Mixed mass spectrometry device

Abstract

This invention relates to a hybrid mass spectrometry apparatus. The mass spectrometry apparatus (100) for analyzing analyte samples includes: an ion source (1) from which a certain amount of analyte ions from the analyte sample can be obtained to provide an ion beam (7, 11); a mass analyzer (9) for filtering the analyte ions of the ion beam (7, 11) based on their mass-to-charge ratio; a first detector unit (A) for analyzing the ions of the ion beam (7, 11); and a second detector unit (B) based on the time-of-flight principle and including a second detector (15) for analyzing the ions of the ion beam (7, 11). The invention also relates to a method for analyzing analyte samples using the mass spectrometry apparatus (100) according to the invention.

Description

Technical Field

[0001] This invention relates to a mass spectrometry apparatus for analyzing analyte samples and a method for analyzing analyte samples using a mass spectrometry apparatus. Background Technology

[0002] Today, mass spectrometry is widely used in various fields for the analysis and / or characterization of analyte samples. Many different types of mass spectrometers are known from existing technology, such as sector field, quadrupole, or time-of-flight mass spectrometers, or even inductively coupled plasma mass spectrometers. The operating modes of various mass spectrometers have been described in numerous publications and will not be elaborated upon here.

[0003] In a mass spectrometer, molecules or atoms of the analyte sample are first transferred to the gas phase and ionized. Various methods known in the art for ionization are available, such as inductively coupled plasma ionization (ICP), collisional ionization, electron collisional ionization, chemical ionization, photoionization, field ionization, or so-called rapid atomic bombardment, matrix-assisted laser desorption / ionization, or electrospray ionization.

[0004] After ionization, the ions pass through an analyzer (also called a mass analyzer), where they are separated according to their mass-to-charge ratio m / z. Different types of analyzers and operating modes are based on, for example, the application of static or dynamic electric and / or magnetic fields or on the different times of flight of different ions. In particular, different types of mass analyzers include single, multiple, or mixed arrangements of analyzers, such as quadrupoles, triple quadrupoles, time-of-flight (TOF), ion traps, orbital traps, or magnetic sectors.

[0005] Finally, the separated ions are directed to a detector, such as a photoionizer, an ion-electron multiplier, a Faraday collector, a Daly detector, a microchannel plate, or a channel multiplier.

[0006] Typically, the components of a mass spectrometer are combined according to the intended purpose, involving the selection of the most suitable detector in the end region of the mass spectrometer to detect target ions. In the case of a hybrid mass spectrometry setup, this detector can be positioned after a single mass analyzer or more than one mass analyzer. Hybrid mass spectrometry devices combine the different performance characteristics offered by different types of mass spectrometers into a single device. Known forms of hybrid mass spectrometry devices include, for example, quadrupole and TOF mass analyzers (Q / TOF), quadrupole and ion trap (Q-Trap), linear ion trap and orbital trap (LTQ-Orbitrap), or quadrupole and orbital trap mass analyzers.

[0007] Inductively coupled plasma mass spectrometry (ICP-MS) involves, for example, the complete atomization and subsequent ionization of the test sample via a plasma source before quantification of the resulting elemental ions by a spectrometer. Quadrupole mass filters are frequently used in this regard due to their excellent dynamic range and sensitivity, as well as their robustness and high analytical speed. However, some applications (such as nanoparticle detection, laser ablation, or tissue imaging) require parallel mass spectrometry obtained via time-of-flight (TOF) or quadrupole time-of-flight (Q / TOF) devices, which offer relatively higher detection speeds and simultaneous mass range coverage. On the other hand, such devices, compared to quadrupole-based mass spectrometry alone, include significantly lower dynamic range, lower sensitivity, and increased system cost. Therefore, it is desirable to combine the advantages of both different types of mass spectrometry devices to improve analytical capabilities. Summary of the Invention

[0008] Today, this is achieved either by leveraging certain aspects and features of various hybrid approaches or by utilizing two separate devices. These solutions either fail to benefit from the overall idea behind the hybrid approach or are inefficient and costly. Therefore, the object of this invention is to provide a hybrid mass spectrometry device that allows for comprehensive characterization of analyte samples.

[0009] This objective is achieved by a mass spectrometry apparatus and a method of operating the mass spectrometry apparatus according to the invention.

[0010] Regarding the mass spectrometry apparatus, this objective is achieved by a mass spectrometry apparatus for analyzing analyte samples, the mass spectrometry apparatus comprising: an ion source from which a certain amount of analyte ions from the analyte sample can be obtained to provide an ion beam; a mass analyzer for filtering the analyte ions of the ion beam based on their mass-to-charge ratio; a first detector unit for analyzing the ions of the ion beam; and a second detector unit based on the time-of-flight principle and including a second detector for analyzing the ions of the ion beam.

[0011] The present invention therefore provides a hybrid mass spectrometry device comprising two distinct and separate detector units that can advantageously be used for different purposes. This combines two different independent mass spectrometry devices for different aspects of sample characterization within a single instrument, thereby saving space and cost, and resulting in a highly compact and versatile instrument.

[0012] In relation to the present invention, several different types of ion sources can be used. For example, the ion source can be an inductively coupled plasma ion source, including a microwave generator (especially a microwave generator including a dielectric resonator, such as those described in DE202020106423U1, US2016 / 0026747A1 or WO2017 / 176131A1), an ion source, a spark source, a laser source, or a glow discharge source.

[0013] In one embodiment of the mass spectrometry apparatus, the first detector unit comprises a quadrupole detector. Quadrupole detectors are particularly advantageous because they are fully tunable and include high sensitivity and dynamic range. Conversely, the TOF detector used as the second detector unit is characterized by high acquisition speed. Thus, this combination combines the advantages of both types of detector units.

[0014] In another embodiment of the mass spectrometry apparatus, the second detector is a filter or a quadrupole in the detector. Such quadrupole ion filters are known in the field of Q / TOF mass spectrometry devices. Therefore, the second detector unit is a Q / TOF detector unit.

[0015] In one embodiment, the mass analyzer is a quadrupole mass analyzer. The mass analyzer is preferably positioned between the ion source and the first and second detector units, such that the ion beam passes through the mass analyzer regardless of which detector unit is used for subsequent detection.

[0016] Regarding the quality analyzer, it is advantageous that the quality analyzer includes at least one transmission optics located in front of the quality analyzer, in particular a Brubaker pre-filter or a Brubaker lens, and is used to guide the ions of the ion beam to the quality analyzer, thereby improving the transmission rate of the ions of the ion beam through the quality analyzer.

[0017] More advantageously, the mass spectrometry apparatus includes at least two mass analyzers. One mass analyzer may be arranged between the ion source and the first and second detector units. Another mass analyzer may be arranged between the first mass analyzer and the second detector of the second detector unit, for example, a time-of-flight mass analyzer. This mass analyzer may also be part of the second detector unit. However, another mass analyzer may be arranged between the first mass analyzer and the first detector of the first detector unit, and it may also be part of the first detector unit.

[0018] Further preferably, the first mass analyzer arranged between the ion source and the first and second detector units, as well as the additional mass analyzer arranged between the first mass analyzer and the first detector, are both quadrupole mass analyzers, and both the first and second detectors are quadrupole detectors. This further improves the measurement sensitivity with respect to the first detector unit.

[0019] In addition, the second detector unit may include a time-of-flight mass analyzer disposed between the first mass analyzer and the second detector unit.

[0020] One embodiment includes a first detector unit arranged parallel to a first plane and a second detector unit arranged parallel to a second plane, the first plane and the second plane having a predetermined angle with each other, and wherein the mass spectrometer is configured to guide an ion beam received from a mass analyzer to the first or second detector unit.

[0021] In another embodiment, the mass spectrometry apparatus further includes at least one first guiding optics, such as an ion guide or ion optics, which is arranged and / or configured to guide the ion beam received from the mass analyzer to a first flow direction parallel to a first plane and / or along a second flow direction parallel to a second plane.

[0022] Further embodiments may include guiding optics comprising at least first and second guiding optics units, the first guiding optics unit being configured to guide an ion beam received from a mass analyzer to a first flow direction, and the second guiding optics unit being configured to guide an ion beam received from a mass analyzer to a second flow direction.

[0023] Guiding optics can include any arrangement capable of deflecting a certain amount of ions between two non-parallel planes, such as ion mirrors, reflectors, deflectors, quadrupole ion deflectors, electrostatic energy analyzers, magnetic ion optics, or ion multiconductors. However, it is advantageous that the guiding optics include at least one electrode and / or lens arrangement or ion mirror. For example, the electrode arrangement can be embodied in the form of push and / or pull electrodes, and the lens arrangement can be embodied in being manipulated based on electric and / or magnetic fields. On the other hand, in the case of ion mirrors, refer to U.S. Patent Nos. 6,614,021, 5,559,337, 5,773,823, 5,804,821, 6,031,579, 6,815,667, 6,630,665, or 6,6306,651.

[0024] Furthermore, regarding the guiding optics, it is advantageous that the mass spectrometry apparatus, particularly the guiding optics, also includes a switching device for switching at least one component of the guiding optics between a first state in which the ion beam is guided to or directed in a first flow direction and a second state in which the ion beam is guided to a second flow direction. For example, the electric or magnetic field can be switched, for instance, by applying a switching voltage to at least one component.

[0025] Preferably, the guiding optics are arranged between the mass analyzer (especially the first mass analyzer) and the first and second detector units. Therefore, the guiding optics are arranged such that they receive the ion beam from the mass analyzer and redirect the ion beam to a first or second flow direction.

[0026] More preferably, the first and second detector units are arranged in the first and second flow directions, respectively. Therefore, the guiding optics are configured to guide the ion beam to the first or second detector unit.

[0027] Several different options are possible regarding the arrangement of the first and second detector units and the first and second flow directions, all of which fall within the scope of this invention.

[0028] In one embodiment, the first plane, and therefore the first flow direction, is parallel to the longitudinal axis of the quality analyzer.

[0029] In another embodiment, the first plane and the second plane, and therefore the first and second flow directions, are orthogonal to each other. However, other angles between the first and second flow directions may also be provided. In particular, the first and second flow directions may also be antiparallel to each other.

[0030] One embodiment includes the device further comprising at least one collision pool disposed between the mass analyzer and the first and second detector units.

[0031] In another embodiment, the mass spectrometer further includes at least one second guiding optics arranged to redirect an ion beam flowing from the ion source along a first initial flow direction to flow along a second initial flow direction. The first and second initial flow directions have a predetermined angle, particularly an orthogonal angle, between them to minimize the effective footprint of the apparatus. The second initial flow direction is preferably parallel to the longitudinal axis of the mass analyzer. For this embodiment, refer to WO2012 / 100299A1.

[0032] The object of the present invention is also achieved by a method for analyzing analyte samples using a mass spectrometry apparatus according to the present invention, the method comprising the following steps:

[0033] - Record at least one first mass spectrum using the first detector unit, and

[0034] - Record at least one second mass spectrum using a second detector unit, and

[0035] - Specifically, the first and second mass spectra are analyzed by combination.

[0036] The first and second spectra recorded using the first and second detector units can be recorded alternately or as needed for the current purpose. Several possibilities are possible for combining spectra from different detectors, all of which fall within the scope of this invention.

[0037] For example, a TOF detector can be used to record the spectrum of the full mass range of interest, followed by high-resolution, high-sensitivity, and / or high-dynamic-range spectra of a specific smaller mass range, or vice versa.

[0038] This combination of two separate, independent, and staggered working detector units supports comprehensive characterization, nanoparticle detection, laser ablation, or tissue imaging of a variety of analyte samples (e.g., complex samples, especially those without prior knowledge). Different substances can be detected using different detector units. The TOF detector can be used to detect isotopes in the analyte sample, while the first detector unit can be used for different targets. The recording scheme for the different detector units can be determined before use. On the other hand, the rules for selecting a specific detector unit can also be modified or defined during use. Algorithms for selecting one of the two detector units at a certain point in time can also be provided, and such algorithms can be self-learning algorithms.

[0039] It should be noted that the embodiments described in connection with this device, with necessary modifications, are also applicable to this method, and vice versa. Attached Figure Description

[0040] Based on Figures 1 to 3b The present invention and its preferred embodiments are further described below.

[0041] Figure 1 A traditional quadrupole mass spectrometry setup is shown;

[0042] Figure 2a and Figure 2b A preferred embodiment of the device according to the invention is shown, wherein the first and second flow directions are orthogonal to each other; and

[0043] Figure 3a and Figure 3b A preferred embodiment of the device according to the invention is shown, in which the first and second flow directions are antiparallel to each other.

[0044] In the accompanying drawings, the same elements have the same reference numerals. Detailed Implementation

[0045] exist Figure 1The image shows a conventional quadrupole-based mass spectrometry apparatus 100 for analyzing analyte samples. Apparatus 100 includes an ion source 1 from which a quantity of analyte ions from the analyte sample is obtained to provide an initial ion beam 7. Apparatus 100 also includes interface means for transferring the analyte sample into the analytical section of the mass spectrometry apparatus 1, including a sampling cone 2 and a cutoff cone 3. The cutoff cone has a cutoff cone body 4 and a channel 5 for introducing a substance or mixture, for example, as described in US 7,329,863 B2 and US 7,119,330 B2. However, the presence of channel 5 is optional and by no means essential for realizing the basic idea of ​​the invention.

[0046] The device 100 also includes at least one second guiding optics 6, which is arranged to redirect the ion beam 7, supplied by the ion source 1 and flowing along a first initial flow direction if1, to flow along a second initial flow direction if2. In this embodiment, the two initial flow directions if1 and if2 are exemplary orthogonal to each other, while the second initial flow direction if2 is parallel to the longitudinal axis L of the mass analyzer 9, which is embodied here as a quadrupole mass analyzer. A brubaker pre-filter 8, which guides the ion beam 11 into the mass analyzer 9, is arranged prior to the mass analyzer 9. A detector unit 10, in the form of a quadrupole detector, is arranged in the end region of the mass analyzer 9.

[0047] On their way toward detector unit 10, ion beams 7 and 11 pass through different vacuum stages 16, 17, and 18, and... Figures 2a to 3b In the case of 19, it was also passed.

[0048] The present invention now provides a mass spectrometry apparatus 100, wherein two separate, independent, and staggered detector units A and B are combined. Without diminishing the scope of protection of the particular embodiments included in the drawings, the following drawings relate to a case comprising a first detector unit A including a quadrupole detector 10 and a second detector unit B including a TOF detector 15, allowing for quadrupole-based or TOF-based detection, or both in a quasi-parallel manner. The mass analyzer 9 is exemplarily embodied in the form of a quadrupole mass analyzer, in front of which is a brubaker pre-filter 8, similar to... Figure 1 The situation.

[0049] Figure 2a and Figure 2b A preferred embodiment relates to a first detector unit A and a second detector unit B arranged orthogonally to each other. The first detector unit A includes... Figure 1The situation is similar to that of the quadrupole detector 10. The second detector unit B includes an arrangement of push / pull electrodes 13 for guiding the ion beam 11, a TOF mass analyzer 14 defining the reflection portion, and a TOF detector 15, which can also be embodied, for example, in the form of a quadrupole detector, thus producing a second detector unit B in the form of a Q / TOF detector unit.

[0050] The first detector unit A is arranged parallel to the first plane E1, and the second detector unit B is arranged parallel to the second plane E2. The first plane E1 and the second plane E2 are orthogonal to each other. The first plane E1 is parallel to the first initial flow direction if1 and the longitudinal axis of the mass analyzer 8.

[0051] for Figure 2a In the embodiment shown, the device 100 further includes a first guiding optics C, which includes electrodes 12 for guiding the ion beam 11 in a first flow direction f1 or a second flow direction f2. This guiding optics C is not essential to the present invention. Instead, it can be used as, for example... Figure 2a Other components of the push / pull electrode 13 device 100 (e.g., components of the first detector unit A and the second detector unit B) guide the ion beam 11 toward the first detector unit A and / or the second detector unit B. Alternatively, the guiding optics C may include multiple different electrons and / or lenses or may include at least one ion mirror.

[0052] and Figure 2a on the contrary, Figure 2b The apparatus 100 shown includes: a mass analyzer 9, equivalent to Figure 1 or Figure 2a The situation is as follows: An additional mass analyzer 26 is arranged between the first mass analyzer 9 and the first detector 10. The ion beam 11 received from the first mass analyzer 9 passes through a guiding optics C, which also includes a first ion optics 25 for injecting the ion beam 11 into region 29. From region 29, particularly the push / pull region, ions are either transferred as an ion beam 27 detected by the first detector unit A to the second mass filter 26, or as an ion beam 28 to the second detector unit B, which includes the TOF mass analyzer 14.

[0053] Figure 3a and Figure 3b In a preferred embodiment of the device 100 according to the invention, the first flow direction f1 and the second flow direction f2 are antiparallel to each other. Except... Figures 1 to 2b The device 100 shown, Figure 3aThe apparatus 100 shown further includes an optional collision pool 20 having a gas control line 21 for controlled injection of a collision or reaction gas or a mixture of at least two gases. Figure 2a and Figure 2b The situation shown is the opposite, in Figure 3a In this case, the first flow direction f1 and the second flow direction f2 are antiparallel to each other.

[0054] Figure 3b The embodiments shown are similar to Figure 3a The embodiment shown. However, the guiding optics C here also includes: an ion optics 30 for transferring the ion beam 11 from the collision cell 20 or the mass analyzer 9 to the region 29; and an electrode arrangement 31 for guiding the ions of the ion beam 8 to a first flow direction f1 and thus to the first detector unit 10, for example by applying a switching voltage.

[0055] Although all preferred embodiments shown in the figures relate to a second detector unit B in the form of a Q / TOF detector unit, the invention is by no means limited to this configuration of the second detector unit B. Similarly, the invention is not limited to a first detector unit A comprising a quadrupole detector.

[0056] However, in the case of a combination of a Q / TOF-based device and a quadrupole-based device, the present invention enables the integration of a first detector unit A into the push-pull region 29 of a second TOF-based detector unit B, such that ions from the ion beam 11 received from the mass analyzer 9 or the collision cell 20 are directed to the first detector 10 or the second detector 15. This significantly reduces the cost and complexity of setting up the combined device. In principle, the first detector unit A can be integrated into the second TOF-based detector unit B without affecting its characteristics, meaning that the characteristics of both the quadrupole-based and TOF-based devices can be fully maintained in the combined hybrid device 100.

[0057] An advantage of this invention is that staggered recording of mass spectra using either the first detector 10 or the second detector 15 is possible within a single device 100, particularly depending on the information obtained from the sample. For example, after sample ionization (or atomization), a first Q / TOF-based mass spectrum can be recorded to reveal overall mass range information about the dynamic range of ions contained in the sample. In one or more subsequent steps, a quadrupole-based mass spectrum can be recorded to analyze low-abundance ion clusters or ions with very stringent quantification requirements. The two spectra can also be combined into a final spectrum. Another mode of operation can also begin with analysis based on the first detector unit a, i.e., a quadrupole-based analysis, which can then trigger the recording of a TOF-based spectrum to obtain advanced information or to obtain a pre-defined decision tree for further processing. However, other possible modes of operation include analyzing different components of the sample using two different detectors 10, 15, for example, analyzing particles by the second detector 15 and homogeneously dissolved components by the first detector 10, or using the second detector to analyze isotope distribution patterns and using the first detector 10 to analyze other targets.

[0058] In summary, the apparatus 100 and method according to the invention offer several advantages over prior art devices: mass spectra with sensitivity and robustness comparable to classical quadrupole-based mass spectrometry devices can be recorded, while simultaneously acquiring spectra related to all elements contained in the sample. Different acquisition speeds, sensitivities, and dynamic ranges of quadrupole-based and TOF-based devices can be advantageously combined depending on the application, resulting in higher overall measurement speeds.

[0059] Figure Labels

[0060] 1. Ion source

[0061] 2 Sampling cone

[0062] 3. Cutting the cone

[0063] 4. Cut the cone

[0064] 5. Extract the channel in the cone

[0065] 6 Second guiding optics

[0066] 7. Ion Beam Trajectory

[0067] 8 Brubaker pre-filter

[0068] 9. Quality Analyzer

[0069] 10 First Detector

[0070] 11 Ion beam

[0071] 12 Push / Pull Electrodes

[0072] 13 Electrode Arrangement

[0073] 14. Time-of-Flight (TOF) mass analyzer reflection section

[0074] 15 TOF detectors

[0075] 16-19 Various vacuum levels

[0076] 20 Collision Pools

[0077] 21 Gas pipeline

[0078] 25 Ion optical devices or electrodes

[0079] 26 Second Mass Analyzer

[0080] 27 Ion beam guided to the first detector

[0081] 28 Ion beam guided to the second detector

[0082] 29 regions

[0083] 30 Ion Optical Devices

[0084] 31 Electrodes

[0085] 100 mass spectrometry device

[0086] A First Detector Unit

[0087] B Second Detector Unit

[0088] C Guiding optics

Claims

1. A mass spectrometry apparatus (100) for analyzing analyte samples, comprising: An ion source (1) is provided, capable of acquiring a certain amount of analyte ions from the analyte sample to provide an ion beam. A mass analyzer, used to filter analyte ions from the ion beam based on their mass-to-charge ratio, and A first detector unit (A) is used to analyze the ions in the ion beam. A second detector unit (B) is based on the time-of-flight principle and includes a second detector (15) for analyzing ions from the ion beam. The first detector unit (A) is arranged parallel to a first plane (E1), and the second detector unit (B) is arranged parallel to a second plane (E2). The first plane (E1) and the second plane (E2) have a predetermined angle relative to each other. The mass spectrometry device (100) is configured to guide the ion beam received from the mass analyzer to either the first detector unit (A) or the second detector unit (B). At least one first guiding optics (C) is arranged and / or configured to guide an ion beam received from the mass analyzer along a first flow direction (f1) parallel to the first plane (E1) and / or along a second flow direction (f2) parallel to the second plane (E2), wherein the first flow direction and the second flow direction are antiparallel to each other.

2. The mass spectrometry apparatus (100) according to claim 1, in, The first detector unit (A) includes a quadrupole detector (10).

3. The mass spectrometry apparatus according to claim 1 or 2, in, The second detector (15) is a TOF or Q / TOF detector.

4. The mass spectrometry apparatus (100) according to claim 1 or 2, in, The quality analyzer is a four-pole quality analyzer.

5. The mass spectrometry apparatus (100) according to claim 1 or 2, Includes at least two quality analyzers.

6. The mass spectrometry apparatus (100) according to claim 1, in, The guiding optics (C) includes at least one electrode (12, 13, 25, 30, 31) and / or a lens assembly or ion mirror.

7. The mass spectrometry apparatus (100) according to claim 1 or 2, in, The mass spectrometer (100) further includes a switching device for switching at least one component of the guiding optics (C) between a first state and a second state, in which the ion beam is guided or directed to the first flow direction (f1) and in the second state, the ion beam is directed to the second flow direction (f2).

8. The mass spectrometry apparatus (100) according to claim 1 or 2, in, The guiding optics (C) are arranged between the quality analyzer and the first detector unit (A) and the second detector unit (B).

9. The mass spectrometry apparatus (100) according to claim 1 or 2, in, The first plane (E1) is parallel to the longitudinal axis (L) of the mass analyzer.

10. The mass spectrometry apparatus (100) according to claim 1 or 2, in, The device (100) further includes at least one collision pool (20) disposed between the mass analyzer and the first detector unit (A) and the second detector unit (B).

11. The mass spectrometry apparatus (100) according to claim 1 or 2, It also includes at least one second guiding optics (6) arranged to redirect an ion beam supplied by the ion source (1) flowing along a first initial flow direction (if1) to flow along a second initial flow direction (if2), the first initial flow direction (if1) and the second initial flow direction (if2) having a predetermined angle between them, in order to minimize the effective footprint of the device (100).

12. The mass spectrometry apparatus (100) according to claim 11, in, The first initial flow direction (if1) and the second initial flow direction (if2) are orthogonal to each other in order to minimize the effective floor space of the device (100).

13. A method for analyzing an analyte sample using a mass spectrometry apparatus (100) according to any one of claims 1 to 12, comprising the following steps: - Record at least one first mass spectrum using the first detector unit (A), and - Record at least one second mass spectrum using the second detector unit (B), and -Analyze the first mass spectrometer and the second mass spectrometer.

14. The method according to claim 13, in, The first mass spectrum and the second mass spectrum are analyzed by combination.

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