Mass spectrometer and method

Abstract

A charge detection mass spectrometer (CDMS) is described, comprising an electrostatic sector field ion trap (40) and an induced charge detector (400), the electrostatic sector field ion trap (40) configured to at least partially define an ion path through the induced charge detector (400). A method is also described.

Description

[Technical Field]

[0001] This invention relates to charge detection mass spectrometers (CDMS). [Background technology]

[0002] Charge-detection mass spectrometry (CDMS) is a technique that enables the deconvolution of the complex spectra of polymers. As molecular size increases, the number of different charge states that a polymer can acquire increases. In the extreme, superimposing the charge states of molecules with different masses results in a blurred continuum on the mass-versus-charge m / z scale of conventional mass spectrometers (MS). Such mass spectra provide little to no analytically useful information, as individual species no longer stand out as distinct peaks. This is particularly problematic in the case of electrosplashing of polymers, as this ionization technique yields many different charge states as molecular weight increases. In contrast to MS, which determines the mass-versus-charge m / z of an ion, CDMS determines the mass (i.e., not just mass-versus-charge m / z) by determining both the mass-versus-charge m / z and charge z of the ion. In conventional CDMS, individual ions are injected into an ion trap and made to vibrate back and forth through an inductive charge detection tube. When a specific ion enters an induced charge detection tube, it induces a small, measurable voltage whose amplitude is proportional to its charge. The measured period time of the oscillation yields the mass-to-charge ratio (m / z) of the specific ion, and the product of these two measurements gives the true mass of the specific ion. Allowing for numerous oscillations within the ion trap and analyzing the resulting signal by Fourier transform (FT) improves the accuracy of both the charge measurement and the mass-to-charge ratio (m / z) measurement. The measurement of true mass is in contrast to conventional MSs such as orthogonal-acceleration time-of-flight (oa-TOF) MSs, which only determine the mass-to-charge ratio (m / z). The accuracy of CDMS depends on two limiting factors: electronic noise in the detection electronics, which gives uncertainty in the charge measurement, and the energy spread of the incident ion, which gives variability in the oscillation period.

[0003] In 2012, Contino and Jarrold[1] presented a charge-detection mass spectrometer (CDMS, as is evident from the context, also known as a CDMS analyzer) with a limitation of detecting 30 elementary charges for a single ion. This paper provides a comprehensive review of CDMS at that time and is incorporated by reference in whole to this specification. This CDMS comprises a cone trap incorporating an electrospray source coupled to a dual hemispherical deflection analyzer (HDA), followed by an enantiomer-charge detector. The ion was selected by the dual HDA at the energy before entering the trap. The fundamental vibrational frequency of the trapped ion was extracted by fast Fourier transform (FFT). The vibrational frequency and kinetic energy gave the mass-to-charge ratio m / z of the trapped ion. The magnitude of the FFT at the fundamental frequency was proportional to the charge. In particular, this CDMS required the use of dual HDAs as energy filters to limit the spread of ion energy entering the electrostatic cone trap, thereby reducing the variation in oscillation frequency, in order to achieve the limit of detecting 30 elementary charge for a single ion. However, limiting the spread of ion energy entering the electrostatic cone trap reduced the throughput of the CDMS. Low-noise electronics, by 2015, Keifer, Shinholt, and Jarrold[2] had shown improved charge accuracy better than integer levels, which meant that this was sufficient for determining the true mass.

[0004] In 2018, Hogan and Jarrold[3] used a segmented electrostatic linear ion trap (ELIT) with lower dependence of ion energy on vibrational period than their previous CDMS cone trap. This CDMS also required the use of dual HDA energy filters, while retaining considerable dependence of ion energy on vibrational frequency due to the spread and radial position. In particular, for this CDMS, the kinetic energy dependence of ion vibration frequency was reduced by an order of magnitude, which should have resulted in an order of magnitude reduction in the uncertainty of the mass-to-charge ratio (m / z) determination. However, only four factors of improvement due to the orbital dependence of ion vibration frequency were achieved.

[0005] Therefore, there is a need to improve the CDMS. [Overview of the Initiative] [Problems that the invention aims to solve]

[0006] Among many objectives of the present invention is to provide a CDMS that eliminates or partially eliminates at least some of the drawbacks of the prior art, whether or not they are identified herein. For example, an objective of embodiments of the present invention is to provide a CDMS having an ion trap geometry that eliminates the need for an upstream energy filter or selector. For example, an objective of embodiments of the present invention is to provide a CDMS that improves the isochronism of the ion oscillation period, for example, by reducing dependence on initial ion conditions. For example, an objective of embodiments of the present invention is to provide a CDMS having an ion trap geometry that eliminates the need for an upstream energy filter or selector while improving the isochronism of the ion oscillation period, for example, by reducing dependence on initial ion conditions. [Means for solving the problem]

[0007] The first aspect is, Electrostatic sector field ion trap and inductive charge detector, comprising A charge detection mass spectrometer (CDMS) is provided, in which an electrostatic sector field ion trap is configured to at least partially define an ion path via an induced charge detector.

[0008] A second aspect is a process of moving ions along an ion path at least partially defined by an electrostatic sector field ion trap, thereby passing through an induced charge detector; a process of inducing a signal in the induced charge detector by moving the ions; a process of determining the mass of the ions using the induced signal; and provides a method for determining the mass of ions.

[0009] <Detailed Description of the Invention> According to the present invention, a CDMS as described in the appended claims is provided. A method is also provided. Other features of the present invention will be apparent from the dependent claims and the following description.

[0010] A first aspect comprises an electrostatic sector field ion trap and an induced charge detector; A charge detection mass spectrometer (CDMS) is provided, in which an electrostatic sector field ion trap is configured to at least partially define an ion path via an induced charge detector.

[0011] The inventors recognized that a major limitation of modern CDMS instruments lies in the dependence of the ion vibration frequency on the initial angle, position, and especially the energy spread of the incident ion. A further limitation is the low space charge capacity of modern electrostatic reflection traps. Slow ions are known to interact more strongly with each other than fast ions. The low space charge capacity results from the deceleration of ions to near-zero velocity when they reverse direction within the mirror section of the reflection trap. This low space charge capacity of these reflection traps generally necessitates sequential injection of single ion species, and consequently, low duty cycles and long experimental times.

[0012] The inventors recognized that the need for an improved CDMS trap was provided by the ionic optical properties of an aberration-free TOF analyzer equipped with an electrostatic sector field. In a highly influential 1972 paper by Poschenrieder[4] (incorporated herein), a general theory of isochronous focusing using a combination of a toroidal electrostatic sector and a field-free drift region was presented. The study directed towards a classical time-of-flight analyzer with inlet and outlet apertures, using a destructive electron multiplier-based detector. It was shown that the effects of initial energy and angular spread could be eliminated to the first order, and in certain special cases, positional spread could also be eliminated. An analyzer that satisfies all three initial conditions in the detector plane, namely energy, position, and angle, to the first order is known as an aberration-free analyzer. In this paper, Poschenrieder presented a special geometry utilizing two opposing spherical field sectors arranged to deliver ions in a stereoscopic diagram of eight paths. The consideration of symmetry results in aberration-free behavior for the proposed geometry, as well as stable ion confinement for many round trips in the analyzer. The use of this geometry presents problems for TOF analyzers, as injection and detection are difficult due to the closed paths taken by ions. Closed-path multiple round-trip analyzers are well known to suffer from mass range limitations when ions of different masses overtake each other, resulting in aliased spectra.

[0013] Unlike TOF, CDMS does not inject ions in isochronous packets; rather, sections of the ion beam containing individual ions are allowed to enter the device, trap them, and they can oscillate independently along a closed ion path. Such a diagram of an 8-sector TOF meets the requirements for improved ion trapping for CDMS instruments due to its superior ion optics in terms of energy and lateral acceptance. During operation, ions are injected through holes in an outer sphere which are held at a low potential during injection and can then be raised to trap the ions over a desired time period. Such an injection method for a 8-sector TOF diagram is described in a patent by Ishihara

[13] .

[0014] <Electrostatic Sector Field Ion Trap> It should be understood that an electrostatic sector-field ion trap is a periodic structure that defines a closed ion path (also known as an orbit) so that ions can repeatedly move along the closed ion path (e.g., an integer or non-integer number of turns) (also known as oscillation). Generally, ions move along the ion path through at least one turn, preferably at least N turns, where N is a natural number greater than or equal to 1, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 50, 100, 200, 500 or greater. Thus, an electrostatic sector-field ion trap may be known as a multi-turn (also known as a multi-path) electrostatic sector-field ion trap, and a CDMS may be known as a multi-turn CDMS. Generally, increasing the number of turns the ions move and therefore the measurement time reduces the uncertainty in mass determination. However, increasing the number of turns also increases the analysis time, while increasing the possibility of loss of specific ions due to residual gases, other ions, and / or collisions with the walls of the CDMS. The vacuum should be, for example, no higher than 2.7 x 10⁻⁶. -7 Pa(2x10 -9By improving to Torr or higher, the possibility of loss of specific ions due to collisions with residual gases can be reduced, thereby increasing the number of turns. Thus, the number of turns for ion movement can be balanced accordingly. The fundamental frequency f of ions moving along the ion path is measured using an inductive charge detector, as described below, depending on the mass-to-charge ratio m / z. If the electrostatic sector-field ion trap is isochronous to the first order, the mass uncertainty can be reduced, for example, compared to the ELIT in reference [3], as described in more detail below.

[0015] It should be understood that an electrostatic sector-field ion trap is configured to define at least partially the ion path through an inductive charge detector. That is, when in use, the electrostatic sector-field ion trap defines at least partially the ion path through the inductive charge detector. It should be understood that at least partially, the ion path may be defined entirely by the electrostatic sector-field ion trap, or alternatively, partially defined by the electrostatic sector-field ion trap and partially defined by one or more ion optical elements, such as lenses and / or magnets. In one example, the electrostatic sector-field ion trap is configured to define (i.e., entirely) the ion path through an inductive charge detector. It should be understood that the ion path is the ion optical axis for a hypothetical complete ion, the ion optical axis is arc-shaped, and the closed line defines a plane. In contrast, the spread of energy, along with the angular and spatial deviations of the ion population, means that each ion orbit deviates in and out of the plane from the ion optical axis so that the ion path sweeps volumetrically around the ion optical axis. It should be understood that the cross-section of the ion path, e.g., the shape and / or dimensions of the cross-section, and the orthogonality thereto, can vary along the ion path. In particular, as will be explained in more detail below, ions can be transported along the ion path, for example, to point focus and parallel focus, while a spherical electrostatic sector can, for example, cause an ion path that is at least partially spherical. Furthermore and / or alternatively, the ion path may be described and / or defined as an ion beam.

[0016] It should be understood that when ions move along an ionic path in a constant direction, this can be called unidirectional in that the direction of the orbit is constant, even though the instantaneous direction of the ion's motion is constantly changing. In contrast, in ELITs such as those in references [2] and [3], ions move alternately in opposite directions, back and forth, which can be called bidirectional or reciprocal in convenience, resulting in mutual interaction between ions moving in opposite directions, which excludes introducing more than a single ion into the system. More specifically, typically thousands of ions are measured to produce a mass spectrum depending on the heterogeneity of the sample. According to the sequential (or random) trapping modes in reference [3], the probability that an ELIT contains zero ions, one ion, or two or more ions is given by a Poisson distribution such that the maximum number of ELIT trapping events of a single ion that can occur is exactly 37% (i.e., a 37% duty cycle). During a trapping period of 100 ms, the optimal rate of single ion trapping events is equal to the maximum of approximately 13,300 single ion events per hour for ELIT (i.e., when the signal is stable and the number of single ion trapping events is close to the maximum possible value), so that a spectrum of a uniform sample can be acquired within 30 minutes under optimal conditions. In contrast, a unidirectional closed ion path, at least partially defined by an electrostatic sector-field ion trap, may be used to simultaneously determine the respective masses of multiple ions, for example, as described in detail below, thereby reducing the acquisition time compared to ELIT. In particular, as mentioned above, a unidirectional ion path reduces or eliminates the mutual interactions between multiple of those ions, so the space charge capacity of an electrostatic sector-field ion trap is increased compared to a reflection-based ion trap, where ions must slow down to a low velocity when ions change direction within the mirror section.Furthermore, for example, the ion paths for an electrostatic sector-field ion trap generally allow ions to spread laterally with respect to the ion optical axis, for example, in an arc. Therefore, for a given ion path length, the effective average cross-sectional area of ​​the ion path, and thus its volume, is larger for an electrostatic sector-field ion trap than for an ELIT. Thus, an electrostatic sector-field ion trap can be filled with a relatively larger number of ions, for example, an order of magnitude or more, compared to an ELIT, while the kinetic energy of the ions remains relatively constant. Moreover, the bidirectional or round-trip ion paths of the ELIT in references [2] and [3] resulted in overlapping signals being induced in the charged tube when, for example, two or more ions were trapped, thereby hindering mass determination. In contrast, a unidirectional ion path means that the possibility of overlapping signals induced in the induced charge detector by two or more ions is reduced. Generally, partially overlapping induced signals can be separated within the frequency domain, but it should be understood that completely overlapping induced signals, for example, due to phase-coherent ions, overtake ions, or ions moving in opposite directions, can exclude mass determination. Therefore, to avoid phase-coherent ions, ion packets or clouds are preferably avoided, while unidirectional paths eliminate movement in opposite directions. In particular, as described below, more specifically, multiple ions may be introduced so as to be spatially and / or temporally separated from one another, thereby reducing or eliminating the possibility of overlapping signals induced in the induced charge detector. Thus, with respect to ELIT, by increasing the number of ions in the electrostatic sector-field ion trap by as little as 10, and since the duty cycle is not limited to only 37%, the same mass spectrum can instead be obtained in less than one minute.

[0017] Generally, the ion-light description of ion transfer between the inlet and outlet of an analyzer can be represented as a transfer matrix or by ray tracing. A curvilinear coordinate system (x,y,z) can be defined such that its origin lies on the optical axis and z is along it. For ions of equal mass, such a transfer matrix is:

[0018]

number

[0019] Regarding the applications of interest, the ions are generated from low-luminosity light sources and have relatively low energy (i.e., low-energy ions), but have a relatively large energy spread δK.

[0020] When (δT|δK)=0, ions with the same mass-to-charge ratio m / z but different energies move through the analyzer in the same amount of time. Such an analyzer is energy isochronous. In one example, |(δT|δK)|≦0.1, preferably |(δT|δK)|≦0.05, and more preferably |(δT|δK)|≦0.01. That is, the analyzer can be quasi-energy isochronous, thereby allowing for a relatively large number of turns while relaxing the geometric tolerances. The ranges of (δT|X), (δT|A), (X|δK), and / or (A|δK) can be similarly defined.

[0021] It should be understood that the focal plane is the position where ions sent from the optical axis with an angular distribution are transported after passing through the analyzer. In one dimension x, this is mathematically expressed in the aberration theoretical notation as (x|a)=0. If (x|a)=(y|b)=0 at the focal plane, the analyzer behaves aberration-free (i.e., it is aberration-free).

[0022] More generally, ions having the same mass-to-charge ratio m / z but different energies and inlet angles will move through the outlet independently of the energy and inlet angle of the inlet angle, if (X|A)=(A|X)=(A|δK)=0. Such analyzers are aberration-free and achromatically focusing, and the orbits are mirror-symmetric. In one example, |(X|A)|, |(A|X)|, and / or |(A|δK)|≦0.1, preferably |(X|A)|, |(A|X)|, and / or |(A|δK)|≦0.05, more preferably |(X|A)|, |(A|X)|, and / or |(A|δK)|≦0.01. That is, the analyzer can be quasi-aberration-free and / or quasi-achromatic, thereby allowing for a relatively large number of turns while relaxing the geometric tolerances.

[0023] Generally, an achromatic system is one in which the transfer matrix elements for the ax-coordinate are independent of momentum. Generally, an isochronous system is one in which the elapsed time of a trajectory through the system is independent of the initial coordinates. It is well known that first-order achromatic systems are also isochronous, except for their pure momentum dependence. The converse is also true. This result can be extended to higher orders. The condition is that for a system in which all chromatic terms vanish up to a certain order, the elapsed time can be found to be independent of the ax-coordinate up to the same order. Under the same conditions, the converse is also true.

[0024] However, the spatial focusing requirement (X|A)=(A|X)=0 requires identical ionic orbitals for a given ion for each turn. For applications of interest, the spatial focusing requirement only requires that a given ion moves stably in phase space, and therefore, -2 ≤ (X|X) + (A|A) ≤ 2 This may be mitigated by requiring [something].

[0025] In this way, specific ions can move along different orbits during different turns. This relaxation can, for example, increase design degrees of freedom and / or tolerate construction errors, while alternatively and / or further, accommodate spatial and / or angular deviations arising from ion implantation, for example.

[0026] Conversely, perfect spatial and temporal focusing eliminates ion beam divergence and degradation of mass resolution by returning specific ions to the same position and the same tilt angle at every turn as the number of turns increases. Geometry of TOF MS analyzers having such perfect spatial and temporal focusing has been proposed (plans of MULTUM, MULTUM II, and 8), which is partly constructed with reference to

[15] , as described in more detail below, and

[15] is incorporated in whole into this specification.

[0027] In one example, an electrostatic sector-field ion trap comprises a set of electrostatic sectors, including a first electrostatic sector and a second electrostatic sector. It should be understood that the first and second electrostatic sectors are spaced apart from each other, for example, by a field-free region (also known as drift space), and traversed by an ion path. It should be understood that an induced charge detector is positioned within the field-free region. The induced charge detector may be positioned in the electric field, but direct capacitive coupling of noise from the power supply limits detection. In one example, an electrostatic sector-field ion trap comprises a set of electrostatic sectors, including a first and second electrostatic sector, and a set of electrostatic quadrupole lenses, including Q quadrupole lenses, for example, where Q is a natural number greater than or equal to 1, and Q is four or six times the number of electrostatic sectors. Generally, quadrupole lenses focus in one coordinate direction and defocus in mutually orthogonal coordinate directions. Therefore, a single quadrupole lens cannot be used, for example, to focus an ion beam to a point or to generate a two-dimensional image. However, two-dimensional focusing can be achieved using combinations of quadrupole lenses, such as two quadrupole lenses (doublets) and three quadrupole lenses (triplets). For example, two quadrupole lens doublets may be placed corresponding to the inlet and outlet of the electrostatic sector, respectively. In one example, an electrostatic sector field ion trap does not have a set of electrostatic quadrupole lenses and / or RF electric lenses, thereby reducing complexity. The electrostatic sector comprises two corresponding electrodes spaced radially apart from each other, having radii of curvature corresponding to two mutually orthogonal dimensions, to which corresponding and opposing DC electric potentials are applied, thereby providing a toroidal electric field that defines the ion optical axis passing through it, preferably the electric potential on the ion optical axis (i.e., the central orbit) is the same as the electric potential in the field-free region, e.g., ground. It should be understood that an electrostatic sector field ion trap is equipped with an electrically coupled set of power sources, such as a DC power supply.

[0028] Furthermore and / or alternatively, an electrostatic sector-field-ion trap can be defined by a set of cells (also known as a unit or element) comprising a first cell and a second cell, the first cell comprising a set of drift spaces, and the set of electrostatic sectors comprising the first electrostatic sector and, as appropriate, a set of quadrupole lenses. It should be understood that the second cell may be as described with respect to the first cell. The symmetric geometry of the cells is more easily understood, but the principle extends to asymmetric geometry cells. An electrostatic sector-field-ion trap defined by four cells can be thought of as a bisymmetric geometry of two cells, such as MULTUM and MULTUM II in reference

[15] . At first glance, the plan view of the geometry of eight in reference

[15] appears to be defined by two cells, but complete focusing is achieved after two turns, and therefore this plan view of the geometry of eight is also defined by four cells.

[0029] In one example, the first electrostatic sector comprises a cylindrical electrostatic sector, a toroidal electrostatic sector, or a spherical electrostatic sector, and / or a cylindrical electrostatic sector, a toroidal electrostatic sector, or a spherical electrostatic sector. The cylindrical electrostatic sector gives the simplest geometry and effectively has a single radius of curvature in only one dimension (the second radius of curvature in mutually orthogonal dimensions is infinite), but does not confine ions in its orthogonal dimension, for example, in the y-direction, and thus generally requires confinement of the electric field in the y-direction (curvilinear coordinates). The cylindrical electrostatic sector is generally used in conjunction with electrostatic quadrupole lenses. Planar diagrams of the MULTUM and 8 geometries in reference

[15] show four and two cylindrical electrostatic sectors, respectively, each with eight electrostatic quadrupole lenses. A toroidal electrostatic sector has two different radii of curvature in two mutually orthogonal dimensions, the ratio of which must be determined for effectiveness, and can confine ions in both dimensions without requiring an electrostatic quadrupole lens. Because toroidal electrostatic sectors have two different radii of curvature, their construction is relatively more complex. MULTUM II in reference

[15] and the oblong rectilinear geometry in reference

[16] each feature four toroidal electrostatic sectors and do not require an electrostatic quadrupole lens. A spherical electrostatic sector is a special case of a toroidal electrostatic sector with two identical radii of curvature, and can confine ions in both dimensions without requiring an electrostatic quadrupole lens. The figure of geometry 8 in reference [4] features two spherical electrostatic sectors and does not require an electrostatic quadrupole lens. Thus, by basing cells on spherical electrostatic sectors, the number of ion optical components can be reduced compared to cells based on cylindrical or toroidal electrostatic sectors.

[0030] In one example, the first electrostatic sector has a deflection angle ψ0 greater than 45.0°, preferably at least 60.0°, for example, in the range of greater than 60.0° to 270.0°, preferably in the range of 90.0° to 240.0°. In one example, the second electrostatic sector is such that it is described with reference to the first electrostatic sector, and for example, has the same or a different deflection angle ψ0. In one example, each electrostatic sector of a pair of electrostatic sectors has the same deflection angle ψ0. In this way, complexity is reduced and / or symmetry is increased. In one example, the alternative electrostatic sectors of a pair of electrostatic sectors have the same respective deflection angles ψ0.

[0031] In one example, a pair of electrostatic sectors have a total deflection angle ψ0 greater than 360.0°, preferably at least 390.0°, for example, in the range of greater than 360.0° to 720.0°, and preferably in the range of 390.0° to 660.0°. That is, the ion path includes a crossover.

[0032] In one example, a set of electrostatic sectors may or may not consist of a ring of eight 45° toroidal electrostatic sectors. In one example, the first and second electrostatic sectors are opposite each other, for example, directly, obliquely, and / or diametrically, and the ion path and / or ion optical axis is linear between the exit of the first electrostatic sector and the inlet of the second electrostatic sector. In one example, the ion path and / or ion optical axis between the exit of the first electrostatic sector and the inlet of the second electrostatic sector is within a field-free region. That is, for example, the ion path and / or ion optical axis between the exit of the first electrostatic sector and the inlet of the second electrostatic sector does not include a quadrupole lens.

[0033] In one example, a set of electrostatic sectors comprises only a first electrostatic sector and a second electrostatic sector, preferably the first and second electrostatic sectors being spherical electrostatic sectors of radius r with a deflection angle ψ0 of nominal 199.2°, for example, in the range of 198.2° to 200.2°, preferably in the range of 198.7° to 199.7°, more preferably in the range of 199.0° to 199.4°, for example 199.2°, and the electrostatic sector field ion trap has a nominal length g of 5.9r (for example, within 2%, preferably within 1%). r It features four field-free regions, thereby providing three-dimensional diagrams of eight geometries according to reference [4].

[0034] In one example, an electrostatic sector field ion trap comprises a pair of field-free regions (also known as drift regions) including a first field-free region and a second field-free region. In one example, the length of the ion path through the pair of field-free regions is at least 50%, preferably at least 55%, more preferably at least 60%, and most preferably at least 65% of the total length of the ion path. In this way, an inductive charge detector can be positioned within the pair of field-free regions so as to extend along about 50% of the ion path, thereby increasing the measurement duty cycle.

[0035] In one example, the first electrostatic sector comprises a set of shunts, including a first shunt positioned to define the field by the first electrostatic sector. In this way, the edge field by the first electrostatic sector can be controlled and / or the induced charge detector is shielded from the field. For example, the shunt can attenuate noise coupled to the induced charge detector by several orders of magnitude. For instance, a 100V power supply electrically coupled to the first electrostatic sector may exhibit <1mV RMS noise. Using the shunt, this noise can be attenuated to approximately 1μV RMS, and is therefore compatible with a suitable charge-sensitive amplifier with a sensitivity of typically 0.6μV / charge.

[0036] In one example, an electrostatic sector-field-ion trap (i.e., its behavior) is isochronous up to the first order with respect to energy (i.e., energy isochronism), for example, after one turn and / or an integer number of turns, as described above. In this way, the uncertainty of the mass-to-charge ratio m / z is reduced compared to ELITs such as ELIT in reference [3]. Exemplary geometries for such electrostatic sector-field-ion traps include Figure 8 in reference [4], the plan view of MULTUM, MULTUM II, and 8 in reference

[15] , and the long-rhombus in reference

[16] . Other geometries are known. In one example, an electrostatic sector-field-ion trap is isochronous up to the first order with respect to energy and has residual up to the second order, for example, parabolic residual up to the second order. In this way, the uncertainty of the mass-to-charge ratio m / z is further reduced due to the small dispersion of ion energy ΔE. Second-order spatial aberrations result in ions being perturbed as they orbit, which can be controlled using a limiting electric field to prevent ion losses resulting from perturbations in electrostatic sector-field ion traps based on cylindrical and / or toroidal electrostatic sectors, or, for example, spherical electrostatic sectors, which can enable electrostatic sector-field ion traps.

[0037] In one example, an electrostatic sector field ion trap is configured to at least partially define ion paths in two or three mutually orthogonal dimensions. For example, an electrostatic sector field ion trap can be configured to at least partially define ion paths in two mutually orthogonal dimensions such as x and z dimensions, and may be called a planar electrostatic sector field ion trap, where the ion optical axis defines the plane. It should be understood that deviations in position, tilt angle, and / or energy cause ions to move away from the ion optical axis, so that they can be represented, for example, in phase space, by the distribution through which the ion beam traverses it. Exemplary planar electrostatic sector field ion traps include the planar MULTUM, MULTUM II, and 8 in reference

[15] , as well as the oblong rhombus in reference

[16] . The construction of such a planar electrostatic sector field ion trap can be simplified and may be based on a cylindrical electrostatic sector, a toroidal electrostatic sector, and / or a spherical electrostatic sector, including quadrupole lenses as needed.

[0038] In one example, the ion paths defined by the electrostatic sector-field ion trap include crossover or point focusing, e.g., the planar diagrams of MULTUM, MULTUM II, and 8 in reference

[15] , and the diagram of 8 in reference [4]. In this way, the electrostatic sector-field ion trap can be isochronous with respect to energy, while the length of the ion path is increased with respect to a given periphery or area of ​​the electrostatic sector-field ion trap, for example, compared to a ring.

[0039] <Induced Charge Detector> CDMS is equipped with an inductive charge detector, and the ion path is determined via (i.e., through) the inductive charge detector. In other words, the inductive charge detector surrounds or encloses at least a portion of the ion path.

[0040] Generally, when ions move through an induced charge detector, the ions induce a charge, which is detected by a charge-sensitive amplifier, and the charge-sensitive amplifier outputs a signal. The induced charge detector comprises a charge-sensitive amplifier and a suitable digitizer that can be communicatively coupled to or coupled to a computer with a processor and memory, and it should be understood that the mass of the ions can be determined using the signal by, for example, Fourier analysis using the Fourier transform (FT) or fast Fourier transform (FFT), least squares, filtered diagonalization (FDM), and / or maximum likelihood method. In one example, the signal comprises and / or is a time-domain signal, and the time-domain signal can be amplified and / or digitized for analysis. The use of FFT allows, for example, detection of charges that do not exceed noise in the time domain and reduces the LOD to <7e (elementary charge). The mass-to-charge ratio m / z is,

[0041]

number

[0042] In one example, the induced charge detector comprises a first set of charge detection tubes, including a first charge detection tube. For example, the charge detection tubes can be arranged in one or more field-free regions, for example, in all of the field-free regions. For example, the first set of charge detection tubes may comprise a segmented charge detection tube comprising multiple charge detection tubes, and / or a segmented charge detection tube comprising multiple charge detection tubes. In one example, the induced charge detector comprises a set of C charge detection tubes, including the first set of charge detection tubes, where C is a natural number greater than or equal to 1, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more, and for example, C is equal to the number of field-free regions. In this way, the duty cycle of induced charge detection can be increased. In one example, the first set of charge detection tubes comprises a segmented charge detection tube, for example, a charge detection tube segmented axially and / or radially, and / or a segmented charge detection tube, for example, a charge detection tube segmented axially and / or radially. By segmenting the charge detection tube axially such that the segments are in series or tandem, signals can be continuously induced segment by segment as ions move through them. For example, increasing the length of the segments beyond approximately twice the width of the segments, as described below, does not substantially increase the magnitude of the induced signal, while multiple segments and thus induced signals improve the measurement statistics. By segmenting the charge detection tube radially such that the segments are parallel, two ions can occur substantially simultaneously in the z dimension (curvilinear coordinates) but are separated from each other in the x and / or y dimensions, inducing signals in different radial segments, thereby reducing the possibility of signal overlap by the two ions, otherwise the charge would move together through the detected tube. In this way, the ion capacity of the CDMS can be increased. In one example, the internal cross-section of the induced charge detector, e.g., its shape, corresponds to, e.g., the cross-section of the ion path through it, e.g., its shape, or is similar to it.For example, a charge detection tube having a cylindrical lumen is generally suitable for cylindrical ion paths, but the first charge detection tube may be configured to have a tapered lumen corresponding to a frustoconical ion path entering and / or exiting an electrostatic quadrupole lens, or to provide an annular or tapered annular portion to an ion path entering and / or exiting a spherical electrostatic sector. In one example, the first charge detection tube comprises an outer electrode and an inner electrode, thereby providing an annular or tapered annular portion through which an ion path passes, and optionally comprising one or more supports between them, for example, arranged and / or having cross-sections configured to reduce the possibility of ion collisions with them.

[0043] In one example, a first charge detection tube having length L and width W has a ratio in the range of 3:2 to 8:2, preferably in the range of 3:2 to 5:2, for example, a length L to width W ratio of 2:1, and / or at least a length L to width W ratio of 2:1. In particular, the magnitude of the induced signal does not substantially increase by making the first charge detection tube longer relative to its width.

[0044] For example, a portion of the ion path through the induced charge detector is within the range of 30% to 70%, preferably 40% to 60%, for example, 50%, of the ion path defined by the electrostatic sector-field ion trap. In this way, artifacts such as signal processing artifacts in the time-domain signal of ions, which are analyzed by FT, are reduced. In particular, when a portion of the ion path through the induced charge detector is about 50% of the ion path defined by the electrostatic sector-field ion trap, even harmonics when analyzing the time-domain signal by FT can be reduced or eliminated. An ideal 50% duty cycle square wave has no even harmonics in its FFT, and fewer harmonics result in a larger fundamental peak. Since the magnitude of the fundamental peak is proportional to the ion charge, an increase in magnitude can reduce the uncertainty of the charge by increasing the signal-to-noise ratio of the fundamental peak.

[0045] In one example, the CDMS comprises a set of electrostatic focusing lenses, including a first electrostatic focusing lens positioned to at least partially restrict the ion path traversing it to a first dimension. In other words, the ion path can be compressed, for example, uniaxially. In another example, the set of electrostatic focusing lenses is positioned to at least partially restrict the ion path to a second dimension traversing it, and the first and second dimensions are orthogonal to each other. In other words, the ion path can be compressed, for example, biaxially. In this way, the construction of the CDMS can be simplified while the spatial aberrations caused by the set of electrostatic focusing lenses, if any, are not too large. Furthermore and / or alternatively, by restricting the ion path, the internal dimensions of the inductive charge detector, e.g., the inner diameter, can be reduced because the cross-sectional area of ​​the ion path is reduced, thereby improving its rise time. In one example, the first dimension is orthogonal to the direction of the ion path through the inductive charge detector. In one example, the first focusing lens comprises a cylindrical lens, an Einzel lens, and / or a plate lens, and / or a cylindrical lens, an Einzel lens, and / or a plate lens, arranged, for example, across a crossover in an ion path. In this way, symmetry with respect to the crossover can be maintained, while the geometry is simplified. For example, the Einzel lens can maintain at least rotational symmetry. In one example, a pair of electrostatic focusing lenses is arranged, for example, to at least partially restrict an ion path traversing it to a second dimension, where the first and second dimensions are orthogonal to each other. It should be understood that the pair of electrostatic focusing lenses, including the first focusing lens, is arranged, for example, to at least partially restrict an ion path to a first dimension, rather than an RF field and / or magnetic field.

[0046] In one example, the cross-section of the ion path via the induced charge detector is arcuate with a central angle within the range from -3° to +3°, preferably within the range from -2° to +2°, more preferably within the range from -1° to +1°. Such an ion beam is confined to a relatively narrow arc, and the cross-sectional area of the ion path is reduced, whereby the inner dimension of the induced charge detector, for example, the inner diameter, can be reduced, thereby improving its rise time.

[0047] In one example, the induced charge detector is configured to operate at a ground potential. In this way, its noise level is reduced, thereby enabling the detection of very low induced signals.

[0048] <Ion introduction> In one example, the CDMS includes means for introducing ions into the ion pathway. In one example, ion introduction is via a field-free region by the displacement of ions switched in the x and / or y directions (curvilinear coordinates), for example, using deflection electrodes as described in

[14] . In one example, ion introduction is via an electrostatic sector field-ion trap, with the necessary modifications, for example, by switching a first electrostatic sector, for example, only the first electrostatic sector, or by switching a set of electrostatic sectors, for example, two or more or all of the electrostatic sectors, for example, as described in

[13] . By switching only the first electrostatic sector, the remaining electrostatic sectors are operated at their respective operating potentials. When the first electrostatic sector is switched back to its respective operating potential, ions can be continuously introduced into the ion pathway to fill the ion pathway until the first ion to be introduced reaches proximal to the first electrostatic sector. For example, for a geometry figure of 8, ions can be introduced to fill the upper 3 / 4 of the figure of 8. Conversely, by switching all electrostatic sectors of a set of electrostatic sectors, the control is simplified, while the number of power supplies required is reduced. In one example, an electrostatic sector field ion trap, for example, the first electrostatic sector, has an ion inlet for introducing ions into an ion pathway. In one example, the ion inlet has a passage through the outer electrode of the first electrostatic sector and / or a passage through the outer electrode of the first electrostatic sector.

[0049] <Energy Filter> In one example, the CDMS does not have an energy filter to limit the spread of ion energy entering the electrostatic sector-field ion trap, e.g., a dual HDA, as previously described. In contrast to the cone traps and ELITs of references [2] and [3], the CDMS of the electrostatic sector-field ion trap has a relatively wide tolerance for the spread of ion energy, as well as / or radial and / or angular positional deviations of ions, while ions outside this relatively wide tolerance, e.g., high-energy or misaligned ions, are unstable and thus rapidly collide with the walls of the electrostatic sector-field ion trap without adversely affecting the mass determination of other ions. In one example, the CDMS has an energy acceptance greater than 0.40%, preferably at least 0.5%, more preferably at least 1%, most preferably at least 2%, 3%, or 4%. In one example, the CDMS has an energy acceptance of at most 20%, preferably at most 15%, more preferably at most 10%.

[0050] <Lift Device> In one example, the CDMS includes a lift device configured to increase the ionic energy of ions that will be introduced into the ionic pathway. In one example, the lift device is configured to trap ions that will be introduced into the ionic pathway. In this way, ions can be gate-controlled for introduction into an electrostatic sector-field ion trap, for example, to spatially and / or temporally separate multiple ions introduced therein, so that multiple ions move and are generally spatially and / or temporally separated from one another at the same time around there. In one example, the lift device is configured to collimate ions that will be introduced into the ionic pathway, thereby providing a pencil of ions that are spatially separated from one another. In one example, the lift device is configured to introduce a plurality of P ions (i.e., a group of ions), where P is a natural number greater than 1, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 50, 100 or more ions, preferably P is at least 4, and more preferably P is at least 10, 10, 20, 50, 100 or more ions. P is the average number of ions introduced, and typically the number of ions has a Poisson distribution, and it should be understood that the ions are spatially and / or temporally separated from one another, so as to be spatially and / or temporally separated, so as to be spatially and / or temporally separated from one another, by adopting substantially random discrete initial positions along a portion of the ion path, i.e., multiple ions move and are spatially and / or temporally separated from one another at the same time around that point. At the high-intensity limit, such as on a magnetic sector, an ion beam contains many ions per straight-line distance along the beam. At the other end of the scale, ions are injected individually according to a Poisson distribution (but ions are still beams in their behavior, space charge considerations aside). In one example, a lift device is configured to introduce ions into an ion path by pulsed ions into the ion path.More generally, in one example, a CDMS comprises means for introducing ions into an ionic pathway, as generally described with reference to a lift device, but increasing the ionic energy as appropriate. In one example, the means for introducing ions into an ionic pathway comprises means for introducing multiple P (i.e., a group) of ions into an ionic pathway, where P is a natural number greater than 1, and the multiple ions each adopt substantially random discrete initial positions along a portion of the ionic pathway such that the multiple ions move and are generally spatially and / or temporally separated from each other at the same time around there. That is, typically, when ions, e.g., multiple ions, are focused for introduction into a conventional mass-versus-charge analyzer, e.g., a quadrupole analyzer, a time-of-flight analyzer, or an ion trap analyzer, e.g., a three-dimensional quadrupole ion trap, a cylindrical ion trap, a linear quadrupole ion trap, or an orbitrap, ions, e.g., multiple ions, are not spatially and / or temporally focused. In other words, no effort is made to focus the ions. Rather, a disordered collection of ions is introduced into the ion pathway, for example, by thermally kineticating ions in a gas cell, thereby reducing the ion energy distribution without focusing. If these ions are trapped before being introduced into the ion pathway, and / or if the energy of each ion is increased (e.g., using a lift device), then the ions can be introduced into the ion pathway by adding a potential gradient that substantially maintains spatial and / or temporal disorder and / or uncorrelatedness of the ions upon introduction into the ion pathway.

[0051] <Power supply> In one example, the CDMS comprises a set of power supplies, such as a DC power supply, including a first power supply electrically coupled to the electrostatic sector field ion trap. In another example, the set of power supplies comprises a first power supply and a second power supply electrically coupled to the inner and outer electrodes of a set of electrostatic sectors, respectively. In yet another example, the CDMS comprises a set of electrostatic focusing lenses, including a first focusing lens, and the set of power supplies includes a third power supply electrically coupled to the set of electrostatic focusing lenses, such as the first focusing lens.

[0052] <Ion source> In one example, a CDMS includes an ion source, such as an atmospheric pressure ionization (API) source, an electrospray ionization (ESI) source, or a nanospray ionization source. Other ion sources are known.

[0053] <Magnet> In one example, the CDMS does not include a magnetic deflector or sector. That is, the CMS may include only an electrostatic sector and may, as appropriate, include an electrostatic quadrupole lens and / or an electro-lens, as described herein.

[0054] <Ion treatment> In one example, the CDMS includes one or more devices upstream and / or downstream of an electrostatic sector field ion trap for ion processing, such as activation of ions using externally injected particles such as reagent ions or precursor ions trapped with reagent ions, interaction with electrons (e.g., precisely injected), preferably manipulation of the mass-to-charge ratio of ions by electron detachment (e.g., using energetic charged particles including high-speed electrons), proton addition or charge reduction, interaction between ions in the ground or excited state and neutral molecules (e.g., externally injected), interaction with photons, excitation of ion motion using variations in the duty cycle of an auxiliary alternating current waveform or RF trapping waveform, ion separation using an alternating current waveform or duty cycle control, collision-activated dissociation, ion accumulation, and transfer. The processing can involve one or more of the above functions being performed simultaneously or sequentially.

[0055] <Vacuum system> In one example, the CDMS includes a vacuum system that includes, for example, a chamber that houses an electrostatic sector field ion trap and an inductive charge detector internally, a vacuum pump, and a controller. In one example, the chamber is a differentially pumped chamber having a vacuum of at most 1.3 x 10 -7 Pa (1 x 10 -8 Torr), preferably at most 6.7 x 10 -7 Pa (5 x 10 -9 Torr), more preferably at most 2.7 x 10 -7 Pa (2 x 10 -9 Torr), or better vacuum.

[0056] <Mass spectrometer> In one example, the CDMS includes a stand-alone CDMS and / or is a stand-alone CDMS. Conversely, in one example, the CDMS is included in a mass spectrometer, such as being integrally included therein (i.e., from the beginning), or included as an upgrade or retrofit.

[0057] <Preferred example> In a preferred example, a charge-detection mass spectrometer (CDMS) is used. It comprises an electrostatic sector field ion trap and an induced charge detector, The electrostatic sector-field ion trap is configured to define, at least partially, an ion path through an induced charge detector. The electrostatic sector-field-ion trap comprises a set of electrostatic sectors including a first electrostatic sector and a second electrostatic sector, the first and second electrostatic sectors being spaced apart from each other by a field-free region traversed by an ion path, and the electrostatic sector-field-ion trap is a periodic structure, at least partially defining a closed ion path such that ions repeat, for example, an integer or non-integer number of turns along the closed ion path. CDMS provides means for introducing multiple P ions into an ionic pathway, where P is a natural number greater than 1, and the multiple ions each adopt substantially random discrete initial positions along a portion of the ionic pathway such that the multiple ions move and are generally spatially and / or temporally separated from one another at the same time.

[0058] <Method> The second aspect is, A step of moving ions along at least partially defined ion paths using an electrostatic sector field ion trap, thereby passing them through an induced charge detector, The process involves inducing a signal in an induced charge detector by moving ions, A step of determining the mass of an ion using an induced signal, The present invention provides a method for determining the mass of an ion, comprising the following features.

[0059] Ions, ion pathways, induced charge detectors, and / or electrostatic sector-field ion traps may be as described with reference to the first embodiment. In one example, the method according to the second embodiment is performed using the CDMS according to the first embodiment.

[0060] In one example, the method comprises the step of providing ions, for example, using an ion source, as described with reference to the first aspect. In one example, the method comprises the step of processing ions upstream and / or downstream of an electrostatic sector field ion trap, as described with reference to the first aspect. In one example, the method comprises the step of introducing ions into an ion path, for example, through a field-free region, by displacing the ions, for example, in the x and / or y directions (curvilinear coordinates), using, for example, a deflection electrode as described in

[14] and / or through an ion inlet in a first electrostatic sector as described in

[13] , for example, the ion inlet comprising a passage through the outer electrode of the first electrostatic sector and / or a passage through the outer electrode of the first electrostatic sector. In one example, the process of introducing ions into an ion pathway via an ion inlet includes the steps of controlling the electrical potential applied to a first electrostatic sector, maintaining the first electrostatic sector with a first electrical potential, such as a ground electrical potential, while introducing ions, and applying a second electrical potential, such as an operating electrical potential, to the first electrostatic sector after introducing ions into the ion pathway. In other words, the first electrostatic sector may be grounded, for example, during ion implantation, and subsequently, the applied electrical potential is increased (or decreased) (depending on the polarity of the ions). In another example, the process of introducing ions into an ion pathway via an ion inlet includes the step of controlling the electrical potential applied to a second electrostatic sector, for example, applying a second electrical potential to the second electrostatic sector while introducing ions. In other words, the electrical potential applied to the second electrostatic sector may be maintained during ion implantation. In one example, the step of introducing ions into an ionic pathway comprises the step of introducing multiple ions into an ionic pathway, and the ions are spatially and / or temporally separated from each other so that the multiple ions move and are generally spatially and / or temporally separated at the same time in that area, as described with reference to the first embodiment. In one example, the multiple ions include P ions, as described with reference to the first embodiment.In other words, in contrast to TOF MS, multiple ions are not packets, but rather distinct. Packeted ions (also known as bundles or clouds) typically given by a pusher and / or spatially focused require TOF MS to reduce uncertainty in TOF measurements. By separating multiple ions spatially and / or temporally from each other, the mass of each individual ion in the group of ions can be determined. Thus, in particular, the signals of each ion are unlikely to overlap, even after multiple turns, and even with the same mass-to-charge ratio m / z, because the ionic path is unidirectional, not bidirectional or round-trip. Even if the ionic path has a crossover as shown in the figure of geometry 8, the interaction between two of the multiple ions proximal to the crossover is unlikely while these ions are moving at a constant velocity along the ionic path. In contrast, the linear reflection of multiple ions results in the duplication of their respective signals as the ions move bidirectionally or reciprocally through an induced charge detector between opposing reflectors, so conventional CDMSs such as ELIT in reference [3] are limited to determining the mass of only a single ion. Furthermore, the interaction between two ions can be considerable in the opposing reflectors, causing the ions to decelerate to rest before accelerating from there. In one example, the method comprises the step of increasing the ionic energy of an ion and / or multiple ions that will be introduced into the ionic path, as described with reference to the first aspect. In one example, the method comprises the step of collimating multiple ions that will be introduced into the ionic path, as described with reference to the first aspect. In one example, the method does not comprise the step of energy filtering the ions and / or multiple ions to limit the spread of ionic energy entering the electrostatic sector field ion trap.

[0061] In one example, the step of moving an ion along an ionic path includes the step of moving the ion along the ionic path by at least one turn, preferably at least N turns, where N is a natural number of 1 or more, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 50, 100, 200, 500 or more. In one example, as described with reference to the first embodiment, the step of moving an ion along an ionic path includes the step of moving the ion quasi-energy isochronically or isochronically. In one example, the step of moving an ion along an ionic path includes the step of focusing the ion spatially and / or temporally. In one example, as described with reference to the first embodiment, the step of moving an ion along an ionic path includes the step of moving the ion through a cylindrical electrostatic sector, a toroidal electrostatic sector, or a spherical electrostatic sector. In one example, the step of moving an ion along an ionic path comprises moving the ion through a total deflection angle ψ0 greater than 360.0°, preferably at least 390.0°, for example, in the range of greater than 360.0° to 720.0°, preferably in the range of 390.0° to 660.0°, and thus through a crossover. In one example, as described with reference to the first embodiment, the step of moving an ion along an ionic path comprises moving the ion through a diagram of the geometry of 8 in two or three dimensions. In one example, as described with reference to the first embodiment, the step of moving an ion along an ionic path comprises at least partially restricting the ion to a first dimension, for example, traversing the ionic path.

[0062] In one example, the step of inducing a signal in an induced charge detector comprises the step of inducing a signal that the induced charge detector is operating at a ground potential. In one example, as described with reference to the first embodiment, the step of inducing a signal in an induced charge detector comprises the step of inducing a set of signals in a first set of charge detection tubes provided in the induced charge detector.

[0063] In one example, as described with reference to the first embodiment, the step of determining the mass of an ion using a signal comprises, for example, a Fourier analysis using the Fourier transform (FT) or fast Fourier transform (FFT) of the signal, least squares, filtered diagonalization (FDM), and / or maximum likelihood method.

[0064] <Definition> Throughout this specification, the terms “comprising” or “comprises” mean that the specified components are included but do not exclude the presence of other components. The terms “consisting essentially of” or “consists essentially of” mean that the specified components are included but exclude other components, except for substances present as impurities, unavoidable substances present as a result of processes used to provide the components, colorants, and other components added for purposes other than achieving the technical effects of the present invention. The terms “consisting of” or “consists of” mean that the specified components are included but exclude other components. Where appropriate, depending on the context, the use of the terms “comprises” or “comprising” may also be interpreted to include the meaning of “consisting essentially of” or “consisting essentially of.” The appropriate features described herein may be used individually or in combination with each other where appropriate, in particular in combinations as described in the appended claims. Appropriate features of each aspect or exemplary embodiment of the Invention as described herein are, where appropriate, also applicable to all other aspects or exemplary embodiments of the Invention. In other words, a person skilled in the art reading this specification will find that appropriate features of each aspect or exemplary embodiment of the Invention are interchangeable and combinable between different aspects and exemplary embodiments.

[0065] To better understand the present invention and to illustrate how its exemplary embodiments may be carried out, references are made to the following accompanying drawings, just as an example. [Brief explanation of the drawing]

[0066] [Figure 1A] A diagram illustrating a conventional CDMS. [Figure 1B] A diagram illustrating a conventional CDMS based on the conventional CDMS shown in Figure 1A. [Figure 2A] A schematic diagram illustrating a conventional electrostatic sector field using a toroidal sector field. [Figure 2B] A schematic diagram illustrating a conventional electrostatic sector field using a toroidal sector field. [Figure 3] A schematic diagram illustrating an electrostatic sector-field ion trap in one exemplary embodiment, further comprising a shunt for controlling the edge field. [Figure 4A] A diagram schematically illustrating a CDMS according to one exemplary embodiment. [Figure 4B] A schematic diagram showing the top, side, and end elevation views of the ion orbital trajectories for CDMS. [Figure 5A] A schematic diagram illustrating a CDMS according to one exemplary embodiment, which includes a lens at the origin to confine ions in the axial (z) dimension. [Figure 5B] A schematic diagram showing the top, side, and end elevation views of the ion orbital trajectories for CDMS. [Figure 5C] Perspective view of ion SIMION simulation for CDMS. [Figure 5D] A more detailed axial cross-sectional view of the CDMS. [Figure 5E] A more detailed fractured perspective CAD image of a portion of the CDMS. [Figure 5F] A more detailed CAD image of a partially disassembled and assembled CDMS (Computer Development Management System). [Figure 5G] A more detailed axial cross-sectional view of the CDMS. [Figure 6] Figures 5A and 5C show graphs of the change in frequency (%) as a function of the ion energy deviation from the ideal (%) for CDMS, compared to conventional CDMS. [Figure 7] Figures 7A and 7B schematically illustrate the advantages of a relatively narrow charge detector tube for increasing the intensity of higher harmonics in the Fourier transform in a CDMS according to one exemplary embodiment. [Figure 8] A schematic diagram of a segmented charge detection tube for providing an increased transient number for each analyzer pass is shown for a CDMS according to one exemplary embodiment. [Figure 9] A schematic diagram showing a CDMS according to one exemplary embodiment that includes a lift device. [Figure 10] A diagram schematically illustrating a CDMS according to one exemplary embodiment. [Figure 11] A diagram schematically illustrating a CDMS according to one exemplary embodiment. [Figure 12] A diagram schematically illustrating a CDMS according to one exemplary embodiment. [Figure 13] A diagram schematically illustrating a CDMS according to one exemplary embodiment. [Figure 14] A diagram schematically illustrating a CDMS according to one exemplary embodiment. [Figure 15] A diagram illustrating a method according to one exemplary embodiment. [Modes for carrying out the invention]

[0067] Figure 1A schematically shows a conventional CDMS10, and Figure 1B schematically shows a conventional CDMS20 based on the conventional CDMS10 in Figure 1A. More specifically, Figure 1A schematically shows the CDMS10 by Contino and Jarrold[1]. The CDMS10 includes an electrospray source 1 and is divided into four differentially pumped regions (I to IV). The first region I includes an ion funnel 2, the second and third regions II and III include a hexapole ion guide 3 respectively, and the fourth region IV provides two binary paths for ions via a focusing lens 4 and a cone trap 7 incorporating a quadrature reflectron time-of-flight mass spectrometer (TOF-MS) 5 or a dual hemispherical deflection analyzer (HDA) 6, followed by an enantiomer charge detector tube. The vibrational frequency of ions in the cone trap 7 is related to the ion's m / z, but also depends on the ion's kinetic energy. To reduce uncertainty in the m / z determination, the dual HDA 6 was used to select a narrow window of ion kinetic energy for introduction into the cone trap 7. HDA6 consists of two concentric hemispherical electrodes, each with a deflection angle ψ0 of 180° and held at different potentials, thereby 1 / r 2An electric field proportional to is generated. As shown in Figure 1A, the two hemispherical electrodes are placed in an S-shaped tandem arrangement, thus defining an open (closed, reference) ion path and allowing the ion beam to maintain its original direction as it exits. The electrode potentials applied to the two hemispherical electrodes determine which kinetic energy is passed through and therefore which ions are filtered. Careful selection of these electrode potentials, as well as the positions and diameters of the inlet and outlet openings, improves the energy resolution of the dual HDA6. The cone trap 7 consists of two conical end caps spaced 95.25 mm apart with an opening of 6.35 mm in diameter, thereby providing an electrostatic linear ion trap. The number of ions entering the cone trap 7 was kept low enough to minimize the probability of trapping more than two ions. The charge detection tube (25.4 mm long, 6.35 mm inner diameter) was held along its central axis by an insulator mounted within a shielded cylinder. When ions pass through a detector tube, enantiomers with equal magnitude but opposite signs are induced.

[0068] More specifically, Figure 1B schematically shows the geometry of the prior art cylindrical ELIT trap (i.e., CDMS20) from reference [3]. This ELIT comprises two mutually corresponding, equally spaced three-electrode mirrors (E1, E2, E3) having grounded shielded ring electrodes (GS) at their respective inlets to create a field-free region between end caps where a charge detection tube (C) is provided. The potentials V1, V2, V3 applied to the ring electrodes V1, V2, V3, respectively, are optimized to generate the minimum vibrational frequency width for 100 axial ions with average FWHM Gaussian energy distributions of 130 eV / z and 1 eV / z. This ELIT has substantially improved energy dependence compared to the cone trap 7 of CDMS10 and replaces the cone trap 7 of CDMS10. In other words, CDMS20 also requires an upstream energy filtering device (i.e., dual HDA6) consisting of dual hemispherical electrostatic energy sectors to minimize the variation in vibrational frequency due to the spread of ion energy. The selection of a low-energy spread of ions reduces the total transmission of CDMS20. As with CDMS10, the number of ions entering ELIT was kept low enough to minimize the probability of trapping two or more ions.

[0069] The objective of this invention is to improve ion permeability by allowing a larger portion of the ions to enter the CDMS trap. Figures 2A and 2B schematically illustrate a conventional electrostatic sector field using a toroidal sector field.

[0070] The inventors of the present invention recognized that better energy focusing characteristics could be achieved by using the geometry first proposed by Poschenrieder[4], which takes into account time-of-flight energy focusing by an electrostatic field. In particular, Poschenrieder considered a linear drift space and field configuration in which the time of flight is no longer a function of the initial energy up to the first order, but only a function of the mass-to-charge ratio m / z. Such a configuration is also known as isochronism. For ions of nearly equal energy, an electrostatic field should be used, since the orbits should be identical for all masses. Poschenrieder limited the treatment to a toroidal sector field, but other configurations are possible, as will be described below.

[0071] Poschenrieder's research proposed the use of a toroidal sector field in a special configuration to compensate for initial ionic conditions for time-of-flight mass spectrometry. Figures 2A and 2B show a general form of such a configuration. The device is considered from both a radial view (Figure 2A) and an axial view (Figure 2B), each having different radii of curvature with respect to the electric field, and thus they are known as toroidal sector field analyzers. A DC potential V1 is applied to the inner electrode having radius R1 in the radial plane, and a DC potential V2 is applied to the outer electrode having radius R2 in the radial plane. The ion optical axis has radius R0 in the radial plane. The device has a deflection angle of ψ0, as well as acceptance angles of 2α0 in the radial direction and 2ω in the axial direction, effectively defined by slits having width u0 in the radial direction and w0 in the axial direction, respectively. The isochronous plane is at an angle η with respect to the ion optical axis, at a distance g from the inlet and outlet of the device. rThey are positioned to provide point focus of ions. The paper presents several geometries intended to operate as time-of-flight (TOF) analyzers, in which packets of ions (also known as clouds) are injected through an inlet opening and detected at the exit plane using an electron multiplier tube or similar destructive detector. Fan-type electric field TOF analyzers have found applications in imaging applications such as TOF-SIMS instruments due to their aberration-free characteristics [5]. However, they are not well suited to the mainstream applications of orthogonal-accelerated (OA) TOF analyzers due to their energy focusing characteristics which are limited to first-order. This is because orthogonal acceleration results in a very large energy spread in the ion beam, which is better compensated by reflectron-based TOF analyzers [6]. In certain cases of CDMS instruments, orthogonal acceleration is not required, and therefore the ion energy variation is given only by the longitudinal variation of the beam energy, as determined by upstream beam conditioning. Typical energy variations of a few percent can be easily addressed by the primary energy focusing characteristics of the electrostatic sector-field ion trap, which are superior to those shown in [3]. The electrostatic sector-field ion trap has an additional advantage in that the ions travel at a substantially constant speed, as determined by the acceleration energy. This improves the space charge capacitance of the sector compared to reflection-based devices, where the ions must slow down to a low speed when they change direction within the mirror section.

[0072] The specific geometry proposed by Poschenrieder for TOF MS (although still problematic regarding injection and detection in TOF MS), and improvements thereto, as first understood by the inventors, is to provide an electrostatic sector-field ion trap for CDMS in one exemplary embodiment.

[0073] Ion Energy

[0074]

number

[0075]

number

[0076] u is the ion deviation from the central path u0, h and k are

[0077]

number

[0078] Next, the time of flight t through the electrostatic sector field e teeth, dt e =r0(1+u)ds / v This is obtained by integral, which is equation (8) of Poschenrieder[4]

[0079]

number

[0080] t to entrance angle α0 e Eliminating the dependency on Poschenrieder[4]'s equation (9)

[0081]

number

[0082] An electrostatic sector field following equation (9) of Poschenrieder[4] simultaneously exhibits no first-order chromatic aberration in the second image. The spread of transmitted energy can be limited here by appropriate stoppers, however, large lateral energy dispersion may be found in the intermediate image.

[0083] The small ion energy spread within the electrostatic sector field is β = ΔE / E a Flight time Δt e The variance is given by Poschenrieder's [4] equation (10)

[0084]

number

[0085] Dispersion Δt along a linear drift tube of length D DThis is the formula (11) of Poschenrieder[4]

[0086]

number

[0087] For the electrostatic sector field to be free, one must Δt e +Δt D This requires =0, which is the focusing condition given by equation 12 of Poschenrieder[4]:

[0088]

number

[0089] The actual linear drift length D is g on the inlet side. r , on the exit side g r ', and it can have some additional drift range d. Therefore, an electrostatic sector field according to Poschenrieder's [4] equation 12 has no energy-dependent dispersion in the time of flight (isochronism) for any two points having a linear drift range of total length D. In addition, this electrostatic sector field is at a distance g from the field edge. r Achromatic radial imaging is performed on point G at [location].

[0090] The intermediate image in the radial and axial directions is ψ i We will investigate electrostatic sector fields using aberration-free imaging performed simultaneously at =ψ0 / 2. a If g represents the distance from the field slit to the entrance for axial focusing based on the directional focusing characteristics of the toroidal sector field, then g is the distance from the field edge to the source point. r This is by equation 20 of Poschenrieder[4]

[0091]

number

[0092] Therefore, h=k and c=1, which corresponds to a spherical capacitor field. Poschenrieder's [4] Equation 12, and D=2g r =2g a Since this is set, Poschenrieder's [4] equation 21 is,

[0093]

number

[0094] A graphical solution is, ψ0 = 199.2° g r =5.9r It yields a value.

[0095] For this electrostatic sector field, the source and its image occur precisely simultaneously, as schematically shown in Figure 3, so that temporal and spatial convergence occurs simultaneously. Poschenrieder[4] showed that this electrostatic sector field is not very suitable for TOF mass spectrometers, but the inventors have conversely found that this electrostatic field is instead well suitable for electrostatic field ion traps. In particular, this electrostatic sector field is perfectly isochronous with respect to energy, and the resolution no longer depends on the slit width. Deflection angle ψ0 = 199.2° and distance g r It should be noted that these values ​​for =5.9r are obtained using graphs, and therefore the calculation method can provide a sophisticated solution. Furthermore, the constructed geometry can allow for interaction between these values ​​to some extent, and / or to compensate for other electric fields, including residual or edge fields. However, the distance gr This can be extremely important in achieving true aberration-free performance.

[0096] Poschenrieder's paper [4] focuses on isochronism (time difference) with respect to the initial beam conditions (all first-order from zero), but there is much less development on its treatment of aberration-free (spatial) aberrations. Poschenrieder [4] does not appear to consider spatial aberrations of 'angle with respect to position' or 'angle with respect to energy'. However, preferably, in order to allow the use of relatively narrow charge tubes as described herein and to avoid ion losses resulting from ions wandering away from the ion path, the aberration-free (imaging) requirement of CDMS is second-order compared to the isochronism requirement of CDMS, and the aberration-free requirement is that the ion orbits are stable enough for induced charge detection.

[0097] Figure 3 schematically shows an electrostatic sector-field ion trap 30 for an exemplary embodiment further comprising a shunt for controlling the edge field. The Cartesian coordinate system (x,y,z) is used appropriately for Figures 3 through 14.

[0098] In this example, the electrostatic sector-field-ion trap 30 comprises a pair of electrostatic sectors 31, including a first electrostatic sector 31A and a second electrostatic sector 31B. In this example, the first electrostatic sector 31A is a spherical electrostatic sector. In this example, the first electrostatic sector 31A and the second electrostatic sector 31B face each other. In this example, the pair of electrostatic sectors 31 includes only the first electrostatic sector 31A and the second electrostatic sector 31B. In this example, the first electrostatic sector 31A comprises a pair of shunts 32, including a first shunt 32A positioned to define the field by the first electrostatic sector 31A. In this example, the electrostatic sector-field-ion trap 30 is isochronous. In this example, the electrostatic sector-field-ion trap 30 is configured to define an ion path IP in three mutually orthogonal dimensions. In this example, the ion path defined by the electrostatic sector-field-ion trap 30 includes a crossover. In this example, the electrostatic sector-field-ion trap 30 includes an ion inlet 33 for introducing ions into the ion path, the ion inlet 33 specifically located within the outer electrode of the first electrostatic sector 31A. In this example, the first electrostatic sector 31A has a deflection angle of ψ0 = 199.2°. In this example, the field-free region extends to the central crossover point (i.e., the origin where point focusing is achieved) g r It has a length of = 5.9r. In this example, the electrostatic sector-field-ion trap 30 has rotational symmetry about the x-axis passing through the origin. In this example, the electrostatic sector-field-ion trap 30 is symmetric in the yz-plane passing through the origin. In this example, the basic unit has two drift spaces (i.e., g rThe apparatus comprises two field-free regions, each having a length of 5.9r, and spherical electrostatic sectors 31A and 31B. In this example, the outer electrode of the first electrostatic sector 31A has an inner radius of 23 mm, and the inner electrode of the first electrostatic sector 31A has an outer radius of 17 mm, thereby creating a spherical radial gap of 6 mm between them. The first shunt 32A has a toroidal opening 4 mm wide, thereby presenting a relatively large inlet opening into the first electrostatic sector 31A. The second electrostatic sector 31B is generally as described with reference to the first electrostatic sector 31A, but does not include an ion inlet 33.

[0099] More specifically, Figure 3 shows a deflection angle ψ0 = 199.2°, and a distance of 5.9R0 (i.e., g) to the central crossover point (i.e., point focus). rA special case is shown of two opposing spherical sectors 31A, 31B (with the same curvature for the radial and axial fields) each having a field-free region of a distance of 5.9r). Poschenrieder understood that the closed path of this arrangement could be proven problematic for injection and detection for traditional TOF analysis and proceeded to propose a more suitable open geometry solution for the injection and detection means. That is, Poschenrieder did not propose an ion inlet 33 for introducing ions. Furthermore, Poschenrieder did not propose the use of such an analyzer for inductive detection when used with a Fourier transform mass spectrometer. To the best of the inventor's knowledge, the use of a toroidal field for inductive detection of small clouds of ions in a Fourier transform trap was first proposed by Wollnik[7] in an arrangement using eight 45° toroidal sectors, but for TOF MS analyzers, it was other unknown geometries arranged in a ring configuration. Later, Verenchikov proposed the use of a toroidal field with Fourier transform detection.[8] However, neither of these proposals considered using such geometry for the CDMS.

[0100] In the configuration shown in Figure 3, ions are injected through a hole in the outer electrode of the first electrostatic sector 31A (i.e., the ion inlet 33), while the potential of the electrode of the first electrostatic sector 31A is held at ground level. When the trap is filled, these potentials are raised to their operating level, and the trapping process begins. Shunts 32A, 32B are added to terminate the electric field of the electrode of the first electrostatic sector 31A; without them, the electric field would leak into the field-free region, rendering the electrostatic sector field-ion trap inoperable. This particular shunt geometry is well known in the art and was proposed by Herzog in 1935 (see Yavor pp230)[9].

[0101] Figure 4A schematically shows a CDMS4 according to one exemplary embodiment, and Figure 4B schematically shows the top, side, and end elevation views of the ion orbital trajectories for the CDMS4. In this example, the CDMS4 comprises an electrostatic sector-field ion trap 40 and an inductive charge detector 400, wherein the electrostatic sector-field ion trap 40 is configured to at least partially define an ion path through the inductive charge detector 400.

[0102] The electrostatic sector field trap 40 is similar to the electrostatic field ion trap 30 described with reference to Figure 3, and its description is omitted for brevity. The same reference numerals indicate the same integer.

[0103] In this example, the electrostatic sector-field-ion trap 40 comprises a pair of electrostatic sectors 41, including a first electrostatic sector 41A and a second electrostatic sector 41B. In this example, the first electrostatic sector 41A is a spherical electrostatic sector. In this example, the basic unit comprises two drift spaces and a spherical electrostatic sector. In this example, the first electrostatic sector 41A and the second electrostatic sector 41B face each other. In this example, a pair of electrostatic sectors 41 comprises only the first electrostatic sector 41A and the second electrostatic sector 41B. In this example, the first electrostatic sector 41A comprises a pair of shunts 42, including a first shunt 42A positioned to define the field by the first electrostatic sector 41A. In this example, the electrostatic sector-field-ion trap 40 is isochronistic up to the first order with respect to energy. In this example, the electrostatic sector-field-ion trap 40 is configured to define ion paths in three mutually orthogonal dimensions. In this example, the ion paths defined by the electrostatic sector-field-ion trap 40 include a crossover. In this example, the electrostatic sector-field-ion trap 40 is provided with an ion inlet 43 for introducing ions into the ion path. In this example, the first electrostatic sector 41A has a deflection angle of ψ0 = 199.2°. In this example, the field-free region extends to the central crossover point (i.e., the origin). rIt has a length of = 5.9r. In this example, the second electrostatic sector 41B is such that it is described with reference to the first electrostatic sector 41A. In this example, the electrostatic sector-field-ion trap 40 has rotational symmetry about the x-axis passing through the origin. In this example, the electrostatic sector-field-ion trap 40 is symmetric in the yz-plane passing through the origin. In this example, the inductive charge detector 400 comprises a first set of charge detection tubes 410, including a first charge detection tube 410A and a second charge detection tube 410B. In this example, the first charge detection tube, having length L and width W, has a length L to width W ratio of, for example, 2:1, in the range of 3:2 to 5:2. In this example, a portion of the ion path through the inductive charge detector 400 is about 50% of the ion path defined by the electrostatic sector-field-ion trap 40.

[0104] The SIMION

[10] simulation was performed using the geometry shown in Figure 4A, and the ions can be trapped for an indeterminate period depending on their initial conditions, as schematically shown in Figure 4B. When the ions are restricted to a narrow axial range (small Δα), the resulting orbits fill a finite arc in the yz plane. Referring again to Figure 4A and noting that the input ion conditions take the form of an ion beam along the orbit T, it can be understood that the radial restoring force is stronger in the axial direction than in the axial direction. The device is rotationally symmetric about the x-axis passing through the origin, and therefore ions with a large angular component β or axial spread Δα will fill the entire ion orbital electrostatic sector after traveling along an ion path that creates a hollow cone shape in the field-free region and a sphere inside the sector. In other words, the ions can be described as a pair of intersecting and mutually opposing cones or rounded projections with roughly hemispherical end caps (corresponding to the gap between the spherical electrodes of the electrostatic sector having a deflection angle ψ0 nominally of 199.2°) trapped within a thin wall (ideally of infinitesimal thickness). A geometric diagram of the ion beam IP (shown in gray) adopted after passing through many analyzers (as required by CDMS) is shown in Figure 4B.

[0105] More specifically, Figure 5A schematically shows a CDMS5 according to an exemplary embodiment that includes a lens at the origin to confine ions in the axial z dimension; Figure 5B schematically shows top, side, and end elevation views of the ion orbital trajectories for the CDMS5; Figure 5C is a perspective view of a SIMION simulation of ions for the CDMS5; Figure 5D is an axial cross-sectional view of the CDMS5; more specifically, Figure 5E is a broken perspective CAD image of a portion of the CDMS5; more specifically, Figure 5F is a disassembled and assembled perspective CAD image of a portion of the CDMS5; and more specifically, Figure 5G is an axial cross-sectional view of the CDMS5.

[0106] CDMS5 is generally similar to CDMS4, as described with reference to Figures 4A and 4B, but that description is omitted for brevity. The same reference sign indicates the same integer.

[0107] In this example, the electrostatic sector-field-ion trap 50 comprises a pair of electrostatic sectors 51, including a first electrostatic sector 51A and a second electrostatic sector 51B. In this example, the first electrostatic sector 51A is a spherical electrostatic sector. In this example, the first electrostatic sector 51A and the second electrostatic sector 51B are opposite each other. In this example, a pair of electrostatic sectors 51 comprises only the first electrostatic sector 51A and the second electrostatic sector 51B. In this example, the first electrostatic sector 51A comprises a pair of shunts 52, including a first shunt 52A positioned to define the field by the first electrostatic sector 51A. In this example, the electrostatic sector-field-ion trap 50 is isochronous up to the first order with respect to energy. In this example, the electrostatic sector-field-ion trap 50 is configured to define ion paths in three mutually orthogonal dimensions. In this example, the ion path defined by the electrostatic sector field ion trap 50 includes a crossover. In this example, the electrostatic sector field ion trap 50 is equipped with an ion inlet 53 for introducing ions into the ion path. In this example, the first electrostatic sector 51A has a deflection angle of ψ0 = 199.2°. In this example, the field-free region extends to the central crossover point (i.e., the origin). rIt has a length of = 5.9r. In this example, the second electrostatic sector 51B is such that it is described with reference to the first electrostatic sector 51A. In this example, the electrostatic sector-field-ion trap 50 has rotational symmetry about the x-axis passing through the origin. In this example, the electrostatic sector-field-ion trap 50 is symmetric in the yz-plane passing through the origin. In this example, the inductive charge detector 500 comprises a first set of charge detection tubes 510, including a first charge detection tube 510A and a second charge detection tube 510B. In this example, the first set of charge detection tubes 510 comprises an axially segmented charge detection tube containing 10 segments. In this example, the first charge detection tube having length L and width W has a length L to width W ratio of, for example, 2:1, in the range of 3:2 to 5:2. In this example, a portion of the ion path through the inductive charge detector 500 is about 50% of the ion path defined by the electrostatic sector-field-ion trap 50.

[0108] Referring again to Figure 4B, the plane of rotation introduces potential topological problems when involved in the construction of some CDMSs. When ions are made capable of rotating around the entire central axis (i.e., the x-axis), supports for the central or inner electrodes of the inductive charge detector 500, as well as / or the inner electrodes of the first electrostatic sector 51A and / or the second electrostatic sector 51B, can be problematic because the ion orbitals surround these inner electrodes entirely in three dimensions. In general, the addition of supports causes ions to collide with them, thereby reducing the possible frequencies within the analyzer. One or more supports, such as support 52AS between the inner and outer electrodes, can be bridged, for example, between the inner and outer electrodes, and the loss of ions through collisions with the supports can be reduced by decreasing their cross-sectional area in the ion path. Furthermore and / or alternatively, the ion path can be restricted to avoid the supports. Thus, a solution to the problem relating to collisions with supports is to include a set of electrostatic focusing lenses, including a first focusing lens, which is positioned to restrict the ion path at least partially to the first dimension. In this example, a planar Einzel lens 54 with three electrodes is shown in Figure 5A at the center of the device at the crossover point, providing further focusing in the z direction (orthogonal coordinates). The geometry of the ions after this first focusing lens is added is shown in Figures 5B(A) to (C). A cross-section through the spherical electrode, together with the support 52AS, is shown in Figure 5B(D). As a result, the ions are then confined to a finite angle, and the support 52AS may be positioned away from the ion beam, thereby aiding in the construction of the CDMS.

[0109] Figure 5A schematically shows a preferred embodiment along with some typical values ​​for device construction. The ion energy of 130 eV / z was chosen to allow a direct comparison with the latest ELIT traps in reference [3]. It should be understood that increasing the operating voltage (ion energy) for these devices can provide higher frequencies, as well as significant improvements in signal-to-noise and resolution. Such methods have not yet been used due to the need to operate the field-free region at a high potential, which implies the possibility of noise injection from the power supply. In the embodiment shown in Figure 5A, two charge tubes 510A and 510B are used on either side of the central z lens 54. Referring again to Figure 3, g r It can be understood that =5.9r provides a relatively long field-free region on either side of the central lens, enabling the use of charge tubes 510A and 510B with a length of approximately 100 mm. Cross-sections of charge tubes 510A and 510B are shown. These charge tubes 510A and 510B do not present a topology problem for construction and can be easily fabricated using techniques known as wire erosion or electrical discharge machining (EDM), for example. A suitable segmented charge tube is described with respect to Figure 8.

[0110] Figures 5D to 5G show the CDMS5 in more detail. In this example, the first electrostatic sector 51A has a deflection angle of ψ0 = 199.2°. In this example, the first electrostatic sector 51A comprises an outer spherical electrode 51AO having an inner radius of 23 mm and an outer radius of 28 mm, and an inner spherical electrode 51AI having an outer radius of 17 mm and concentric with the outer spherical electrode 51AO, with a spherical radial gap of 6 mm between them. In this example, the outer spherical electrode 51AO and the inner spherical electrode 51AI are respectively located in the center of a similarly square, substantially planar frame machined from a suitable electropolished UHV-compatible conductor, such as 304L or 316L stainless steel (or, for example, gold-coated glass). In this example, the shunt 52A is similarly located within such a frame. Each frame includes four circular openings formed at its proximal corners for mounting four corresponding insulators (e.g., ceramics such as alumina or Macor (RTM), or polymers such as PTFE) onto rods 55A to 55D (55C and 55D are not shown) for lateral alignment of the outer spherical electrode 51AO, the inner spherical electrode 51AI, and the shunt 52A. Insulator spacers 56A position the outer spherical electrode 51AO and the inner spherical electrode 51AI axially spaced apart from each other. The outer spherical electrode 51AO, having a wall thickness of 5 mm, bulges quasi-hemispherically from each frame. The solid inner spherical electrode 51AI protrudes quasi-hemispherically from each frame and is supported by two diametrically opposed supports 51AS, arranged so as not to obstruct the diagram of the eight ion pathways IP when flattened by the Einzel lens 54. The inner electrodes of the dished shunt 52A protrude from their respective frames and are supported by two diametrically opposed supports 52AS, as described with general reference to the supports 51AS for the inner spherical electrode 51AI, thereby providing two semicircular openings 521A and 521B (i.e., an inlet and an outlet, respectively) with a radial width of 4 mm.

[0111] Table 1 shows the performance advantages of the present invention over the latest ELIT in reference [3]. Compared to the ELIT in reference [3], the CDMS5 has uniform angular and spatial acceptance but provides more transients per unit time and superior energy acceptance. This greater energy acceptance can result in better resolution / sensitivity characteristics. With careful upstream beam collimation and an energy spread of 0.5 eV / z, a single-pass mass resolution of several thousand is expected for this embodiment.

[0112] [Table 1] Table 1: Performance advantages of CDMS5 by one exemplary embodiment compared to the latest ELIT in reference [3]. 23.26 transients per ms is based on 10 segments in each charge tube. Without segmentation, the number of transients per ms is reduced to 2.326. Even without segmentation, CDMS5 is competitive, simpler, and does not require upstream dual HADs to select a narrow window of ionic kinetic energy to introduce into the electrostatic sector field ion trap 50, for example. Conversely, even higher transient numbers can be achieved using lift devices as described with reference to Figure 9.

[0113] Figure 5C shows a SIMION simulation of ions for CDMS5 after several hundred turns, with no ion loss. The Einzel lens restricts the ion orbits, as shown in Figure 4B, compared to the SIMION simulation of ions for CDMS4.

[0114] Figure 6 is a graph of the change in frequency (%) as a function of ion energy deviation from ideal (%) for CDMS5 in Figures 5A to 5C, compared with conventional CDMS, particularly the CDMS in Figure 1B. In more detail, SIMION simulations were performed to calculate the energy focusing characteristics of CDMS5. It was found that the addition of the z lens 54 does not cause a significant degradation in device resolution. The first-order focusing of this geometry is expected to result in residual aberrations of parabolic nature, which are shown in Figure 6. In other words, the electrostatic sector-field ion trap 50 of CDMS5 is isochronous up to the first order and parabolic in the second order, giving a frequency change of approximately 0.05% for an ion energy deviation of ±3%. In comparison, the ELIT trap in reference [3] is not isochronous up to the first order, but instead has linear residuals in the first order, giving a frequency change of approximately 0.275% for a +3% ion energy deviation and a frequency change of approximately -0.275% for a -3% ion energy deviation. Therefore, the electrostatic sector field ion trap 50 of CDMS5 exhibits superior tolerance to energy spread compared to the ELIT trap in reference [3], which is one of the main advantages of the present invention.

[0115] Figures 7A and 7B schematically illustrate the advantages of a relatively narrow charge detector tube for increasing the intensity of higher harmonics in the Fourier transform in a CDMS according to one exemplary embodiment. More specifically, further advantages of the present invention are provided by the aberration-free or near-aberration-free focusing characteristics of the electrostatic sector-field ion trap. These characteristics mean that the ion beam is confined to a narrow arc as it traverses the analyzer. A narrow ion beam means that it is possible to use an equally narrow charge tube for ion detection. Figures 7A and 7B show how a narrower charge tube produces a sharper transient signal. This signal had an increased harmonic component at higher frequencies as a result of Fourier theory. The signal-to-noise ratio of the processed waveform increases with frequency, and it is well known that mass spectrometry, using higher harmonics in the Fourier transform, gives improved resolution.

[0116] Figure 8 schematically shows an inductive charge detector 800, as described in general reference to the inductive charge detectors 400 and 500, which include a first pair of segmented charge detection tubes 810, including a first segmented charge detection tube 810A and a second segmented charge detection tube 810B, to give an increased number of transients per analyzer pass through a CDMS according to one exemplary embodiment, such as CDMS4 and / or CDMS5. In this example, the first segmented charge detection tube 810A and the second segmented charge detection tube 810B are segmented axially and each contains 10 segments.

[0117] The relatively long charge tubes provided by the geometry of CDMS4 and CDMS5 allow for, for example, axial charge tube segmentation. As a general rule, the induced signal by moving ions can be ignored after they have passed through the tube for a length of twice the tube width, thus wasting excessively long tubes with respect to useful signals. Figure 8 shows how segmentation can be used to give a larger number of transient signals per pass. Such segmentation had been previously proposed using multiple amplifiers

[11] . Such segmentation is known to offer further advantages over the use of a single amplifier, such as the one connected in Figure 8. This principle has been demonstrated in Fourier transform ion cyclotron resonance instruments; see, for example, the work of Nikolaev

[12] .

[0118] Furthermore, the stereoscopic diagrams of the eight paths of the electrostatic sector-field-ion trap 40, and the restricted stereoscopic diagrams of the eight paths of the electrostatic sector-field-ion trap 40, further and / or alternatively, allow for the segmentation of the radial charge tube as previously described.

[0119] Figure 9 schematically shows a CDMS 9 according to an exemplary embodiment, which includes a lift device 99. The CDMS 9 is described in general terms with respect to the CDMS 5. The electrostatic sector-field ion trap 90 and the inductive charge detector 900 are schematically shown as boxes that may represent, for example, the electrostatic sector-field ion trap 50 and the inductive charge detector 500 of the CDMS 5. To increase the throughput of the electrostatic sector-field ion trap in the CDMS according to an exemplary embodiment, it is desirable that a relatively high ion beam operates at a kinetic energy in the range of, for example, 100 eV to 1,000 eV. The advantages of operating at higher energies are faster acquisition and lower aberrations with respect to energy and angle. A first way to increase the kinetic energy is to float the inductive charge detector 900 with a high acceleration potential (negative voltage for positive ions), as is commonly done for TOF analyzers. However, in the case of CDMS, any noise present on the power supply masks the very low induced signal of the CDMS analyzer. Therefore, inductive charge detectors operated at ground potential are much preferable when they can be effectively shielded from noise by an adjacent ground plate and when they are directly coupled to an amplification stage (which is a virtual ground). A second way to increase kinetic energy is to float upstream ion optics by a high potential. This is known to be technically problematic and can cause discharge of components due to field breakdown resulting from Paschen's law. This effect is particularly problematic in the few millibar (mBar) region, where RF ion guides are often used, thereby limiting the applied voltage to about 200V and in turn limiting the kinetic energy of the ions. The solution to the problem is to pulse the tube (i.e., lift device 99) (such as a collimator) to a high potential while filling part of the CDMS cycle. In this way, the problematic discharge can be avoided when the collimator (or other ion optics element) is operated in a high vacuum where voltage breakdown does not occur.Figure 9 shows how such an upstream collimator 99 can be operated in a pulsed manner to increase the kinetic energy of ions within an electrostatic sector field ion trap 90. The ions have a predetermined energy qV. e Then, the collimator tube 99 is filled. At time t1, when the collimator tube 99 is full of ions, it is the increased potential V lift A pulse is sent until t2. This increases the energy of the ion as it enters trap 90, acting as a spatially separated ion pencil, which works further with the ground potential charge tube 900 and shield (i.e., shunt). It should be understood that the electrostatic sector through which the ion passes when introduced is also temporarily ground potential while the ion is being introduced. Trap 90 closes at time t2, and the trapping cycle begins. During the trapping cycle, the sector electrode is subjected to a voltage V related to the ion energy, according to the following equation. i It should be noted that this must have increased.

[0120]

number

[0121] Figure 10 schematically shows a CDMS 10 according to an exemplary embodiment. In this example, the CDMS 10 comprises an electrostatic sector-field-ion trap 100 and an inductive charge detector 1000, wherein the electrostatic sector-field-ion trap 100 is configured to define at least partially the ion path through the inductive charge detector 1000.

[0122] In this example, the electrostatic sector-field-ion trap 100 is as described with reference to the MULTUM in reference

[15] . In this example, the electrostatic sector-field-ion trap 100 comprises a set of electrostatic sectors 101 including four similar cylindrical electrostatic sectors 101A to 101D, each having a deflection angle of ψ0 = 156.87° and a deflection radius of 50 mm. In this example, the electrostatic sector-field-ion trap 100 comprises a set of electrostatic quadrupole lenses 102 including eight electrostatic quadrupole lenses 102A to 102H. In this example, the basic unit comprises four drift spaces, two electrostatic quadrupole lenses, and cylindrical electrostatic sectors. In this example, the electrostatic sector-field-ion trap 100 is isochronous up to the first order with respect to energy. In this example, the ion path defined by the electrostatic sector-field-ion trap 100 includes a crossover and has three-fold planar symmetry passing through it. Ion implantation may be by deflection, as described with reference to reference

[14] , or it may be via an ion inlet.

[0123] In this example, the induced charge detector 1000, as generally described with reference to the induced charge detectors 400, 500, and 800, comprises a first set of segmented charge detection tubes 1010, including four segmented charge detection tubes 1010A, 1010B, 1010C, and 1010D.

[0124] Figure 11 schematically shows a CDMS 11 according to an exemplary embodiment. In this example, the CDMS 11 comprises an electrostatic sector-field ion trap 110 and an inductive charge detector 1100, wherein the electrostatic sector-field ion trap 110 is configured to define at least partially the ion path through the inductive charge detector 1100.

[0125] In this example, the electrostatic sector-field ion trap 110 is as described with reference to the MULTUM linear plus in reference

[15] to enable ion implantation (and efflux), and is as described with reference to the electrostatic sector-field ion trap 100 having an additional electrostatic quadrupole lens.

[0126] In this example, the inductive charge detector 1100, which is generally described with reference to the inductive charge detector 1000, comprises a first set of segmented charge detection tubes 1110, including four segmented charge detection tubes 1110A, 1110B, 1110C, and 1110D.

[0127] Figure 12 schematically shows a CDMS 12 according to one exemplary embodiment. In this example, the CDMS 12 comprises an electrostatic sector-field ion trap 120 and an inductive charge detector 1200, wherein the electrostatic sector-field ion trap 120 is configured to define at least partially the ion path through the inductive charge detector 1200.

[0128] In this example, the electrostatic sector-field-ion trap 120 is as described with reference to the MULTUM in reference

[15] . In this example, the electrostatic sector-field-ion trap 120 comprises a set of electrostatic sectors 121 including four similar toroidal electrostatic sectors 121A to 121D, each having a deflection angle of ψ0 = 157.10°, a deflection radius of 50 mm, and a C1 value of 0.0337. In this example, the electrostatic sector-field-ion trap 120 does not have an electrostatic quadrupole lens. In this example, the basic unit comprises two drift spaces and a toroidal electrostatic sector. In this example, the electrostatic sector-field-ion trap 120 isochronous up to the first order with respect to energy. In this example, the ion path defined by the electrostatic sector-field-ion trap 120 includes a crossover and has three-fold planar symmetry passing through it. Ion implantation may be by deflection, as described with reference to reference

[14] , or it may be via an ion inlet.

[0129] In this example, the inductive charge detector 1200, which is generally described with reference to the inductive charge detector 1000, comprises a first set of segmented charge detection tubes 1210, including four segmented charge detection tubes 1210A, 1210B, 1210C, and 1210D.

[0130] Figure 13 schematically shows a CDMS 13 according to one exemplary embodiment. In this example, the CDMS 13 comprises an electrostatic sector-field ion trap 130 and an inductive charge detector 1300, the electrostatic sector-field ion trap 130 being configured to at least partially define an ion path through the inductive charge detector 1300.

[0131] In this example, the electrostatic sector-field-ion trap 130 is as described with reference to the planar diagram 8 in reference

[15] . In this example, the electrostatic sector-field-ion trap 130 comprises a set of electrostatic sectors 131, including two similar cylindrical electrostatic sectors 131A to 131B, each having a deflection angle of ψ0 = 227.95° and a deflection radius of 50 mm. In this example, the electrostatic sector-field-ion trap 130 comprises a set of electrostatic quadrupole lenses 132, including eight electrostatic quadrupole lenses 132A to 132H. In this example, the basic unit comprises six drift spaces, four electrostatic quadrupole lenses, and a cylindrical electrostatic sector. In this example, the electrostatic sector-field-ion trap 130 isochronous up to the first order with respect to energy. In this example, the ion path defined by the electrostatic sector-field-ion trap 130 includes a crossover and has three-fold planar symmetry passing through it. Ion implantation may be by deflection as described with reference to reference

[14] , or via an ion inlet. In contrast to the three-dimensional geometry of the eight electrostatic sector-field-ion traps 30, 40, and 50, the electrostatic sector-field-ion trap 130 already has a planar geometry of eight, so the topology problems described above do not arise.

[0132] In this example, the induced charge detector 1300, which is generally described with reference to the induced charge detector 1000, comprises a first set of segmented charge detection tubes 1310, including four segmented charge detection tubes 1310A, 1310B, 1310C, and 1310D.

[0133] Figure 14 schematically shows a CDMS 14 according to an exemplary embodiment. In this example, the CDMS 14 comprises an electrostatic sector-field ion trap 140 and an inductive charge detector 1400, wherein the electrostatic sector-field ion trap 140 is configured to at least partially define an ion path through the inductive charge detector 1400.

[0134] In this example, the electrostatic sector-field-ion trap 140 is as described with reference to the rectangular shape in reference

[16] . In this example, the electrostatic sector-field-ion trap 140 comprises a pair of electrostatic sectors 141 including two double toroidal electrostatic sectors 142A, 142B, each containing a first toroidal electrostatic sector 141A with a deflection angle of ψ0 = 156.2° and a second toroidal electrostatic sector 141A with a deflection angle of ψ0 = 23.8°. In this example, the electrostatic sector-field-ion trap 120 does not include an electrostatic quadrupole lens. In this example, the basic unit comprises three drift spaces and two toroidal electrostatic sectors. In this example, the electrostatic sector-field-ion trap 140 isochronous up to the first order with respect to energy. In this example, the ion path defined by the electrostatic sector-field ion trap 140 does not involve crossovers and has a symmetrical plane. Ion implantation can be achieved by deflection as described with reference to reference

[14] or through an ion inlet.

[0135] In this example, the inductive charge detector 1400, which is generally described with reference to the inductive charge detector 1000, comprises a first set of segmented charge detection tubes 1410, including four segmented charge detection tubes 1410A, 1410B, 1410C, and 1410D.

[0136] It should be understood that one of the CDMS4 through 9 interfaces with the hexapole 3 of region III of CDMS10, thereby replacing region IV of CDMS10, or interfaces with the focusing lens 4 of region IV, thereby replacing the HAD6 and modified cone trap with the enantiomer charge detector 7 of region IV, and the orthogonal TOF-MS5 is removed as appropriate.

[0137] Figure 15 schematically shows a method according to one exemplary embodiment. In particular, the method determines the mass of an ion. The method includes the step of moving an ion along at least partially defined ion paths using an electrostatic sector-field ion trap, thereby passing through an induced charge detector (S1501). The method includes the step of inducing a signal in the induced charge detector by the step of moving the ion (S1502). The method comprises the step of determining the mass of the ion using the induced signal (S1503). The method may comprise any of the steps described herein.

[0138] While preferred embodiments have been illustrated and described, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the scope of the invention as defined in the appended claims and as described above.

[0139] Attention is directed to all papers and documents filed in connection with this Specification, concurrently with or prior to this Specification, and made available to the public together with this Specification, the contents of all such papers and documents are incorporated herein by reference.

[0140] All of the features and / or all of the steps of any method or process disclosed herein (including any attached claims and drawings) may be combined in any combination, except for any combination in which many or some of the features and / or steps are mutually exclusive.

[0141] Each feature disclosed herein (including any attached claims and drawings) may be replaced by an alternative feature that performs the same function, is equivalent to or serves a similar purpose, unless otherwise expressly indicated. Thus, unless otherwise expressly indicated, each disclosed feature is merely an example of a general set of equivalent or similar features.

[0142] The present invention is not limited to the details of the embodiments described above. The present invention extends to any novel features or any novel combination of features disclosed herein (including any appended claims and drawings), or to any novel methods or steps of any methods or processes so disclosed herein.

[0143] <References> [1] Charge detection mass spectrometry for single ions with a limit of detection of 30 charges - International Journal of Mass Spectrometry 345-347(2013)153-159 [2] Charge detection mass spectrometry with almost perfect charge accuracy - Anal. Chem. 2015, 87, 10330-10337 [3] Optimized Electrostatic Linear Ion Trap for Charge Detection Mass Spectrometry - J.Am.Soc.Mass Spectrom. (2018) Oct;29(10):2086-2095 [4] Multiple-Focusing Time-of-Flight Mass Spectrometers Part II. TOFMS with Equal Energy Acceleration - International Journal of Mass Spectrometry and Ion Physics, 9(1972):357-373 [5] TOF-SIMS: Materials Analysis by Mass Spectrometry (TOF-SIMS) ISBN:978-1-906715-17-5 [6]Orthogonal acceleration time-of-flight mass spectrometry-Mass Spectrom Rev.2000 Mar-Apr;19(2):65-107 [7] Energy-Isochronous Time-of-Flight Mass Spectrometers - Proceedings of the NATO Advanced Study Institute on Mass Spectrometry in Biomolecular Sciences, Laceo Ameno, Ischia, Italy, June 2-July 5, 1993, pp. 111-146 [8] U.S. Patent No. 9,082,604 [9] Advances in Imaging and Electron Physics - Mikhail Yavor - Optics of Charged Particle Analysers Volume 157 p230

[10] SIMION (C) 2003-2019 Scientific Instrument Services Inc.

[11] WO2012 / 083031A1

[12] Analysis of harmonics for an elongated FTMS cell with multiple electrode detection - International Journal of Mass Spectrometry and Ion Processes, 157 / 158 (1996): 215-232

[13] U.S. Patent No. 6,300,625

[14] Sakurai T, Nakabishi H, Hiasa T, Okanishi K. Nucl. Instrument. Methods A 1999;427:182.

[15] Multi-turn time-of-flight mass spectrometers with electrostatic sectors, Michisato Toyoda, Daisuke Okumura, Morio Ishihara, Itsuo Katakuse, J. Mass Spectrom. 2003;38:1125-1142, https: / / doi.org / 10.1002 / jms.546

[16] M. Nishiguchi, et al., Journal of the Mass Spectrometry Society of Japan 44(2009) 594

Claims

1. A charge-detection mass spectrometer (CDMS) comprising an electrostatic sector-field ion trap, an induced charge detector, and a set of electrostatic focusing lenses including a first focusing lens, The electrostatic sector field ion trap is configured to define at least partially the ion path through the induced charge detector, The mass m of the ion moving along the ion path is determined by determining the mass-to-charge ratio m / z and charge z of the ion using the signal induced by the ion in the inductive charge detector. The electrostatic sector field ion trap comprises a set of electrostatic sectors including a first electrostatic sector and a second electrostatic sector, wherein the ions move along the ion path at a constant speed. The first electrostatic sector and the second electrostatic sector are spherical electrostatic sectors, The first electrostatic sector and the second electrostatic sector face each other, The ion path defined by the electrostatic sector field ion trap includes a crossover, The set of electrostatic focusing lenses, including the first focusing lens, is arranged to at least partially restrict the ion path to a first dimension. The first dimension is orthogonal to the direction of the ion path via the induced charge detector, The first focusing lens comprises a cylindrical lens, an Einzel lens, and / or a plate lens, and / or a cylindrical lens, an Einzel lens, and / or a plate lens, arranged across the crossover in the ion path, in a charge-detection mass spectrometer (CDMS).

2. The CDMS according to claim 1, wherein the set of electrostatic sectors includes only the first electrostatic sector and the second electrostatic sector.

3. The CDMS according to claim 1 or 2, wherein the first electrostatic sector comprises a set of shunts including a first shunt arranged to define a field by the first electrostatic sector.

4. The CDMS according to any one of claims 1 to 3, wherein the electrostatic sector field ion trap is isochronous.

5. The CDMS according to any one of claims 1 to 4, wherein the electrostatic sector field ion trap is configured to at least partially define the ion path in two or three mutually orthogonal dimensions.

6. The CDMS according to any one of claims 1 to 5, wherein the electrostatic sector field ion trap is provided with an ion inlet for introducing ions into the ion pathway.

7. The CDMS according to any one of claims 1 to 6, wherein the induced charge detector comprises a first set of charge detection tubes including a first charge detection tube.

8. The CDMS according to claim 7, wherein the first charge detection tube having length L and width W has a length L to width W ratio in the range of 3:2 to 5:

2.

9. The CDMS according to any one of claims 1 to 8, wherein a portion of the ion path via the induced charge detector is within the range of 30% to 70% of the ion path defined by the electrostatic sector field ion trap.

10. The CDMS according to any one of claims 1 to 9, wherein the induced charge detector is configured to operate at the ground potential.

11. The CDMS according to any one of claims 1 to 10, further comprising a lift device configured to increase the ionic energy of ions to be introduced into the ion pathway.

12. The CDMS according to claim 11, wherein the lift device is configured to trap the ions that will be introduced into the ion pathway.

13. The CDMS according to claim 11 or 12, wherein the lift device is configured to introduce the ions into the ion pathway by pulsed delivery of the ions into the ion pathway.

14. A electrostatic sector field ion trap comprising a set of electrostatic sectors including a first electrostatic sector and a second electrostatic sector, wherein the first electrostatic sector and the second electrostatic sector are spherical electrostatic sectors, and the first electrostatic sector and the second electrostatic sector move ions at a constant velocity along an ion path that is at least partially defined and includes a crossover by the electrostatic sector field ion trap, thereby inducing a signal in the induced charge detector, wherein the ion path is restricted by a set of electrostatic focusing lenses including a first focusing lens to a first dimension orthogonal to the direction of the ion path through the induced charge detector, and the first focusing lens comprises a cylindrical lens, an Einzel lens, and / or a plate lens, and / or a cylindrical lens, an Einzel lens, and / or a plate lens, arranged across the crossover in the ion path, A step of determining the mass m of the ion by determining the mass-to-charge ratio m / z and charge z of the ion using the induced signal, A method for determining the mass of an ion, comprising the following:

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