Tof mass spectrometer operating in negative mode

Abstract

In one aspect, a time-of-flight (TOF) mass analyzer is disclosed that includes an input for receiving a plurality of ions (also referred to herein as "primary ions"); an ion acceleration region through which the received ions are accelerated; a repelling electrode for directing the received ions into the ion acceleration region; and a field-free ion drift region for receiving the accelerated ions, the field-free ion drift region having an ion detector positioned at a distal end thereof. At least one magnet is positioned relative to the field-free region so as to establish a magnetic field in at least a portion of the field-free region for deflecting electrons entering the field-free region so as to suppress the electrons from reaching the ion detector.

Description

[0001] Related applications

[0002] This application claims priority to U.S. Provisional Application No. 63 / 608,438, filed December 11, 2023, entitled “TOF Mass Spectrometer Operated in Negative Mode,” which is incorporated herein by reference in its entirety. Technical Field

[0003] This disclosure generally relates to systems and methods for performing mass spectrometry analysis, and more specifically, to such systems and methods utilizing time-of-flight (ToF) mass analyzers. Background Technology

[0004] This disclosure provides systems and methods for performing mass spectrometry analyses, and in particular, such systems and methods that allow for higher sensitivity and throughput in mass spectrometers using time-of-flight (TOF) mass analyzers.

[0005] Mass spectrometry (MS) is an analytical technique used to determine the structure of chemical substances being tested, with both qualitative and quantitative applications. MS can be used to identify unknown compounds, determine the elemental composition of molecules, determine the structure of compounds by observing their fragmentation, and quantify the amount of a specific chemical compound in a mixed sample. Mass spectrometers detect chemical entities as ions, necessitating the conversion of the analyte into charged ions.

[0006] Time-of-flight mass spectrometry (TOF-MS) relies on different arrival times to separate ions with different m / z ratios. In such systems, the mass analyzer accelerates ions by passing them through a region where an electric field imbues them with kinetic energy. The accelerated ions then enter a field-free ion drift region, where they travel towards the ion detector for detection. The time required for an ion to reach the ion detector from the drift region depends on its m / z ratio, thus allowing ion separation based on its m / z ratio.

[0007] In some applications, particularly in the analysis of negatively charged ions, the transit of ions through a TOF mass analyzer can generate electrons. These electrons can reach the ion detector of the TOF mass analyzer and produce noise in the ion detection data, for example, in the form of continuous bulges in the resulting mass spectrum. Summary of the Invention

[0008] In one aspect, a time-of-flight (TOF) mass analyzer is disclosed, comprising: an input of a plurality of ions (also referred to herein as “primary ions”); an ion acceleration region through which the received ions are accelerated; a repulsion electrode for guiding the received ions into the ion acceleration region; and a field-free ion drift region for receiving the accelerated ions. An ion detector is positioned at a distal end of the field-free ion drift region. At least one magnet is positioned relative to the field-free region to establish a magnetic field in at least a portion of the field-free region for deflecting electrons entering the field-free region to suppress electrons from reaching the ion detector. In various embodiments, the magnet may be a permanent magnet. In other embodiments, an electromagnet or a combination of a permanent magnet and an electromagnet may be utilized.

[0009] In some embodiments, the plurality of ions includes negatively charged ions. Negatively charged ions may carry a single charge or multiple charges.

[0010] In some embodiments, the ion acceleration region extends from the repulsion electrode to the first grid electrode (also referred to herein as the "grid electrode"). For example, applying a voltage difference between the repulsion electrode and a DC bias voltage applied to a field-free region (e.g., the electrode of the ion acceleration region) can generate an electric field to accelerate ions received by the mass analyzer to a target energy, such as to an energy in the range of about 5 keV to about 20 keV.

[0011] In some embodiments, the first ion mirror is positioned downstream of the ion acceleration region and separated from the ion acceleration region via a portion of the field-free region. In some such embodiments, the first ion mirror may include at least a second grid electrode. Not limited to any particular theory, in some cases, collisions between negatively charged ions accelerated by the ion acceleration region of a TOF mass analyzer and one or more grid electrodes of the ion mirror may generate secondary positive ions or electrons. The impact of such secondary positive ions on the mirror plate of the ion mirror can then generate electrons, which are accelerated via the potential difference between the mirror plate and one or more grid electrodes and directed toward the ion detector.

[0012] In some embodiments, the magnet can generate a magnetic field of magnitude ranging from about 0.5 mT to about 100 mT in the portion of the field-free region. For example, in some embodiments, the magnitude of such a magnetic field can be in the range of about 1 mT to about 10 mT, or in the range of about 10 mT to about 20 mT, or in the range of about 20 mT to about 30 mT, or in the range of about 30 mT to about 40 mT, or in the range of about 40 mT to about 50 mT, or in the range of about 50 mT to about 60 mT, or in the range of about 60 mT to about 70 mT, or in the range of about 70 mT to about 80 mT, or in the range of about 80 mT to about 90 mT, or in the range of about 90 mT to about 100 mT.

[0013] Typically, the direction of the magnetic field is not parallel to the overall propagation direction of ions through the field-free region. For example, in various embodiments, the direction of the magnetic field is not parallel to the longitudinal axis of the field-free region, but forms a non-zero angle with it. For example, in many embodiments, the direction of the magnetic field is orthogonal to the overall propagation direction of ions through the magnetic field region in order to optimize the magnitude of the force applied to the electrons, thereby promoting electron redirection and thus preventing them from reaching the downstream ion detector.

[0014] A TOF mass analyzer may include a housing (also referred to herein as a “liner”) that provides a chamber (also referred to herein as a cavity) in which various components of the TOF mass analyzer are positioned. In some embodiments, a magnet may be positioned outside the cavity. In other embodiments, the magnet may be positioned inside the cavity.

[0015] The position of the magnet relative to the ion detector can vary in different embodiments and can be selected based on this teaching to provide sufficient deflection of electrons to reduce and preferably eliminate noise artifacts generated in the resulting mass spectrum due to electrons. For example, in some embodiments, the linear separation between the center of the magnet and the ion detector can be greater than 2 / 3 of the linear distance between the last ion mirror and the downstream ion detector.

[0016] In some embodiments, more than one magnet can be used to alter the propagation direction of electrons in order to suppress their arrival at the ion detector. For example, at least two magnets can be used that are axially and / or radially separated from each other. In such embodiments, the magnitudes of the magnetic fields generated by the magnets can be the same or different. In some embodiments, multiple magnets can be positioned relative to each other to generate a magnetic field gradient along the portion of the (no)electric field region where a magnetic field is applied. For example, such a magnetic field gradient can provide a magnetic field of decreasing magnitude from the last ion mirror to the ion detector.

[0017] In a related aspect, a method for operating a time-of-flight (TOF) mass analyzer is disclosed, the method comprising: introducing a plurality of ions (also referred to herein as “primary ions”) into the time-of-flight (TOF) mass analyzer; accelerating the ions in an ion acceleration region to generate accelerated ions; introducing the accelerated ions into the fieldless ion drift region at a proximal end of the fieldless ion drift region for incident on an ion detector located at a distal end of the fieldless ion drift region; and applying a magnetic field to at least a portion of the fieldless ion drift region to deflect electrons entering the fieldless ion drift region in order to suppress electrons from reaching the ion detector.

[0018] In some embodiments, the ions may be negatively charged ions, including ions with a single charge or multiple charges.

[0019] Generally, a magnetic field includes at least one field component having a direction orthogonal to the overall propagation direction of ions through the magnetic field.

[0020] In some embodiments, the magnitude of the magnetic field (or at least a component of it orthogonal to the overall propagation direction of the ions through the magnetic field region) may be in the range of about 0.5 mT to about 100 mT, or any subrange within this range, such as in the range of about 1 mT to about 10 mT, or in the range of about 10 mT to about 20 mT, or in the range of about 20 mT to about 30 mT, or in the range of about 30 mT to about 40 mT, or in the range of about 40 mT to about 50 mT, or in the range of about 50 mT to about 60 mT, or in the range of about 60 mT to about 70 mT, or in the range of about 70 mT to about 80 mT, or in the range of about 80 mT to about 90 mT, or in the range of about 90 mT to about 100 mT.

[0021] In some embodiments, the magnetic field may be substantially uniform within said at least a portion of the field-free region. Alternatively, the magnetic field may be non-uniform within said at least a portion of the field-free region (e.g., it may exhibit non-uniform magnitude). For example, but not as a limitation, a varying magnetic field may be characterized by a magnetic field gradient exhibiting a magnitude that decreases from the proximal end of the field-free region to the ion detector.

[0022] As described above, although in some embodiments the magnetic field may be generated by one or more magnets located outside the field-free region, in other embodiments the magnetic field may be generated by one or more magnets located within the field-free region.

[0023] A further understanding of the various aspects of this teaching can be obtained by referring to the following description in conjunction with the associated figures briefly described below. Attached Figure Description

[0024] Figure 1 This is a flowchart depicting the various steps of a method for operating a TOF quality analyzer according to an embodiment of this teaching.

[0025] Figure 2A This is a schematic side view of a TOF quality analyzer according to an embodiment of this teaching.

[0026] Figure 2B Depicting in Figure 2A The image shows an axial view of a portion of the field-free region of a TOF mass analyzer, illustrating several magnetic field lines associated with a magnet positioned outside the field-free region of the TOF mass analyzer.

[0027] Figure 3AThis is a side view schematic diagram of a TOF mass analyzer according to an embodiment, wherein three magnets are used to deflect electrons to suppress their arrival at the downstream ion detector of the TOF mass analyzer.

[0028] Figure 3B This illustrates a hypothetical magnetic field gradient that can be established in a field-free region of a TOF mass analyzer according to an embodiment of this teaching.

[0029] Figure 3C This is a side view schematic diagram of a TOF mass analyzer according to an embodiment, which includes a magnet positioned within the chamber of the TOF mass analyzer.

[0030] Figure 3D This is a side view schematic diagram of a TOF mass analyzer according to another embodiment, wherein two radially separated magnets are used to deflect electrons to suppress their arrival at the downstream ion detector.

[0031] Figure 4A This is a schematic side view showing the path of negative ions through the ion mirror and the generation of secondary positive ions through collisions between primary ions and the grid electrodes of the ion mirror, where the secondary positive ions cause the generation of electrons from the mirror plate of the ion mirror.

[0032] Figure 4B The use of two ion mirrors (e.g.) is shown. Figure 2A The background noise measured by the TOF mass analyzer (shown in the diagram), and the timing associated with the various components of the ion mirror as ions pass through, where secondary particles are generated,

[0033] Figure 5A The mass spectra of product ions associated with precursor ions obtained using a TOF mass analyzer, but without applying a magnetic field to the field-free region of the mass analyzer, are shown.

[0034] Figure 5B This illustrates the use of the same TOF mass analyzer, but with an 8 mT magnetic field applied to the field-free region of the mass analyzer, yielding results similar to those obtained from other methods. Figure 5A Mass spectra of product ions with the same product ions.

[0035] Figure 6 A TOF mass analyzer with an ion detector having four ion detection channels is schematically depicted. This TOF mass analyzer is used to generate... Figure 6 The data shown in A-6X,

[0036] Figure 6 A–6X exhibits a precursor ion (sodium trifluoroacetic acid cluster: C) with m / z = -792. 12 HO 12 F 18Mass spectra of Na5 and its associated product ions with CID products under no magnetic field and with different magnetic field strengths.

[0037] Figure 7 The calculated trajectory of an 8 keV electron during its transit from the second ion mirror of the TOF mass analyzer depicted in Figure 2 to its ion detector is shown under different magnetic field conditions.

[0038] Figure 8A It shows the use of similar Figure 2A The electron noise bulge spectrum obtained by the TOF mass analyzer shown in the figure is that the ion is sodium trifluoroacetic acid, and

[0039] Figure 8B It shows Figure 8A The normalized “bulge” intensity of each region is shown in the spectrum. Detailed Implementation

[0040] It should be understood that, for clarity, the following discussion will set forth various aspects of embodiments of the applicant's teachings, while omitting certain specific details where convenient or appropriate. For example, the discussion of similar or analogous features in alternative embodiments may be slightly simplified. For the sake of brevity, well-known ideas or concepts may also not be discussed in detail. Those skilled in the art will recognize that some embodiments of the applicant's teachings may not require certain specifically described details in each implementation, and these details are set forth herein only to provide a thorough understanding of these embodiments. Similarly, it will be apparent that the described embodiments can be readily changed or varied based on common general knowledge without departing from the scope of this disclosure. The following detailed description of the embodiments should not be construed as limiting the scope of the applicant's teachings in any way.

[0041] As used herein, the terms “about” and “substantially equal to” refer to variations in numerical quantities that may occur, for example, through real-world measurement or processing procedures, unintentional errors in these procedures, differences in the manufacture, origin, or purity of the composition or reagent, etc. Generally, the terms “about” and “substantially” as used herein mean 10% greater or less than the value or range of values ​​or complete conditions or states thereof. For example, a concentration value of about 30% or substantially equal to 30% could represent a concentration between 27% and 33%. The terms also refer to variations that would be considered equivalent by those skilled in the art, provided that such variations do not cover known values ​​practiced in the prior art.

[0042] As used herein, the term “and / or” includes any and all combinations of one or more of the associated listed items and may be abbreviated as “ / ”.

[0043] This document uses various terms according to their common meaning in the art. The terms “field-free region” and “field-free ion drift region” and “field-free region” and “field-free ion drift region” are used interchangeably to refer to a region in a TOF mass analyzer where no electric field exists or where any electric field that may exist is not strong enough to cause any significant change in the trajectory of ions passing through the field-free region. For example, any electric field that may exist in the field-free region will have a magnitude less than about 10 V / mm. As discussed herein, in various embodiments, a magnetic field may be applied to the field-free region to cause electrons present in this region to deflect from their original propagation path in order to suppress their arrival at the downstream ion detector.

[0044] The terms “grid electrode” and “grid electrode” are used interchangeably herein to refer to a conductive electrode having an opening through which ions can pass.

[0045] When a Time-of-Flight (TOF) mass analyzer is used to analyze negatively charged ions, ions passing through the analyzer may collide with one or more grid electrodes. In some cases, such collisions result in the generation of high-energy electrons. Alternatively or additionally, collisions between ions entering the mass analyzer and the grid electrodes may generate secondary ions (typically lighter ions), which may then collide with one or more grid or plate electrodes of the mass analyzer to generate electrons (e.g., causing electrons to be ejected from metal electrodes). At least some of these electrons may reach the ion detector, where they can introduce noise into the mass spectrometry data.

[0046] For example, such as Figure 5A As observed, in some cases, background noise generated by electron-bombarded ion detectors can manifest as continuous bulges in the mass spectrum. Such bulges in the mass spectrum can make the identification of certain mass signals difficult or even impractical. Specifically, in mass spectra obtained via electron activated dissociation (EAD), the mass signal associated with the product ions may be very weak. In such cases, noise artifacts (e.g., Figure 5A The bulges shown in the mass spectrum may interfere with the identification of such weak signal segments.

[0047] As discussed in more detail below, in various embodiments, a magnetic field is established in at least a portion of the fieldless ion drift region of the TOF mass analyzer to deflect electrons entering that region, thereby suppressing electron impacts on the ion detector of the mass analyzer. This deflection of electrons can reduce and preferably eliminate noise that might otherwise be generated by electron impacts on the ion detector.

[0048] Figure 1This is a flowchart depicting the various steps of an embodiment of a method for operating a time-of-flight (TOF) mass analyzer according to this teaching, wherein multiple ions (also referred to herein as "primary ions") are introduced into the mass analyzer, and the ions are accelerated to generate multiple accelerated ions. For example, but not as a limitation, the ions can be accelerated to energies in the range of about 5 keV to about 20 keV. The accelerated ions are introduced into the drift region at the proximal end of the field-free ion drift region, such that the accelerated ions can travel through the field-free region to be received by an ion detector positioned at the distal end of the field-free region. A magnetic field may be applied to at least a portion of the field-free region to deflect electrons entering the field-free region (if any) in order to suppress electrons from reaching the ion detector.

[0049] In some embodiments, the magnetic field may exist throughout the entire volume of the field-free region. In other embodiments, the magnetic field may exist only within a portion of the field-free region. For example, the magnetic field may exist within a portion of the field-free region extending from its proximal end (e.g., the end where the last ion mirror of a TOF mass analyzer is located) to the boundary between the last ion mirror and the ion detector. In other words, this portion of the field-free region from the boundary to the ion detector may substantially contain neither an electric field nor a magnetic field.

[0050] Generally, the magnetic field does not exhibit abrupt transitions between the two portions of a field-free region (where the intention is only to establish a magnetic field in one of the portions). In some cases, the transition of the magnetic field between the two portions of the field-free region can be characterized by a gradient (e.g., a linear gradient). Furthermore, in some embodiments, the magnetic field can be substantially uniform within at least a small portion of the field-free region in which the magnetic field is applied.

[0051] In various embodiments, the magnetic field has at least one component orthogonal to the general axial direction along which ions propagate through the field-free region (e.g., along the longitudinal axis of the field-free region, or along a direction forming an angle with the longitudinal axis). The magnitude of the magnetic field can be selected based on the specific application to cause sufficient deflection of electrons to prevent electrons, or at least most electrons, from impacting the ion detector. For example, but not as a limitation, the magnitude of the magnetic field can range from about 0.5 mT to about 100 mT, or any subrange within this range.

[0052] In various embodiments, the primary ion is a negatively charged ion. For example, but not as a limitation, such a negatively charged ion may carry a single charge or multiple charges.

[0053] The methods according to the various embodiments of this teaching can be implemented in a variety of different types of TOF mass analyzers, particularly TOF mass analyzers that include ion mirrors.

[0054] For example, Figure 2A A TOF mass analyzer 100 according to an embodiment is schematically depicted, comprising a housing 101 (also referred to herein as a “liner”) that encloses a evacuated chamber (also referred herein as a cavity) 101a in which various components of the TOF mass analyzer are disposed. The cavity can be characterized by a longitudinal axis (LA) and an orthogonal radial (transverse) axis (TA) extending between the proximal and distal ends of the cavity 101a.

[0055] The TOF mass analyzer includes an inlet 102 for receiving multiple ions and a repulsion electrode 104 for guiding the received ions into an ion acceleration region 106 of the mass analyzer, in which the ions may experience an electric field capable of accelerating them. For example, multiple voltage pulses can be applied to the repulsion electrode to guide ions arriving at the repulsion electrode into the ion acceleration region. The ion acceleration region 106 may include multiple electrodes maintained at a potential with a uniform gradient (or slope) to generate an electric field for inducing ion acceleration. For example, but not as a limitation, ions can be accelerated to kinetic energies in the range of about 5 keV to about 20 keV.

[0056] Ions are accelerated to travel through the fieldless ion drift region 108 of the mass analyzer to reach a first ion mirror 110, which includes a plurality of grid electrodes 110a and a mirror plate electrode 110b. The grid electrodes and the mirror plate electrode are maintained at appropriate potentials in a manner known in the art to slow down the received ions and reverse their propagation direction to propagate to a second ion mirror 112. Similar to the first ion mirror 110, the second ion mirror 112 includes a plurality of grid electrodes 112a and a mirror plate electrode 112b, also causing a reversal of the ion propagation direction to guide the ions to an ion detector 114, which is positioned at the distal end of the fieldless ion drift region of the TOF mass analyzer. The ion detector can generate an ion detection signal in response to ion incident thereon, wherein the ion detection signal can be processed by an analysis module (not shown) to generate a mass spectrum of the ions incident on the ion detector.

[0057] Continue to refer to Figure 2A In this embodiment, a magnet 116 in the form of a permanent magnet is positioned outside the chamber 101 of the TOF mass analyzer, i.e. outside the fieldless region, to generate a magnetic field in at least a portion of the fieldless ion drift region upstream of the ion detector.

[0058] As an example Figure 2B An example of magnetic field lines generated by magnet 116 within a portion of a fieldless ion drift region is shown. Electrons passing through the magnetic field may experience a force (commonly referred to as the Lorentz force), which is proportional to the cross product of the electron's charge and velocity with respect to the applied magnetic field, as shown in the following equation: Equation (1) in, F represents the force vector applied to the electron. q represents the charge of the electron. V represents the velocity vector associated with the electron. B represents the magnetic field vector, and x represents the cross product of the force and magnetic field vectors.

[0059] The magnetic field lines have a component that is not parallel to the direction of electron propagation, ensuring that a deflecting force is applied to the electron passing through the magnetic field. As can be seen from equation (1) above, the Lorentz force generated by the magnetic field on the electron is in a direction perpendicular to the direction of electron motion, thus deflecting the electron from its initial propagation path. In other words, the force applied to the electron by the electron passing through the magnetic field will deflect the electron from its initial propagation path, thus preventing the electron from reaching the downstream ion detector.

[0060] While the above embodiments use a single magnet to deflect electrons, in other embodiments, two or more magnets can be used to deflect electrons passing through the fieldless ion drift region of the TOF mass analyzer. For example, Figure 3A An example of such a TOF mass analyzer 200 is schematically depicted, which is similar in structure to the TOF mass analyzer 100 discussed above, having an ion acceleration stage 202, two ion mirrors 204 / 206 and an ion detector 208 disposed in a vacuum chamber 210.

[0061] While the TOF mass analyzer 100 described above includes a single magnet for deflecting electrons generated in the TOF mass analyzer, the TOF mass analyzer 200 includes three magnets 212a, 212b, and 212c (collectively referred to herein as magnet 212) positioned outside a evacuated chamber of the mass analyzer. The magnetic fields generated by these magnets are superimposed within a portion of a field-free ion drift region to produce a resulting magnetic field that can deflect electrons passing through the field-free region. In some embodiments, the magnitude of the magnetic field generated by each magnet is substantially similar to the corresponding magnitude of the magnetic field generated by any of the other magnets. In other embodiments, the strength of the magnetic fields generated by two or more magnets may differ.

[0062] In some embodiments, the resulting magnetic field generated by a plurality of magnets can provide, for example, a magnetic field gradient extending from the second ion mirror to the ion detector. As an example, Figure 3B The illustration schematically depicts a hypothetical example of such a magnetic field gradient that decreases substantially linearly from the second ion mirror to the ion detector in an example of an implementation of a TOF mass analyzer according to this teaching. In other embodiments, the magnetic field gradient may have a non-linear distribution.

[0063] As an additional example Figure 3C A TOF mass analyzer 300 according to another embodiment is schematically depicted, similar to the TOF mass analyzer 100 discussed above, except that in the mass analyzer 300, the magnet 310 for deflecting electrons to prevent them from reaching the ion detector of the mass analyzer is positioned inside the chamber of the mass analyzer, rather than outside the chamber. Specifically, the TOF mass analyzer 300 includes a housing 302 that surrounds a chamber (vacuum chamber) in which an ion acceleration region 304, two ion mirrors 306a / 306b, and an ion detector 308 are disposed. The magnetic field generated by the magnet 310 can deflect electrons from the path that would otherwise reach the ion detector 308.

[0064] also, Figure 3D A TOF mass analyzer 314 according to another embodiment is shown, which includes two magnets 316a / 316b separated from each other in a radial direction, i.e., in a direction orthogonal to the longitudinal axis of the mass analyzer chamber. In various embodiments, the magnetization directions of the two magnets are parallel. Other components of the TOF mass analyzer 314 and their arrangement are the same as those in the mass analyzer 300. Although in this embodiment both magnets 316a / 316b are located outside the chamber of the mass analyzer, in other embodiments, one or both of these magnets 316a / 316b may be located inside the chamber.

[0065] As ions pass through a TOF mass analyzer, electrons can be generated through various mechanisms. For example, as described above, in some embodiments, collisions between ions entering the mass analyzer and one or more grid electrodes of the ion mirror can generate secondary positive ions, which may then cause electrons to be ejected from the ion mirror's plate.

[0066] The following examples are provided to further illustrate various aspects of this teaching, and are not intended to provide the necessarily optimal way to practice this teaching or the optimal results that can be achieved.

[0067] Example

[0068] Example 1

[0069] Without being limited to any particular theory, it is believed that at least a portion of the electrons reaching the ion detector of the TOF mass analyzer are generated through the following process: (1) a primary negative ion collides with the grid electrodes of the ion mirror of the TOF mass analyzer to generate a secondary positive ion, (2) the positive ion is accelerated toward the mirror plate, and (4) the positive ion collides with the mirror plate to generate electrons, and (3) the generated electrons are accelerated in the direction of the ion detector.

[0070] As an example Figure 4AThe diagram illustrates the entry of ions into an ion mirror 400, which has two grid electrodes 402a / 402b and a mirror plate 402c. In this example, grid electrodes 402a and 402b are maintained at ground potential and +6 kV potential, respectively. After a negative ion passes through grid electrode 402a, the ion decelerates and is eventually reflected back at the ion mirror plate, where it is accelerated away from the ion mirror. A portion of the negatively charged ions strikes the conductive material of grid electrodes 402a and / or 402b to generate multiple secondary positive ions. These secondary positive ions are accelerated toward the ion mirror plate, causing electrons to be ejected from the mirror plate.

[0071] Electrons are then accelerated by the electric field established by the potential between the ion mirror and the grid electrode, and the accelerated electrons travel in the direction of the downstream ion detector. As in this example, the potential difference between the mirror and the grid electrode 402a is 8 kV, and the accelerated electrons will have an energy of 8 keV when they leave the ion mirror.

[0072] Alternatively, a subset of the negatively charged ions bombard the conductive material of the grid electrode 402b to directly generate multiple secondary electrons, without the intermediate stage of generating positive ions. The potential difference between the mirror grid electrodes 402a and 402b is 6 kV, and the accelerated electrons will have an energy of 6 keV when leaving the ion mirror.

[0073] Figure 4B The ion detection data presented confirms the above-mentioned combination. Figure 4A The model for generating electrons is discussed. Figure 4B The background noise spectrum generated by the ion detector is shown, illustrating at least four peak shapes. Figure 4B The time it takes for ions to pass through the grid electrodes of the two ion mirrors is also indicated by multiple arrows, namely 37.1 μs, 39.6 μs, 43.6 μs, and 46.1 μs (at...). Figure 4B The illustrations are labeled “a”, “b”, “c”, “d”, “e” and “d”. Figure 4B The dark traces were recorded without the use of a magnet, while the gray traces were recorded with the use of a magnet, and no electronic noise bumps are observed.

[0074] The position of the arrow indicating the ion's position and the peak shape in the background noise spectrum roughly match. Since electrons are very light particles, their travel time from the second mirror to the ion detector is negligible (essentially instantaneous in the context of a typical TOF timescale).

[0075] Therefore, this data confirms the mechanism for electron generation proposed in this paper.

[0076] Example 2

[0077] Mass spectra of a sample containing 100 ng / mL phospholipids 18:1(9Z) / 18:1(9Z) / PG were obtained using a Sciex Zeno TOF 7600 mass spectrometer, which was modified to include a magnet positioned outside the fieldless chamber to establish a magnetic field within the fieldless region. The mass spectrometer includes components similar to... Figure 2A The TOF mass analyzer shown is a TOF mass analyzer with two ion mirrors. Phospholipids are ionized (or deprotonated) and then electrosprayed to generate a negative precursor. An isolated precursor ion with an energy of 35 eV is electron-activated and dissociated using an electron beam of 3.5 μA to generate multiple product ions.

[0078] Product ions were captured in an ion trap using a standard capture mode with the following parameters: ion loading time = 50 ms, reaction time = 20 ms, and extraction time = 1 ms. The captured product ions were then released for reception by a downstream TOF mass analyzer.

[0079] Two sets of mass spectra of product ions were acquired under (a) no magnetic field applied to the field-free region and (b) a magnetic field applied to the field-free region. Although the mass spectra acquired without a magnetic field showed noise artifacts caused by electrons bombarding the ion detector of the mass analyzer, the corresponding mass spectra acquired with an 8 mT magnetic field applied to the field-free region of the mass analyzer did not show such noise artifacts.

[0080] Specifically, Figure 5A The mass spectrum of the product ions is shown without using a magnetic field to deflect the electrons to suppress electron collisions with the ion detector. This spectrum exhibits a "noise bulge" due to electron-generated noise, making it difficult to detect the weak mass signal.

[0081] In comparison, Figure 5B The mass spectra of the same product ions are shown when a magnetic field of magnitude 8 mT is applied along the ion path in the field-free region. Figure 5B The spectrum shown indicates that the magnetic field has been eliminated. Figure 5A The "noise bulge" observed in the spectrum.

[0082] Example 3

[0083] The data presented in this example was also acquired using a modified Sciex Zeno TOF 7600 system, which was modified by adding magnets to allow a magnetic field to be applied to the field-free region of its TOF mass analyzer. The sample is a sodium trifluoroacetic acid cluster: C 12 HO 12 F 18 Na5, which generates a precursor with m / z = -792 by electrospray ionization using negatively charged charges.

[0084] Because clusters are fragile, fragments generated through collision activation were also observed in Q2. Figure 6 (Periodic peaks in A–6X). Precursor ions are isolated using a quadrupole mass filter and transported to the TOF analyzer via a Q2 collision cell. Product ions are trapped in an ion trap and then subsequently released to reach the TOF mass analyzer.

[0085] like Figure 6 As schematically shown, the ion detector of the TOF mass analyzer comprises four ion channels, referred to herein as MPC ch1, MPC ch2, MPC ch3, and MPC ch4. The set of MCP channels serves as a position detector for electron arrival.

[0086] Figure 6 A, 6B, 6C, and 6D show the mass spectra of product ions obtained without the use of a magnet and by analyzing ion detection data generated in four channels of the ion detector. A “noise bulge” caused by electrons bombarding the ion detector is visible in these spectra. This bulge is strongest at MCP ch1 (e.g., ...). Figure 6 (As shown). This indicates that electrons are flying "upright" from the second mirror towards the detector.

[0087] Figure 6 E, 6F, 6G, and 6H sequentially show the corresponding spectra of the product ions obtained when a magnetic field of 0.06 mT is applied to the fieldless ion drift region of a TOF mass analyzer.

[0088] Figure 6 I, 6J, 6K, and 6L show the corresponding spectra of the product ions obtained when a magnetic field of 0.1 mT is applied to the fieldless ion drift region of a TOF mass analyzer.

[0089] Figure 6 M, 6N, 6O, and 6P show the corresponding spectra of the product ions obtained when a field of 0.3 mT is applied to the fieldless ion drift region of a TOF mass analyzer.

[0090] Figure 6 Q, 6R, 6S, and 6T show the corresponding spectra of the product ions obtained when a field of 1 mT is applied to the fieldless ion drift region of a TOF mass analyzer.

[0091] Figure 6 U, 6V, 6W, and 6X show the corresponding spectra of product ions obtained when a 7 mT magnetic field is applied to the fieldless ion drift region of a TOF mass analyzer.

[0092] Data shows that increasing the strength of the applied magnetic field shifts the noise "bulge" from MCP ch1 to MCP ch4 (see, Figure 6E-6L), and these bulges are swept away when the magnetic field strength is greater than 0.3 mT. Figure 6 M-6X).

[0093] After eliminating the electronic noise bulge, some residual background noise was observed in MCP ch1 (see, Figure 6 M, 6Q, and 6U). The source of this background is believed to be ionic, for example, ions generated by the crushing of ions by residual gas in a grid or TOF vacuum chamber.

[0094] Example 4

[0095] Figure 7 The calculated trajectories of an 8 keV electron during its transit from the second ion mirror of the TOF mass analyzer 100 discussed above to its ion detector are shown under different magnetic field conditions. More specifically, the trajectories are calculated for the following cases: (1) no magnetic field, (2) magnetic field of 0.06 mT, (3) magnetic field of 0.1 mT, (4) magnetic field of 0.3 mT, and (5) magnetic field of 1 mT.

[0096] As illustrated in the depicted electron trajectories, electrons collide with the ion detector in the absence of a magnetic field applied to the fieldless ion drift region. Although applying magnetic fields of 0.06 mT and 0.1 mT causes some deflection of the electrons, in this example, such low magnetic field strengths appear insufficient to provide a significant reduction in the number of electrons colliding with the ion detector. In other words, in this example, such low magnetic field strengths do not appear to significantly reduce the noise artifacts caused by electron collisions with the ion detector. However, the electron trajectories show that as the magnetic field strength increases to 0.3 mT, and especially to 1 mT, the electrons appear to be sufficiently deflected from their original trajectories, thus avoiding the ion detector.

[0097] The above electronic trajectory and Figure 6 The spectral characteristics observed in the mass spectra shown in A-6X are consistent. Specifically, as the applied magnetic field strength increases, the noise artifacts associated with electrons are observed to decrease.

[0098] Example 5

[0099] Figure 8A and 8B The data presented were obtained using N42-grade neodymium magnets with the following dimensions: 1.5” x 0.25” x 0.0625”. The magnetic field strength was controlled by adjusting the number of stacked magnets. The magnet stack was placed outside the TOF vacuum chamber of the Sciex ZenoTOF 7600 mass spectrometer. Figure 2A The location shown (labeled B) indicates the south pole of the magnet's trajectory toward the ion's flight path.

[0100] Figure 8A The electronic "bulge" spectrum is shown, in which the flying ion is the sodium trifluoroacetic acid cluster: C 12 HO 12 F 18 Na₅, where m / z = -792. In region 1, electrons are generated by ion mirror 1. In regions 3 and 4, electrons are generated by mirror 2 (e.g., in...). Figure 4B It is generated at the positions marked "c" and "d".

[0101] Figure 8B The normalized “bulge” intensity for each region is shown, where the intensity is normalized to 100% relative to the case without magnets.

[0102] The data shows that using a single magnet (i.e., not stacked) reduces the electronic noise "bulge," but the "bulge" still exists. Using two stacked magnets makes the noise "bulge" almost negligible in regions 2, 3, and 4, but it still exists in region 1. Using three stacked magnets makes all electronic noise "bulges" almost negligible. Using four stacked magnets does not result in any perceptible additional reduction in background noise.

[0103] When the orientation of the magnets (and thus the applied magnetic field) is reversed, even using four stacked magnets cannot eliminate all electronic noise "bulges" (see, Figure 8B ). refer to Figure 2A In such cases, since the electron source (i.e., mirror 2) is located to the left of the ion detector when the electrons are swept to the right side (e.g., when the N pole of the magnet faces the flight path), a stronger magnetic field is required to completely remove the electron noise.

[0104] As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items and may be abbreviated as " / ". Although some aspects have been described in the context of the device, it is clear that these aspects also represent a description of the corresponding method, where a block or device corresponds to a method step or feature of a method step. Similarly, aspects described in the context of a method step also represent a description of a corresponding block or item or feature of the corresponding device. Some or all of the method steps in the method steps may be performed by (or using) a hardware device (e.g., a processor, microprocessor, programmable computer, or electronic circuit). In some embodiments, one or more of the most important method steps may be performed by such a device.

[0105] According to certain implementation requirements, embodiments of the present invention can be implemented in hardware and / or software. This implementation can be performed using a non-transitory storage medium (such as a digital storage medium, e.g., floppy disk, DVD, Blu-ray, CD, ROM, PROM, EPROM, EEPROM, or flash memory) having electronically readable control signals stored thereon, which cooperate with (or are capable of cooperating with) a programmable computer system to cause the corresponding method to be executed. Therefore, the digital storage medium can be computer-readable.

[0106] Although various embodiments have been illustrated and described in detail in the accompanying drawings and the foregoing description, such illustrations and descriptions should be considered illustrative or exemplary, not restrictive; the embodiments of this disclosure are not limited to those disclosed. Those skilled in the art, by studying the accompanying drawings, this disclosure, and the appended claims, can understand and implement other variations of the disclosed embodiments in practicing the embodiments of this disclosure.

[0107] In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite articles "a" or "an" do not exclude multiple. A single processor or other processing unit can perform the functions of several items recited in the claims. The fact that certain measures are recited only in mutually different dependent claims does not mean that a combination of these measures cannot be used advantageously. Any reference numerals in the claims should not be construed as limiting the scope.

[0108] Those skilled in the art will understand that various changes can be made to the above embodiments without departing from the scope of this teaching.

Claims

1. A time-of-flight (TOF) quality analyzer, comprising: Used to receive input from multiple ions. The ion acceleration region is where the received ions are accelerated. A repulsion electrode, used to guide received ions into the ion acceleration region. A field-free ion drift region for receiving the accelerated ions, the field-free ion drift region having an ion detector positioned at its distal end, and At least one magnet is positioned relative to a field-free region to establish a magnetic field in at least a portion of the field-free region for deflecting electrons entering the field-free region in order to suppress the electrons from reaching the ion detector.

2. The TOF mass analyzer according to claim 1, wherein the plurality of ions includes negatively charged ions.

3. The TOF mass analyzer according to any one of claims 1 and 2, wherein the at least one magnet generates a magnetic field in the portion of the fieldless region with a magnitude ranging from about 0.5 mT to about 100 mT, wherein optionally, the magnetic field is in the range of about 1 mT to about 10 mT.

4. The TOF mass analyzer according to any one of claims 1 and 2, wherein the magnet is oriented relative to the field-free region such that the magnetic field has a component along a direction orthogonal to the longitudinal direction of the field-free region.

5. The TOF mass analyzer according to claim 1 further includes a chamber in which the electric field-free region is established.

6. The TOF mass analyzer according to claim 5, wherein the magnet is positioned outside the chamber.

7. The TOF mass analyzer according to claim 5, wherein the magnet is positioned within the cavity.

8. A method for operating a Time-of-Flight (TOF) quality analyzer, comprising: Multiple ions are introduced into the time-of-flight (TOF) mass analyzer. The ions are accelerated in the ion acceleration region to generate accelerated ions. Ions are introduced into the field-free ion drift region near its proximal end, so as to be incident on an ion detector positioned at the distal end of the field-free ion drift region. A magnetic field is applied to at least a portion of the fieldless ion drift region to deflect electrons entering the fieldless ion drift region in order to suppress the electrons from reaching the ion detector.

9. The method of claim 8, wherein the ions comprise negatively charged ions.

10. The method according to any one of claims 8 and 9, wherein the magnetic field has at least one component along a direction perpendicular to the longitudinal axis of the fieldless ion drift region.

11. The method according to any one of claims 8 and 9, wherein the magnetic field has a magnitude in the range of about 0.5 mT to about 100 mT, and wherein optionally, the magnetic field has a magnitude in the range of about 1 mT to about 10 mT.

12. The method of claim 8, wherein the magnetic field is substantially uniform within at least a portion of the field-free region.

13. The method of claim 8, wherein the magnetic field exhibits a varying magnitude within at least a portion of the field-free region.

14. The method of claim 8, wherein the magnetic field exhibits a decreasing magnitude from the near end of the field-free region to the ion detector.

15. The method of claim 8, wherein the magnetic field is generated by a magnet positioned outside the fieldless ion drift region.

16. The method of claim 8, wherein the magnetic field is generated by a magnet positioned within the field-free ion drift region.

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