (and an initial spark for seeding electrons), a plasma is generated and sustained with temperatures typically in the range of >8000° C.

(9) A sample is introduced through the sample inlet 14, typically in a plasma gas such as Argon. The sample can be an aerosol that is generated by a means of a nebulizer and a spray chamber, as further illustrated in FIG. 2. Optionally, any other gas species to be ionised can be introduced into the ICP source through the sample inlet 14 together with the sample, or alternatively, or additionally, via optional inlets 16, 19 on the auxiliary gas inlet line 15 and/or the cooling gas inlet line 18, respectively.

(10) The sample can be introduced into a sample introduction system such as a spray chamber assembly 30, as illustrated in FIG. 2. The assembly includes a nebulizer 31, which has a sample inlet 32, and a nebulizer gas inlet 34, which typically will be identical to the plasma gas (such as Argon). An optional inlet 33 can be provided on the nebulizer gas inlet, and that can be used to provide any additional gas, in mixture with the nebulizer gas, into the nebulizer.

(11) The nebulizer delivers a sample spray into the spray chamber 37, which has a drain 36 and an outlet 38 that feeds into the sample inlet 14 of the ICP source 10. The spray chamber can optionally further have a gas inlet 35 that can be used to deliver further gas into the spray chamber, where it will form a mixture with the sample aerosol and be delivered into the ICP source through the outlet 38.

(12) Thus, alternative embodiments for delivering sample gas into the spray chamber assembly are possible. These embodiments can be used alternatively, or they can be used in combination.

(13) The ions generated in the plasma enter the mass spectrometer via an interface comprising one or more cones 22.

(14) In FIG. 3, a mass spectrometer that can be used to practice the invention is shown. Downstream from the ICP source 10 there is a quadrupole mass filter 60. The mass filter can be used to selectively transmit ions that are of interest, or ions in a mass range of interest, for delivery into the collision cell and subsequent mass analysis in the downstream mass analyser. Alternatively, the mass filter can be used to selectively transmit the intense ion beam from the ICP source, for ionizing gas inside the collision cell.

(15) The collision cell 40 receives ions that are transmitted by the upstream mass filter 60. The collision cell further has a gas inlet 41, for receiving charge-neutral collision/reaction gas that reacts with ions inside the collision cell. For example, the incoming ions may be ions from the Ar.sup.+ ion beam that is generated in the ICP source, and that have been selectively transmitted by the upstream mass filter 60. The ion beam can ionize the charge-neutral collision gas (e.g., oxygen), and the thus generated ions of the collision/reaction gas can be mass analysed in the downstream mass analyzer.

(16) Alternatively, the gas inlet 41 can be used to deliver analyte gas into the collision cell that can be ionized and/or fragmented inside the collision cell by the incoming ion beam (e.g. the Ar.sup.+ ion beam). The thus generated ions and/or ionized fragments of the analyte can be mass analysed in the downstream mass analyser 50. Thereby, the incoming ion beam is used to ionize the charge-neutral analyte, for subsequent mass analysis.

(17) The ions that are generated inside the collision cell are subsequently directed to a downstream mass analyser 50, wherein the ions are mass analysed. The mass analyser can in principle be any suitable mass analyser, such as a single or dual sector mass analyser (e.g., a dual sector multicollector), a quadrupole mass analyser, an ion trap mass analyser, a time of flight mass analyser, or an electrostatic trap mass analyser, including an orbitrap mass analyser.

(18) The following non-limiting examples provide exemplary descriptions of certain analytical benefits of the present invention.

EXAMPLE 1

(19) This experiment is designed to determine titanium (Ti) isotopic abundances in a sample containing titanium and chromium (Cr). Of specific interest is the abundance of the .sup.50Ti isotope. In this example the sample is directly introduced into the ICP ion source by laser ablation so there is no opportunity to separate Ti from Cr before the analysis and all the specificity in the analysis has to be achieved in the mass spectrometer. This is problematic as the .sup.50Ti isotope has isobaric interferences with .sup.50Cr which must be resolved or corrected for in order to achieve an accurate determination of .sup.50Ti.

(20) The experiment comprises two parts, first using the mass filter to permit a specified mass range into the collision cell, introduce oxygen gas into the collision cell in order to form TiO adduct ion in a mass shift reaction and then mass analyse the adduct ions to determine the isotopic abundance of .sup.50Ti and/or a ratio of .sup.50Ti with another Ti isotope. In the second part the mass filter is set to permit only the intense .sup.40Ar ion beam from the plasma ion source to 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 intense .sup.40Ar beam undergoes charge exchange reactions with the neutral O.sub.2 gas, causing ionisation and dissociation of the O.sub.2 gas. The resulting oxygen ions then exit the collision cell and can be mass analysed for their isotope ratio. The known isotope ratio of the oxygen gas can then be used to more accurately correct for the presence of minor isotope oxides which will be present in the first experiment.

(21) Experiment Details

(22) For the first part the sample is introduced via laser ablation to the Ar plasma ion source of the instrument to produce Ti.sup.+ and Cr.sup.+ ions. As Cr isotopes have isobaric interferences to the target .sup.50Ti isotope these species must be separated in the mass spectrometer. Then use is made of the chemical resolution that can be achieved with the collision cell and introduce oxygen gas into the collision cell. The selective reactivity of the different elements to preferentially promote Ti.sup.+ away from interfering Cr.sup.+ is exploited by forming TiO.sup.+ from the sample Ti.sup.+ and O.sub.2 gas. As this reaction is orders of magnitude more efficient for TiO.sup.+ compared to CrO.sup.+ the Ti species can be successfully separated from Cr in the mass spectrum. The resultant TiO species formed in the collision cell is now present at mass 62-66 in the copper and zinc spectrum and this can be measured in the downstream mass analyser. To avoid a need to make a complicated correction of the potential presence of copper and zinc in the sample, the mass filter located before the collision cell is suitably used to transmit only a selected range of masses. In this example we consider that we have a mass window of ±10 centred on .sup.50Ti. This allows transmission of all isotopes of Ti and Cr but crucially does not allow transmission of copper or zinc into the collision cell. Thus the adduct TiO.sup.+ ions created in the cell can be measured in the copper and zinc mass range but in absence of copper and zinc from the sample as this does not pass the first mass filter. Thus the .sup.50Ti abundance and Ti isotope ratio can be determined in the sample without interference from Cr.

(23) The second part allows for more accurate assessment of the .sup.50Ti abundance to be made in the sample by accounting for the presence of minor oxide isotopes by determining the isotopic composition of the reaction gas (oxygen). Whilst the promotion of Ti.sup.+ ions to TiO.sup.+ ions in the collision cell can effectively separate Ti from Cr in the sample, the oxide promotion scheme creates further isobaric interferences from the presence of TiO.sup.+ species which have been formed from the minor oxygen isotopes .sup.17O and .sup.18O e.g. .sup.48Ti.sup.18O which is isobaric to the target .sup.50Ti.sup.16O. These interferences may only be present in small amounts e.g. .sup.18O is only ˜0.2% of all oxygen but in the case where a major Ti isotope/minor oxygen pair interferes with a minor Ti isotope/major oxygen pair this contribution may be significant enough to lead to an inaccuracy in the Ti isotope measurement. For example .sup.48Ti.sup.18O will contribute about 3% to the beam measured at mass 66 for 50Ti.sup.16O.

(24) Corrections for these interferences can be made by monitoring an uninterfered minor isotope oxide such as 50Ti18O at mass 68 and making corrections based on reference isotope ratios for oxygen. However for the highest accuracy in the determination of Ti isotope abundances and ratios it would be desireable to characterise the isotopic composition of the oxygen gas that is being supplied to the collision cell. This could be achieved by a separate off line analysis of the gas but one would also like to know if introduction to and exit from the collision cell causes isotopic fractionation of the gas. In order to measure this, oxygen is first introduced to the collision cell under identical conditions as for the Ti isotope ratio analysis. The mass filter located before the collision cell is then set to introduce only the dominant .sup.40Ar ion from the plasma into the collision cell. The .sup.40Ar ion has a higher ionisation potential than the O.sub.2 molecule and undergoes charge exchange with the molecule which dissociates and ionises the O.sub.2 to O.sup.+. The oxygen ions then exit the collision cell and the isotopic composition of the oxygen gas can be analysed in the main mass analyser. This determination of the isotope ratio of the oxygen reaction gas can then be used to correct for the contribution of minor oxide species to the Ti isotope ratio measurements made in the experiment in part 1. This method has advantages over using reference ratio for the reaction gas isotope ratio as it allows for correction of any fractionation in the isotope composition which may occur in the introduction of the reaction gas to the cell or when molecular adduct ion leaves the reaction cell.

(25) The atomic and molecular species considered from this example are shown below in Table 1.

(26) TABLE-US-00001 TABLE 1 Atomic and molecular species considered in Example 1. Mass 46 47 48 49 50 51 52 Species .sup.46Ti .sup.47Ti .sup.48Ti .sup.49Ti .sup.50Ti .sup.50V .sup.51V .sup.50Cr .sup.52Cr Mass 62 63 64 65 66 67 68 Species .sup.16O .sup.46Ti.sup.16O .sup.47Ti.sup.16O .sup.48Ti.sup.16O .sup.49Ti.sup.16O .sup.50Ti.sup.16O .sup.17O .sup.46Ti.sup.17O .sup.47Ti.sup.17O .sup.48Ti.sup.17O .sup.49Ti.sup.17O .sup.50Ti.sup.17O .sup.18O .sup.46Ti.sup.18O .sup.47Ti.sup.18O .sup.48Ti.sup.18O .sup.49Ti.sup.18O .sup.50Ti.sup.18O

(27) For example, it can be seen that the .sup.46Ti.sup.16O species can be measured uninterfered at mass 62. The measured abundance (intensity) at mass 63, however, is made up mainly of .sup.47Ti.sup.16O with a small contribution from .sup.46Ti.sup.17O. From the isotopic measurement of the oxygen reaction gas, the ratio of .sup.16O:.sup.17O is known, and hence the abundance of .sup.46Ti.sup.17O can be determined from the measured abundance of the uninterfered .sup.46Ti16O. As the abundance of .sup.46Ti.sup.17O is now determined, the corrected abundance of .sup.47Ti.sup.16O can be determined from the mass 63 measurement and hence the corrected isotope ratio .sup.47Ti:.sup.46Ti can be obtained. This method can be applied to the other mass measurements to obtain corrected isotope ratios of the other Ti isotopes.

EXAMPLE 2

(28) This experiment is designed to determine the site specific isotope 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 select only the .sup.40Ar.sup.+ ion which is an intense ion beam and transmit this into the collision cell. Through the gas inlet of the collision cell we introduce the propane analyte gas. Propane is a saturated alkane molecule with a three-carbon chain. Using an accelerating electrode located before the collision cell, the ion energy is controlled of the incident .sup.40Ar.sup.+ ion which interacts with the propane molecule causing fragmentation and ionisation of the molecule along the C.sub.1 to C.sub.2 bond. Thus the charge neutral propane molecule with three carbons and 8 hydrogens is split into two fragments one of 1 carbon and 3 hydrogens and a second of 2 carbons and 5 hydrogens.

(29) These molecular ion fragments then exit the collision cell and may be mass analysed by the second mass analyser. The power of this technique is that by monitoring the both masses 15 (.sup.12CH.sub.3) and 16 (.sup.13CH.sub.3), as well as 24 (.sup.12C.sub.2H.sub.3) and 25 (.sup.13C.sup.13C.sub.3) one 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 C.sub.1 carbon and the C.sub.2-3 carbon cluster. If the incident .sup.40Ar.sup.+ can be used to induce further fragmentation of the propane molecule in the collision cell and sufficient mass resolution can be achieved in the second mass analyser (m/Δm ˜3500) then one may even choose to monitor masses 14 (.sup.12CH.sub.2) and 15 (.sup.13CH.sub.2) for the isotopic composition of the C.sub.2 carbon at the same time as the 15 (.sup.12CH.sub.3) and 16 (.sup.13CH.sub.3) for the isotopic composition of the C.sub.1.

(30) As used herein, including in the claims, singular forms of terms are to be construed as also including the plural form and vice versa, unless the context indicates otherwise. Thus, it should be noted that as used herein, the singular forms “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise.

(31) Throughout the description and claims, the terms “comprise”, “including”, “having”, and “contain” and their variations should be understood as meaning “including but not limited to”, and are not intended to exclude other components.

(32) The present invention also covers the exact terms, features, values and ranges etc. in case these terms, features, values and ranges etc. are used in conjunction with terms such as about, around, generally, substantially, essentially, at least etc. (i.e., “about 3” shall also cover exactly 3 or “substantially constant” shall also cover exactly constant).

(33) The term “at least one” should be understood as meaning “one or more”, and therefore includes both embodiments that include one or multiple components. Furthermore, dependent claims that refer to independent claims that describe features with “at least one” have the same meaning, both when the feature is referred to as “the” and “the at least one”.

(34) It will be appreciated that variations to the foregoing embodiments of the invention can be made while still falling within the scope of the invention can be made while still falling within scope of the invention. Features disclosed in the specification, unless stated otherwise, can be replaced by alternative features serving the same, equivalent or similar purpose. Thus, unless stated otherwise, each feature disclosed represents one example of a generic series of equivalent or similar features.

(35) Use of exemplary language, such as “for instance”, “such as”, “for example” and the like, is merely intended to better illustrate the invention and does not indicate a limitation on the scope of the invention unless so claimed. Any steps described in the specification may be performed in any order or simultaneously, unless the context clearly indicates otherwise.

(36) All of the features and/or steps disclosed in the specification can be combined in any combination, except for combinations where at least some of the features and/or steps are mutually exclusive. In particular, preferred features of the invention are applicable to all aspects of the invention and may be used in any combination.