Apparatus and method for transporting gaseous ionic sample material for subsequent analysis

Abstract

The invention relates to a device for transporting a gaseous ionic sample material for subsequent analysis, in particular mass analysis, comprising: a first vacuum chamber through which the ionic sample material is guided, the first vacuum chamber being maintained within a first pressure range; a second downstream vacuum chamber through which the ion sample material is directed, the second downstream vacuum chamber maintained within a second pressure range substantially higher than the first pressure range; and a first gas introduction assembly substantially located in the second vacuum chamber and designed and configured to directionally introduce a gaseous substance that is not from the first vacuum chamber into the second vacuum chamber. The invention also relates to a corresponding method for transporting a gaseous ionic sample material for subsequent analysis, in particular mass analysis.

Description

Technical Field

[0001] The present invention relates to devices, apparatus, assemblies and methods generally useful in the fields of mass analysis and mass spectrometry. Background Art

[0002] The prior art will be explained below with reference to a particular aspect. However, this should not be construed as a limitation of the invention disclosed below. Useful further developments and modifications of the prior art known content may also be applicable outside the relatively narrow scope of this introduction, as will be apparent to those skilled in the art after reading the disclosure of the invention following this introduction.

[0003] refer to Figure 1 In its simplest form, a mass spectrometer can be described as comprising an ionization part (A) in which a sample of an arbitrary or generic nature is transferred into the gas phase (if not already gaseous, such as the eluent or headspace sample from a gas chromatograph) and ionized. Examples of ionization mechanisms include electrospray, matrix-assisted laser desorption / ionization (MALDI), electron ionization, and photoionization.

[0004] Downstream of the ionization section (A), an ion manipulation, selection, separation or fragmentation section (B) may be arranged. Manipulation may be achieved through mechanisms such as collision cooling and radial focusing / alignment; selection may be achieved through mass filters or ion traps; separation may be achieved, for example, through ion mobility analyzers; fragmentation may be achieved through collision induced dissociation, charge transfer induced fragmentation or light induced fragmentation, and the specific method is determined by those skilled in the art.

[0005] After the manipulation, selection, separation or fragmentation part (B), there is arranged an analysis part (C), which can operate according to the principle of time of flight, cyclotron resonance, radio frequency driven stability-instability, etc. In certain embodiments, the functions of the ion manipulation, selection, separation or fragmentation part (B) and the function of the analysis part (C) can be combined in one device in a mass spectrometer, for example, sometimes called a tandem time method compared to the tandem space method of a triple quadrupole mass analyzer, etc.

[0006] The detection section (D) following the analysis section (C) acquires data representative of the ion current of interest and allows its composition to be deduced. For example, the detection section (D) may contain elements such as dynodes and microchannel plates (destructive or depleting detection type) or image current pickup electrodes (non-destructive or non-depleting detection type). Since all of the above sections in a mass spectrometer may be located in different pressure environments, it can be considered that the ion transport between these sections is essential for the operation of the mass spectrometer.

[0007] In a mass spectrometer, various components in the ion path from the ion source region to the final detector, typically located in a mass spectrometer, may have to be maintained at different pressure levels. While it may be preferable to establish a monotonically decreasing pressure level along the ion path so that the propagation of gaseous ion species along this direction is facilitated by the drag on the ion species by a substantially continuous gas flow, certain intermediate stages in the ion path may have to be maintained at higher pressure levels than adjacent upstream and / or downstream vacuum stages. For example, intermediate ion mobility separators and fragmentation cells using collision-induced dissociation produce such spatially variable pressure profiles, which are typically sandwiched between two devices such as ion traps, mass filters, or mass analyzers that operate at lower pressure levels than those of the intermediate ion mobility separators and fragmentation cells that use collision-induced dissociation.

[0008] The presence of two relatively low pressure stages adjacent to a high pressure stage means that the gas will flow along a pressure gradient from high pressure to low pressure. While this effect can be beneficial at the interface between a high pressure stage and a subsequent low pressure stage, as it imparts additional momentum to the ionic species leaving the high pressure stage in the downstream direction, it can also be a hindrance to the ionic species entering the high pressure stage from the preceding low pressure stage, as the counterflow of the gas tends to slow down the ionic species, push it back and cause it to disperse. These opposing forces can be overcome by applying an appropriate electromotive force at the respective interfaces. However, the gas counterflow may result in spatial expansion and momentum dispersion of the ionic species as they enter the downstream stage, which may be undesirable as it may hinder further processing of the ionic species. In the worst case, this may result in the loss of ionic species, for example, when the interface between the upstream low pressure stage and the high pressure stage includes a relatively small aperture, opening or orifice, such as a transfer capillary.

[0009] The following publications provide further insights into the technical background of the present disclosure but are not guaranteed to be complete:

[0010] The article by Vyacheslav N. Fishman et al. (International Journal of Mass Spectrometry 177 (1998) 175-186) relates to a simplified injector flange for a selected ion flow tube.

[0011] The study by DJ Douglas et al. (J Am Soc Mass Spectrom 1992, 3, 398-408) reported the collision focusing effect in a radio frequency (RF) quadrupole. Similarly, patent US 4,963,736 by the same author / inventor also relates to a mass spectrometer and a method for improving ion transmission.

[0012] Patent application publication US2012 / 0228492A1 relates to a mass spectrometer, in particular to ions guided by a gas flow in a radio frequency multipole system, and also to a radio frequency quadrupole mass filter and its operation using a gas flow in a tandem mass spectrometer.

[0013] Patent US 9,437,410 B2 discloses a mass spectrometry system having an ion source for generating ions at substantially atmospheric pressure. The system has a sampling component having an orifice therein. The sampling component forms a vacuum chamber having a mass spectrometer. The system also has a curtain plate between the ion source and the sampling component. The curtain plate has a hole having a cross section and is spaced from the sampling component to form a flow channel between the curtain plate and the sampling component and an annular gap between the orifice and the hole. The area of ​​the annular gap is less than the cross-sectional area of ​​the hole. The system also has a power supply for applying a voltage to the curtain plate, and a curtain gas flow mechanism for directing a curtain gas into the flow channel and the annular gap.

[0014] Patent application publication US2016 / 0351382 A1 discloses a method for coupling a first chamber containing a first gas and a second chamber containing a second gas in a mass spectrometer or an ion mobility spectrometer. The method includes providing an intermediate region operating at a lower pressure between the first chamber and the second chamber to fundamentally prevent or reduce the first gas from entering the second chamber and / or the second gas from entering the first chamber.

[0015] Patent application publication US2020 / 0381241 A1 relates to a hybrid IMS / MS system (IMS = ion mobility separator, MS = mass spectrometer), and provides a hybrid IMS / MS system, which includes a radio frequency funnel, an ion mobility analyzer and a mass analyzer, wherein the radio frequency funnel is arranged non-collinearly with the ion mobility analyzer, preferably a TIMS analyzer (TIMS = trapped ion mobility spectrometer).

[0016] Tom Covey’s review (Rapid Commun Mass Spectrom. 2022; e9354) discusses why the sensitivity of atmospheric pressure ionization triple quadrupole (API-QqQ) systems using electrospray ionization (ESI) has increased a million-fold over the past few decades, while the sensitivity of the other major method for producing ions at atmospheric pressure, atmospheric pressure chemical ionization (APCI), has also increased almost a million-fold.

[0017] In summary, ion transmission in mass spectrometer components still needs to be improved. A person skilled in the art will easily recognize further goals that need to be achieved when reading the following disclosure. Summary of the invention

[0018] In a first aspect, the present invention relates to an apparatus for transporting gaseous ion sample material for subsequent analysis, the apparatus comprising: - a first vacuum chamber comprising a first inlet through which gaseous matter including ion sample material is introduced; a first outlet through which gaseous matter including ion sample material exits; and one or more first radio frequency ion guides for receiving and directing ion sample material along a path from the first inlet to the first outlet, the first vacuum chamber being maintained within a first pressure range; - a second vacuum chamber comprising a second inlet through which gaseous matter including ion sample material exiting the first vacuum chamber is introduced, the second inlet being fluidically coupled to the first outlet and defining an axis; a second outlet through which gaseous matter including ion sample material exits; and one or more second radio frequency ion guides for receiving and directing ion sample material along a path from the second inlet to the second outlet, the second vacuum chamber being maintained within a second pressure range, the second pressure range being substantially higher than the first pressure range, and - a first gas introduction assembly substantially adjacent to the second inlet and designed and configured to introduce gaseous matter not from the first vacuum chamber into the second vacuum chamber in a direction substantially along the axis.

[0019] The gaseous substance introduced by the first gas introduction assembly may be a chemically inert or non-active gas or a mixture of such gases, for example, selected from a group including molecular nitrogen, helium, argon, sulfur hexafluoride, etc. The introduced gaseous substance may in particular be electrically neutral. The gaseous substance may be injected at a temperature level between equal to or lower than 473 Kelvin (about 200° C.) and equal to or higher than the liquefaction temperature of the gas species under consideration, for example, about 77 Kelvin at atmospheric pressure for nitrogen. It is particularly preferred that the temperature of the additional gaseous substance introduced into the second vacuum chamber by the first gas introduction assembly is about room temperature (293-298 Kelvin or about 20-25° C.). The purity grade of the gaseous substance may be N4.0 or higher, for example N5.0, N6.0 or any other suitable purity grade.

[0020] A vacuum chamber can be a housing with a predetermined airtightness or sealing relative to an atmosphere or surrounding environment. The vacuum chamber can be connected to a vacuum source, such as a pump fluid. Despite being airtight or sealed, the vacuum chamber can still accept a certain amount of gas load, such as through an inlet, and can be designed and configured to deliver a certain amount of gas load, such as through an outlet or a vent or exhaust port. Such a gas load generally includes electrically neutral or inert or non-active gaseous substances and / or ionic sample materials. The ionic sample material can be a substance from a biological source, such as body fluids such as whole blood, plasma, lymph, cerebrospinal fluid, etc. Subdivided to the molecular level, the relevant ionic sample material can be selected from the following groups: proteins, peptides, lipids, polysaccharides, nucleotides, metabolites, etc. The ionic sample material can also be derived or extracted from any kind of atmospheric source or environmental source, such as any gas, liquid or condensed phase found in the atmosphere or environment. A specific example of a relevant ionic sample material at the molecular level is chlorofluorocarbons (CFCs), such as trichlorofluoromethane (R-11), bromochlorodifluoromethane (R-12B1), and carbon tetrachloride (CCl 4 ).

[0021] In various embodiments, the first gas introduction assembly may include one or more nozzles. Preferably, the one or more nozzles may include one of (i) multiple individual nozzles and (ii) an annular or ring-shaped nozzle. Further preferably, the multiple individual nozzles can be aligned so that the gaseous material is introduced at an angle less than 60° to the axis. The introduction angle relative to the axis can generally vary between about 60° and 0°, where 0° means that the (one or more) nozzles are arranged parallel to the axis. An introduction angle between 45° and 0° is particularly desirable. In general, the introduction angle relative to the axis can be selected from the following group, including 60°, 55°, 50°, 45°, 40°, 35°, 30°, 25°, 20°, 15°, 10°, 5°, 0°, and any other angle between 0° and 60°, particularly between 0° and 45°.

[0022] In an alternative embodiment, the first gas introduction assembly may include a manifold plate housed at the interface of the first vacuum chamber and the second vacuum chamber and having an embedded gas channel extending from a substantially peripheral portion of the manifold plate to a substantially central portion of the manifold plate, where the embedded gas channel discharges through one or more openings into a first region substantially proximate, near, or near a first side surface of the manifold plate, wherein the manifold plate includes a substantially central orifice for allowing gaseous species and ionic sample material to pass from a second region substantially proximate, near, or near a second side surface of the manifold plate to a first region substantially proximate, near, or near a first side surface of the manifold plate, and wherein gaseous species not from the first vacuum chamber are ejected into the second vacuum chamber through the one or more openings. The manifold plate may be designed and constructed according to the principles disclosed in patent application publication US2016 / 0086784 A1, the entire contents of which are incorporated herein by reference. The thickness of the manifold plate may be on the order of 2 mm, 3 mm, 4 mm, 5 mm, etc.

[0023] In various embodiments, the first gas introduction assembly can be designed and configured to introduce the gaseous material in a manner that is substantially one of (i) coaxial with the axis and (ii) concentric with the axis. Such embodiments can be used to establish a substantially turbulent-free gas flow in the second vacuum chamber, or when an electrically neutral or chemically inert or inactive gaseous material is introduced into the second vacuum chamber, the gas flow loses any degree of turbulence within a short distance from the introduction point.

[0024] In various embodiments, the device may further include one or more transmission pipes or capillaries coupling the second inlet to the first outlet fluid. One or more transmission pipes or capillaries may have a lateral extension, the configuration and size of which allow the first gas introduction assembly to be installed substantially adjacent to and close to the second inlet. One or more transmission pipes or capillaries may include a spatial contraction between the first vacuum chamber and the second vacuum chamber, and allow the first gas introduction assembly to be installed in the space left by such contraction. The volumes of the first vacuum chamber and the second vacuum chamber may not be affected by such spatial optimization design. In an alternative embodiment, the second inlet and the first outlet may be fluidically coupled through one or more openings, holes or orifices located at corresponding positions of the first vacuum chamber and the second vacuum chamber, respectively. The axis may be defined as a line passing through the center of such an opening, hole or orifice and perpendicular to the area of ​​the corresponding opening, hole or orifice.

[0025] In various embodiments, the first pressure range may be 10 -1 mbar, 10 -2The second pressure range may be in the order of Δp=1, 2, 3, 4, 5, 6, 7, 8, 9 mbar or any other value between 1 and 9 mbar. The pressure in the second vacuum chamber may include a substantially constant pressure gradient, with a higher pressure at the second inlet and in a region near the second inlet, and a lower pressure at the second outlet and in a region near the second outlet, so as to form a gas flow in the second vacuum chamber. The pressure gradient in the second vacuum chamber may generally span a pressure range of about Δp=1, 2, 3, 4, 5, 6, 7, 8, 9 mbar or any other value between 1 and 9 mbar from the second inlet to the second outlet.

[0026] The gaseous substance can be introduced into the second vacuum chamber by the first gas introduction component, and its flow rate is selected from the following group: 0.1L / min, 0.2L / min, 0.3L / min, 0.4L / min, 0.5L / min, 0.6L / min, 0.7L / min, 0.8L / min, 0.9L / min, 1.0L / min, 1.5L / min, 2.0L / min, 2.5L / min, 3.0L / min, 3.5L / min, 4.0L / min, 4.5L / min, 5.0L / min, and any other value between 0.1L / min and 5.0L / min. The numerical range between 0.5L / min and 1.0L / min is particularly preferred. The volume flow rate proposed here should be at standard temperature and pressure (STP; T 0 =~273 Kelvin, p 0 =1000 mbar).

[0027] In various embodiments, the one or more second RF ion guides may include one or more ion mobility separators. In particular, the one or more second RF ion guides may include one or more field asymmetric ion mobility separators (FAIMS). FAIMS typically works by applying a radio frequency (RF) high voltage asymmetric waveform and a static (DC) waveform between two electrodes. The RF waveform forms a high field environment for a short period of time, followed by a low field environment for a longer period of time. The DC waveform generates a compensation field that balances the drift of the ion sample material caused by the RF waveform. Ion sample materials with different mobilities in high and low fields will produce different net displacements after one waveform cycle. By adjusting the DC compensation field, ion sample materials with different mobilities can be selectively transmitted or filtered out of the device. The transmitted ion sample material can then be detected in a mass analyzer.

[0028] In various embodiments, one or more ion mobility separators may include one or more trapped ion mobility separators (TIMS). TIMS typically works by applying an electric field gradient that keeps the ion sample material stationary relative to the moving gas flow. The moving gas flow can push the ion sample material forward, for example, along the direction from the second inlet of the second vacuum chamber to the second outlet. The electric field strength can change along the length of the device, thereby establishing a correlation between the collision cross section or mobility of the ion sample material and its equilibrium position. By changing the electric field strength over time, ion sample materials with different mobilities can be released from the device in sequence. The released ion sample material can then be detected in a mass analyzer. An embodiment of TIMS can be found in patent US7,838,826B1, which is incorporated herein by reference in its entirety.

[0029] In different embodiments, one or more second RF ion guides may adopt a substantially airtight design. This design allows airflow to be transmitted through the one or more second airtight RF ion guides from the end where the gaseous material enters to the end where the gaseous material is discharged without causing substantial loss of the gaseous material, thereby maintaining the mass balance in the one or more second RF ion guides substantially stable. In a specific embodiment, the one or more second RF ion guides adopting a substantially airtight design may be connected and / or mounted and / or fixed to the second entrance of the second vacuum chamber in a substantially airtight manner. In this way, the one or more second RF ion guides adopting a substantially airtight design may simultaneously achieve the functions of guiding ion sample materials and materializing the second vacuum chamber. In this example, there is no separate vacuum housing surrounding or containing the one or more second RF ion guides, which may facilitate a compact design of the second vacuum chamber and may significantly reduce the pumping requirements of the second vacuum chamber.

[0030] In various embodiments, the apparatus may further include a mass balance system that operates to maintain a mass balance of the gaseous material introduced into the second vacuum chamber, thereby generating a substantially continuous or stable flow of gaseous material within the second vacuum chamber. The substantially continuous or stable flow of gaseous material is preferably one of (i) segmentally and (ii) completely substantially laminar along its path within the second vacuum chamber. More preferably, the substantially continuous or stable flow of gaseous material may be generated within one or more second RF ion guides. In particular, the substantially continuous or stable flow of gaseous material may be generated within a trapped ion mobility separator located within the second vacuum chamber. The mass balance system may operate one or more vacuum sources, such as one or more pumps connected to the second vacuum chamber fluid.

[0031] In various embodiments, one or more second RF ion guides may include one or more ion guides having at least one of (i) an RF funnel design and (ii) an RF tunnel design. The RF funnel may focus and transport a beam of ion sample material from one pressure region to a subsequent or downstream pressure region. The RF funnel may include a series of annular electrodes with decreasing inner diameters that may be connected to an RF voltage generator and a DC voltage source. The RF voltage may generate an oscillating electric field to capture and confine the ion sample material radially, while the DC voltage may generate a static electric field to push the ion sample material axially. The RF voltage generator and / or the DC voltage source may be tuned to flexibly adjust the guiding conditions of the ion sample material.

[0032] In various embodiments, the one or more second RF ion guides may include one or more stacked ring ion guides. The stacked ring ion guides may be well suited to establish a potential gradient along their longitudinal extension to drive or push the ion sample material. To this end, multiple rings in the stacked ring or each ring in the stacked ring may be connected to one or more tunable RF and DC voltage sources.

[0033] In various embodiments, the first vacuum chamber may include one or more vents for extracting excess gaseous material. The one or more vents may be fluidly connected to a vacuum source, such as one or more pumps, to establish and substantially maintain a predetermined first pressure range in the first vacuum chamber.

[0034] In various embodiments, one or more first RF ion guides may include at least one of (i) a stacked annular ion guide and (ii) a RF multipole assembly. Preferably, the stacked annular ion guide may include one or more electrode rings having a multipole design, for example selected from the following group: a quadrupole design, a hexapole design, an octupole design, and a multipole design of any other order and superpositions thereof. Examples of such multipole designs may be found in patent application publication US2006 / 0108520A1, the entire text of which is incorporated herein by reference. Further preferably, the RF multipole assembly may include one or more segmented multipoles. The segmentation of the multipole rods may establish an electric potential gradient along the longitudinal extension of the RF multipole assembly, for example, to drive or push the ion sample material to move in a desired direction.

[0035] In various embodiments, the RF multipole assembly may include one or more additional electrodes to establish an electric potential gradient along its length. One or more DC voltages may be provided to the one or more additional electrodes, and the one or more additional electrodes may be further located on the corresponding RF multipole assembly so that the one or more DC voltages affect the electric field conditions inside the RF multipole assembly through the gaps between the poles or electrodes of the RF multipole assembly.

[0036] In various embodiments, at least one of (i) the one or more first RF ion guides and (ii) the one or more second RF ion guides may be substantially aligned along an axis. The axis may be one of linear, straight, non-straight, and curved. The axis may be a common axis defined by the second inlet and the first outlet.

[0037] In various embodiments, one or more potentials may be applied to at least one of (i) the one or more first RF ion guides and (ii) the one or more second RF ion guides to drive the ion sample material in a direction substantially from the first vacuum chamber to the second vacuum chamber. Such measures may reduce the tendency of the ion sample material to flow back.

[0038] In various embodiments, the apparatus may further include one or more trapping membranes or lenses located in the first vacuum chamber at at least one of (i) the first inlet, (ii) the first outlet, and (iii) a position between the first inlet and the first outlet, and one or more trapping potentials may be temporarily provided to the one or more trapping membranes or lenses to substantially block the propagation of the ionic sample material. In alternative embodiments, one or more radio frequency voltages may be provided to the one or more trapping membranes or lenses to temporarily establish one or more pseudo potential barriers for the associated ionic sample material.

[0039] In various embodiments, the apparatus may further include (i) a mass analyzer and (ii) at least one of a fragmentation, activation or reaction unit in fluid communication with the second outlet. The mass analyzer may be: a time of flight (TOF) analyzer, such as an orthogonal acceleration (OTOF) analyzer, and optionally further including one or more reflectron stages to extend the flight path and perform velocity and / or energy focusing of the ionic sample material; an ion cyclotron resonance (ICR) analyzer; a Kingdon type analyzer, such as (Thermo Fisher); quadrupole mass analyzer, etc. The fragmentation, activation or reaction unit can work according to one of the following principles: collision induced dissociation (CID), electron induced dissociation (such as electron transfer dissociation (ETD) and electron capture dissociation (ECD)), light induced dissociation (such as ultraviolet photodissociation (UVPD) and infrared multiphoton dissociation (IRMPD)), surface induced dissociation (SID), etc.

[0040] In various embodiments, the device may further include a third vacuum chamber, comprising: a third inlet through which gaseous matter including ionic sample material enters; a third outlet fluidly coupled to the first inlet through which gaseous matter including ionic sample material exits; and one or more vents for extracting excess gaseous matter; and one or more deflectors for redirecting and directing ionic sample material along its path from the third inlet to the third outlet, the third vacuum chamber being substantially maintained within a third pressure range, the third pressure range being substantially higher than the first pressure range. The device preferably also includes a radio frequency funnel fluidly coupling the third outlet to the first inlet for directing and conditioning the ionic sample material. It is further preferred that the third pressure range can be a single-digit millibar range between 0.2 and 50 millibars. The third vacuum chamber may include a pressure gradient approximately between the third inlet and the one or more vents, the pressure gradient may span a single-digit millibar range, for example, selected from the following group: Δp=1, 2, 3, 4, 5, 6, 7, 8, 9 millibars, or any other millibar value in the single-digit range. It is further preferred that the third inlet may include one or more transfer pipes or capillaries.The third outlet may be aligned with the axis defined by the second inlet, or may be aligned with the common axis defined by the second inlet and the first outlet.

[0041] In various embodiments, one or more deflectors can be designed and configured to deflect the ion sample material from the introduction direction to the third outlet by an angle of more than 45°. Preferred deflection angles can be selected from the following group, including 45°, 50°, 55°, 60°, 65°, 70°, 75°, 80°, 85°, 90° (vertical deflection), 95°, 100°, 105°, 110°, 115°, 120°, 125°, 130°, 135°, 140°, 145°, 150°, 155°, 160°, 165°, 170°, 175°, 180° (U-turn deflection), and any other angle substantially between 45° and 180°. One or more deflectors can be connected to a DC voltage source or multiple DC voltage sources, which can optionally be tunable. The polarity of the potential applied to the one or more deflectors is selected so as to produce one of a repulsive and an attractive effect on ionic sample material entering the third vacuum chamber through the third inlet. In an alternative embodiment, the one or more deflectors can be connected to a radio frequency voltage source or multiple radio frequency voltage sources that are selectively tunable to change the propagation direction of the ionic sample material using one or more pseudo potentials.

[0042] In various embodiments, the third inlet may be in fluid communication with an ion source. The ion source may generate ionized sample material at substantially atmospheric or ambient pressure (about 1000 mbar), such as an electrospray ion source or a chemical ionization source at atmospheric or ambient pressure. The ion source may be mounted in a chamber that may be substantially aerodynamically isolated from the atmosphere or environment and may further be supplied or flushed with a clean gaseous substance that may be substantially electrically neutral, chemically inert or inactive, such as molecular nitrogen.

[0043] In various embodiments, the apparatus may further include a second gas introduction assembly, which is substantially located near the third outlet and is designed and configured to introduce a gaseous substance into the third vacuum chamber. Injecting the gaseous substance, which may be particularly electrically neutral, chemically inert and / or inactive, in a direction substantially opposite to the direction of propagation of the ion sample material along its path from the third inlet to the third outlet may strip away from the ion sample material of interest unwanted and undesirable gaseous substances, such as mixtures of water and solvents (e.g., volatile organic compounds, particularly methanol, acetonitrile and isopropanol), which may be residuals of the ionization process, thereby facilitating the reduction of background substances.

[0044] In another aspect, the present invention relates to a method for transporting gaseous ion sample material for subsequent analysis, the method comprising: - introducing gaseous matter including ion sample material into a first vacuum chamber through an inlet of the first vacuum chamber, - receiving and guiding the ion sample material along its path from the inlet to the outlet of the first vacuum chamber using one or more first radio frequency ion guides in the first vacuum chamber, - releasing the gaseous matter including ion sample material through the outlet of the first vacuum chamber, - during this process, maintaining the first vacuum chamber in a first pressure range, - passing the gaseous matter including ion sample material released from the first vacuum chamber through a second vacuum chamber - introducing the ion sample material into a second vacuum chamber through an inlet thereof, the inlet of the second vacuum chamber being fluidically coupled to the outlet of the first vacuum chamber and defining an axis, - receiving and guiding the ion sample material along its path from the inlet to the outlet of the second vacuum chamber using one or more second RF ion guides in the second vacuum chamber, - releasing the gaseous material including the ion sample material through the outlet of the second vacuum chamber, - during this process, maintaining the second vacuum chamber within a second pressure range, the second pressure range being substantially higher than the first pressure range, and - introducing the gaseous material not from the first vacuum chamber into the second vacuum chamber at a position substantially adjacent to the inlet of the second vacuum chamber in a direction substantially along the axis.

[0045] The velocity of the gaseous substance introduced (by the first gas introduction assembly) at a position substantially adjacent to the second inlet of the second vacuum chamber may be selected from the group consisting of 100 m / s, 200 m / s, 300 m / s, 400 m / s, 500 m / s, 600 m / s, 650 m / s, 700 m / s, 750 m / s, 800 m / s, 900 m / s, 1000 m / s, and any other velocity within the range of 100 m / s to 1000 m / s.

[0046] The pressure profile of the first vacuum chamber may have a first pressure level at the inlet of the first vacuum chamber, a second pressure level at the outlet of the first vacuum chamber, and a third pressure level at a location between the inlet and the outlet of the first vacuum chamber, wherein the first pressure level is generally higher than the second pressure level, generally substantially higher than the third pressure level, or the third pressure level is generally lower than the second pressure level, generally substantially lower than the first pressure level, or the second pressure level is generally higher than the third pressure level, generally lower than the first pressure level. The first pressure level is generally in the order of 0.15 to 0.4 millibars. The second pressure level is generally in the order of 0.05 to 0.15 millibars. The third pressure level is generally in the order of 0.01 to 0.05 millibars.

[0047] As one of ordinary skill in the art realizes, all embodiments, explanations and details given above with respect to the apparatus aspects of the present invention apply equally and equally to the method aspects of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] The present invention may be better understood with reference to the following figures. The elements in the figures are not necessarily drawn to scale, but are intended to illustrate the principles of the present invention (usually schematically):

[0049] Figure 1 A typical assembly of components in a mass spectrometer is schematically depicted.

[0050] Figure 2A An ion transport device operating in accordance with the principles of the present invention is schematically illustrated, particularly depicting a first design of a fluid coupling between a first outlet and a second inlet.

[0051] Figure 2B An ion transport device operating in accordance with the principles of the present invention is schematically illustrated, particularly depicting a second design of fluid coupling between a first outlet and a second inlet.

[0052] Figure 2C An ion transport device operating in accordance with the principles of the present invention is schematically illustrated, particularly depicting a third design of fluid coupling between a first outlet and a second inlet.

[0053] Figure 2DAn ion transport device operating in accordance with the principles of the present invention is schematically illustrated, particularly depicting a fourth design of fluid coupling between a first outlet and a second inlet.

[0054] Figure 3A Schematically shows the Figure 2A A variant of the RF ion guide in a fine or medium vacuum chamber.

[0055] Figure 3B Schematically shows the Figure 2A Another variation of the RF ion guide in a fine or medium vacuum chamber.

[0056] Figure 4A Schematically shows the Figure 2A A variation of the gas introduction assembly at the entrance of a fine or medium vacuum chamber.

[0057] Figure 4B Schematically shows the Figure 2A Another variation of the gas introduction assembly at the inlet of a fine or medium vacuum chamber.

[0058] Figure 5 A schematic diagram of one possible ion mobility - mass spectrometer combination is shown in which the principles of the invention may be implemented and serves primarily to provide context for the teachings presented. DETAILED DESCRIPTION

[0059] While the invention has been shown and described with reference to several different embodiments thereof, those skilled in the art will recognize that various changes in form and details may be made without departing from the scope of the invention as defined in the following claims.

[0060] Figure 2AAn embodiment of an ion transport device (2) is shown. An ion source (not shown) is used to convert any type of sample material into gaseous ionic sample material. The ion source may be located in a separate chamber (not shown), for example, as an electrospray ion source at a substantially ambient or atmospheric pressure of about 1000 mbar. The transport capillary (4) may connect the ion source to and enter a post-source vacuum chamber (6), which may be maintained at a low rough vacuum pressure level in the range of about 1 mbar to 10 mbar (Δp=~9 mbar). The post-source vacuum chamber (6) may include a plurality of deflection electrodes (8), for example, which may be provided with repelling DC and / or RF voltages. The deflection electrodes (8) and the DC and / or RF voltages applied thereto may be configured to rotate the ionic sample material by about 90° (curved arrow 10) and be directed toward the outlet of the post-source vacuum chamber and the RF ion funnel (12) connected thereto. Excess gases from the ion source and introduced into the post-source vacuum chamber (6), such as water clusters, solvents, and analytical ion species, may be substantially unaffected by the deflection electrode (8) assembly and may flow directly within the post-source vacuum chamber (6) toward a vent or exhaust port (14) where they are pumped away. In the process, gaseous species, such as water and solvent species and clusters, which may be residuals of the ionization process and have less analytical value, may be separated from the gaseous ion sample material and discarded.

[0061] The RF ion funnel (12) receives the deflected ion sample material and can concentrate it into a thin beam that is well suited for passing through an opening, orifice or hole in the wall of a downstream fine or medium vacuum chamber (16). The fine or medium vacuum chamber (16) can be fully evacuated to about 10°C in its center by a plurality of vents or evacuation ports (18) arranged in the side walls. -1 mbar, 10 -2 mbar or lower (e.g. 10 -4 The side walls are substantially perpendicular to the walls including openings, orifices or holes through which gaseous ionic sample material enters at a pressure level of 100 mbar (mbar).

[0062] At the interface between the post-source vacuum chamber (6) and the fine or medium vacuum chamber (16) including the radio frequency ion funnel (12), the ion transmission device (2) may include a gas introduction assembly (20) substantially adjacent to the outlet of the post-source vacuum chamber (6) and also adjacent to the inlet of the radio frequency ion funnel (12). The gas introduction assembly (20) may be designed and configured to introduce gaseous substances into the post-source vacuum chamber (6) so as to establish gas dynamic conditions and gas flows in the post-source vacuum chamber (6) that substantially prevent unnecessary or undesirable gaseous substances other than the gaseous ion sample material of interest from being transmitted through the radio frequency ion funnel (12) and entering the fine or medium vacuum chamber (16) together with the ion sample material of interest.

[0063] The fine or medium vacuum chamber (16) may include: a first stacked annular ion guide (21') located opposite the entrance, for initially receiving gaseous ion sample material; a central multipole assembly (21"), such as a quadrupole assembly, for transferring the ion sample material from the first stacked annular ion guide (21') to a second stacked annular ion guide (21'"), the second stacked annular ion guide (21'") being located upstream of and opposite to the exit of the fine or medium vacuum chamber (16), for guiding the ion sample material through the fine or medium vacuum chamber (16) and out of it. The multipole assembly (21") may be a quadrupole assembly, which Tunable RF and DC voltages may be provided so that the transmission characteristics of the multipole assembly (21") can be switched between a so-called pure RF mode (in which the multipole assembly (21") operates as a full mass range ion guide, transmitting essentially all incoming mass or m / z species of ionic sample material) and one of a low-pass, high-pass and band-pass mode (in which the multipole assembly (21") provides a stable trajectory for ionic sample material passing through it only for a selected mass or m / z ratio or a selected range thereof, or imposes upper and lower limits, or imposes limitations only at one end while being essentially unrestricted at the other end of the mass or m / z range).

[0064] The outlet of the fine or medium vacuum chamber (16) can be fluidically connected to a transfer tube or capillary assembly (22), which in turn can be connected to a separation vacuum chamber (24) at its other end, and can have a contracted design compared to the size of the fine or medium vacuum chamber (16) and the separation vacuum chamber (24), which can allow more components to be installed adjacent to and / or near the entrance of the separation vacuum chamber (24) without excessive space constraints. The separation vacuum chamber (24) can include a stacked annular ion guide assembly (26), which in this example can be monolithic, i.e., the assembly does not include any interruptions along a common axis defined by the outlet of the fine or medium vacuum chamber (16) and the entrance of the separation vacuum chamber (24) (and one or more transfer capillaries or tubes 22 therebetween). The first part of the stacked ring ion guide (26) assembly can adopt a funnel design (26'), which means that the inner hole or width of the stacked ring through which the ion sample material passes when passing through the separation vacuum chamber (24) can gradually become smaller along the axis to further concentrate and calibrate the ion sample material into a thin beam close to the axis. At the smallest funnel hole, the stacked ring ion guide (26) can transition to a radio frequency tunnel design (26"), which means that the inner hole or width of the stacked ring located there can remain essentially constant within a predetermined distance along the axis. After the predetermined distance, the stacked ring ion guide (26) can transition again to a funnel design (26'") to adjust the transmitted ion sample material into an even thinner beam, which can leave the separation vacuum chamber (24) through an outlet.

[0065] like Figure 2A As shown, one or more transfer capillaries or tubes (22) are coaxially arranged with the inlet of the stacked annular ion guide (26). Alternatively, the funnel inlet (26') of the stacked annular ion guide (26) can also be set at a position offset from the symmetry center of the one or more transfer capillaries or tubes (22) to facilitate the removal of excess gaseous matter while still receiving ion sample material and further transferring it to subsequent parts of the stacked annular ion guide (26).

[0066] The tunnel portion (26") of the stacked annular ion guide (26) in the separation vacuum chamber (24) can be designed to be airtight, that is, the gaps between the stacked rings are filled with non-conductive, preferably chemically inert or inactive insulating materials, while the funnel portions (26', 26'") at the beginning and end of the stacked annular ion guide (26) can adopt a gas-dynamic open design to allow some electrically neutral gaseous substances to escape laterally. The tunnel portion (26") can be embodied as a captured ion mobility separator, which collects ion sample materials driven by the basic laminar flow of gaseous substances against electric field barriers, and then elutes them in a graded manner into parcels of different ion mobilities or collision cross sections (CCS), in the order of eluting the ion sample materials with low ion mobility first and eluting the ion sample materials with high ion mobility later, and elutes them into subsequent mass analysis chambers or fragmentation, activation or reaction chambers (not shown). The tunnel portion (26") can also be embodied as a TIMS with parallel accumulation capability, as disclosed in patent application publication US2016 / 0231275A1, which is incorporated herein by reference in its entirety.

[0067] Adjacent to the inlet of the separation vacuum chamber (24) and at the end to which one or more transfer capillaries or pipes (22) point, another gas introduction assembly (28) can be located in the constricted space between the fine or medium vacuum chamber (16) and the downstream separation vacuum chamber (24), which constricted space remains open due to the narrow design of the one or more transfer capillaries or pipes (22). The gas introduction assembly (28) can include a plurality of nozzles that are substantially parallel to the axis of the fine or medium vacuum chamber outlet and the separation vacuum chamber inlet. Chemically inert or non-reactive gas, such as cryogenic molecular nitrogen N 2 , can be injected into the separation vacuum chamber (24) to produce fluid dynamic conditions that largely or substantially prevent the backflow of gaseous materials from the separation vacuum chamber (24) at a significantly higher pressure through one or more transfer capillaries or tubes (22) to the fine or medium vacuum chamber (16) at a relatively lower pressure. In this way, the introduction of gaseous materials can at least partially, if not mostly, compensate for the adverse static pressure difference by offsetting the static pressure difference with the dynamic pressure difference, thereby reducing or even almost completely eliminating the interference with the propagation of ion sample material that may be caused by the backflow of gaseous materials. This practice improves the receiving conditions at the stacked annular ion guide (26) located in the separation vacuum chamber (24), thereby improving the transmission efficiency of the ion sample material.

[0068] Using COMSOL TM right Figure 2ASimulations of the operation of one embodiment of the gas delivery apparatus (2) shown, having a gas introduction assembly (28) at a separation vacuum chamber (24) comprising four nozzles symmetrically located about one or more delivery capillaries or tubes (22) and substantially axially aligned, showed that backflow of gaseous material could be reduced by approximately 25% compared to an embodiment in which additional gaseous material is simply introduced into the separation vacuum chamber (24) substantially perpendicular to the ion propagation path, such as a curtain gas arrangement in the prior art.

[0069] Figure 2B Shown Figure 2A A variant of the embodiment in the embodiment of FIG. 1 is provided, wherein the design of the fine or medium vacuum chamber (16) is different, and the fluid coupling between the first outlet and the second inlet is also different. In order to avoid unnecessary repetition, the following will focus on explaining in detail the parts of the variant that are different from the previously described embodiment, and will not further explain the parts of the variant that are the same as the previous embodiment.

[0070] The fine or medium vacuum chamber (16) can be divided into three pressure sub-stages (16', 16", 16'') along the axis from the first inlet to the first outlet. The pressure of the first pressure sub-stage (16') is maintained at about 1-10 -2 mbar, e.g. 10 -1 mbar, may comprise a stacked annular RF ion funnel which receives ion sample material at its wide end through an outer RF ion funnel (12) and focuses it to its narrow end where it passes through an orifice in the cavity substage boundary wall where it enters a second substage (16") maintained at a pressure of about 10 -2 Below millibar, for example, as low as 10 -5 mbar. A multipole assembly (21") located in the second substage (16"), such as a quadrupole mass filter, can filter the received ion sample material according to a set pass characteristic, or transmit the ion sample material substantially unaffected in a pure RF mode. After exiting the multipole assembly (21") or the quadrupole mass filter, the ion sample material can be received at its wide end by another stacked annular RF ion funnel and focused toward its narrow end to pass through an orifice in another substage boundary wall, where it enters the third substage (16"'), the pressure of which is maintained at about 10 -1mbar, similar to the pressure level of the first substage (16'). The third substage (16'") may include a stacked annular RF ion funnel-ion tunnel assembly that receives ion sample material at its wide RF ion funnel end and conveys it downstream to a separation vacuum chamber (24) at its narrow RF ion tunnel end. The gaps between some of the stacked annular electrodes in the upstream portion of the stacked annular RF ion funnel-ion tunnel assembly may be unfilled and allow excess gas to be vented and pumped away, while the gaps between some of the stacked annular electrodes in the downstream portion of the stacked annular RF ion funnel-ion tunnel assembly may be filled with a chemically inert and electrically neutral material, such as polytetrafluoroethylene (PTFE) or polyetheretherketone (PEEK), as shown in the shaded area, so as to form a boundary interface with a relatively narrow opening between the third substage (16'") of the fine or medium vacuum chamber (16) and the downstream separation vacuum chamber (24). The gap between the last stacked ring of the stacked annular RF ion funnel-ion tunnel assembly and the chamber wall also filled with an electrically neutral material may have an embedded gas supply conduit, for example for receiving molecular nitrogen N 2 The gas supply conduit points from radially outward to radially inward, and the supplied gas can be discharged from there through an annular nozzle opening or an arrangement of multiple individual nozzles, and can be discharged into the separation vacuum chamber (24) in a direction substantially along the central axis.

[0071] The stacked annular electrodes of various stacked annular electrode assemblies within the three sub-stages (16', 16", 16'") of the fine or medium vacuum chamber (16) can be of monopole design, i.e., each ring and axial position only receives a single-phase RF or AC voltage, or can be of multipole design, i.e., include peripheral segments that can receive RF or AC voltages of different phases, such as generating a quadrupole, hexapole, octupole radial confinement field or a similar field. Similarly, each ring and axial position can also receive a different DC voltage bias to drive ions to move axially or block the movement of ions. The intracavity boundary walls between different sub-stages (16', 16", 16') can be provided with only a DC voltage, or only an RF or AC voltage, or a combination of RF or AC and DC voltages.

[0072] and Figure 2A Compared with the embodiment, Figure 2B The variation shown includes an axially substantially seamless transition from the third substage (16'") of the fine or medium vacuum chamber (16) to the subsequent separation vacuum chamber (24), represented by a single orifice, opening or hole. The ionic sample material is directed toward the exit of the fine or medium vacuum chamber (16) using a stacked annular electrode assembly supplied with radio frequency or alternating or direct current voltages, thereby facilitating radial confinement of the ionic sample material along its path through such stacked annular electrode assembly and further allowing the establishment of an axial potential gradient as a driving force for the ionic sample material to move forward axially.

[0073] Figure 2C Another variant of a fine or medium vacuum chamber (16) is shown, which has three sub-stages (16', 16", 16'"), with Figure 2B The main difference is that Figure 2C The third substage (16'") has only one RF ion tunnel, i.e., a stacked annular electrode assembly whose inside width does not vary along the axis, but maintains the same inner diameter through which ionic sample material can pass until transitioning to the downstream separation vacuum chamber (24).

[0074] Figure 2D Another variant of a fine or medium vacuum chamber (16) is shown, which is Figure 2A The fine or medium vacuum chamber is more similar to the one in the example above, as it is not divided into sub-stages and is maintained at approximately 10 -2 mbar. Instead, it has a central multipole assembly (21"), such as a quadrupole mass filter, which is sandwiched by a first stacked annular RF ion funnel upstream that focuses ion sample material received from an outer RF ion funnel (12) to a relatively small beam diameter before transmitting it to the multipole assembly (21") and a second stacked annular RF ion funnel downstream that receives ion sample material passing through the multipole assembly at its wide end and focuses it to a smaller beam diameter before transmitting it to a subsequent separation vacuum chamber (24). In the example shown, the second RF ion funnel has open gaps between its stacked annular electrodes for ventilation and removal of excess gas. Only the gap between the last stacked annular electrode of the second RF ion funnel and the dividing wall between the vacuum chamber (16, 24) contains a gas supply conduit that exhausts gas into the separation vacuum chamber (24), as previously described with reference to FIG. Figure 2B Variant as described.

[0075] Figure 3A A variant of one or more radio frequency ion guides included in a fine or medium vacuum chamber (16) is schematically shown. The fine or medium vacuum chamber (16) may include a multipole rod assembly (21*) having one or more rod segments instead of Figure 2A The first stacked annular ion guide described in . The rods of the multipole assembly can be segmented to allow different DC potentials to be applied to each individual segment, which helps to establish a potential gradient along the longitudinal axis of the multipole assembly (21*) to drive or push the ion sample material in a desired direction. Multipole assemblies, especially low-order multipole assemblies such as quadrupole assemblies, can promote radial confinement of ion sample material in a pseudo-potential well relatively close to the axis of the assembly.

[0076] Figure 3BAnother variant of one or more radio frequency ion guides located in a fine or medium vacuum chamber (16) is schematically illustrated. The fine or medium vacuum chamber (16) may include a multipole assembly (21**) having one or more additional electrodes (30) located in the gap (one or more) between two rods of the multipole assembly (21**) or close to the gap on the outside, instead of Figure 2A The second stacked annular ion guide described in . One or more additional electrodes (30) may be of conical design and may be coaxially aligned with the rods of the multipole assembly (21**), which helps to establish a potential gradient along its longitudinal extension within the assumed limits of the multipole assembly (21**) for propagation of ion sample material. One or more additional electrodes (30) may be selectively segmented (not shown).

[0077] Figure 4A A variation of a gas introduction assembly (28) adjacent to the inlet of a separation vacuum chamber (24) is schematically depicted. Figure 2A Unlike the multiple individual nozzles shown in , which each inject a separate additional gaseous substance into the separation vacuum chamber, the improved gas introduction assembly (28*) may include an annular or ring-shaped nozzle, which is concentrically arranged around one or more transfer capillaries or pipes (22). This design can more comprehensively cover the circumferential angle range for injecting gaseous substances around the inlet of the separation vacuum chamber (24) and help prevent or reduce turbulence conditions at the point of introduction of gaseous substances in the separation vacuum chamber (24).

[0078] Figure 4B Another variation of the gas introduction assembly is shown schematically, and its location is adjacent to the inlet of the separation vacuum chamber (24). The improved gas introduction assembly (28**) (here schematically represented by a plurality of separate nozzles) is not as Figure 2A and Figure 4A Instead of being strictly parallel to a common linear axis defined by the outlet of an upstream fine or medium vacuum chamber (16), the inlet of a downstream separation chamber (24), and one or more intermediate transfer capillaries or tubes (22), the arrangement may be such that the gaseous material is introduced into the separation chamber (24) at an acute angle relative to the central axis. Such a design may help to establish a continuous or steady or even substantially laminar gas flow within and through the separation chamber (24) and / or (possibly) one or more radio frequency ion guides contained therein.

[0079] Figure 5 is a schematic diagram of one possible modular ion mobility mass spectrometer (50) in which the principles of the present invention may be implemented.

[0080] As shown in (52), the sample may first be separated on a chromatographic stage. The chromatographic stage may include a liquid chromatography stage having a chromatographic column containing a suitable stationary phase through which the sample dissolved in a suitable mobile phase flows. Depending on the chromatographic conditions applied, the result may be a series of chromatographic peaks eluting sequentially at characteristic retention times.

[0081] As shown in (54), the chromatographic eluent can enter an ion source, which can convert sample molecules in the elution peak into gaseous ion species. The ion source can be an electrospray ion source, which uses a high voltage difference established at a nozzle relative to a counter electrode to atomize and ionize a liquid sample, such as a sample eluted from a liquid chromatography column. In general, ions can be generated, for example, by using spray ionization (such as electrospray (ESI) or thermal spray), desorption ionization (such as matrix-assisted laser / desorption ionization (MALDI) or secondary ion mass spectrometry (SIMS) ionization), chemical ionization (CI), photoionization (PI), electron impact ionization (EI), gas discharge ionization, etc.

[0082] As shown in (56), the gaseous ion sample material can be collected and funneled into a well-collimated beam for efficient transmission to the transmission and ion mobility separation stage. The device for transmitting the gaseous ion sample material can be implemented according to any one of the examples provided in the present invention. The ion mobility separation stage can utilize the interaction of the gaseous ion sample material with the moving or stationary gas, while being acted upon by an electric field, which can remain constant or vary with time. For example, the ion mobility separation stage can be designed and configured according to the principle of trapped ion mobility separation (TIMS). US7,838,826B1, cited herein and incorporated herein in its entirety, discloses an example of a TIMS separation stage. Depending on the mobility separation conditions applied, the result of the ion mobility separation can be a series of ion mobility peaks that elute successively at characteristic times. Other suitable types of gas phase ion mobility separators may include a drift tube ion mobility separator (DTIMS), a traveling wave ion mobility separator (TWIMS), and a gas phase ion mobility filter (such as a field asymmetric ion mobility separator (FAIMS)).

[0083] The eluted mobility peak can be passed through an ion guide stage, as shown at (58), which functions to pass the ion sample material through the pressure difference between the relatively high pressure in the ion mobility separation stage and the lower pressure maintained in the subsequent stage for further gas phase ion processing and manipulation. Such an ion guide stage can include various ion guides, such as a multipole assembly and / or a stacked annular ion guide, as previously described.

[0084] As shown at (60), the filtering stage may follow the ion guide stage (58). The filtering stage may include a mass filter, such as a quadrupole mass filter, which may facilitate transmission of the gaseous ion sample material in a broadband or precursor screening mode (the purpose of which is to sort out as few ion species as possible, or in other words, to transmit as many incoming ion species as possible) and any of a bandpass filter mode, a highpass filter mode, and a lowpass filter mode (the purpose of which is to narrow the transmission window to a relatively narrow mass or mass-to-charge ratio (m / z) range, thereby excluding ion species that are not within this transmission window). The broadband or precursor screening mode and any of the filter modes may be alternated (rapidly) in succession using a tunable RF and / or DC voltage supplied to the mass filter.

[0085] As shown in (62), the filtration stage (60) may be followed by a fragmentation stage. The fragmentation stage may include an ion guide filled with a collision gas and further equipped with an electrode that facilitates switching of an accelerating voltage to pull the gaseous ion sample material into the collision gas at high speed, thereby inducing dissociation. Precursor ion species selected from the gaseous ion sample material may be fragmented into a plurality of characteristic fragment ion species. In general, the gaseous ion sample material may be fragmented in the fragmentation stage, for example, by collision induced dissociation (CID), surface induced dissociation (SID), photodissociation (PD), electron capture dissociation (ECD), electron transfer dissociation (ETD), collision activation after electron transfer dissociation (ETcD), activation simultaneously with electron transfer dissociation (AI-ETD), fragmentation by reaction with highly excited or free radical neutral particles, and the like.

[0086] As shown in (64), the gaseous ion sample material from the collision cell can be delivered to a mass analysis stage. The mass analysis stage can be in the form of a reflection time of flight (rTOF) stage using an orthogonal ion injection TOF flight tube. At the end of the curved flight path in the flight tube, the ion sample material may be recorded by an impact detector, such as a secondary electron multiplier detector. The result may be a spectrum that plots ion abundance, such as ion intensity, and molecular weight or mass-related scales, such as flight time. Together with information from the chromatographic stage (52) and the transmission and ion mobility separation stage (56), the spectral data can be represented by different graphs, such as a three-dimensional graph, in which each axis corresponds to a scale of physicochemical properties (i) retention time from the chromatographic stage (52), (ii) gas phase ion mobility or related properties from the ion mobility separation stage (56), and (iii) mass or mass-to-charge ratio or related properties from the mass analysis stage (64), and the abundance of the signal peak can be represented by color or other suitable graphical features.

[0087] The present invention has been shown and described above with reference to several different embodiments of the present invention. However, those skilled in the art will appreciate that various aspects or details of the present invention may be changed, or various aspects or details of different embodiments may be combined arbitrarily, if feasible and without departing from the scope of the present invention. For example, a device according to the principles disclosed in the present invention and a method for executing the principles disclosed in the present invention may be implemented in an embodiment of a mass spectrometer as shown in patent application publication US2020 / 0381241 A1, which is cited in the introduction and incorporated herein by reference in its entirety. In general, the above description is for illustrative purposes only and is not intended to limit the present invention, which is defined solely by the appended claims, including any equivalent embodiments, as the case may be.

Claims

1. An apparatus for transporting gaseous ionic sample material for subsequent analysis, the apparatus comprising: a first vacuum chamber comprising: a first inlet through which gaseous matter including ionic sample material is introduced; a first outlet through which gaseous matter including ionic sample material exits; and one or more first radio frequency ion guides for receiving and directing the ionic sample material along its path from the first inlet to the first outlet, the first vacuum chamber being maintained within a first pressure range; a second vacuum chamber comprising: a second inlet through which gaseous matter including ionic sample material exiting the first vacuum chamber is introduced, the second inlet being fluidly coupled to and defining an axis with the first outlet; a second outlet through which gaseous matter including ionic sample material exits; and one or more second RF ion guides for receiving and directing ionic sample material along its path from the second inlet to the second outlet, the second vacuum chamber being maintained within a second pressure range that is substantially higher than the first pressure range, and - a first gas introduction assembly substantially adjacent to the second inlet and designed and arranged to introduce a gaseous substance not from the first vacuum chamber into the second vacuum chamber in a direction substantially along said axis.

2. The apparatus of claim 1, wherein the first gas introduction assembly comprises one or more nozzles.

3. The apparatus of claim 2, wherein the one or more nozzles comprise one of (i) a plurality of individual nozzles and (ii) an annular or ring-shaped nozzle.

4. Apparatus according to claim 3, wherein the plurality of individual nozzles are aligned so that the gaseous material is introduced at an angle of less than 60° to the axis.

5. The apparatus of claim 1, wherein the first gas introduction assembly is designed and configured to introduce the gaseous substance in a manner substantially one of (i) coaxial with the axis and (ii) concentric with the axis.

6. The device of claim 1, further comprising one or more transfer conduits or capillaries fluidically coupling the second inlet to the first outlet.

7. The device according to claim 1, wherein the first pressure range is 10 -1 The second pressure range is the single digit millibar range between 0.2 and 50 millibar.

8. The apparatus of claim 1, wherein the one or more second radio frequency ion guides comprise one or more ion mobility separators.

9. The apparatus of claim 8, wherein the one or more ion mobility separators comprise one or more trapped ion mobility separators.

10. The apparatus of claim 1, wherein the one or more second RF ion guides are of substantially airtight design.

11. The apparatus of claim 1, further comprising a mass balance system that operates to maintain a mass balance of the gaseous material introduced into the second vacuum chamber, thereby generating a substantially continuous or steady flow of the gaseous material within the second vacuum chamber.

12. The apparatus of claim 11, wherein the substantially continuous or steady flow of the gaseous material is one of (i) segmentally and (ii) completely substantially laminar along its path within the second vacuum chamber.

13. The apparatus of claim 11, wherein the substantially continuous or steady flow of gaseous material is produced within one or more second RF ion guides.

14. The apparatus of claim 1, wherein the one or more second RF ion guides include one or more ion guides having at least one of (i) a RF funnel design and (ii) a RF tunnel design.

15. The apparatus of claim 1, wherein the one or more second RF ion guides comprise one or more stacked annular ion guides.

16. The apparatus of claim 1, wherein the first vacuum chamber comprises one or more vents for extracting excess gaseous material.

17. The apparatus of claim 1, wherein the one or more first RF ion guides comprise at least one of (i) a stacked annular ion guide and (ii) a RF multipole assembly.

18. The apparatus of claim 17, wherein the stacked annular ion guide comprises one or more electrode rings having a multipole design.

19. The apparatus of claim 17, wherein the radio frequency multipole assembly comprises one or more segmented multipole rods.

20. The apparatus of claim 17, wherein the radio frequency multipole assembly includes one or more additional electrodes to establish an electrical potential gradient along its length.

21. The apparatus of claim 1, wherein at least one of (i) the one or more first RF ion guides and (ii) the one or more second RF ion guides are substantially aligned along an axis.

22. The apparatus of claim 1, wherein one or more electrical potentials are applied to at least one of (i) one or more first RF ion guides and (ii) one or more second RF ion guides such that the ion sample material is driven in a direction substantially from the first vacuum chamber to the second vacuum chamber.

23. The device of claim 1 , further comprising one or more trapping membranes or lenses located at at least one of (i) the first inlet, (ii) the first outlet, and (iii) a position between the first inlet and the first outlet in the first vacuum chamber, temporarily providing one or more trapping potentials to the one or more trapping membranes or lenses, thereby substantially blocking the propagation of ionic sample material.

24. The apparatus of claim 1, further comprising (i) a mass analyzer and (ii) at least one of a fragmentation, activation or reaction cell in fluid communication with the second outlet.

25. The apparatus according to claim 1, further comprising a third vacuum chamber comprising: a third inlet through which gaseous matter including ionic sample material is introduced; a third outlet fluidly coupled to the first inlet through which gaseous matter including ionic sample material exits; one or more vents for extracting excess gaseous material; and one or more deflectors for redirecting and directing ionic sample material along its path from the third inlet to the third outlet, the third vacuum chamber being substantially maintained within a third pressure range that is substantially higher than the first pressure range.

26. The apparatus of claim 25, further comprising a radio frequency funnel fluidically coupling the third outlet to the first inlet for directing and conditioning the ionic sample material.

27. The apparatus of claim 25, wherein the third pressure range is a single digit millibar range between 0.2 and 50 millibars.

28. The device of claim 25, wherein the third inlet comprises one or more transfer tubes or capillaries.

29. The apparatus of claim 25, wherein the one or more deflectors are designed and configured to deflect the ion sample material from an introduction direction toward the third outlet by an angle of more than 45°.

30. The apparatus of claim 25, wherein the third inlet is in fluid communication with the ion source.

31. The apparatus of claim 25, further comprising a second gas introduction assembly substantially adjacent to the third outlet, designed and configured to introduce a gaseous substance into the third vacuum chamber.

32. A method for transporting a gaseous ionic sample material for subsequent analysis, the method comprising: - introducing gaseous matter including ionic sample material into the first vacuum chamber through an inlet of the first vacuum chamber, - receiving and directing ion sample material along its path from an entrance to an exit of the first vacuum chamber using one or more first radio frequency ion guides in the first vacuum chamber, - releasing gaseous matter including ionic sample material through an outlet of the first vacuum chamber, - During this process, the first vacuum chamber is maintained in a first pressure range, - introducing gaseous matter including ionic sample material released from the first vacuum chamber into the second vacuum chamber through an inlet of the second vacuum chamber, the inlet of the second vacuum chamber being fluidically coupled to an outlet of the first vacuum chamber and defining an axis, - receiving and directing ion sample material along its path from an entrance to an exit of the second vacuum chamber using one or more second radio frequency ion guides in the second vacuum chamber, - releasing gaseous substances including ionic sample material through the outlet of the second vacuum chamber, - during this process, maintaining the second vacuum chamber in a second pressure range, the second pressure range being substantially higher than the first pressure range, and - introducing a gaseous substance not coming from the first vacuum chamber into the second vacuum chamber at a position substantially adjacent to the inlet of the second vacuum chamber in a direction substantially along said axis.

Images