Apparatus and method for ion implantation into an electrostatic trap

Abstract

A mass spectrometry method includes storing a first ion packet within an ion storage device; transferring the first ion packet through a set of electrostatic lenses into an electrostatic trap mass analyzer, wherein during the transfer the lenses are operated in a first mode of operation or an injection voltage having a first predetermined magnitude is applied to electrodes of the mass analyzer; mass analyzing the first ion packet using the mass analyzer; storing a second ion packet within the ion storage device; transferring the second ion packet through the set of lenses into the mass analyzer, wherein during the transfer the lenses are operated in a second mode of operation or the injection voltage having a second predetermined magnitude is applied to the electrodes of the mass analyzer; and mass analyzing the second ion packet using the electrostatic trap mass analyzer.

Description

Technical Field

[0001] This invention relates generally to mass spectrometry and mass spectrometers, and more particularly to the operation of an electrostatic trap mass analyzer and the operation of a mass spectrometer system employing an electrostatic trap mass analyzer. Background Technology

[0002] An electrostatic trap is a type of ion optical device in which moving ions undergo multiple reflections or deflections in a substantially electrostatic field. Unlike trapping in an RF field ion trap, trapping in an electrostatic trap is only possible for moving ions. Therefore, a high vacuum is required to ensure sufficient data acquisition time T. m When this motion occurs internally, the energy loss of ions due to collisions is minimal. ORBITRAP TM The mass analyzer, belonging to the category of electrostatic trap mass analyzers, has been widely recognized as a useful tool for mass spectrometry analysis since its commercial introduction in 2005. In short, ORBITRAP... TM The mass analyzer (available from Thermo Fisher Scientific of Waltham, Massachusetts, USA) is an electrostatic trap mass analyzer that is a significant improvement over the earlier Kingdon ion trap. Figures 1A and 1B, which respectively provide information about the ORBITRAP mass analyzer, will be discussed further below. TM Mass spectrometer system and ORBITRAP TM Schematic diagram of the components of the mass analyzer. The electrostatic capture mass spectrometer system and mass analyzer of the type shown in Figures 1A and 1B provide accurate mass-to-charge ratio (m / z) measurements and high m / z resolution, similar to that achievable with Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry, without the need for high-intensity magnets. ORBITRAP TM The structural and operational details of the mass analyzer and the mass spectrometer employing such a mass analyzer are described in Makarov, Electrostatic Axially Harmonic Orbital Trapping: A High-Performance Technique of Mass Analysis, Analytical Chemistry, 72(6), 2000, pp. 1156-1162, and in U.S. Patent No. 5,886,346 to Makarov and U.S. Patent No. 6,872,938 to Makarov et al.

[0003] In FT-ICR and ORBITRAP TMIn a mass analyzer, ions are forced to undergo collective oscillatory motion within the analyzer, which induces corresponding oscillatory image charges in adjacent detection electrodes, thereby enabling ion detection. The oscillatory motion used for detection can take various forms, including, for example, circular oscillations in the case of FT-ICR, and axial oscillations around a central electrode orbit in the case of mass spectrometer systems or mass analyzers schematically shown in Figures 1A and 1B. The oscillatory image charges, in turn, induce oscillatory image currents and corresponding voltages in the circuitry connected to the detection electrodes. This signal is then typically amplified, digitized, and stored in computer memory. This signal-time recording is called a transient (instantaneous signal in the time domain).

[0004] Oscillating ions induce oscillating image charges and oscillating currents at frequencies associated with their mass-to-charge ratio (m / z) values. Each ion with a given mass-to-charge ratio (m / z) will oscillate at a corresponding given frequency, causing the aggregate ion image current to generate a signal, which typically takes the form of a periodic wave at a given frequency. Thus, the detected transient total image current is the sum of the image currents at all present frequencies (i.e., the sum of periodic signals). Transient spectral analysis (e.g., Fourier transform) yields the oscillation frequencies associated with the specific oscillating ion detected; based on these frequencies, the ion's m / z value can be determined by known equations whose parameters have been established from previous calibration experiments (i.e., mass spectrometry).

[0005] More specifically, ORBITRAP TM The mass analyzer includes an outer cylindrical electrode and a central spindle-shaped electrode along its axis. Referring to Figure 1A, it includes ORBITRAP. TMA portion of the mass spectrometer system of the mass analyzer is schematically shown in a longitudinal cross-sectional view. The mass spectrometer system 1 includes an ion storage device 2 and an electrostatic orbit trap mass analyzer 4. In this case, the ion storage device 2 is a curved multipole trap (referred to as a "C-trap"). Ions are radially ejected from the "C-trap" into the orbit trap in pulses. For details regarding the curved trap or C-trap device and its coupling with the electrostatic trap, see U.S. Patents 6,872,938; 7,498,571; 7,714,283; 7,728,288; and 8,017,909, each of which is incorporated herein by reference in its entirety. The C-trap can receive and trap ions from an ion source 3, which can be any known type of source, such as an electrospray (ESI) ion source, a matrix-assisted laser desorption / ionization (MALDI) ion source, a chemical ionization (CI) ion source, an electron ionization (EI) ion source, etc. Additional processing components (not shown), such as ion guiding components, mass filtering components, linear ion trapping components, ion fragmentation components, etc., may optionally be included between ion source 3 and C trap 2, or between the C trap and other components of the mass spectrometer. Other components of the mass spectrometer, not shown, are conventional, such as additional ion optics, vacuum pump systems, power supplies, etc.

[0006] Other types of ion storage devices can be used instead of C-trap. For example, U.S. Patent No. 6,872,938 teaches the use of an implantation assembly comprising a segmented quadrupole linear ion trap having an inlet segment, an outlet segment, an inlet lens adjacent to the inlet segment, and an outlet lens adjacent to the outlet segment. By appropriately applying a “direct current” (DC) voltage to the two lenses and the bars of each segment, a temporary axial potential trap can be generated in the axial direction within the outlet segment. The pressure inside the trap is selected such that the ions lose sufficient kinetic energy during their first passage through the trap, causing them to accumulate near the bottom of the axial potential trap. Subsequently, an appropriate voltage pulse is applied to the outlet lens, and the voltage on the central spindle electrode is gradually varied, causing the ions to be emptied from the trap axially through the outlet lens electrode and enter the electrostatic orbit capture mass analyzer 4.

[0007] The electrostatic orbital capture mass analyzer 4 comprises a central mandrel electrode 6 and surrounding outer electrodes divided into two halves 8a and 8b. Figure 1B is an enlarged cross-sectional view of the inner and outer electrodes. The annular space 17 between the inner mandrel electrode 6 and the outer electrode halves 8a and 8b is the volume in which ions orbit and oscillate, and contains the measurement chamber, in which the motion of ions within this volume induces a measurement signal for determining the ion m / z ratio and relative abundance. The inner and outer electrodes (central electrode 6 and outer electrodes 8a, 8b) are specifically shaped such that when a suitable voltage is supplied, corresponding electric fields are generated. These electric fields interact to produce a so-called “quadr-logarithmic potential” U (sometimes also called a “superlogarithmic potential”) within the measurement chamber 17, which is described in cylindrical coordinates (r, z) by the following equation:

[0008]

[0009] Where a, b, c, and d are constants determined by the dimensions of the orbital trap analyzer electrodes and the voltage applied to them, and z = 0 is taken at the axial position of the symmetrical equatorial plane 7 corresponding to the electrode structure. The “four logarithmic potential” depends on the “bottom” or zero axial gradient point of the portion of the axial displacement (i.e., the portion that determines the axial dimension z of the motion along the longitudinal axis 9) occurring at the equatorial plane 7. This potential field has a harmonic potential well along the axial (Z) direction, which allows ions to be axially trapped within the potential well if there is insufficient kinetic energy to escape. It should be noted that Equation 1 represents the ideal functional form of the potential, and the actual potential in any particular physical device will include higher-order terms in z and r.

[0010] The motion of the trapped ions is associated with three characteristic oscillation frequencies: the rotational frequency around the central electrode 6, the orbital frequency around the nominal rotational radius, and the axial oscillation frequency along the z-axis. For the oscillation frequency to be detected, the motion of the ions for a given m / z needs to be coherent. For ions with the same m / z, radial and rotational oscillations are only partially coherent because the difference in the average orbital radius and the magnitude of the radial oscillation corresponds to different orbital and radial frequencies. Coherence is most easily induced in the axial oscillation when the ions move with an axial harmonic potential; therefore, the axial oscillation frequency is independent of the oscillation amplitude and depends only on m / z. Thus, the axial oscillation frequency is the only frequency used to determine the mass-to-charge ratio. The outer electrodes are formed as two parts 8a and 8b as described above, as shown in Figure 1B. According to the following equation 2, the ions oscillate sinusoidally in the potential trap of the field along the axial direction at a frequency ω (harmonic motion):

[0011]

[0012] Where k is a constant. As the ions oscillate back and forth along the axis, one or both portions 8a, 8b of the external electrodes are used to detect the image current. Therefore, the induced ion image current signal can be converted from the time-domain Fourier transform frequency domain to generate a mass spectrum in a conventional manner. This detection mode enables high-resolution mass spectra.

[0013] Ions with various M / Z values ​​captured in the C-trap are preferably injected in short temporal or spatial packets from the C-trap through an ion inlet orifice 5 located at an axial position offset from the equatorial plane 7 of the analyzer into the electrostatic orbital capture mass analyzer 4. This off-center ion implantation geometry enables so-called "excitation by implantation," whereby the ions in the ion packet immediately begin orbital motion around the central electrode 6 and other oscillations within the mass analyzer at a fourth logarithmic potential. The ions in the packet are injected into the ion inlet orifice 5 along an initial implantation trajectory that is substantially tangential to the stable orbital trajectory within the mass analyzer. The ions oscillate axially between the two outer electrodes 8a and 8b, while simultaneously orbiting around the inner electrode 6. The axial oscillation frequency of the ions depends on the m / z values ​​of the ions contained in the ion packet, such that ions with different m / z values ​​in the packet begin to oscillate at different frequencies.

[0014] Two external electrodes 8a and 8b serve as detection electrodes. The oscillation of ions in the mass analyzer induces image charges in electrodes 8a and 8b, and the resulting image current in the connected circuit is sensed as a signal, which is amplified by amplifier 10 (FIG. 1A) connected to the two external electrodes 8a and 8b. The amplified signal is digitized by digital converter 12. The resulting digitized signal (i.e., transient) is then received by information processor 14 and stored in computer-readable memory. The memory may be part of information processor 14, or alternatively, may contain separate components. For example, information processor 14 may contain a computer running a program with program code elements designed to process the transient. Computer 14 may be connected to output device 16, which may include one or more of the following: computer memory, output visual display unit, printer, or data writer, etc.

[0015] Information processor 14 performs a Fourier transform (or other mathematical transformation) on the received transient data. For example, the mathematical method of discrete Fourier transform can be used to convert the transient in the time domain into a spectrum in the frequency domain. The transient in the time domain contains mixed periodic transient signals caused by the mixed m / z present between the measured ions. If necessary, the frequency domain spectrum can be converted to the m / z domain by direct calculation at or after this stage. The discrete Fourier transform produces a spectrum with contour points for each frequency or m / z value, and these contour points form peaks at those frequencies or m / z locations where the ion signal is detected (i.e., the locations of ions with the corresponding m / z in the analyzer).

[0016] The mass spectrometer system 1 also includes one or more power supplies 18, which supply appropriate oscillating radio frequency (RF) and non-oscillating (DC) voltages to the electrodes of the ion source 3, ion storage device 2, electrostatic orbital capture mass analyzer 4, and other mass spectrometer components (not shown) via various wires or cables, such as wires or cables 27a, 27b, and 27c. These voltages are necessary for the proper operation of the mass spectrometer. The electrodes to which voltages are supplied include various electrostatic lenses and ion guides, some of which are described herein. The information processor 14 may contain one or more computers and / or logic controllers and provides control signals to the one or more power supplies 18, which control the timing and amplitude of the voltages supplied by the one or more power supplies 18 via wires or cables 27a to 27c. The timing of the application of the various voltages can be controlled by computer-readable instructions via algorithms, which are embedded within or accessible to the information processor 14. Such instructions are generally adaptable to the analytical requirements of various users and / or various samples. As commonly understood, the mass spectrometer system 1 also includes various vacuum pumps and associated vacuum lines (not shown), and may include various other mass filtration, ion capture, and / or ion reaction components (not shown).

[0017] Compared to other mass spectrometry ion manipulation techniques, ORBITRAP ion implantation... TM Electrostatic trap mass analyzers and other electrostatic trap mass analyzers involve complex processes. This complexity arises from the need to set the initial conditions for the implanted ions relatively far from their detection location. The ions to be implanted reach their thermal velocity at approximately 1 mTorr nitrogen pressure within the C-trap or other ion storage device 2. Subsequently, in practice, the potential of the C-trap is increased from ground potential to an appropriate voltage (e.g., approximately 2400 V if the central spindle electrode 6 is at approximately -5 kV), which causes the ions to move towards the ORBITRAP. TM Ion inlet tank 5 is sprayed. In the path to the electrostatic trap mass analyzer, the ions pass through several electrostatic lenses, some of which are necessary for differential pumping, while others attempt to shape the beam itself.

[0018] Figure 1C schematically illustrates the C-trap and ORBITRAP TM A common lens configuration between the electrostatic trap mass analyzers. Lens 33 contains individual electrodes 33a, 33b, 33c, and 33d, the purpose of which is to deflect the ion trajectory 31 by an offset distance Δy. inj In practice, this is typically 2 mm, which helps to counteract the flow of neutral gas molecules from the C-trap to the ORBITRAP. TMThe influence of this field on the ion implantation process is as follows: Typically, electrodes 33a and 33d are maintained at ground potential during ion implantation, while electrodes 33b and 33c are maintained at the same voltage V0, the polarity of which depends on the polarity of the implanted ions. For example, assuming the implanted ions are positively charged, the voltage V0 could be approximately -300V. Assuming the ions between electrodes 33a and 33b experience the same field strength as those between electrodes 33c and 33d, the ions enter and exit lens 33 at the same angle.

[0019] As shown in Figure 1C, the single lens (Einzel lens 36) (Szilagyi, M, *Electron and Ion Optics*, Plenum Press, 1988) is set in ORBITRAP TM The mass analyzer housing includes via electrode plates 37a, 37b, and 37c that focus the beam onto an ion implantation aperture 5, typically arranged in the form of a slit. Electrode plate 37b is typically maintained at approximately 1200V (depending on the specific configuration), while electrodes 37a and 37c are maintained at ground potential. A secondary function of lens 36 is to counteract any beam spread that may occur between the exit of lens 33 and the entrance of lens 36. Finally, deflector electrodes 34, mounted adjacent to the implantation slit, force ions into the measurement chamber 17 along a curved trajectory, then “close the door” by a potential change, minimizing the slit’s influence on the ion trajectory within the measurement chamber 17. For efficient trapping, the implanted ion bundle is typically focused into the entrance slit 5; thus, all ions enter the trap with similar energy and trajectory.

[0020] The aforementioned ion implantation mechanism works well, at least for "first-order" effects, such as ion trapping and the observation of precise mass distribution and ion abundance. However, for "second-order" effects, such as ion-ion interactions and long-term ion cloud stability, the details of the implantation process can become important. In particular, if the beam is spatially very small at the time of implantation, the likelihood of ion-ion interactions is greater, and this improves long-term ion cloud stability. Conversely, if the beam is more dispersed at the time of implantation, ion-ion interactions are reduced, and achieving the highest mass resolution becomes more difficult. The principle underlying ion-ion interactions in electrostatic trap mass spectrometry is ion cloud coupling, where two clouds with small intervals in their motion frequencies tend to acquire the same frequency, resulting in the observation of a single mass spectral peak, where there should be two. This phenomenon is called peak coalescence.

[0021] Typically, slight variations in injection conditions can lead to subtle changes in mass spectrometry performance characteristics. Specifically, if the beam is tightly focused, the ion cloud may be compressed, resulting in stronger ion-to-ion interactions. Strong interactions between different ion species with varying mass-to-charge ratios (m / z) negatively impact ion cloud coupling, mass spectrometry representation, and peak aggregation. Conversely, if the beam is spatially expanded upon entering the trap, weaker ion-to-ion interactions result in improved resolution for smaller peaks (e.g., isotope variant peaks).

[0022] Peak coalescing can be reduced by changing specific injection and transfer voltages, but these changes may adversely affect other mass spectrometry properties, such as micro-separation cloud loss of coherence, leading to a loss of isotope ratio fidelity. Summary of the Invention

[0023] This disclosure describes a method utilizing ion optical lens aberrations to disperse ion packets upon entry into an electrostatic trap, thereby achieving better space charge tolerance without affecting other important performance characteristics. The novel method according to the teachings of the invention utilizes transfer lens aberrations to control the degree of dispersion of ion packets at the injection slit of the electrostatic trap. According to one aspect of the teachings of the invention, if the ion packets are guided slightly away from the central axis of the focusing lens, ion optical geometric aberrations will take effect, and not all portions of the ion packets will have the same focal point at the slit. In other words, each ion packet will be spatially dispersed at the injection slit. As described herein, guiding the ion packets can be achieved by changing the field strength of one or more transfer lenses upstream of the focusing lens, thereby inducing lens asymmetry. In this asymmetric configuration, ions can exit the transfer lens with a trajectory at an angle to the trajectory of the ions entering the transfer lens. Ions that have passed through the resulting partially deflected trajectory will then enter the focusing lens along a line offset from the central axis of the focusing lens. Therefore, the focal region can be slightly shifted upstream or downstream from the ion inlet aperture of the electrostatic trap, and the ions of each packet will be spatially dispersed upon entry into the trap.

[0024] According to some embodiments of the teachings of the present invention, a method for operating a mass spectrometer system including an electrostatic trap mass analyzer includes:

[0025] A portion of the ion stream generated by the ion source from the sample is stored as a first ion pack within the ion storage device of the mass spectrometer system;

[0026] The stored first ion pack is transferred to the electrostatic trap mass analyzer through a set of electrostatic lenses, wherein, during the transfer of the first ion pack to the electrostatic trap mass analyzer, the electrostatic lenses operate in a first operating mode, or an injection voltage having a first predetermined value is applied to the electrodes of the mass analyzer.

[0027] The first ion pack was mass analyzed using an electrostatic trap mass analyzer.

[0028] The second portion of the ion stream from the sample is stored as a second ion pack within the ion storage device;

[0029] The stored second ion packet is transferred to an electrostatic trap mass analyzer via a set of electrostatic lenses, wherein, during the transfer of the second ion packet to the electrostatic trap mass analyzer, the electrostatic lenses operate in a second operating mode, or an injection voltage having a second predetermined value is applied to the electrodes of the mass analyzer; and

[0030] The second ion pack was mass analyzed using an electrostatic trap mass analyzer.

[0031] According to some other embodiments of the teachings of the present invention, a mass spectrometer system is provided, the system comprising:

[0032] Ion source;

[0033] An ion storage device, configured to receive ions from an ion source;

[0034] An electrostatic trap mass analyzer, configured to receive ion packets from an ion storage device, comprises:

[0035] Inner axis electrode; and

[0036] One or more external electrodes;

[0037] The space between the inner axis electrode and one or more outer electrodes; and

[0038] One or more external electrode ion inlet holes;

[0039] A set of ion lenses is placed between the ion storage device and the electrostatic trap mass analyzer;

[0040] The power supply is electrically coupled to the ion storage device, the electrostatic trap mass analyzer, and a set of ion lenses; and

[0041] An information processor, electrically coupled to one or more of a power supply, an ion storage device, an electrostatic trap mass analyzer, and a set of ion lenses, and containing computer-readable instructions capable of operating for:

[0042] A portion of the ion stream generated by the ion source is stored as a first ion pack within the ion storage device;

[0043] The first ion pack stored is transferred through a set of electrostatic lenses into the space of the electrostatic trap mass analyzer, wherein, during the transfer of the first ion pack into the space, the electrostatic lenses operate in a first operating mode, or an injection voltage having a first predetermined value is applied to the spindle electrode.

[0044] The electrostatic trap mass analyzer is used to analyze the mass of the first ion pack.

[0045] The second portion of the ion flow is stored as a second ion pack within the ion storage device.

[0046] The stored second ion packet is transferred to an electrostatic trap mass analyzer via a set of electrostatic lenses, wherein, during the transfer of the second ion packet to the electrostatic trap mass analyzer, the electrostatic lenses operate in a second operating mode, or an injection voltage having a second predetermined value is applied to the electrodes of the mass analyzer; and

[0047] The electrostatic trap mass analyzer is used to perform mass analysis on the second ion pack.

[0048] The first and second ion packs can be obtained from a single sample or from separate samples. By using a first and second operating mode of the electrostatic lens for transferring the ions from the first and second ion packs, respectively, or by applying a first and second injection voltage during the transfer of the first and second ion packs, respectively, different mass spectrometry characteristics can be optimized during the first and second mass analyses. For example, during one of the mass analyses, the operating mode or injection voltage can be selected such that the introduced ion pack is carried to the line focus or, in other cases, the diffuse focusing region upon entering the electrostatic trap, thereby reducing the charge density within the trap during analysis. This reduction in charge density can reduce unwanted peak aggregation within the mass spectrum generated by the mass analysis, but may adversely affect other mass spectrometry characteristics, such as overall resolution and isotope ratio fidelity.

[0049] If two ion packs are obtained from a single sample, the lens operating mode or the applied injection voltage can be selected during the injection of the other pack to optimize these other mass spectrometry properties. If the two ion packs contain different ion population sizes because they come from different samples or different portions or fractions of the same sample, the first lens operating mode can be changed to a second lens operating mode or the first injection voltage can be changed to a second injection voltage based on and in response to the different ion population sizes. For example, a lens operating mode and / or injection voltage that disperses the focus and ion cloud within the mass analyzer can be used for large ion populations (i.e., ion packs with a large number of ions), while a lens operating mode and / or injection voltage that maintains a tight focus and compact ion cloud within the mass analyzer can be used to analyze small ion populations.

[0050] The computer instructions of the mass spectrometer system's information processor are also capable of digitally analyzing the mass spectrum generated by the mass analysis of the first ion pack, and automatically changing the operating mode of the electrostatic lens from a first operating mode to a second operating mode or changing the injection voltage from a first predetermined value to a second predetermined value in response to the digital analysis of the mass spectrum. For example, if the digital analysis detects an undesirable peak aggregation level in the mass spectrum, the computer instructions can automatically change the operating mode of the electrostatic lens from the first operating mode to the second operating mode or change the injection voltage from the first predetermined value to the second predetermined value in response to the detected peak aggregation level, thereby reducing the peak aggregation level in subsequent mass analyses of the second ion pack. On the other hand, if the digital analysis detects an acceptable low level of peak aggregation in the mass spectrum, the computer instructions can automatically change the operating mode of the electrostatic lens from the first operating mode to the second operating mode or change the injection voltage from the first predetermined value to the second predetermined value, thereby improving the overall resolution or isotope ratio fidelity in subsequent mass analyses of the second ion pack. Attached Figure Description

[0051] The above and various other aspects of the invention will become apparent from the following description, which is given by way of example only and with reference to the accompanying drawings, which are not drawn to scale, wherein:

[0052] Figure 1A shows a mass analyzer including an electrostatic trap, specifically ORBITRAP. TM A schematic diagram of a part of a mass spectrometer system with an electrostatic trap mass analyzer;

[0053] Figure 1B is an enlarged cross-sectional view of the electrostatic trap mass analyzer in Figure 1A;

[0054] Figure 1C is a schematic diagram of a known configuration of an ion lens used to transfer and focus accumulated ions from an ion storage device onto an electrostatic trap mass analyzer.

[0055] Figure 2A This is a schematic diagram of a method for using an asymmetrically applied voltage to an ion transfer lens so that the trajectory of ions leaving the lens forms a small angle with the trajectory of ions entering the lens.

[0056] Figure 2B This is a schematic diagram of a method for positioning the electrode components of an offset ion transfer lens so that the trajectory of ions leaving the lens forms a small angle with the trajectory of ions entering the lens.

[0057] Figure 3A This is a schematic diagram of the perturbed and undisturbed ion paths through the focusing lens and into the ion implantation slit of the electrostatic trap mass analyzer. The perturbed path is caused by shifting the position of the electrode components of the upstream ion transfer lens, such as... Figure 2B As shown;

[0058] Figure 3B yes Figure 3A A magnified view of a portion of the perturbed and undisturbed ion paths at the ion implantation slit, and also showing the nominal focus of ions following the undisturbed path;

[0059] Figure 4A It is a schematic depiction of a method of shifting the position of an ion focusing lens to cause a shift in the focal position or spatial dispersion of ions passing through the focusing lens;

[0060] Figure 4B This is a schematic diagram of an ion focusing lens device and a method for operating the device to cause a shift in the focal position or spatial dispersion of ions passing through the focusing lens;

[0061] Figure 5A This is a schematic diagram of a quadrupole lens that guides ions into an ion injection slit of an electrostatic trap mass analyzer according to the teachings of the present invention.

[0062] Figure 5B yes Figure 5A A schematic diagram of the focusing characteristics of a quadrupole lens;

[0063] Figure 6 These are a set of schematic diagrams of ion trajectories within an electrostatic trap device of the type shown in Figures 1A and 1B. When projected onto a cross-section perpendicular to the longitudinal z-axis, different cross-sections relate to different implantation voltages applied to the inner axis electrode during ion implantation; and

[0064] Figure 7 This is a flowchart of a method for operating a mass spectrometer system including an electrostatic trap mass analyzer, as taught in this invention. Detailed Implementation

[0065] The following description is presented to enable any person skilled in the art to make and use the invention, and is provided in the context of a particular application and its requirements. Various modifications to the described embodiments will be apparent to those skilled in the art, and the general principles herein can be applied to other embodiments. Therefore, the invention is not limited to the embodiments and examples shown, but is given the broadest possible scope based on the features and principles shown and described. Specific features and advantages of the invention will become clearer in conjunction with the following description and drawings.

[0066] In this description of the invention, it should be understood that, unless otherwise implicitly or explicitly understood or stated, words appearing in the singular form encompass their plural counterparts, and words appearing in the plural form encompass their singular counterparts. Furthermore, it should be understood that, unless otherwise implicitly or explicitly understood or stated, any possible candidates or alternatives listed for any given component or embodiment described herein may generally be used individually or in combination with each other. Additionally, it will be understood that any list of such candidates or alternatives is illustrative only and not restrictive, unless otherwise implicitly or explicitly understood or stated. Furthermore, it should be understood that the drawings shown herein are not necessarily drawn to scale, and only some elements may be drawn for clarity of the invention. Additionally, reference numerals may be repeated in various figures to indicate corresponding or similar elements.

[0067] Unless otherwise defined, all other technical and scientific terms used herein have the meanings commonly understood by one of ordinary skill in the art to which this invention pertains. In case of conflict, this specification (including the definitions) shall prevail. It should be understood that the implied word “about” precedes quantitative terms mentioned in the description of this invention, such that minor and non-substantial deviations are within the scope of this invention. In this application, the singular is used to include the plural unless otherwise specifically stated. Furthermore, the use of “comprise”, “comprises”, “contain”, and “include” is not intended to be restrictive. As used herein, “a” or “an” may also refer to “at least one” or “one or more”. And the use of “or” is inclusive, such that the phrase “A or B” is true when “A” is true, “B” is true, or both “A” and “B” are true.

[0068] As used herein, the term “DC” (for “direct current”) is used only to specify a non-oscillating voltage or non-oscillating potential applied to an electrode and does not necessarily imply the presence of a current carried by the movement of electrons through a wire, electrode, or other conductor. Therefore, the term “DC” is used herein to distinguish the voltage mentioned from the applied periodic oscillating voltage, which may themselves be referred to as “RF” (radio frequency) or “AC” voltage.

[0069] Figures 2A to 2BTwo exemplary methods for causing slight perturbations during the operation of the ion transfer lens 33, as shown in Figure 1C, are schematically illustrated. As noted in the background section of this document, the nominal function of the ion transfer lens 33 is to offset the position of the beam path while maintaining the direction of motion of ions leaving the lens parallel to the direction of motion of ions entering the lens. When the ion transfer lens 33 and the focusing lens 36 are nominally operated in proper alignment with the ion storage device 2, the ion implantation aperture 5 of the electrostatic trap 4, and each other, the ions are geometrically focused within the aperture 5, and the ion trajectories are substantially tangential to the stable ion trajectory motion within the electrostatic trap. However, it has been observed that this nominal operation can sometimes lead to the coalescence of mass spectral peaks corresponding to ion species with close m / z intervals (e.g., isotopic variants of ions that are otherwise identical). The inventors have recently recognized that peak coalescence can be significantly reduced by making subtle changes to the nominal alignment of the lens between the ion storage device 2 and the electrostatic trap 4 and / or the nominal voltage applied to the lens.

[0070] In the following discussion, electrodes 33a and 33b of lens 33 are referred to as the inlet electrodes of the lens because ions arriving from ion storage device 2 first enter the lens between these two electrodes. Similarly, electrodes 33c and 33d are referred to as the outlet electrodes because ions exit lens 33 between this latter pair of electrodes. Electrodes 33b and 33c are referred to herein as “radially opposite each other” or “a pair of radially opposite electrodes” because they are disposed relative to each other at opposite ends of lens 33 and also on opposite sides of the ion paths (31, 32, 39) through lens 33. For similar reasons, electrodes 33a and 33d are also referred to herein as “radially opposite each other” or “a pair of radially opposite electrodes.”

[0071] The nominal operation of the transfer lens 33 is achieved when the ion path entering the lens is precisely located between a pair of inlet electrodes 33a, 33b and a pair of outlet electrodes 33c, 33d, and when the electric field between electrodes 33c, 33d is precisely opposite to the electric field between electrodes 33a, 33b (i.e., the same magnitude but opposite direction). Therefore, by manipulating the electric field between the inlet and outlet electrode pairs and / or by manipulating the positions of the electrodes, the direction of motion of the departing ions can be made non-parallel to the direction of motion of the entering ions. This latter operation, where the ion trajectories entering and leaving the ion transfer lens 33 are not parallel to each other, is referred to herein as a lens perturbation operation or a non-nominal operation.

[0072] Figure 2AThis schematically illustrates how an asymmetric voltage is applied to the ion transfer lens 33 to control the angle at which ions leave the lens without any manipulation of the electrode positions relative to their nominal positions. As described above, the nominal operation of the lens involves applying a voltage V0 to electrodes 33a and 33d while holding electrodes 33b and 33c at ground potential. Figure 2A The operation shown applies one or more disturbance voltages to the corresponding individual electrodes. For example, as... Figure 2A As schematically illustrated, separate perturbation voltages ΔV1 and ΔV2 can be applied to the voltage V0 applied to electrodes 33a and 33d, respectively. The perturbation voltages ΔV1 and ΔV2 can be positive or negative in sign, and one of them can be equal to zero. However, ΔV1 and ΔV2 cannot be equal in magnitude and sign. Due to the asymmetry caused by the applied perturbation voltages, the magnitude of the ion path deflection from path segment 39a to path 39b is no longer precisely compensated for by the ion path deflection from path segment 39b to 39c as in the nominal operation of lens 33. Therefore, when an ion leaves lens 33, the exit path segment 39c is not parallel to the initial path segment 39a of the ion entering the lens. In this example, there is an angle α between the trajectories of the entering and exiting ions. Although the perturbation voltages ΔV1 and ΔV2 are... Figure 2A The image is shown as being applied only to the nominal energized electrodes 33a and 33b, but the perturbation voltage may alternatively be applied to the nominal grounded electrodes 33b and 33c, or even further alternatively, the perturbation voltage may be applied to all three or all four electrodes of the lens 33.

[0073] Figure 2B The illustration schematically depicts how the position of one or more electrodes of the ion transfer lens 33 can be manipulated relative to its nominal position to control the angle at which ions leave the lens, while the voltage applied to the lens electrodes is the same as the voltage applied during the nominal operation of the lens. For example, as Figure 2B As shown, electrode 33a is depicted as being offset by an offset distance Δy relative to its nominal position (shown as a dashed line). 33 This allows the path segment 39a of the ions entering lens 33 to initially pass through lens 33a closer to lens 33a than lens 33b.

[0074] Figure 3A This is a schematic diagram of the perturbed and undisturbed ion paths through the focusing lens 36 and into the electrostatic trap mass analyzer 4 via the ion implantation slit 5, as calculated by a computer program for ion trajectory simulation. The ion implantation slit 5 is a hole forming one of the half-electrodes 8a and 8b of the outer electrode portion of the electrostatic trap 4 (Figure 1A). Figures 3A to 3B For illustrative purposes, the slit is depicted as passing through half electrode 8b. Figure 3BThis is a magnified view of a portion of the same calculated perturbed and undisturbed ion paths near the injection slit. The undisturbed ion path 31 corresponds to the ion transfer lens 33. Figures 3A to 3B The nominal operation (not shown in the diagram). Perturbation path 32 corresponds to a modification operation of the ion transfer lens, in which it is assumed that the position of one member of the electrode pair of the ion transfer lens 33 is offset by 50 μm in the direction of the other inlet electrode, similar to... Figure 2B The offset Δy depicted in 33 Each simulation assumes that ions are introduced into the center of the ion transfer lens. In the simulations of the nominal operating mode and the perturbation operating mode, ions are forced into a curved trajectory under the influence of the electric field generated by the deflector electrode 34, causing the ions to enter the measurement chamber 17 through the ion injection slit 5 in the outer half electrode 8b.

[0075] like Figure 3A As shown, ion trajectory calculations indicate that, upon entering the focusing lens 36, ions moving through the undisturbed lens system follow a path 31 along the central axis of the focusing lens 36. Such ions undergo a balanced compressive force within the lens 36, which causes each ion packet to reach the focal point f31. Figure 3B The focal point is the nominal focal point of the focusing lens 36. According to the nominal operation of the lens system, the lens 36 is positioned relative to the injection slit 5 of the electrostatic trap mass analyzer such that the focal point is located within the slit.

[0076] Figure 3A The schematic depiction of ion trajectories in the diagram also shows that the ion path 32 of the moving perturbation lens system moves from the central axis of the focusing lens 36. Due to this movement, ions passing through path 32 experience an unbalanced repulsive force from the electric field generated by the electrode 37b of the energized central plate. For example, when projected onto… Figure 3A When projected onto the drawing plane, ions whose trajectories are close to the edge 47 of the central plate electrode 37b experience a force toward the central axis 38 of the lens 36, which is greater than the force experienced by ions whose trajectories are closer to the central axis. Therefore, when projected onto the drawing plane... Figure 3A When plotted on the drawing plane, the ion pack appears to be focused at point f32, which moves upstream from the nominal focus f31 within the ion implantation slit 5. Although not on... Figures 3A to 3B The diagram is illustrated in detail, but the focusing of ions passing through the perturbed lens system is expected to be astigmatic; in other words, the ion trajectory is expected to be perpendicular to... Figure 3A The projection of the drawing plane onto the plane produces an apparent focal point that does not coincide with point f32.

[0077] The inventors reason that the larger calculated width w32 of the ion packet entering the electrostatic trap from the perturbed lens system, compared to the calculated width w31 of the ion packet entering the trap from the nominal lens system, stems from the combined phase aberration effect of focus shift and astigmatism introduced by the controlled perturbation. Theoretically, the greater initial spatial dispersion of ions introduced from the perturbed lens system reduces unwanted coupling ion interactions between ion species with different mass-to-charge ratios within the electrostatic trap, thereby reducing peak coalescence. This idea was tested in the laboratory using a nominally symmetrical transfer lens 33. Similar to... Figure 2B The depiction was performed using a lens in its nominal (symmetric, undisturbed) state and a 50 μm shim inserted near the entrance aperture. The degree of peak aggregation was measured by measuring the A+2 peak of the tetrapeptide mass spectrometry calibration standard H-Met-Arg-Phe-Ala-OH (MRFA) at a mass spectrometry resolution of 240,000 m / z at 200 Th, in order to decompose the peak into... 34 S peak and 2× 13 C peak. Based on the observed mass spectra of isotopic variants, monitoring showed that as the concentration of the target ion increased, [the following occurred]. 34 The signal-to-noise ratio (S / N) of the peaks was then recorded. The point where the two peaks coalesced was then considered the coalescence threshold. Table 1 below shows the measurement differences with and without a shim. In both cases, the isotope ratio was largely unaffected, while the coalescence threshold doubled. The results shown in the table demonstrate that introducing lens perturbation significantly reduces coalescence.

[0078] Table 1

[0079] Operating mode Experimental conditions coalescence threshold nominal No gasket 1500 Disturbance 50μm gasket at the entrance 3100

[0080] The above discussion concerns increasing the spatial dispersion of ion packets entering the electrostatic trap mass analyzer by introducing perturbations into the ion transfer lens that guides the ion packets from the ion storage device into the mass analyzer. A similar effect can be achieved by introducing perturbations into the focusing upstream of the ion implantation orifice of the mass analyzer. Therefore, Figure 4A This is a schematic diagram of a method according to the present invention for shifting the position of the ion focusing lens 36 to cause a shift or spatial dispersion of the focal point of ions passing through the focusing lens 36. Figure 4A In this context, the x-axis is defined as the central axis 41 parallel to the nominally constructed lens 36, and the y-axis is defined as perpendicular to the x-axis.

[0081] According to some methods taught by the present invention, the entire lens 36, including the perforated plate electrodes 37a, 37b and 37c, can be translated as a unit relative to its nominal position. Figure 4A The shaded electrode in the diagram represents the electrode position after translation; the nominal electrode position is indicated by a dashed line. The lens can be translated parallel to the x-axis by a distance Δx. 36 Or translate parallel to the y-axis by a distance Δy 36Alternatively, the translation of the lens can be described as the vector sum of the translations along the x-axis and y-axis.

[0082] The ion focusing lens 36 is simply translated parallel to the x-axis, causing the lens focal point to shift parallel to the same axis upstream or downstream of the ion inlet aperture 5 relative to the nominal focal point within the aperture. In each case, the focal point shifts by the same distance Δx as the lens shift. 36 As the ion pack enters the electrostatic trap mass analyzer, the lens focus moves (e.g., to) upstream of the ion inlet orifice. Figure 3A The spatial dispersion of the ion pack is expanded near point f32, thereby reducing the aggregation of mass spectrometry peaks as described above.

[0083] A simple translation of the ion-focusing lens 36 parallel only to the y-axis causes a shift in the lens's central axis 41, so that it no longer coincides with the center of the ion-entry path 39 (assuming this path is fixed by the ion transfer lens 33). In this case, ions passing through path 39 experience an unbalanced repulsive force from the electric field generated by the energized central plate electrode 37b. Therefore, such a shift can perturb the lens focusing characteristics of lens 36 in a manner similar to the perturbation of the ion transfer lens 33 described above. Specifically, the lens focal point will move upstream from its nominal position, thereby increasing the spatial dispersion of the ion pack as it enters the electrostatic trap mass analyzer.

[0084] According to the alternative operating mode of the ion focusing lens 36, the lens assembly remains in a fixed position instead of moving the lens, and the focal length of the lens is perturbed by adjusting the voltage applied to the center plate electrode 37b of the lens. Increasing this voltage relative to its nominal value reduces the focal length, thereby allowing the ion path 39 to reach the focal point upstream of the ion implantation aperture 5 of the electrostatic trap device 4. Subsequently, the voltage applied to the center plate electrode can be reduced so that the focal point moves backward toward the ion implantation aperture in the opposite direction, and possibly beyond the ion implantation aperture. As described above, the adjustment of the focal point position relative to the nominal operating conditions increases the spatial dispersion of the ion pack entering the electrostatic trap, and this increased spatial dispersion reduces mass spectrometry peak aggregation.

[0085] Figure 4B This is a schematic diagram of an improved ion focusing lens device 36b and a corresponding method according to the teachings of the present invention, used to perturb the operation of the ion focusing lens to cause a shift in the focal position of the ions or spatial dispersion. Figure 4B The method shown does not require any physical translation of the focusing lens relative to its nominal position. Instead, it utilizes the ability to change the electric field strength across a central electrode aperture defined between a pair of central electrode plates 37d and 37e. Specifically, in lens device 36b ( Figure 4B In the ion transfer lens device 36 (Figure 1C), Figure 4AThe single central electrode plate 37b is replaced by two electrode plates 37d and 37e, which are positioned relative to each other across the central axis 41 of the modified ion transfer lens 36b. Electrical connections to the electrode plates 37d and 37e are configured such that a potential difference can be applied between the two electrode plates. When ions enter the ion inlet aperture of the electrostatic trap mass analyzer, an unbalanced electric field generated across the width of the ion path 39 can cause lens aberrations, resulting in an unclear and spatially dispersed focusing area.

[0086] Figure 5A This is a schematic diagram of a quadrupole lens 43, which can be used as an alternative to a single-lens focusing lens 36 (e.g., Figure 1C). As shown, lens 43 is a so-called "DC quadrupole" device containing four quadrupole electrodes 44. Figure 5A Two of the electrodes are shown in the image. For example... Figure 5B As shown in more detail, the quadrupole electrodes are configured as a pair of "x electrodes" 44x and a pair of y electrodes 44y. The electrodes of each pair are arranged opposite each other around axis 41 of the ion path 31. For descriptive purposes, axis 41 is defined herein as the z-axis of the xyz Cartesian coordinate system. A line (not shown) connecting the centers of the x electrodes defines the x-axis, and a second line (not shown) connecting the centers of the y electrodes defines the y-axis, which is substantially orthogonal to the x-axis. The four electrodes are preferably arranged equidistantly around axis 41. Although in Figure 5B Lieutenant generals describe quadrupole electrodes as plates with a circular cross-section, but they are not limited to this shape.

[0087] Figure 5BArrow 46 in the diagram indicates the direction of ion propagation, parallel to the z-axis (axis 41), along ion transport path 31 from ion storage device 2 into electrostatic trap mass analyzer 4. Let V0 represent the potential at point 48, located between the x-electrode and the y-electrode. According to the first operating mode of the quadrupole lens device 43, a DC voltage V0 + ΔV is applied to the y-electrode 44y, which causes the trajectory of ions passing through lens 43 (i.e., in the space between all four electrodes) to be generally deflected toward the xz plane. Simultaneously, a DC voltage V0 - ΔV is applied to the x-electrode 44x, which causes the ion trajectory to generally deviate from the y-axis. Depending on the magnitude and sign (positive or negative) of ΔV, the voltage applied to the x-electrode may have the same polarity as or opposite to the voltage applied to the y-electrode. This first operating mode can be used in situations where suppressing peak aggregation by reducing the charge density or total number of ions within the electrostatic trap is considered more important or advantageous than optimizing certain other mass spectrometry properties (e.g., isotope ratio fidelity). For example, if a large ion cluster is introduced into the electrostatic trap mass analyzer, it may be advantageous to manipulate lens 43 to produce focal line 45 or other diffuse focusing regions in order to reduce the charge density within the trap and thereby reduce peak coalescence.

[0088] As described above under the first operating mode, a first voltage and a second voltage are applied to lens 43 to cause the ion trajectory to converge to focal line 45, instead of using a single-lens focusing lens 36 as in other cases. Figure 3A , 3B That would cause them to converge at point foci f31 and f32. For example, if the ions are positively charged, then an appropriately chosen positive value ΔV can produce... Figure 5B The lines shown are focused. It should be noted that, for clarity... Figure 5B The effect of deflector electrode 34 on ion trajectory Figure 5B Not shown in the diagram. Therefore, according to the action of the deflector electrode 34, the trajectory of the ions is effectively extended away from the z-axis and curved towards the ion inlet aperture 5 after the ions pass through the lens 43. The length of the focal line 45 and its position relative to the ion inlet aperture 5 can be controlled by selecting a value of ΔV. Upon passing through the ion inlet aperture 5, the ions are captured by the electric field within the electrostatic trap, and their subsequent trajectories within the trap are influenced not only by these internal fields but also by the initial position of the ions upon entering the trap. Because the lens 43 spatially disperses each introduced ion packet along the focal line 45, the ions within the packet remain spatially separated within the trap, thereby reducing unwanted interactions between ion species with different m / z values ​​and thus reducing peak coalescence effects.

[0089] According to the second operating mode of the quadrupole lens 43 (not shown in the accompanying drawings), a voltage of V0 + ΔV (which can be negative or positive) is applied to the two pairs of electrodes of the lens, causing the ion trajectories to converge to a point focal point, similar to... Figure 3A , 3B The point focal points f31 and f32 are depicted in the diagram. For example, if the ions are positively charged, a point focal point can be produced by using an appropriately chosen positive value ΔV. This second operating mode can be used in situations where optimizing specific mass spectrometry characteristics (e.g., isotope ratio fidelity) is more desirable or advantageous than suppressing peak aggregation. For example, if small ion clusters are introduced into an electrostatic trap mass analyzer, it may be advantageous to operate lens 43 to produce a tight point focus in order to maintain isotope ratio fidelity and overall peak resolution. The operating mode of the quadrupole lens 43 can be changed from the first mode to the second mode and vice versa, depending on the requirements of the specific analysis or specific analytical set.

[0090] Figure 6 These are a set of simulated initial trajectory trajectories within an electrostatic trap of the type shown in Figures 1A to 1B, calculated using three different injection voltages applied to the central spindle electrode 6. Figure 6 The results described support alternative ion implantation methods for controlling peak coalescence or for balancing the loss of spectral resolution caused by peak coalescence with other quality analyzer performance characteristics. These alternative ion implantation methods do not rely on controlling the ion transfer electrode or inlet lens, but rather on controlling a voltage pulse temporarily applied to the central spindle electrode during ion implantation to “pull” ions into the measurement chamber 17. In use, the implantation voltage applied to the central spindle electrode is supplemented by a “push” into the measurement chamber provided by a voltage of opposite polarity applied to the deflector electrode 34.

[0091] Figure 6 Figures 72, 74, and 76 illustrate the injection of positively charged ions into an electrostatic trap under increasingly negative injection voltages applied to the central mandrel electrode. As the injection voltage pulses become increasingly negative, the initial trajectory of the ions bends further toward the central electrode as they are "captured" by the pull of the central electrode. Typically, as shown in Figure 72, the injection voltage on the inner mandrel electrode is maintained at an optimal value. This ensures that the degree of ion pull towards the central electrode is well matched to the ion entry energy. Under these existing ion implantation conditions, the initial trajectory of the ions around the central electrode follows path 73, in which the ions maintain a substantially circular trajectory in the cross-sectional projection. However, if the actual applied implantation voltage V... 注入 Not equal to The basic form of the orbital changes. For example, as the injection voltage increases, the ion trajectory bends more strongly toward the central electrode, and the paths of subsequent orbits 75 and 77 become increasingly elliptical, as shown in figures 74 and 76. Ions in elliptical orbits eventually collide with the inner electrode and are neutralized. Similarly, if V 注入 The value is less than If the value is greater than that shown in Figure 72, the ions will follow orbital trajectories that bring them closer to the outer electrode 4 than those shown in Figure 72.

[0092] In many measurement scenarios, increasing the orbital ellipticity around the central electrode can lead to one or more of the following adverse effects: reduced overall resolution, lower signal-to-noise ratio, reduced dynamic range, and decreased isotope ratio fidelity. (Note that the term "isotope ratio fidelity" refers to the degree to which the experimentally observed isotope abundance ratio matches the expected isotope abundance ratio.) Nevertheless, the same phenomenon can provide beneficial effects in some other measurement scenarios. In particular, increasing the orbital ellipticity results in each introduced ion packet occupying a larger proportion of the measurement chamber 17 of the electrostatic trap, such as... Figure 6 As shown, the average distance between ions increases and the average space charge density within the measurement chamber decreases. In some cases, the reduced space charge density can lead to a favorable reduction in peak aggregation due to decreased interaction between different ion species with similar m / z.

[0093] From the above considerations, the inventors have recognized that it is advantageous for operators of electrostatic trap mass analyzers to be able to control the ion implantation conditions entering the electrostatic trap to balance generally favorable metrics such as signal-to-noise ratio and isotope ratio fidelity with, at other times, the advantageously increased inter-ion separation. In some cases, ion implantation conditions can be varied between analyses of different samples in response to different analytical needs. In other cases, ion implantation conditions can be varied during repeated analyses of a single sample or even a single analyte to maximize the type and / or quality of information obtained about the analyte. Therefore, Figure 7 This is a flowchart of method 50 according to the invention, used to controllably change ion implantation conditions during the introduction of ions into the electrostatic trap mass analyzer of a mass spectrometer system. In addition to the electrostatic trap mass analyzer, the mass spectrometer system also includes, in particular, an ion storage device and an ion transfer and focusing lens system disposed between the ion outlet of the ion storage device and the ion inlet orifice of the electrostatic trap mass analyzer.

[0094] In step 51 of method 50 Figure 7In step 52, a portion of the ions from the incoming ion stream is accumulated and stored in the ion storage device; this stored portion is referred to herein as an ion pack. During the accumulation of ions within the ion storage device, the ion transfer and focusing lens system is electrically configured such that ions are not released from the ion storage device to the mass analyzer.

[0095] After a predetermined amount of ions has been stored in the ion storage device, or equivalently, after ions have accumulated for a predetermined duration, the next step 53 is performed. In this step, the ion transfer and focusing lens system is configured such that the accumulated ion pack exits the ion storage device toward the mass analyzer. The ion pack is released from the ion storage device under the influence of a potential difference applied between the lens system and the ion storage device.

[0096] During the transfer of the ion pack in step 53, the ion transfer and focusing lens system may, in some cases, be configured in a first configuration to allow the ion pack to enter the ion inlet orifice of the mass analyzer in a spatial configuration that enables the mass analyzer to generate a mass spectrum according to a first desired performance characteristic or a set of desired performance characteristics. In other instances of performing step 53, a voltage of a first predetermined value may be applied to the electrodes of the mass analyzer to generate a mass spectrum according to the first desired performance characteristic. In other instances of performing step 53, the ion transfer and lens system, as well as the mass analyzer injection voltage, may be configured according to the desired performance characteristics. By way of example only, the first desired performance characteristic may involve reducing the aggregation of mass spectral peaks corresponding to individual ion species (e.g., isotopic variants of a single molecular ion species) with very similar m / z values.

[0097] If the ion transfer and focusing lens system is not already in a suitable operating configuration for producing a mass spectrum with the desired performance characteristics before performing step 53, then performing step 53 includes reconfiguring the ion transfer and focusing lens system to a suitable operating configuration. Reconfiguration may include mechanically moving one or more electrodes of the lens system, such as... Figure 2B The movement Δy shown 33 As shown, or as Figure 4A The movement Δy shown 36 and Δx 36 One or both of these are shown. Although mechanical movement can be achieved by any suitable mechanical translation device, one or more piezoelectric transducers are preferred for this purpose. In practice, electrode or lens support structures can be mounted on or adjacent to such transducers. Alternatively, the reconfiguration of the ion transfer and focusing lens system can be performed by controlling the voltage applied to the lens electrodes, such as... Figure 2A and Figure 4B As shown.

[0098] Once the ion pack has been transferred from the ion storage device to the electrostatic trap mass analyzer, step 54 is performed. In this step, the ion transfer and focusing lens system is reconfigured such that no additional ions are transferred out of the ion storage device and the transferred ion pack is trapped within the mass analyzer. During this step, the mass analyzer performs a mass analysis of the ion pack and generates mass spectrometry data. The execution of method 50 then returns to step 52, in which a new ion pack is accumulated within the ion storage device. The complete or partial accumulation of the new ion pack in the ion storage device (step 52) can occur simultaneously with the mass analysis of the previous ion pack in the electrostatic trap mass analyzer (step 54). After the mass analysis is completed, any remaining ions from the previous ion pack are evacuated from the mass analyzer, and execution can optionally return to step 52 once a new accumulated ion pack is ready to be transferred from the ion storage device. Optionally, the execution of method 50 can be repeated in steps 52 through 54 a variable number of times. The exact number of cycles m (where m ≥ 1) depends on many experimental variables, such as the nature and concentration of the compounds in the sample, the type of analysis performed, etc.

[0099] After completing m iterations of steps 52 to 54, where m ≥ 1, execution of method 50 branches to step 55. Steps 55, 56, and 57 are similar to steps 52, 53, and 54, respectively. Specifically, ion storage step 55 and mass analysis step 57 are identical to steps 52 and 54, respectively. Intermediate step 56 is similar to step 53, but differs in that, in step 56, the ion transfer and focusing lens system or the mass analyzer electrode injection voltage (or both) is reconfigured to cause the mass analyzer to generate a mass spectrum according to a second desired performance characteristic or a second set of desired performance characteristics. In some cases, execution of step 56 may involve reconfiguring the ion transfer and focusing lens system in a second configuration to allow ion packets to enter the ion inlet orifice of the mass analyzer in a second spatial configuration that causes the mass analyzer to exhibit one or more desired performance characteristics. In other instances of executing step 56, a second predetermined voltage value may be applied to the electrodes of the mass analyzer to generate a mass spectrum according to a first desired performance characteristic. In other instances of performing step 56, the ion transfer and lens system, as well as the mass analyzer injection voltage, can be configured according to the desired performance characteristics.

[0100] Steps 55 to 57 contain a second set of steps, which may optionally be repeated a variable number of times. In other words, the set of steps 55 to 57 may be performed a total of n times, where n ≥ 1. While the first set of potentially iterative steps (steps 52 to 54) contains a set of mass analyses during which a first desired mass spectrometry characteristic or a first set of desired mass spectrometry characteristics is optimized, the second set of iterative steps (steps 55 to 57) contains another set of mass analyses during which a second desired mass spectrometry characteristic is optimized. For example, the second desired performance characteristic may involve improving the mass spectrometry signal-to-noise ratio by allowing a certain level of coalescence of isotope variant peaks.

[0101] Typically, the first and second mass spectrometry characteristics or sets of characteristics described above correspond to different types of mass spectrometry information, and simultaneous optimization of both is difficult to achieve. For example, if the mass spectrometry resolution of a given compound's dense isotopes is the analytical target, it might be desirable to operate the mass spectrometer system with the electrostatic trap mass analyzer in a manner that minimizes peak coalescence as described above. Conversely, if it is desired to use mass analysis to accurately quantify low concentrations of a known compound in a sample, the lower limit of quantification can be improved by utilizing the signal-to-noise ratio improvement that occurs when isotope coalescence is allowed. In a first example, the ion transfer and focusing optics can be configured and / or operated such that the path of the ion pack is defocused or otherwise spatially dispersed when it enters the electrostatic trap mass analyzer at its ion inlet orifice. In a second example, the ion transfer and focusing optics can be configured and / or operated according to nominal operation, wherein the ion path is tightly focused at the location of the ion inlet orifice.

[0102] The execution of steps 52 to 54 and steps 55 to 57 of method 50 can both involve the same sample composition, possibly as part of a single analysis. This can be applied when optimal measurements of the first and second mass spectrometric characteristics of a single sample are desired. Alternatively, the execution of steps 52 to 54 and steps 55 to 57 can involve different sample compositions obtained from different samples or from a single sample. In the latter case, different sample compositions can be continuously introduced into the mass spectrometer due to the separation or fractionation of sample components by a separation or fractionation device (e.g., a chromatograph) supplying sample material to the mass spectrometer system. In this case, the change from executing steps 52 to 54 (if repeated) to executing steps 55 to 57 can be automated in response to the analysis of mass spectrometric data generated by the mass spectrometer. After possible repetitions of steps 55 to 57 are completed, as a result of the determination made in determination step 58, the execution of method 50 can return to step 52, after which the set of steps 52 to 54 can be executed again, possibly multiple times.

[0103] The discussion included in this application is intended to serve as a basic description. Although the invention has been described with reference to the various embodiments shown and described, it will be readily apparent to those skilled in the art that variations may be made to the embodiments and that such variations should be within the spirit and scope of the invention. The reader should be aware that the specific discussion may not explicitly describe all possible embodiments, and many alternatives are implicit. Therefore, many such modifications can be made by those skilled in the art without departing from the spirit and essence of the invention. The descriptions and terminology are not intended to limit the scope of the invention. Many patents, patent applications, patent application publications, or other documents mentioned herein are incorporated herein by reference in their entirety as if fully set forth herein.

Claims

1. A method for controlling mass spectral clumping during operation of a mass spectrometer system comprising an electrostatic trap mass analyzer, the method comprising: storing a portion of an ion stream generated by an ion source as a first ion packet within an ion storage device of the mass spectrometer system; transferring the stored first ion packet as a beam through one or more electrostatic lenses into an injection slit of the electrostatic trap mass analyzer, wherein, applying one or more first voltages to the one or more electrostatic lenses causing an adjustment in a focal position of the beam within the injection slit or to the spindle electrode of the mass analyzer causing an increase in the ellipticity of ion orbit trajectories within the mass analyzer during transfer of the first ion packet into the electrostatic trap mass analyzer; mass analyzing the first ion packet using the electrostatic trap mass analyzer such that mass spectral clumping is reduced due to the adjustment in the focal position or the increase in the orbital ellipticity; storing a second portion of the ion stream as a second ion packet within the ion storage device; transferring the stored second ion packet as a second beam through the one or more electrostatic lenses into the injection slit of the electrostatic trap mass analyzer, wherein one or more second voltages are applied to the one or more electrostatic lenses causing an adjustment in a focal position of the beam within the injection slit or to the spindle electrode causing a decrease in the ellipticity of ion orbit trajectories within the mass analyzer during transfer of the second ion packet into the electrostatic trap mass analyzer; and mass analyzing the second ion packet using the electrostatic trap mass analyzer such that isotopic ratio fidelity or signal-to-noise ratio is reduced due to the adjustment in the focal position or the decreased ellipticity.

2. The method for controlling mass spectral clumping during operation of a mass spectrometer system comprising an electrostatic trap mass analyzer according to claim 1, wherein the voltages applied to the electrostatic lenses or the spindle electrode are changed from the first voltages to the second voltages in response to a difference between ion population sizes of the first ion packet and the second ion packet.

3. The method for controlling mass spectral clumping during operation of a mass spectrometer system comprising an electrostatic trap mass analyzer according to claim 1 or 2, wherein changing the one or more voltages applied to the electrostatic lenses or the spindle electrode comprises changing at least one voltage applied to a DC quadrupole lens.

4. The method for controlling mass spectral clumping during operation of a mass spectrometer system comprising an electrostatic trap mass analyzer according to claim 1 or 2, wherein the one or more voltages applied to the electrostatic lenses or the spindle electrode are changed from the first voltages to the second voltages between consecutive mass spectral analyses of a single sample or between consecutive mass spectral analyses of a single analyte.

5. The method for controlling mass spectral clumping during operation of a mass spectrometer system comprising an electrostatic trap mass analyzer according to claim 1 or 2, wherein the one or more voltages applied to the electrostatic lenses or the spindle electrode are changed from the first voltages to the second voltages between mass analysis of a first sample and mass analysis of a second sample or between mass analysis of a first analyte and mass analysis of a second analyte. ​ 6. A mass spectrometer system comprising: an ion source; an ion storage device configured to receive ions from the ion source; an electrostatic trap mass analyzer configured to receive ion packets from the ion storage device, the electrostatic trap mass analyzer comprising: an inner hub electrode; and one or more outer electrodes; a measurement cell comprising a space between the inner hub electrode and the one or more outer electrodes; and ion inlet apertures of the one or more outer electrodes; a set of ion lenses disposed between the ion storage device and the electrostatic trap mass analyzer; one or more power sources electrically coupled with the ion storage device, the electrostatic trap mass analyzer, and the set of ion lenses; and an information processor electrically coupled with one or more of the one or more power sources, the ion storage device, the electrostatic trap mass analyzer, and the set of ion lenses, and comprising computer readable instructions operable to cause the information processor, the one or more power sources, and the mass spectrometer system to perform the method of any of claims 1-5. ​ ​

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