Mass spectrometry apparatus

Abstract

The invention relates to a mass spectrometry device. The invention relates to a method of operating an inductively coupled plasma mass spectrometry device for analyzing an analyte sample, the mass spectrometry device comprising a plasma ion source, a mass analyzer and an interface device located between the plasma ion source and the mass analyzer of the mass spectrometer, the interface device comprising at least an interface structure in the form of a cone of the interface device, such as a sampling cone or a skimmer cone, and at least one channel having an inlet and an outlet, the channel leading from outside the interface structure (32) to a reaction zone formed in an area surrounding the outlet of the channel, the method comprising the steps of generating a plasma using the plasma ion source and forming a plasma flux flowing to the mass analyzer, providing an analyte sample into the reaction zone via the channel such that the analyte sample interacts with the plasma flux, and analyzing the analyte sample using the mass analyzer.

Description

Technical Field

[0001] The present invention relates to a method for operating an inductively coupled plasma mass spectrometry (ICP-MS) apparatus for analyzing molecular analytes or mixtures of at least two substances. Background Technology

[0002] Inductively coupled plasma mass spectrometry (ICP-MS) is used, for example, for trace element analysis. Typically, ICP-MS analysis involves the complete atomization and subsequent ionization of the test sample using a plasma source before quantification of the elemental ions obtained by the spectrometer. Several different types of ICP-MS are available to date, such as quadrupole ICP-MS or time-of-flight ICP-MS.

[0003] A common problem in any ICP-MS analysis is the potential for interference caused by newly formed polyatomic ions or molecules. This interference is typically addressed through the reaction / collision chamber of the corresponding ICP-MS system. Therefore, reagent gases are added to the reaction / collision chamber to provide separation of analyte ions from interfering substances based on the energy difference between the analyte ions and the interfering substances. Exemplary ICP-MS systems for improving interference attenuation are described in US 7,329,863B2 and US 7,119,330B2.

[0004] ICP-MS systems are not well-suited, or even unsuitable, for molecular analysis, which is typically performed using mass spectrometry employing different types of ionization sources, such as electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI). These methods are optimized for molecular ionization and do not result in their atomization.

[0005] Other mass spectrometry systems suitable for molecular analysis include, for example, selective ion flow tube mass spectrometer (SIFT-MS) or proton transfer reaction mass spectrometer (PTR-MS).

[0006] However, to date, no mass spectrometry system is available that allows the analysis of atomized and ionized molecules in a single device. Summary of the Invention

[0007] Therefore, the objective technical problem to be solved by the present invention is to provide the possibility of analyzing atomized and ionized molecules in a single device.

[0008] This objective is achieved by the method described in the present invention and the application described in the present invention.

[0009] Regarding this method, the objective is achieved by a method of operating an inductively coupled plasma mass spectrometry (ICP-MS) analyzer for analyzing analyte samples. The ICP analyzer includes a plasma ion source, a mass analyzer, and an interface device located between the plasma ion source and the mass analyzer of the mass spectrometer. The interface device includes at least an interface structure in the form of a cone (e.g., a sampling cone or a truncation cone) and at least one channel having an inlet and an outlet, the channel extending from the outside of the interface structure to a reaction zone formed in a region surrounding the outlet of the channel.

[0010] The method includes the following steps:

[0011] Plasma is generated using a plasma ion source, forming a plasma flux that flows toward the mass analyzer.

[0012] The analyte sample is supplied to the reaction zone via a channel, allowing the analyte sample to interact with the plasma flux, and

[0013] The analyte sample was analyzed using a quality analyzer.

[0014] The analyte or mixture may initially be provided in the form of a gas, vapor, or liquid. The analyte sample is preferably a molecular analyte or a mixture of at least two substances.

[0015] The interface structure may include one or more cones. For example, it may include a sampling cone and a truncating cone, or a sampling cone, a truncating cone, and at least one additional cone.

[0016] The channels used to introduce substances or mixtures can be those described in US7,329,863B2 and US7,119,330B2. In the context of this invention, both references are fully understood. However, the channels in the given references are used for entirely different purposes, namely, attenuating interference. Nevertheless, as suggested by this invention, the same apparatus can also be used to facilitate molecular analysis by ICP-MS.

[0017] This invention advantageously allows for the analysis of analyte samples, particularly molecular samples, using ICP-MS with an inlet-based collision / reaction cell. The analyte sample is provided via at least one channel, such that an ion beam is formed in the reaction zone toward the mass analyzer.

[0018] In a typical ICP-MS setting, the plasma introduced into the analyte sample is usually at a relatively high pressure (e.g., atmospheric pressure). The plasma evaporates and ionizes the sample, and the ions are subsequently extracted and transferred to a mass analyzer via a differential pump interface. The mass analyzer typically operates at relatively low pressures, usually <10. -5The process involves a stepped reduction in space between successive cones. By introducing the analyte sample into the channel rather than directly supplying it to the plasma-generating region, ionization of the analyte sample becomes possible. This ionization process is much softer and does not lead to molecular decomposition, especially complete decomposition, compared to the standard process used in ICP-MS. The proposed process further enables parallel ionization of polar and nonpolar analytes, as well as ionization of gaseous and liquid analytes, and also achieves targeted molecular fragmentation.

[0019] In one embodiment of the invention, at least one reagent substance is added, which is used to generate specific ions from the analyte sample by chemical ionization. The reagent substance may be added, for example, via at least one channel.

[0020] Advantageously, the reagent is one of H2, O2, H2O, NH3, NO3 or any of its ionized, protonated or deprotonated derivatives.

[0021] Another embodiment includes using a microwave-induced plasma source as a plasma ion source. Using an ion source including a microwave generator has the advantages of achieving high field strength and low power consumption. Therefore, a uniform and energy-efficient plasma can be achieved directly. In this regard, see DE202020106423U1, US2016 / 0026747A1, and WO2017 / 176131A1. In particular, such a microwave-based plasma ion source may include a dielectric resonator.

[0022] Advantageously, argon, nitrogen, krypton, xenon, neon, helium, or any mixture of at least two gases can be used as the carrier gas for the plasma ionization source. The choice of carrier gas depends on the reaction to be induced. In this respect, nitrogen, in particular, induces additional reactions with reagent gases or molecules, and can be used as a carrier gas for ionization.

[0023] One embodiment includes the analyte sample being divided into at least two sub-fractions based on at least one physical and / or chemical property (e.g., size or charge) of its components before being provided to the reaction zone via a channel, wherein the sub-fractions are provided to the reaction zone individually, one after another. This division can advantageously be achieved by various separation and / or fractionation methods, such as gas or liquid chromatography, or particularly capillary electrophoresis. For this purpose, the mass spectrometry apparatus may include suitable means for the separation, division, or fractionation of the analyte sample, such as a gas or liquid chromatography or electrophoresis unit.

[0024] Another embodiment includes a mass spectrometer equipped with an ion optics system that establishes a reflective electrostatic field to reflect ions along a desired path toward the mass analyzer. Such an ion optics system can include any device capable of deflecting a quantity of ions between two non-parallel planes, such as an ion mirror, reflector, deflector, quadrupole ion deflector, electrostatic energy analyzer, magnetic ion optics, ion multiguide, etc. A preferred embodiment employs an arrangement of an ion optics device called an "IonMirror," as described in U.S. Patent No. 6,614,021 (incorporated herein by reference), or those disclosed in US 5,559,337, US 5,773,823, US 5,804,821, US 6,031,579, US 6,815,667, US 6,630,665, or US 6,630,651. The use of an ion mirror further improves the sensitivity of the ICP-MS device.

[0025] In another embodiment of the method, the interface structure is as follows:

[0026] The first vacuum region, located on the first surface of the adjacent interface structure and at a relatively high pressure, is separated from the second vacuum region, located on the second surface of the adjacent interface structure and at a relatively low pressure. The first vacuum region receives plasma flux from the plasma ion source, while the second vacuum region leads to the mass analyzer.

[0027] A hole is provided that extends axially, forming a reaction zone between a first surface and a second surface of the interface structure. Plasma flux flows through the hole from the first region to the second region.

[0028] The channel leads to the reaction zone formed in the hole of the interface structure.

[0029] Therefore, the analyte sample is guided into the reaction zone, where it interacts with the plasma, which is already at a lower pressure compared to the region of the plasma ion source. This results in much softer ionization and significantly less fragmentation.

[0030] One embodiment includes an interface device comprising at least a sampling cone and a snipping cone, the snipping cone being arranged behind the sampling cone.

[0031] However, in another embodiment, at least two channels are provided in the interface device. The at least two channels can be located in the same cone or in two different cones, for example, one in the intercept cone and one in the sampling cone. By providing more than one channel, more than one reaction zone is created, enabling multiple reactions to occur.

[0032] In one embodiment, the channel is entirely located within at least one cone—such as a sampler, a cutting cone, or any other cone. Such a device is proposed, for example, in US 7,329,863 B2.

[0033] However, in another embodiment, the channel is located behind the sampling cone, snipping cone, or any other cone, as described in US7,119,330 B2.

[0034] In another embodiment, the analyte sample and / or reagent substance are provided via a channel at least during a first time interval and to the region of the plasma ion source that forms the plasma at least during a second time interval. Through this process, conventional ICP-MS analysis associated with structural analysis can be combined with molecular analysis. The first and second time intervals can be performed alternately or initiated as needed.

[0035] The object of the present invention is further achieved by using an inductively coupled mass spectrometry (ICMMS) analysis apparatus comprising a plasma ion source, a mass analyzer, and an interface device located between the plasma ion source and the mass analyzer in the mass spectrometer. The interface device includes at least an interface structure in the form of a cone (e.g., a sampling cone or a truncation cone) of the interface device, and at least one channel having an inlet and an outlet, the channel extending from the outside of the interface structure to a reaction zone formed in a region surrounding the outlet of the channel for analyzing molecular analyte samples. By performing a method according to at least one of the above embodiments, the mass spectrometry analysis apparatus is particularly suitable for molecular analysis. Attached Figure Description

[0036] Based on Figures 1-3 The present invention and its preferred embodiments will be further explained.

[0037] Figure 1 A conventional ICP-MS according to the prior art is shown;

[0038] Figure 2 illustrates exemplary and preferred embodiments of an interface device having at least one cone, the cone having at least one channel for introducing an analyte sample; and

[0039] Figure 3 This is the mass spectrum of propane obtained by the method of this invention.

[0040] In the accompanying drawings, the same elements have the same reference numerals. Detailed Implementation

[0041] Figure 1A conventional ICP-MS 10 with an ion source 20 in the form of an inductively coupled plasma torch is schematically illustrated. The inductively coupled plasma torch has a central tube for delivering an analyte sample AS in a carrier gas to the plasma 28 generated in the torch. The ion source 20 further includes an intermediate tube for delivering a plasma-forming gas 24 and an auxiliary gas 26—which may be, for example, argon or nitrogen—and a radio frequency coil 30 arranged around an outer tube.

[0042] The mass spectrometer further includes an interface device 32 for transferring the analyte sample and plasma flux 28 to the analytical section of the ICP-MS. This interface device 32 includes an interface structure comprising a sampling cone 34 and a truncating cone 40. Each of the two cones 34, 40 has an aperture 36, 42 at its apex through which the plasma flux 28 enters from the ion source 20 into a first vacuum region 38 and a second vacuum region 44. The cones 34, 40 are typically water-cooled. In the illustrated embodiment, the second vacuum region 44 further includes an ion extraction electrode 46 and other ion optics [not shown], all of which are part of an ion optics system for extracting the ion beam from the plasma flux 28 into a third pumped vacuum region 48 and directing it toward a mass analyzer 50 and a detector 52. The mass analyzer 50 separates ions according to their mass-to-charge ratio, and in the detector 52, the detected ions are read out by a recording device 54. Different mass analyzers 50 may be employed, such as quadrupole or time-of-flight (TOF) mass analyzers 50. The TOF analyzer has the advantage of being able to identify polyatomic ions.

[0043] An interface device 32 for performing the method according to the invention includes at least one channel having an inlet and an outlet, the channel leading from the outside of the interface structure to a reaction zone formed in a region surrounding the outlet of the channel, as illustrated in FIG2, which shows an exemplary embodiment of an interface device 32 having at least one channel in at least one cone.

[0044] Figure 2a The interface device 32 shown has a similar Figure 1 The sampling cone 34 and the snipping cone 40 are shown. An ion plasma flux 28 flows into a first vacuum region 38 through an aperture 36 in the sampling cone 34 and into a second vacuum region 44 through an aperture 42, the second vacuum region 44 being maintained at a pressure lower than that of the first vacuum region. The snipping cone 40 includes a channel 60 leading from an inlet 62 to an outlet 63 at the aperture 42 of the snipping cone 40. While this arrangement is typically used to create reaction / collision zones, the present invention uses the channel 60 to supply analyte material AS to a reaction zone 64, where the analyte material AS interacts with the plasma 28, thereby gently ionizing the analyte material AS. The exact size of the reaction zone 64 depends on several factors, such as the nature of the plasma. Therefore, Figure 2a The shape of the reaction zone in the diagram is merely exemplary and may vary depending on the device.

[0045] A second preferred embodiment of the interface device 32 is shown in FIG2b. Figure 2a In contrast to the embodiment shown, in the case of FIG. 2b, the sampling cone 34 includes a second channel 74 having an inlet 72 and an outlet 75, creating a second reaction zone 76 near the orifice 36. The two channels 60 and 74 can be used in different ways. For example... Figure 2a As shown, reagent gas RG can be provided via channel 74, while analyte sample AS can be provided via channel 60. However, in other embodiments, for example, reagent substance RS can also be provided via channel 60, while analyte sample AS can be provided via channel 74. A single channel 60, 74 can also be used to provide both reagent substance RS and analyte sample AS.

[0046] The third preferred embodiment of the interface device 32 is in Figure 2c As shown in Figure 2b, the truncating cone 40 is provided with two channels 60 and 88, in contrast to the embodiment shown in Figure 2b. The third channel 88 also has an inlet 90 and an outlet 91, which in this embodiment leads to the first reaction zone 64. Similarly, many different possibilities exist for using different channels 60, 74, 88, and for providing one or more reagent substances RS and analyte samples AS, all of which fall within the scope of this invention.

[0047] Finally, another preferred embodiment of the interface device 32 is as follows: Figure 2d For reference. Similarly, interface device 32 includes a sampling cone 34 and a snipping cone 40, followed by an ion optics system including an ion extraction electrode 45 and other electrodes 46 and 47 mounted on the snipping cone 40 via a dielectric seal 45a to extract an ion beam 58. In this embodiment, at least one channel 94 is provided behind the snipping cone 40 for providing the analyte sample AS into the reaction zone 95.

[0048] It should be noted that different embodiments of the interface device 32 shown can be arbitrarily combined with each other. Furthermore, it should be noted that the invention is by no means limited to the embodiments shown. For example, any embodiment of the interface device 32 or interface structures 34, 40 may be as disclosed in, for example, US 7,329,863 B2 and US 7,119,330 B2.

[0049] In summary, this invention provides the possibility of combining conventional ICP-MS for elemental analysis with organic molecular analysis in a single device. To achieve this, channels 60, 74, 88, and 94 (now and for the first time) typically provided to reduce interference by supplying a collision gas are used to supply analyte samples AS to the mass spectrometry device. The analyte samples AS, particularly molecular samples, are introduced into a cooled plasma, residual plasma, or are ionized by, for example, a carrier gas derived from ion source 20.

[0050] In addition, additional reagent substance RD can be added via at least one channel 60, 74, 88, 94 to generate specific product ions by chemical ionization, which can be analyzed by the subsequent mass spectrometry analysis section.

[0051] Figure 3 Two mass spectra of propane are shown: mass spectrum 1 obtained using a conventional ICP mass spectrometer apparatus 10 and mass spectrum 2 obtained using the method and apparatus 10 according to the invention, i.e., the analyte sample AS is introduced via channels 60, 74, 88, and 94 of interface device 32, using an inlet-based collision / reaction cell. By introducing the analyte sample AS into channels 60, 74, 88, and 94 instead of directly supplying it to the region generating plasma, the ionization process of the analyte sample AS becomes softer and does not lead to molecular breakdown (spectrum 2) compared to the standard process used in ICP-MS (spectrum 1). Only in spectrum 2, Figure 3 The analyte sample AS shown has propane molecules that remain intact (44 Da) or are partially fragmented (e.g., 43 Da - corresponding to the loss of one hydrogen, 26-30 Da - corresponding to various C2H atoms). n (fragment). Therefore, this invention directly extends the application scope of ICP-MS equipment to molecular analysis.

[0052] Reference symbol

[0053] 10ICP-MS

[0054] 20 ion sources

[0055] 28 plasma

[0056] 24. Plasma forming gas

[0057] 26 auxiliary gases

[0058] 30 RF coil

[0059] 32-interface device

[0060] 34 sampling cones

[0061] 40-section cone

[0062] 36-well sampling cone

[0063] 42-hole cutting cone

[0064] 38 First Vacuum Region

[0065] 44 Second Vacuum Region

[0066] Electrodes of ion optical systems 45, 46, and 47

[0067] 50 Quality Analyzer

[0068] 52 detectors

[0069] 54 Recording device

[0070] Channels 60, 74, 88, and 94

[0071] Entrances 62, 72, and 90

[0072] Exports of 63, 75, and 91

[0073] Reaction zones 64, 76, and 95

[0074] AS analyte sample

[0075] RS reagents

Claims

1. A method for operating an inductively coupled plasma mass spectrometry (10) apparatus (10) for analyzing analyte samples (AS), The mass spectrometry analysis apparatus (10) includes a plasma ion source (20), a mass analyzer (50), and an interface device (32) located between the plasma ion source (20) and the mass analyzer (50) of the mass spectrometry analysis apparatus (10). The interface device (32) includes at least an interface structure (34, 40) in the form of a cone, and at least one channel (60, 74, 88, 94) having an inlet (62, 72, 90) and an outlet (63, 75, 91). The channel (60, 74, 88, 94) extends from the outside of the interface structure (34, 40) to a reaction zone (64, 76, 95) formed in a region surrounding the outlet (63, 75, 91) of the channel (60, 74, 88, 94). The method includes the following steps: Plasma (28) is generated using the plasma ion source (20) and a plasma flux (28) flows toward the mass analyzer. The analyte sample (AS) is provided to the reaction zone (64, 76, 95) via the channels (60, 74, 88, 94), such that the analyte sample (AS) interacts with the plasma flux (28), and The analyte sample (AS) is analyzed using the quality analyzer (50).

2. The method according to claim 1, wherein, The interface structure (34, 40) is in the form of a sampling cone (34) or a truncation cone (40).

3. The method according to claim 1, in, At least one reagent substance (RS) is added to generate specific ions of the analyte sample (AS) by chemical ionization.

4. The method according to claim 3, in, The reagent substance (RS) is one of H2, O2, H2O, NH3, NO3 or any of its ionized, protonated or deprotonated derivatives.

5. The method according to any one of claims 1-4, in, Microwave-induced plasma sources were used as plasma ion sources (20).

6. The method according to claim 5, in, Argon, nitrogen, krypton, xenon, neon, helium, or any mixture of at least two gases are used as the carrier gas of the plasma ion source (20).

7. The method according to any one of claims 1-4, in, Before the analyte sample (AS) is provided to the reaction zone (64, 76, 95) via the channels (60, 74, 88, 94), it is divided into at least two sub-parts based on at least one physical and / or chemical property of its components.

8. The method according to claim 7, in, The sub-parts are individually provided to the reaction zones (64, 76, 95) one after another.

9. The method according to any one of claims 1-4, in, The mass spectrometry analyzer (10) is provided with an ion optical system (45-47) that establishes a reflective electrostatic field for reflecting ions along a desired path toward the mass analyzer (50).

10. The method according to any one of claims 1-4, in, The interface structures (34, 40) are as follows: A first vacuum region (38) at a relatively high pressure on a first surface adjacent to the interface structures (34, 40) is separated from a second vacuum region (44) at a relatively low pressure on a second surface adjacent to the interface structures (34, 40). The first vacuum region receives plasma flux (28) from the plasma ion source (20), and the second vacuum region leads to the mass analyzer (50). An axially extending orifice is provided, forming a reaction zone (64, 76, 95) between a first surface and a second surface of the interface structure (34, 40), through which the plasma flux (28) flows from the first vacuum region (38) to the second vacuum region (44). The channels (60, 74, 88, 94) lead to the reaction zones (64, 76, 95) formed in the holes of the interface structures (34, 40).

11. The method according to any one of claims 1-4, in, The interface device (32) includes at least a sampling cone (34) and a cutting cone (40), the cutting cone (40) being arranged behind the sampling cone (34).

12. The method according to any one of claims 1-4, in, At least two channels (60, 74, 88, 94) are provided in the interface device (32).

13. The method according to any one of claims 1-4, in, The channels (60, 74, 88, 94) are entirely located within the sampling cone (34), the intercepting cone (40), and / or any additional cones.

14. The method according to any one of claims 1-4, in, The channels (60, 74, 88, 94) are located behind the sampling cone (34), the intercepting cone (40), and / or any additional cones.

15. The method according to claim 3, in, At least during the first time interval, the analyte sample (AS) and / or the reagent substance (RS) are provided via the channels (60, 74, 88, 94), and During at least the second time interval, the analyte sample (AS) and / or the reagent substance (RS) are provided to the region of the plasma ion source (20).

16. Use of an inductively coupled mass spectrometry (ICM) analysis apparatus (10), the ICM analysis apparatus (10) comprising a plasma ion source (20), a mass analyzer (50), and an interface device (32) located between the plasma ion source (20) and the mass analyzer (50) of the ICM analysis apparatus (10), the interface device (32) comprising at least an interface structure (34, 40) in the form of a cone of the interface device (32), and at least one channel (60, 74, 88, 94) having an inlet (62, 72, 90) and an outlet (63, 75, 91), the channel (60, 74, 88, 94) extending from the outside of the interface structure (34, 40) to a reaction zone (64, 76, 95) formed in a region surrounding the outlet (63, 75, 91) of the channel (60, 74, 88, 94), for performing molecular analysis of a molecular analyte sample (AS).

17. The use of the inductively coupled mass spectrometry analysis device (10) according to claim 16, wherein, The interface structure (34, 40) is in the form of a sampling cone (34) or a truncation cone (40).

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