Device for reacting analyte ions with electrons

Abstract

An ion-electron reaction device includes a first tubular magnet, a second tubular magnet disposed coaxially with the first tubular magnet, and a gasket located between the first tubular magnet and the second tubular magnet. The gasket is arranged and configured such that the first tubular magnet and the second tubular magnet provide a substantially uniform magnetic field along a central axis of the device.

Description

Cross-reference to related applications

[0001] This application claims priority and benefit to UK Patent Application No. 2317276.0, filed on 10 November 2023, the entire contents of which are incorporated herein by reference. Technical Field

[0002] This invention relates to a method for mass spectrometry and / or ion mobility spectrometry, wherein analyte ions react with electrons to produce charge-reduced analyte ions, fragment ions, or other product ions. The invention also provides a mass spectrometer or mobility spectrometer configured to perform this method. Background Technology

[0003] In the field of mass spectrometry, ion-electron reactions are well-known during the analysis of analyte ions. Examples of such reactions include electron capture dissociation (ECD) and electron-induced dissociation (EID). To perform ECD, multiple protonated analyte molecules (i.e., analyte ions) can be confined together with low-energy electrons, causing the analyte molecules and electrons to react with each other, thereby fragmenting the analyte molecules into daughter ions.

[0004] Mass analysis using electron-based fragmentation techniques (such as those described above) is beneficial because it can be more informative than other fragmentation techniques (such as collision-induced dissociation (CID)) because the product ions produced by the reaction retain unstable post-translational modifications. Furthermore, during the aforementioned ion-electron interactions, some analyte molecules may not dissociate into fragment ions but may instead become charge-reduced. This charge reduction can be used to separate ions that would otherwise have overlapping charge states, thus enabling reliable charge annotation. Moreover, electron-based fragmentation techniques can generate higher-quality (more complete) or complementary fragment information for polymers such as peptides.

[0005] Although ion-electron reaction devices are known, their design is often complex, and their operation can be challenging, for example, due to the difficulty in confining analyte ions and low-energy electrons in the same region for a sufficient time and to a sufficient density for the reaction to occur. For instance, known ECD devices use an RF electric field to confine analyte ions, but this RF field increases the energy of the reactant electrons, thus reducing the probability of analyte ions capturing electrons and consequently the probability of a reaction occurring. Furthermore, for devices where electrons are captured, the additional energy they receive from the RF field causes them to be lost from the electron-capturing field. Other known reaction devices use strong magnetic fields to confine electrons to low energies, but these also present difficulties in confining both analyte ions and reactant electrons in the same region so that the reaction occurs at the desired rate. For example, difficulties may arise if the magnetic field is too weak or inhomogeneous. Summary of the Invention

[0006] In a first aspect, the present invention provides an ion-electron reaction apparatus comprising: a first tubular magnet; a second tubular magnet arranged coaxially with the first tubular magnet; and a spacer located between the first and second tubular magnets; wherein the spacer is arranged and configured such that the first and second tubular magnets provide substantially uniform magnetic fields along the central axis of the apparatus.

[0007] The first and second tubular magnets are spaced apart along the central axis, and the spacer is axially positioned between the magnets.

[0008] Each of the first tubular magnet and the second tubular magnet can be a cylindrical magnet.

[0009] The spacer can be arranged and configured such that the first tubular magnet and the second tubular magnet provide a substantially uniform magnetic field in a continuous region extending along: at least a portion of the central axis within the first tubular magnet; the entire central axis passing through the spacer; and at least a portion of the central axis within the second tubular magnet.

[0010] A uniform magnetic field may have magnetic field lines extending from a first tubular magnet to a second tubular magnet within a volume arranged around a central axis, wherein the magnetic field lines are substantially linear and parallel to the central axis for at least 30% of the length of the reaction device.

[0011] Advantageously, a uniform magnetic field extends over a relatively large volume, allowing electrons to be confined within such a large volume. Therefore, the magnetic field lines can be substantially linear and parallel to the central axis for at least 40%, 50%, 60%, 70%, 80%, or 90% of the length of the reaction device. "Length of the reaction device" refers to the distance from the upstream end of the first tubular magnet to the downstream end of the second tubular magnet (i.e., between the ends of the two magnets that are far apart from each other).

[0012] The gasket is preferably in direct contact with the first tubular magnet and the second tubular magnet.

[0013] The gasket is preferably tubular, such as cylindrical, and arranged coaxially with the first and second tubular magnets.

[0014] The gasket is preferably ferromagnetic.

[0015] The first tubular magnet may be arranged such that its north magnetic pole is adjacent to the pad, and the second tubular magnet may be arranged such that its south magnetic pole is adjacent to the pad; or the first tubular magnet may be arranged such that its south magnetic pole is adjacent to the pad, and the second tubular magnet may be arranged such that its north magnetic pole is adjacent to the pad.

[0016] The first and second tubular magnets are arranged coaxially along an axis. Each magnet can be axially magnetized such that its poles are located at opposite ends of the magnet along the central axis. Therefore, the axial end of the first magnet closest to the second magnet preferably has a pole opposite to the pole at the axial end of the second magnet closest to the first magnet. That is, the first and second magnets are arranged along the axis from north to south, or from south to north.

[0017] The reaction apparatus may include an electron generator arranged to generate free electrons and supply them to the location of a uniform magnetic field.

[0018] An electron generator can generate free electrons outside the tubular magnet and supply them to that location. Alternatively, the electron generator can generate free electrons inside the tubular magnet at that location.

[0019] An electron generator may include a voltage source and a filament arranged and configured to generate free electrons.

[0020] The wire can be arranged such that it has a distal end disposed on the central axis; or the wire can be formed into a loop at its distal end, wherein the loop surrounds the central axis.

[0021] The distal end or ring may be arranged on the central axis at an axial position between the first tubular magnet and the second tubular magnet, such as substantially halfway between the magnets.

[0022] The wire can pass through the hole in the gasket.

[0023] An electrical insulating sheath can be placed between the wire and the gasket to prevent current from flowing from the wire to the gasket.

[0024] The electrical insulating sheath may be a portion of the filament that extends radially inward relative to the inner wall of the gasket.

[0025] The reaction apparatus may include a heat sink that contacts the pad to transfer heat from the filaments out of the pad and to the heat sink.

[0026] The filament may not pass through the gasket, but may instead pass through an opening in the axial outer end of the first or second tubular magnet.

[0027] The wire can be long and thin and has a longitudinal axis, which is arranged at an obtuse or acute angle with the central axis passing through the tubular magnet.

[0028] The reaction apparatus can be configured to receive analyte ions such that they travel substantially along the central axis.

[0029] Therefore, an ion source can be provided to supply ions.

[0030] The reaction apparatus may include electrodes and one or more voltage sources configured to apply one or more DC voltages to the electrodes to generate a DC electric field for confining electrons radially about a central axis and / or axially about a central axis; and / or may include electrodes and one or more voltage sources configured to apply one or more DC and / or RF voltages to the electrodes to generate a DC and / or RF electric field for confining ions radially about a central axis and / or axially about a central axis.

[0031] Although the two tubular magnets are described as being stacked with a spacer between them, it is conceivable that more than two such tubular magnets could be stacked together to form a reaction device, with a spacer between each pair of adjacent magnets.

[0032] In a second aspect, the present invention provides an ion-electron reaction apparatus comprising: an elongated tubular magnet having a length of at least 5 mm; and an electron generator arranged to supply free electrons to a position within the tubular magnet; wherein: (i) the electron generator is arranged to supply free electrons to a position within the tubular magnet substantially on the central longitudinal axis of the tubular magnet, and wherein the ratio of the length to the inner radius of the tubular magnet is ≥3; or (ii) the electron generator is arranged to supply free electrons to a position within the tubular magnet radially outward relative to the central longitudinal axis of the tubular magnet, and wherein the ratio of the length to the inner radius of the tubular magnet is <3.

[0033] Tubular magnets can be cylindrical tubes.

[0034] The tubular magnet is expected to have or not have a length of at least 5 mm.

[0035] The radial position within the tubular magnet into which electrons are supplied can be selected based on the ratio of the length to the inner radius of the tubular magnet; and / or the ratio of the length to the inner radius of the tubular magnet used in the reaction apparatus can be selected based on the radial position within the tubular magnet where electrons are desired to be supplied.

[0036] According to option (i), the ratio of the length to the inner radius of the tubular magnet can be ≥3.2, ≥3.4, ≥3.6, ≥3.8 or ≥4.

[0037] According to option (ii), the ratio of the length to the inner radius of the tubular magnet can be ≤2.8, ≤2.6, ≤2.4, ≤2.2, ≤2.0, ≤1.8, ≤1.6, ≤1.4, ≤1.2 or ≤1.0.

[0038] An electron generator can be arranged to supply free electrons in a tubular magnet at a radial position, where the magnetic flux along the longitudinal axis is most uniform.

[0039] An electron generator can generate free electrons outside the tubular magnet and supply them to a location inside the tubular magnet. Alternatively, the electron generator can generate free electrons at a location inside the tubular magnet, either inside the magnet itself or at a location within the magnet.

[0040] A tubular magnet can be configured to produce a substantially linear, uniform magnetic field along its central axis, wherein the uniform magnetic field has magnetic field lines extending from one end of the tubular magnet to the other end within a volume arranged around the central axis, wherein the magnetic field lines are substantially linear and parallel to the central axis for at least 30% of the length of the tubular magnet.

[0041] Advantageously, the uniform magnetic field extends over a large volume. Thus, the magnetic field lines can be substantially linear and parallel to the central axis for at least 40%, 50%, 60%, 70%, 80%, or 90% of the length of the tubular magnet.

[0042] An electron generator can be arranged to generate free electrons and supply them to the location of a uniform magnetic field.

[0043] An electron generator may include a voltage source and a filament arranged and configured to generate free electrons.

[0044] An electron generator may include a voltage source and a filament arranged and configured to generate free electrons on or around a central axis passing through a tubular magnet.

[0045] The wire can be arranged such that it has a distal end disposed on the central axis; or the wire can be formed into a loop at its distal end, wherein the loop surrounds the central axis.

[0046] The distal end or ring may be arranged on or around the central axis at an axial position between the axial ends of the tubular magnet, such as along essentially half of the tubular magnet.

[0047] The wire can pass through an opening in the axial end of the tubular magnet.

[0048] The wire can be long and thin and has a longitudinal axis, which is arranged at an obtuse or acute angle with the central axis passing through the tubular magnet.

[0049] The reaction apparatus can be configured to receive analyte ions such that they travel substantially along the central axis.

[0050] Therefore, an ion source can be provided to supply ions.

[0051] The reaction apparatus may include electrodes and one or more voltage sources configured to apply one or more DC voltages to the electrodes to generate a DC electric field for confining electrons radially about a central axis and / or axially about a central axis; and / or may include electrodes and one or more voltage sources configured to apply one or more DC and / or RF voltages to the electrodes to generate a DC and / or RF electric field for confining ions radially about a central axis and / or axially about a central axis.

[0052] The tubular magnet can be configured to have the following length: such that a substantially linear, uniform magnetic field is provided along the entire annular region between the central axis of the tubular magnet and the inner wall of the tubular magnet; wherein the uniform magnetic field has magnetic field lines extending from one end of the tubular magnet to the other end of the tubular magnet within the annular region, wherein the magnetic field lines are substantially linear and parallel to the central axis for at least 30% of the length of the tubular magnet.

[0053] The magnetic field lines (in the toroidal region) may be substantially linear and parallel to the central axis for at least 40%, 50%, 60%, 70%, 80%, or 90% of the length of the tubular magnet.

[0054] The reaction apparatus may include an electron generator arranged to generate free electrons and supply them to a toroidal region.

[0055] An electron generator may include a voltage source and a filament arranged and configured to generate free electrons.

[0056] The filament can be arranged such that it has a distal end located within the annular region. The filament can be formed into a loop at its distal end.

[0057] The distal end or ring may be arranged in the annular region at an axial position between the axial ends of the tubular magnet, such as along essentially half of the tubular magnet.

[0058] The wire can pass through an opening in the axial end of the tubular magnet.

[0059] The wire can be long and thin and has a longitudinal axis, which is arranged at an obtuse or acute angle with the central axis passing through the tubular magnet.

[0060] The reaction apparatus can be configured to receive analyte ions in a toroidal region such that the ions travel along an axis that does not intersect with the filament.

[0061] Therefore, an ion source can be provided to supply ions.

[0062] Ions can be arranged along their axis of travel on the side opposite to the side where the filament is located, passing through the central axis of the magnet.

[0063] The reaction apparatus may include a shielding member positioned between the ions along their axis of travel and the filament for shielding the analyte ions from the electric field generated by the filament.

[0064] The shielding component can be positioned along the central axis of the tubular magnet.

[0065] The shielding component can be non-ferromagnetic.

[0066] The reaction apparatus may include electrodes and one or more voltage sources configured to apply one or more DC voltages to the electrodes to generate a DC electric field for radially confining electrons within a toroidal region and / or axially confining electrons along the toroidal region; and / or the reaction apparatus may include electrodes and one or more voltage sources configured to apply one or more DC and / or RF voltages to the electrodes to generate a DC and / or RF electric field for radially confining ions within a toroidal region and / or axially confining ions along the toroidal region.

[0067] The elongated tubular magnet according to the second aspect of the invention can be a single magnet. However, it is conceivable that the elongated tubular magnet can instead be formed of multiple tubular magnets stacked together with an electrical insulator between them, such that different voltages can be applied to the different magnets.

[0068] Therefore, in a third aspect, the present invention provides an ion-electron reaction apparatus comprising: a plurality of tubular magnets coaxially stacked together, wherein an electrical insulator is located between them; and one or more voltage sources configured to apply a voltage to one or more of the magnets.

[0069] The one or more voltage sources can be configured to apply different voltages to different magnets in the magnet.

[0070] The one or more voltage sources can be configured to continuously apply a DC voltage to a continuous magnet, such that a DC potential travels along the central axis through the tubular magnet. The applied DC voltage can accelerate electrons and / or ions within the reaction device.

[0071] The one or more voltage sources may be configured to apply one or more DC voltages to the magnet to generate a DC electric field for confining electrons radially and / or axially around the central axis of the tubular magnet.

[0072] The one or more voltage sources may be configured to apply one or more DC and / or RF voltages to the magnet to generate DC and / or RF electric fields for confining ions radially and / or axially around the central axis of the tubular magnet.

[0073] Multiple tubular magnets can be cylindrical magnets.

[0074] Magnets can be stacked together with their adjacent opposing magnetic poles.

[0075] The reaction apparatus according to the third aspect of the invention may have any of the features described above with respect to the second aspect of the invention, except that the features described with respect to the tubular magnets of the second invention are applicable to the stacking of tubular magnets.

[0076] In a fourth aspect, the present invention provides an ion-electron reaction apparatus comprising: a magnet having a substantially flat planar surface; and an electron generator for supplying free electrons; wherein the reaction apparatus is configured such that a magnetic field from the magnet confines the free electrons to a region adjacent to the planar surface.

[0077] The magnet can be a bar magnet.

[0078] The reaction apparatus can be configured to receive analyte ions along the ion axis, allowing the ions to enter a region adjacent to the planar surface.

[0079] The ion axis can be arranged between the planar surface of the magnet and the first electrode, which is spaced apart from the planar surface in a first direction.

[0080] The reaction apparatus may include a second electrode and a third electrode arranged on opposite sides of the ion axis and between the bar magnet and the first electrode, wherein the second electrode and the third electrode are spaced apart in a direction orthogonal to the first direction.

[0081] The first electrode and / or the second electrode and / or the third electrode may be non-ferromagnetic electrodes.

[0082] The first electrode and / or the second electrode and / or the third electrode may be planar electrodes. Alternatively, the first electrode and / or the second electrode and / or the third electrode may have other configurations, such as being rod electrodes.

[0083] The reaction apparatus may include one or more voltage sources configured to apply one or more DC or RF voltages to a first electrode and / or a second electrode and / or a third electrode and / or a magnet to generate a DC or RF electric field that confines analyte ions introduced into the reaction apparatus to the vicinity of the planar surface of the magnet.

[0084] The reaction apparatus may include one or more voltage sources configured to apply one or more DC voltages to a first electrode and / or a second electrode and / or a third electrode and / or a magnet to generate a DC electric field that confines electrons along the axial direction of the apparatus. For example, any of the first, second, or third electrodes and / or the magnet may be axially segmented, and different voltages may be applied to different axial segments to achieve this.

[0085] Alternatively or otherwise, the one or more voltage sources may be configured to allow a DC potential to travel through the region, for example, to accelerate ions or electrons therein.

[0086] An electron generator can be arranged to generate free electrons and supply those free electrons to the region.

[0087] An electron generator may include a voltage source and a filament arranged and configured to generate free electrons.

[0088] The filament can be arranged to generate electrons on a planar surface adjacent to a magnet.

[0089] The wire can be arranged such that it has a distal end adjacent to the planar surface. The wire can be formed into a loop at its distal end.

[0090] The filament may extend through an opening into the reaction apparatus, such as an opening through which ions enter or exit the apparatus. Alternatively, the filament may extend through one of an electrode or a magnet.

[0091] The reaction apparatus can be configured to receive analyte ions such that they travel substantially adjacent to a planar surface.

[0092] Therefore, an ion source can be provided to supply ions.

[0093] In one embodiment, the present invention provides a mass spectrometer comprising: a reaction apparatus as described above; and an ion source arranged to supply analyte ions to the reaction apparatus.

[0094] The present invention also provides a method for mass spectrometry analysis, the method comprising: providing a mass spectrometer as described above; supplying ions from an ion source to a reaction apparatus; and providing electrons in the reaction apparatus such that the electrons react with the ions. Attached Figure Description

[0095] Various embodiments of the invention will now be described by way of example only and with reference to the accompanying drawings, wherein:

[0096] Figure 1 A schematic diagram of a reaction apparatus according to an embodiment of the present invention is shown, the reaction apparatus comprising two magnets joined by a gasket, and a filament assembly for generating electrons through a hole in the gasket;

[0097] Figure 2 A schematic diagram of a reaction apparatus according to another embodiment of the invention is shown, the reaction apparatus comprising a single elongated magnet and a filament for generating electrons that enter the reaction apparatus through an outlet hole in the magnet;

[0098] Figure 3a Examples Figure 2 A schematic diagram of half of the reaction apparatus, the ratio of the length to the inner radius of the reaction apparatus is 4; Figure 3b Examples are shown along different radial locations of the reaction apparatus. Figure 3a A graph showing the magnetic flux density along the length of the reaction device;

[0099] Figure 4a Examples Figure 2 A schematic diagram of half of the reaction apparatus, the ratio of the length to the inner radius of the reaction apparatus is 1.8; Figure 4b Examples are shown along different radial locations of the reaction apparatus. Figure 4a The flux density curve of the reaction device;

[0100] Figures 5a to 5c A schematic diagram of a reaction apparatus according to another embodiment of the invention is shown, the reaction apparatus comprising a ring magnet and a filament for generating electrons, the filament being arranged off-axis relative to the central axis of the magnet;

[0101] Figures 6a to 6b A schematic diagram of a reaction apparatus according to another embodiment of the invention is shown, the reaction apparatus including a bar magnet for confining electrons;

[0102] Figure 7 A schematic diagram of a reaction apparatus according to another embodiment of the invention is shown, the reaction apparatus comprising a plurality of stacked annular magnets; and

[0103] Figure 8 A schematic diagram of a mass spectrometer according to an embodiment of the present invention is shown. Detailed Implementation

[0104] Embodiments of the present invention provide an ion-electron reaction apparatus for reacting analyte ions with electrons. The analyte ions may be positively charged ions. Electrons may be confined within the reaction apparatus without the use of any RF electric field. For example, a magnetic field may be used alone to confine the electrons. The analyte ions may also be trapped within the reaction apparatus during their reaction with electrons. Alternatively, the analyte ions may be simply transported through the reaction apparatus, wherein electrons are trapped, such that the reaction can occur without trapping the analyte ions within the reaction apparatus.

[0105] The reaction apparatus can be used to react analyte ions with electrons to cause a reduction in the charge of the analyte ions and / or to cause the analyte ions to dissociate into fragment ions (e.g., ECD or EID).

[0106] Figure 1 A schematic diagram of a reaction apparatus according to an embodiment of the invention is illustrated. The reaction apparatus includes a first magnet 2 and a second magnet 4, which are spaced apart in a first dimension. These magnets may be permanent magnets and may be substantially identical, for example, identical in form or shape. For example, these magnets may be tubular (e.g., cylindrical) magnets arranged coaxially along a central axis extending in the first dimension.

[0107] The first and second magnets can each be axially magnetized such that their magnetic poles (in the direction along the central axis) are located at opposite ends of the magnets. The axial end of the first magnet closest to the second magnet preferably has a magnetic pole opposite to the magnetic pole at the axial end of the second magnet closest to the first magnet. That is, the first and second magnets are arranged from north to south, or from south to north. This allows the magnetic fields of the respective magnets to be aligned in the same direction, which enables the magnetic field lines to extend substantially parallel to the central axis over the relatively long length of the reaction device, as will be further described below.

[0108] The gasket 10 is axially positioned between the magnets and preferably in direct contact with them. The gasket may have the same form or shape as the magnet. For example, the gasket may be tubular (e.g., cylindrical) and arranged coaxially with the magnet along its central axis. The gasket is formed of a soft ferromagnetic material, such as steel.

[0109] The shims are arranged and configured to increase the uniformity of the magnetic field generated by the magnets in the volume surrounding the central axis of the reaction apparatus. The shims are arranged and configured such that, in the volume surrounding the central axis of the reaction apparatus, magnetic field lines from the upstream axial end of the first magnet 2 pass through the reaction apparatus to the downstream axial end of the second magnet 4 (or vice versa). Therefore, the magnetic field lines in the volume surrounding the central axis of the reaction apparatus are substantially parallel to the central axis over most of the length of the reaction apparatus. This is beneficial for maintaining the radial trapping of electrons, allowing them to react with the analyte ions, as will be discussed below.

[0110] like Figure 1 As illustrated, ferromagnetic spacers are included between the magnets such that the magnetic field lines are substantially parallel to the central axis over the relatively large volume and length of the reaction device. The magnetic field lines are substantially parallel to the central axis, even at radial distances relatively far from the central axis. Therefore, the spacers are configured to provide a uniform magnetic field along the central axis.

[0111] The reaction apparatus is configured to introduce electrons into a magnetic field within the apparatus, thereby confining the electrons by the magnetic field. The reaction apparatus may include a heated filament 12 for supplying free electrons into the reaction apparatus. The filament may extend into a magnetic field region within the reaction apparatus, allowing electrons to be released from the filament into the magnetic field region. Therefore, the filament may comprise a non-ferromagnetic material suitable for generating free electrons. The filament is preferably configured to release electrons into a uniform region of the magnetic field, such as at a location substantially at the central axis of the reaction apparatus. For example, the distal end of the filament may be positioned at the central axis of the reaction region.

[0112] The filament may be a substantially straight line having a loop 14 at its distal end. As will be discussed below, the addition of the loop allows at least some of the analyte ions to pass through the loop, and thus through the reaction apparatus, without being obstructed by the filament.

[0113] A voltage source 16 connected to the filament can be configured to supply current to the filament to heat its distal end and release electrons. Thus, the filament can generate low-energy free electrons, advantageously with the kinetic energy of the ECD approaching the thermal energy, or the kinetic energy of the EID being higher. As discussed above, the distal end of the filament can be positioned on the central axis of the reaction apparatus such that the electrons are confined by a magnetic field. More specifically, the electrons spiral around magnetic field lines arranged substantially parallel to the central axis. Therefore, the electrons are radially confined within the reaction apparatus to a volume arranged around the central axis.

[0114] To supply the filament into the interior of the reaction apparatus, a gasket may include holes through which the filament passes. The filament may be positioned orthogonal to the central axis. The holes may be machined into the gasket, which is relatively easy since the gasket is preferably made of steel. Furthermore, the gasket may be configured to conduct heat away from the filament and away from the magnet, which is advantageous because the magnet tends to lose its strength at high temperatures. This can be facilitated by providing a heat sink in direct contact with the gasket. An electrically insulating sheath may be provided around the filament to prevent current from flowing from the filament to the gasket. The sheath may extend beyond the radial inner wall of the gasket.

[0115] The reaction apparatus may also have electrodes and voltage sources (not shown) arranged and configured to generate a DC electric field within the reaction apparatus that helps confine electrons and / or guide or focus ions and / or ion-derived products through the apparatus. For example, the reaction apparatus may include a plurality of electrodes and voltage sources spaced along a first dimension, the voltage sources configured to apply a DC voltage to these electrodes to generate a DC electric field that confines electrons radially and / or axially (i.e., in the first dimension) within the reaction apparatus. For conductive materials, such as nickel-coated samarium cobalt or neodymium iron boron, magnets may also be used as electrodes.

[0116] The reaction apparatus includes an analyte inlet, which may be an orifice, for receiving analyte ions 18 into the reaction apparatus, such that the analyte ions are transported to a region where electrons are confined, thereby causing the analyte ions to react with electrons and dissociate to produce fragment ions and / or other product ions, such as analyte ions with reduced charge. As described above, electrons can be introduced into the reaction apparatus through a filament having an annular portion. Analyte ions can be introduced into the reaction apparatus along an axis passing through the annular portion (e.g., along a central axis) such that the filament does not interfere with at least some of the ions passing through the reaction apparatus.

[0117] The reaction apparatus also includes an outlet, which may be a hole, to allow debris or product ions to leave the reaction apparatus.

[0118] The inlet and outlet can be arranged such that the axis passing through them extends along a first dimension through the region in which electrons are trapped, for example, along the central axis of the reaction apparatus. Thus, analyte ions can be propelled into the inlet with sufficient energy in the first dimension, causing fragments and / or product ions derived from them to exit through the outlet.

[0119] The reaction apparatus may include multiple electrodes (not shown) for axially and / or radially confining analyte ions and / or electrons within the apparatus. For example, the multiple electrodes may form an ion director within the reaction apparatus. One or more DC voltages may be applied to the multiple electrodes to radially confine analyte ions in a dimension orthogonal to the first dimension. Alternatively or additionally, an RF voltage may be applied to the electrodes to increase the electron energy of the EID or to confine ions and / or electrons. However, for ECD, it is preferred that the electrodes be DC-only electrodes, i.e., no RF voltage is applied to the electrodes, such that the captured electrons are not excited by the RF electric field.

[0120] Figure 2 It was shown to be related to Figure 1 Another embodiment operates in the same manner as described, except that the first magnet 2, the second magnet 4, and the spacer 10 are replaced by a single tubular magnet 20. The magnet 20 is elongated in the first dimension and may be cylindrical.

[0121] The filament can be received through an inlet or outlet port, in which case the filament can extend at an angle to the central axis into the reaction apparatus, such that most of the filament is not arranged at the central axis and therefore does not interfere with the passage of analytes, debris, and / or product ions. As described above, the distal end of the filament may have an annular portion. The distal end of the filament can be located at any position along the central axis of the reaction apparatus, although it is advantageously located at approximately half the length of the reaction apparatus. Alternatively, it is conceivable that the filament can extend through a magnet into the reaction region, rather than through an inlet or outlet port, although this is less preferred.

[0122] In operation, electrons are generated along the central axis within the reaction apparatus using a long filament. As described above, the electrons are radially trapped as they spiral around the magnetic field lines, i.e., along the central axis. The density of trapped electrons eventually accumulates to a level sufficient to provide a reaction density with the analyte, such as an ECD reaction.

[0123] The analyte ions are also introduced into the reaction apparatus along the central axis through the inlet orifice. As the analyte ions pass through the reaction apparatus, they can react with electrons to produce fragment ions or product ions, such as analyte ions with reduced charge. The fragment or product ions, along with the analyte ions that have not yet reacted with electrons, then exit the reaction apparatus through the outlet orifice for mass analysis by a mass analyzer downstream of the reaction apparatus.

[0124] Figure 3a Examples Figure 2A schematic diagram of the upper part of the reaction device, wherein the magnet 20 has a length of 20 mm and an inner radius of 5 mm, that is, the ratio of length to inner radius is 20:5 (i.e., a ratio of 4). The region between the central axis of the magnet and the inner diameter is depicted as being divided by five longitudinal lines, each longitudinal line representing a different radial position in the magnet.

[0125] Figure 3b It shows that in the form of Figure 3a The longitudinal lines in the diagram indicate different radial locations along... Figure 3a The magnetic flux density of the length of the magnet. Specifically, Figure 3b The first peak on the left side indicates along the middle Figure 3a The magnetic flux density is represented by the first longitudinal line (i.e., along the central axis), the second peak represents the magnetic flux along the adjacent longitudinal line radially adjacent to the first longitudinal line, and so on.

[0126] like Figure 3b As shown, the magnetic flux density along the central axis is more uniform than the magnetic flux density at other radial locations away from the central axis. This is because the magnet is relatively long compared to its inner radius, i.e., it has a relatively high length-to-inner-radius ratio. In this embodiment, the magnet has a length of 20 mm and an inner radius of 5 mm. However, in other embodiments, the magnet can have different lengths and / or inner radii, and still provide a relatively high length-to-inner-radius ratio. For example, the magnet can have a length of at least 5 mm in the first dimension, but optionally not exceeding 100 mm. Therefore, the relatively high ratio provides a relatively uniform magnetic flux along the central axis. Magnets with a relatively high ratio can be used in embodiments in which electrons are injected into or generated within a reaction apparatus at a location along the central axis, such as... Figure 2 As shown. This helps to confine electrons more effectively.

[0127] Figure 4a Examples Figure 2 Another schematic diagram of the upper part of the reaction device, except that the magnet 20 has a length of 20 mm and an inner radius of 11 mm, that is, the ratio of length to inner radius is 20:11 (i.e., a ratio of 1.8). Here, the area between the central axis of the magnet and the inner diameter is depicted as being divided by eleven longitudinal lines, each longitudinal line representing a different radial position in the magnet.

[0128] Figure 4b It shows that in the form of Figure 4a The longitudinal lines in the diagram indicate different radial locations along... Figure 4a The magnetic flux density of the length of the magnet. (In relation to...) Figure 3b In a similar way, Figure 4b The first peak on the left side indicates along the middle Figure 4aThe magnetic flux density is represented by the first longitudinal line (i.e., at the central axis), the second peak represents the magnetic flux along the adjacent longitudinal line radially adjacent to the first longitudinal line, and so on.

[0129] like Figure 4b As shown, the magnetic flux density along the reaction device is most uniform in the ninth peak, i.e., in Figure 4a The radial location is indicated by the ninth longitudinal line. It has been found that as the ratio of the magnet's length to its inner radius decreases (e.g., below 3:1), the magnetic field along the reaction device becomes more uniform at radial locations further away from the central axis. For example, it has been found that for a magnet with a length-to-inner-radius ratio of 2.2, the magnetic field is most uniform at a radial location located at a distance of 55% of the inner radius from the central axis. In contrast, for... Figures 4a to 4b The magnet shown has a length-to-inner-radius ratio of 1.8 (i.e., 20:11). The magnetic field is most uniform at a radial location, which is located at a distance of 72% of the inner radius from the central axis.

[0130] In this scenario, when the magnet has a relatively low length-to-inner-radius ratio, electrons may not be introduced into or generated within the reaction apparatus at locations along the central axis. Instead, electrons can be introduced into or generated within the reaction apparatus at radial locations off-axis of the magnet. For example, electrons can be introduced or generated at radial locations along the most uniform magnetic flux of the apparatus. This helps to confine electrons more effectively.

[0131] Electrons can be introduced or generated at radial locations selected based on the ratio of the magnet's length to its inner radius. Alternatively, the ratio of the magnet's length to its inner radius can be selected based on the desired location for electron introduction or generation. In these embodiments with relatively low length-to-inner-radius ratios, it is still preferable that the magnet has a minimum length to provide a relatively large electron confinement / reaction area. For example, the magnet can have a length of at least 5 mm.

[0132] Figures 5a to 5c Showing about Figure 2 The described embodiment is the same as the view of the embodiment except that electrons are introduced into the reaction apparatus at a position radially outward relative to the central axis. For this purpose, the distal end of the filament is positioned radially outward relative to the central axis of the reaction apparatus.

[0133] As described above, for magnets with a relatively low length-to-inner-radius ratio (e.g., a ratio less than 3), the magnetic field of the magnet is stronger and more uniform closer to the radial inner wall of the magnet than along the central axis. Therefore, in this embodiment, electrons can be better confined by the magnet even at relatively high electron energies. Furthermore, this achieves axial trapping of electrons within the reaction region when the magnetic field lines converge at each axial end of the magnet.

[0134] As in other embodiments described above, electrons spiral around the magnetic field lines and thus move back and forth in the first dimension. Electrons are also capable of circumferentially drifting around the central axis at a substantially constant radial distance from it, such as... Figure 5b and Figure 5c As shown. Therefore, electrons remain radially confined within a relatively large toroidal volume within the magnet.

[0135] Analyte ions can be introduced into the reaction apparatus at any location, allowing them to interact with electrons trapped in the toroidal region. However, because electrons are trapped in the toroidal region, this allows analyte ions to be readily introduced into the reaction apparatus along axes that do not intersect with electron filaments. For example, as... Figure 5a and Figure 5c As shown, analyte ion 18 can be introduced into the reaction apparatus along an axis on the side opposite the location of the distal end of the filament on the central axis. This allows the filament to be positioned within the reaction apparatus without interfering with the introduction of the analyte ion. This is also true even if the filament extends into the reaction apparatus along an axis parallel to the central axis.

[0136] refer to Figure 5c The shielding member 22 can be positioned between the distal end of the filament and the path of the analyte ions to shield them from the electric field generated by the filament. For example, the shielding member can be positioned along the central axis of the reaction apparatus. The shielding member can have any form or shape. For example, the shielding member can be an elongated rod or plate. The shielding member can be formed of any non-ferromagnetic material.

[0137] Figures 6a to 6b A schematic diagram of a reaction apparatus according to another embodiment of the invention is illustrated. The reaction apparatus includes an elongated bar magnet 24, which may be a permanent magnet. The bar magnet may be planar or another linear shape. The bar magnet includes a north pole at one axial end and a south pole at the other axial end. The reaction apparatus also includes a filament 12 for generating electrons, which may have any of the features described with respect to the characteristics of a filament in the previous embodiments, such as an annular portion 14 through which the analyte ions 18 can pass.

[0138] like Figure 6aAs can be seen, the distal end of the filament is located relatively close to the bar magnet, causing the electrons generated therefrom to spiral along its magnetic field lines, and thus in accordance with the above regarding... Figures 5a to 5c The described method corresponds to the way electrons are trapped relative to a magnet (except that a bar magnet traps electrons in a curved plane rather than a toroidal volume). The analyte ion 18 then passes through the region in which the electrons are trapped, which may pass through the toroidal end of the filament or along the axis that does not pass through the filament.

[0139] The reaction apparatus may also include electrodes for focusing or otherwise guiding ions and / or electrons. For example, the reaction apparatus may include a first electrode 26, a second electrode 28, and a third electrode 30, which, together with a magnet 24, form a conduit through which the analyte ions pass. The third electrode may have a planar surface spaced apart from and facing the magnet. The first and second electrodes may be located between the magnet and the third electrode. The first and second electrodes may be planar, wherein their main surfaces are positioned spaced apart from each other and, for example, parallel to each other.

[0140] The electrodes can be formed from any suitable non-ferromagnetic material.

[0141] Any of the first, second, or third electrodes may include a hole through which the filament passes. However, in other embodiments, the filament may enter the reaction region through an inlet or outlet hole for the entry or exit of analyte ions, respectively.

[0142] The distal end of the filament can be positioned along the central axis of the reaction device or closer to the bar magnet. Then, as described above, an electric current is passed through the distal end of the filament, causing electrons to be released from the distal end and captured along the magnetic field lines.

[0143] Analyte ions are introduced into the reaction apparatus, and a DC voltage is applied to the first, second, and third electrodes to generate a DC electric field that guides the analyte ions through the regions where electrons reside. A voltage can also be applied to magnet 24 to aid in ion guidance, for example, causing the magnets and electrodes 26 to 30 to provide a quadrupole ion guide.

[0144] It is conceivable that the electrodes can be segmented along the central axis and different voltages can be applied to them to drive ions through the reaction apparatus. Additionally or alternatively, the electrodes can be angled relative to each other or to a magnet to drive ions through the reaction apparatus.

[0145] Although the electrodes are described as planar electrodes, they may alternatively have other geometries, such as rod electrodes.

[0146] Figure 7 Showing about Figure 2Another embodiment of the same implementation described herein differs in that the magnet is formed by a plurality of magnets 32 stacked together in a first dimension, wherein at least some of the magnets are electrically insulated from each other, such that different DC or RF voltages can be applied to the different magnets. Some of the adjacent magnets may not be electrically insulated from each other, such that they remain at the same potential. Each of the plurality of magnets may be identical in form or shape.

[0147] The reaction apparatus may also include a filament (not shown) for generating electrons, which may have any of the features of a filament described with respect to the previous embodiments, such as an annular portion through which analyte ions can pass. The filament can be supplied into the interior of the reaction apparatus through a hole in one of the electrically insulators arranged between adjacent magnets, for example, to... Figure 1 A similar approach.

[0148] The magnets are arranged such that any pair of directly adjacent magnets have opposite magnetic poles at their facing ends. Therefore, the magnetic field generated by multiple magnets is substantially the same as that generated by a single elongated magnet. However, a voltage can be applied to the magnets, for example, to control the movement of ions within them. For instance, a voltage can be applied to the magnets so that they operate as electrostatic lenses. That is, multiple magnets can be configured to focus analyte ions as they pass through the reaction apparatus.

[0149] The reaction apparatus may have a voltage source configured to apply different DC voltages to different corresponding (electrically insulated) magnets in a plurality of magnets to generate an electric field that focuses analyte ions in a first dimension and / or confines analyte ions in a dimension orthogonal to the first dimension.

[0150] Different voltage sources can be configured to apply different DC voltages to different corresponding (electrically insulated) magnets within multiple magnets to generate one or more secondary potentials, thereby axially trapping analyte ions and / or electrons within the reaction apparatus. In this way, multiple magnets can operate as ion and / or electron traps (e.g., penning traps). By trapping analyte ions along with electrons, the efficiency of ion-electron reactions can be improved.

[0151] Additionally or alternatively, different voltage sources may be configured to continuously apply instantaneous voltages to a series of (electrically insulated) magnets in a plurality of magnets to repeatedly travel a DC potential along the reaction apparatus, for example to increase the energy of trapped electrons or force ions through the reaction apparatus. This may be desirable, for example, during EID.

[0152] Additionally or alternatively, an RF voltage may be applied to the magnet, for example, to increase the energy of electrons and / or confine ions.

[0153] The reaction apparatus described herein is advantageously maintained at a pressure below atmospheric pressure, for example, to make the collision rate between the background gas and electrons relatively low. However, the gas pressure within the reaction apparatus can also be high enough to help reduce the thermal energy of the electrons trapped therein and / or the thermal energy of the analyte ions introduced into the reaction apparatus. Therefore, the gas pressure in this region can be 10... -7 millibars to 10 -1 Between millibars. The gas can be an inert gas.

[0154] Figure 8 A schematic diagram of an embodiment of a mass spectrometer including the reaction apparatus as described herein is shown. The spectrometer includes an ion source 70 and a reaction apparatus 72. The ion source may be an electrospray ionization (ESI) ion source. Any other type of ion source may be used instead of an ESI ion source, but an ion source that generates analyte ions with a high charge state is preferred. The analyte ions generated in the ion source, or ions derived therefrom, are transferred to the reaction apparatus. The ions may be filtered, for example, in a quadrupole mass filter 74, and / or separated by mobility in an ion mobility separator 76 before entering the reaction apparatus. The quadrupole mass filter 74 and the ion mobility separator 76 may be arranged in any order. The ions transferred to the reaction apparatus react with electrons therein, for example via an ECD or EID reaction, to produce fragment or product ions, such as charge-reduced analyte ions. These ions may be ejected or released from the reaction apparatus and transferred downstream for analysis. For example, these ions may be analyzed to determine their ion mobility through the ion mobility separator 78 and / or their mass-to-charge ratio may be determined using a mass analyzer 80 downstream of the reaction apparatus.

[0155] Although embodiments in which the captured electrons react with analyte ions have been described, it is conceivable that the captured electrons may alternatively or additionally react with background gas molecules in the reaction apparatus to ionize these gas molecules and form radical or non-radical cations and anions, for example, via electron collision ionization (EI). Based on knowledge of what the gas comprises, the types of cations and anions generated can be predicted, and thus the true mass-to-charge ratio of such ions can be known. Therefore, these cations or anions can be mass-analyzed by the same mass analyzer used for mass analysis of fragment or product ions, and can thus be used as calibration or lock-in mass ions for the calibration of the mass analyzer, i.e., for correcting the mass-to-charge ratio of ions detected by the mass analyzer. Alternatively, radical or non-radical cations and anions may be captured in the reaction region and react with analyte ions, for example, via ETD.

[0156] Embodiments in which the analyte ions have opposite polarity to the electrons to produce a reaction have been described. For example, the reaction can be ECD or EID, in which a positive analyte ion reacts with a negative electron. However, the invention is also applicable to reactions between analyte ions having the same polarity as the electrons, for example, to electron separation and dissociation (EDD) reactions between a negative analyte ion and a higher-energy electron.

[0157] Although the invention has been described with reference to various embodiments, those skilled in the art will understand that various changes in form and detail may be made without departing from the scope of the invention as set forth in the appended claims.

Claims

1. An ion-electron reaction device, the ion-electron reaction device comprising: First tubular magnet; A second tubular magnet is arranged coaxially with the first tubular magnet. and A gasket, the gasket being located between the first tubular magnet and the second tubular magnet; The spacers are arranged and configured such that the first tubular magnet and the second tubular magnet provide a substantially uniform magnetic field along the central axis of the device.

2. The reaction apparatus of claim 1, wherein the uniform magnetic field has magnetic field lines extending from the first tubular magnet to the second tubular magnet within a volume arranged around the central axis, wherein the magnetic field lines are substantially linear and parallel to the central axis for at least 30% of the length of the reaction apparatus.

3. The reaction apparatus according to claim 1 or 2, wherein the first tubular magnet is arranged such that its north magnetic pole is adjacent to the gasket, and the second tubular magnet is arranged such that its south magnetic pole is adjacent to the gasket; or the first tubular magnet is arranged such that its south magnetic pole is adjacent to the gasket, and the second tubular magnet is arranged such that its north magnetic pole is adjacent to the gasket.

4. The reaction apparatus according to claim 1, 2 or 3, wherein the reaction apparatus includes an electron generator arranged to generate free electrons and supply the free electrons to the location of the uniform magnetic field.

5. The reaction apparatus of claim 4, wherein the electron generator comprises a voltage source and a filament, the voltage source and the filament being arranged and configured to generate the free electrons.

6. The reaction apparatus of claim 5, wherein the filament is arranged such that it has a distal end disposed on the central axis; or wherein the filament is formed into a loop at its distal end, wherein the loop surrounds the central axis.

7. The reaction apparatus according to claim 5 or 6, wherein the wire passes through a hole in the gasket.

8. The reaction apparatus according to any one of claims 5 to 7, the reaction apparatus comprising a heat sink in contact with the gasket for transferring heat from the filament out of the gasket and to the heat sink.

9. The reaction apparatus according to any of the preceding claims, wherein the reaction apparatus is configured to receive analyte ions such that they travel substantially along the central axis.

10. The reaction apparatus according to any preceding claim, the reaction apparatus comprising electrodes and one or more voltage sources configured to apply one or more DC voltages to the electrodes to generate a DC electric field for confining electrons radially about the central axis and / or axially along the central axis; and / or It includes electrodes and one or more voltage sources configured to apply one or more DC and / or RF voltages to the electrodes to generate DC and / or RF electric fields for confining ions radially around the central axis and / or axially along the central axis.

11. An ion-electron reaction device, said ion-electron reaction device comprising: A long, thin tubular magnet having a length of at least 5 mm; and An electron generator, the electron generator being arranged to supply free electrons to a location within the tubular magnet; in: (i) The electron generator is arranged to supply free electrons to a position within the tubular magnet substantially along the central longitudinal axis of the tubular magnet, wherein the ratio of the length to the inner radius of the tubular magnet is ≥3; or (ii) The electron generator is arranged to supply free electrons to a position within the tubular magnet that is radially outward relative to the central longitudinal axis of the tubular magnet, wherein the ratio of the length to the inner radius of the tubular magnet is <3.

12. The reaction apparatus of claim 11, wherein the tubular magnet is configured to produce a substantially linear, uniform magnetic field along its central axis, wherein the uniform magnetic field has magnetic field lines extending from one end of the tubular magnet to the other end of the tubular magnet within a volume arranged around the central axis, wherein the magnetic field lines are substantially linear and parallel to the central axis for at least 30% of the length of the tubular magnet.

13. The reaction apparatus according to claim 11 or 12, wherein the electron generator comprises a voltage source and a filament, the voltage source and the filament being arranged and configured to generate free electrons on or around the central axis passing through the tubular magnet.

14. The reaction apparatus according to claim 11, 12 or 13, wherein the tubular magnet is configured to have a length such that a substantially linear, uniform magnetic field is provided along the magnet in the entire annular region between the central axis of the tubular magnet and the inner wall; wherein the uniform magnetic field has magnetic field lines extending from one end of the tubular magnet to the other end of the tubular magnet in the annular region, wherein the magnetic field lines are substantially linear and parallel to the central axis for at least 30% of the length of the tubular magnet.

15. The reaction apparatus of claim 14, the reaction apparatus comprising an electron generator having a voltage source and a filament, the voltage source and the filament being arranged and configured to generate free electrons in the annular region.

16. The reaction apparatus of claim 15, wherein the reaction apparatus is configured to receive analyte ions in the annular region such that the ions travel along an axis that does not intersect the filament.

17. The reaction apparatus of claim 16, wherein the ions are arranged along the axis of their travel on a side opposite to the side where the filament is located, passing through the central axis of the magnet.

18. The reaction apparatus according to claim 16 or 17, the reaction apparatus comprising a shielding member positioned between the axis along which the ions travel and the filament for shielding the analyte ions from the electric field generated by the filament.

19. An ion-electron reaction apparatus, said ion-electron reaction apparatus comprising: Multiple tubular magnets are stacked coaxially together, with an electrical insulator located between them; and One or more voltage sources are configured to apply a voltage to one or more magnets in the magnet.

20. An ion-electron reaction device, the ion-electron reaction device comprising: A magnet having a substantially flat planar surface; and An electron generator for supplying free electrons; The reaction device is configured such that a magnetic field from the magnet confines the free electrons to a region adjacent to the planar surface.

21. The reaction apparatus according to claim 20, wherein the magnet is a bar magnet.

22. A mass spectrometer, the mass spectrometer comprising: The reaction apparatus according to any of the preceding claims; and An ion source is arranged to supply analyte ions to the reaction apparatus.

23. A method for mass spectrometry analysis, the method comprising: Provide a mass spectrometer according to claim 22; Ions are supplied from the ion source to the reaction apparatus; as well as Electrons are provided in the reaction apparatus so that they react with the ions.

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