Differential quadrupole array and mass spectrometer having same

Abstract

The present invention relates to a differential quadrupole array and a mass spectrometer having same. The differential quadrupole array comprises a plurality of differential quadrupoles. Each differential quadrupole comprises four metal plates extending on a radial plane of the differential quadrupole array and having a same contour line, and the four metal plates are arranged rotationally symmetrically in the radial plane. The plurality of differential quadrupoles are arranged in a sequential and aligned mode along an axial direction and form an ion transmission channel extending along the axial direction, wherein each differential quadrupole is individually controlled by a digital driving circuit. The differential quadrupole array and the mass spectrometer having same of the present invention are easy to manufacture and can implement a plurality of functions, including ion acceleration / deceleration, ion convergence / divergence, ion selection, ion collision, linear ion trap, and ion mobility separation, in a same mass spectrometer, and the order of the functions can be defined as required.

Description

Differential quadrupole array and mass spectrometer having the same Technical Field

[0001] The present invention relates to the technical field of mass spectrometers, and in particular to a differential quadrupole array and a mass spectrometer having the differential quadrupole array. Background Art

[0002] Mass spectrometers are widely used to detect and analyze substances, such as determining their atomic mass or relative abundance. During the detection process, the substance to be analyzed is first ionized to form an ion source. The resulting ions have a specific mass-to-charge ratio. The ions then enter a mass analyzer, which generates a specific electric field to separate the ions according to their mass-to-charge ratio. The separated ions then enter an ion detector, which collects and amplifies the ion signals to form a mass spectrum.

[0003] Mass spectrometers, including quadrupole mass spectrometers and ion trap mass spectrometers, perform a variety of functions, including ion focusing, ion guiding, mass selection, ion collision, ion trapping, and ion mobility separation. These various mass spectrometers have different structures depending on their capabilities. Different mass spectrometry applications require different types of mass spectrometers. Therefore, different mass spectrometry analyses require different mass spectrometers, resulting in high instrument costs.

[0004] The quadrupole mass selector (quadrupole for short) is the core component of a quadrupole mass spectrometer. Four electrode rods are placed in parallel on two perpendicular planes. The two electrode rods on the same plane are applied with the same radio frequency alternating voltage, while the voltages applied by the two groups of electrode rods on the two planes are in opposite phases. The radial inner profile of the ideal four electrode rods is a hyperbola, and the electric field formed thereby can maximize ion transmission and ion selection. However, the hyperbolic profile is quite difficult to process, resulting in low yield and high cost of quadrupoles with a hyperbolic profile.

[0005] The quadrupole can be constructed as a single quadrupole or as a series quadrupole. By applying appropriate voltages, the quadrupole can operate in three modes, namely, True Total Ion (TTI), scanning, and Selected Ion Monitoring (SIM). In the TTI mode, no DC voltage is applied to the quadrupole but only RF voltage is applied, so that ions are not filtered and all charged ions pass through the quadrupole. In the scanning mode, the signal of each mass number is collected in turn within a given mass-to-charge ratio range. In the SIM mode, only the ion signals of a specified mass-to-charge ratio or several specified mass-to-charge ratios are collected. A single quadrupole operating in the above modes can realize a primary mass spectrometry (MS 1 ).

[0006] A tandem quadrupole system consists of multiple sets of quadrupoles connected in series. A typical tandem quadrupole system includes three sets of quadrupoles (QQQ) connected in series. Spacers are placed between the first and third sets of quadrupoles at either end and the second set of quadrupoles in the middle. These spacers separate the three sets of quadrupoles into three different isolated chambers, each equipped with a suction port to ensure the required vacuum level within each chamber. The spacers are provided with through-holes for ions to pass through, located where the ion optical axis passes. These through-holes are small enough not to affect the required vacuum level within each chamber. An air inlet is provided within the isolation chamber containing the second set of quadrupoles, allowing inert gas to be released into the isolation chamber, thereby forming a collision cell under the isolation of the spacer. By applying appropriate voltages to each set of quadrupoles, a variety of applications can be achieved, including full scans, selected ion monitoring, daughter ion scans, parent ion scans, neutral loss scans, neutral gain scans, and multiple reaction monitoring (MRM). For example, in order to realize the application of MRM, the first group of quadrupoles can be operated in SIM mode to select precursor ions, the second group of quadrupoles can be operated in TTI mode to form a collision cell, and the third group of quadrupoles can be operated in SIM mode to select fragment ions. Thus, the functions of mass selection or ion selection are realized in the first group of quadrupoles and the third group of quadrupoles, and the function of ion collision is realized in the collision cell. During the ion collision process, the precursor ions selected by the first group of quadrupoles collide with the rare gas molecules in the collision cell and dissociate (this process is also called collision induced dissociation, Collision Induced Dissociation, CID), and then the fragment ions generated enter the ion detector through the selection of the third group of quadrupoles to form a mass spectrum, and the structure of the precursor ions can be inferred through the mass spectrum. Thus, the secondary mass spectrometry (MS) is realized. 2 ).

[0007] However, to achieve more advanced mass spectrometry (MS n , n>2), more quadrupoles need to be connected in series, which increases the space occupied by the instrument. Therefore, more advanced mass spectrometry is usually achieved with the help of ion trap mass spectrometers.

[0008] The linear ion trap has a structure similar to that of a quadrupole, with the difference being that two plates are provided at both ends of the quadrupole, and a voltage opposite to the polarity of the ions is applied to the plates, allowing the ions to shuttle back and forth between the plates, thereby realizing the function of a linear ion trap. At the same time, among the quadrupoles in a group of two, at least one group of quadrupoles has a narrow slit. In the initial state, inverted radio frequency alternating voltages are applied to the quadrupoles in different groups, so that all ions can be retained in the ion trap; then another group of alternating voltages is applied to the group of quadrupoles with narrow slits, causing the ions to enter an unstable state and then be ejected from the narrow slits. At the same time, the ion trap can be filled with a certain concentration of inert gas, so that the ions collide with the inert gas multiple times in the ion trap and produce multiple dissociations. By adjusting the voltage, the fragmented ions obtained by the dissociation can be ejected from the narrow slit in turn and enter the ion detector to form a mass spectrum. The structure of the precursor ion can be inferred through the mass spectrum. In this way, a multi-stage mass spectrometry (MS) is realized. n ).

[0009] Ion mobility mass spectrometry (IMMS) is a mass spectrometry method that uses the ion mobility (IM) of each ion to separate them, effectively performing ion mobility separation. The main difference between IMMS and conventional mass spectrometers is that IMMS includes an ion drift tube, with an electric field applied at both ends to propel the ions forward. The ion drift tube is filled with a buffer gas of a certain concentration, such as nitrogen, helium, carbon dioxide, sulfur hexafluoride, ammonia, or carbon tetrafluoride.

[0010] Because single quadrupole mass spectrometers, tandem quadrupole mass spectrometers, ion trap mass spectrometers, and ion mobility mass spectrometers have different structures and each has unique components, such as the spacer that forms the collision cell, the narrow slit on the quadrupole that forms the linear ion trap and the plates at both ends, the ion drift tube, etc., the functions of these mass spectrometers cannot be implemented on the same device.

[0011] Summary of the Invention

[0012] The purpose of the present invention is to provide a differential quadrupole array that is easy to manufacture and can realize multiple functions, and a mass spectrometer having the differential quadrupole array, so that multiple functions such as ion acceleration / deceleration, ion convergence / divergence, ion selection, ion collision, linear ion trap, ion mobility separation, etc. can be realized in any section of the same mass spectrometer.

[0013] According to one aspect of the present invention, a differential quadrupole array is provided, comprising multiple groups of differential quadrupoles, each group of differential quadrupoles comprising four metal plates extending in a radial plane of the differential quadrupole array and having the same contour lines, the four metal plates being rotationally symmetrically arranged in the radial plane, the multiple groups of differential quadrupoles being arranged in a sequential and aligned manner along an axial direction and forming an ion transmission channel extending along the axial direction, wherein each group of differential quadrupoles is individually controlled by a digital drive circuit.

[0014] Compared to rod-shaped quadrupoles formed by turning or grinding, the differential quadrupole array of the present invention is much easier to manufacture. For example, metal plates with a desired profile, such as a hyperbolic profile, can be precision-stamped or laser-cut in batches from large metal sheets or printed circuit boards. These plates can then be assembled through precise positioning and / or calibration to form the differential quadrupole array of the present invention. This manufacturing method offers high precision, a high yield, and low cost.

[0015] Each set of differential quadrupoles can form a sub-electric field through its radially inner edge, and the multiple sub-electric fields formed by multiple sets of differential quadrupoles can be superimposed to form a combined electric field, which is similar to the electric field formed by ordinary quadrupoles. For example, a first radio frequency alternating voltage with a certain DC voltage component is applied to a pair of opposing metal plates in each set of differential quadrupoles, and a second radio frequency alternating voltage with a certain DC voltage component is applied to another pair of opposing metal plates in each set of differential quadrupoles, and the first radio frequency alternating voltage and the second radio frequency alternating voltage have the same coefficient and opposite phase. Then, these differential quadrupoles can form an electric field similar to that of a quadrupole operating in SIM mode, so that these differential quadrupoles also operate in SIM mode and select ions passing through these differential quadrupoles.

[0016] Each set of differential quadrupole rods is individually controlled by a digital drive circuit, meaning the voltage applied to each set can be controlled independently. This allows each set of differential quadrupole rods to form distinct functional regions along different axial segments, depending on the applied voltage. These functional regions can perform functions including ion acceleration / deceleration, ion convergence / divergence, ion selection, ion collisions, linear ion traps, and ion mobility separations.

[0017] Preferably, by controlling the digital drive circuit, the differential quadrupole array can be configured into a pre-quadrupole, a single quadrupole, a tandem quadrupole, a linear ion trap, an ion drift tube and a combination thereof, thereby realizing the functions of ion convergence / divergence, ion selection, ion collision, linear ion trap and / or ion mobility separation in any order on the differential quadrupole array.

[0018] Preferably, at least one modulatable electric field distributed along an axial direction is formed on the differential quadrupole array by controlling the digital drive circuit. For example, by applying a DC voltage to two sets of differential quadrupoles, an axially modulatable electric field can be formed between the two sets of differential quadrupoles. The axially modulatable electric field can achieve functions such as ion acceleration / deceleration. Furthermore, the direction, intensity, and / or axial length of the modulatable electric field can be changed by the digital drive circuit.

[0019] In particular, the modulatable electric field is a plurality of electric fields with different directions, intensities and / or axial lengths.

[0020] Preferably, one or more groups of differential quadrupoles at any position of the differential quadrupole array are configured as ion gates by controlling the digital drive circuit. For example, a pulse voltage may be applied to a group of differential quadrupoles to configure the group of differential quadrupoles as an ion gate, wherein when the pulse voltage has the same polarity as the ions, the ions cannot pass through the group of differential quadrupoles, causing the ion gate to be in a closed state; and when the pulse voltage is, for example, zero or opposite in polarity to the ions, the ions can pass through the group of differential quadrupoles, causing the ion gate to be in an open state.

[0021] Preferably, the radial inner profile of the metal plate is a hyperbola, so that the electric field formed thereby can maximize ion transmission and ion selection.

[0022] Preferably, the metal plate is formed by precision stamping or laser cutting on a metal plate or a printed circuit board.

[0023] Preferably, the metal plate has a thickness of 0.1-2 mm. A metal plate of a certain thickness can form a desired electric field at the radially inner edge. However, an excessively thick metal plate is not conducive to forming by stamping or laser cutting. Based on the applicant's research, the metal plate should preferably be designed to have a thickness of 0.1-2 mm.

[0024] Preferably, the axial spacing between the metal plates in the axial direction is 0.1-2 mm. If the spacing between the metal plates is too narrow, there is a risk of voltage breakdown; if the spacing between the metal plates is too wide, the resulting combined electric field differs significantly from the electric field formed by conventional quadrupoles, affecting the functionality of the various functional areas of the differential quadrupole array, for example, reducing the accuracy of ion selection. Based on the applicant's research, the metal plates are preferably designed to have an axial spacing of 0.1-2 mm.

[0025] Preferably, an insulating structure is provided between the metal plates. The insulating structure can be an insulating coating applied to the axial end surfaces of the metal plates or an insulating sheet provided between adjacent metal plates. The insulating structure can prevent voltage breakdown between the metal plates, ensuring that the axial spacing between the metal plates in the axial direction is less than 2 mm, and particularly less than 0.1 mm. This improves the performance of the combined electric field, thereby enhancing the functionality of each functional region of the differential quadrupole array, for example, improving the accuracy of ion selection.

[0026] Preferably, the metal plate is kept at a constant temperature, for example, 100 degrees Celsius, in a working state by a heating device and a temperature sensor, so that ions or neutral molecules cannot accumulate on the metal plate, thereby preventing the metal plate from being contaminated.

[0027] According to another aspect of the present invention, a mass spectrometer is provided, comprising a housing, an ion source, and an ion detector mounted within the housing, wherein the mass spectrometer is provided with the aforementioned differential quadrupole array between the ion source and the ion detector. Based on the differential quadrupole array, multiple functions can be implemented in any order within the same mass spectrometer via individually controlled digital drive circuits, including ion acceleration / deceleration, ion convergence / divergence, ion selection, ion collisions, linear ion traps, and ion mobility separation.

[0028] Preferably, one or more gas inlets are provided on the inner wall of the mass spectrometer and on one or more radial planes within the range of the differential quadrupole array, and the gas inlets are configured to release gas into the differential quadrupole array to form a gas space corresponding to the position of the gas inlet, so as to cooperate with the electric field formed by the voltage applied to the differential quadrupole array, so that ions can realize functions such as ion collision and ion mobility separation in the gas space.

[0029] In one embodiment, a radio frequency alternating voltage is applied to the differential quadrupole in the gas space by the digital drive circuit to achieve ion acceleration and ion collision functions in the gas space. Preferably, the radio frequency alternating voltage applied to the differential quadrupole in the gas space is increasing. The increasing radio frequency alternating voltage can achieve the ion acceleration function, and precursor ions with a certain speed collide with the gas in the gas space, particularly the inert gas, and dissociate into ion fragments, thereby achieving the ion collision function.

[0030] In another embodiment, a DC voltage and / or a radio frequency alternating voltage is applied to the differential quadrupole at both ends of the gas space by the digital driving circuit to realize the function of a linear ion trap in the gas space. By applying a DC voltage and / or a radio frequency alternating voltage to both ends of the gas space, an axial confinement field can be formed, and ultimately the function of an ion trap can be realized in the gas space. Preferably, after a predetermined time has passed, the DC voltage and / or the radio frequency alternating voltage is stopped from being applied to the differential quadrupole at the end of the gas space by the digital driving circuit, so that the ion fragments formed by multiple collisions and dissociations can reach the ion detector.

[0031] In another embodiment, a DC voltage is applied to the differential quadrupoles at both ends of the gas space, or a DC increasing voltage is applied to the differential quadrupoles within the gas space, by the digital drive circuit, to achieve ion acceleration and ion mobility separation functions within the gas space. Applying a DC voltage to the differential quadrupoles at both ends of the gas space, or applying a DC increasing voltage to the differential quadrupoles within the gas space, can configure the differential quadrupoles in the gas as ion drift tubes, causing ions to be accelerated in the gas space. Ions with appropriate velocities will obtain different velocities in the gas space according to their ion mobility, thereby resulting in separation.

[0032] Preferably, there are no radially extending spacers between the multiple groups of differential quadrupoles to form isolated chambers. The spacers typically extend radially from the inner wall of the chamber where the differential quadrupole array is located toward the ion optical axis, i.e., the central axis of the ion transmission channel, and form through holes only at the location where the ion optical axis passes, allowing ions to pass through. The through holes are typically small enough so as not to affect the vacuum levels required in the isolated chambers on both sides of the spacer. The lack of spacers between the differential quadrupoles facilitates the flexible implementation of the above-mentioned functions at any location in the differential quadrupole array. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] To better understand the above and other objects, features, advantages, and functions of the present invention, reference may be made to the preferred embodiments shown in the accompanying drawings. Like reference numerals in the accompanying drawings refer to like components. Those skilled in the art should understand that the accompanying drawings are intended to illustrate preferred embodiments of the present invention by way of illustration and are not intended to limit the scope of the present invention. The components in the drawings are not drawn to scale.

[0034] FIG1 shows a schematic diagram of a first embodiment of a mass spectrometer of the present invention;

[0035] FIG2 shows a side view of a first group of differential quadrupoles in the differential quadrupole array of the present invention;

[0036] FIG3 shows a schematic diagram of a second embodiment of a mass spectrometer of the present invention;

[0037] FIG4 shows a schematic diagram of a third embodiment of a mass spectrometer of the present invention;

[0038] FIG5 shows a schematic diagram of a fourth embodiment of a mass spectrometer of the present invention;

[0039] FIG6 shows a schematic diagram of a fifth embodiment of a mass spectrometer of the present invention;

[0040] FIG7 shows a schematic diagram of a sixth embodiment of a mass spectrometer of the present invention; and

[0041] FIG8 shows a schematic diagram of another embodiment of the differential quadrupole array of the present invention. DETAILED DESCRIPTION

[0042] Now referring to the accompanying drawings, the specific embodiments of the present invention will be described in detail. What is described here is only the preferred embodiment of the present invention. Those skilled in the art can think of other ways to implement the present invention based on the preferred embodiment, and the other ways also fall within the scope of the present invention.

[0043] Figures 1 and 3 through 7 illustrate various exemplary embodiments of a mass spectrometer 1 according to the present invention. These embodiments are all based on the same mass spectrometer and implement different functions, including ion acceleration / deceleration, ion convergence / divergence, ion selection, ion collisions, linear ion traps, and ion mobility separation. The primary difference between these embodiments lies in the different voltages applied by the digital drive circuit to each set of differential quadrupoles. The structure of the mass spectrometer 1, and in particular the differential quadrupole array 10, is described in detail below.

[0044] 1 , a mass spectrometer 1 of the present invention includes a housing 40, and an ion source 20 and an ion detector 30 located within the housing 40. A differential quadrupole array 10 of the present invention is located between the ion source 20 and the ion detector 30 and includes eight groups of differential quadrupoles 101 to 108. Each group of differential quadrupoles includes four metal plates (see FIG. 2 ) extending in a radial plane of the differential quadrupole array 10 and having the same contour line. The four metal plates are rotationally symmetrically arranged in the radial plane. The eight groups of differential quadrupoles 101 to 108 are arranged in a sequential and aligned manner along the axial direction of an axis L and form an ion transmission channel 110 extending along the axial direction. Each group of differential quadrupoles is individually controlled by a digital drive circuit and is applied with independent voltages U1 to U8. That is, the voltages applied to each group of differential quadrupoles can be independently controlled. The independently applied voltages U1 to U8 cause each set of differential quadrupoles to form sub-electric fields on their radially inner edges. The sub-electric fields are further superimposed to form a combined electric field, which controls the ion motion path 200 in the ion transport channel 110. By controlling the digital drive circuit, the voltage applied to each set of differential quadrupoles can be individually controlled, thereby controlling the sub-electric fields and the combined electric field formed by the superposition of the sub-electric fields, thereby achieving control of the ion motion path 200.

[0045] One or more gas inlets can be provided on the inner wall of the mass spectrometer 1, in particular on the housing 40, and the gas inlets are located on one or more radial planes within the range of the differential quadrupole array 10. For example, referring to FIG1 , a first gas inlet 120 is provided on a first radial plane S1 between the two sets of differential quadrupoles 103 and 104, and a second gas inlet 122 is provided on a second radial plane S2 between the two sets of differential quadrupoles 105 and 106 closer to the ion detector 30. The first gas inlet 120 and the second gas inlet 122 are configured to release gas into the interior of the differential quadrupole individually or in coordination to form a gas space corresponding to the position of the first gas inlet 120 and / or the second gas inlet 122. The gas space is used to perform specific functions, such as ion collision and ion mobility separation. Preferably, a suction port 130 is provided on the opposite side of the first gas inlet 120 and the second gas inlet 122 and closer to the ion source 20. Suction port 130 is used to draw gas, particularly gas released from the gas inlet, to maintain the vacuum within the chamber. By selecting and using gas inlets at different locations and adjusting the gas release rate from the inlets, the axial distribution and concentration of gas molecules can be controlled. This allows the position and concentration of gas molecules in a gas space, such as a collision cell, to be adjusted.

[0046] Spacers 50 and 60 are respectively disposed between the ion source 20 and the differential quadrupole array 10, and between the differential quadrupole array 10 and the ion detector 30. Spacers 50 and 60 have small holes formed at locations where the axis L passes through, facilitating the passage of ions. Furthermore, a vacuum pressure difference can be formed in the spaces separated by spacers 50 and 60, which is beneficial during the operation of the mass spectrometer.

[0047] No spacers are provided between the groups of differential quadrupoles 101 to 108, which allows for more flexible use of the differential quadrupole array 10. However, in other embodiments, spacers may be provided between the groups of differential quadrupoles to limit the vacuum level within a specific space, form a specific gas space, and / or reduce the influence of the electric field between adjacent differential quadrupoles.

[0048] FIG2 shows the first set of differential quadrupoles 101 and its four metal plates 101A, 101B, 101C, and 101D in FIG1 from a side view. The radially inner profiles of the metal plates are hyperbolic, so that the resulting electric field maximizes ion transmission and ion selection. The metal plates may also have radially inner profiles of other shapes, such as a spire, an arc, or a straight line.

[0049] As shown in FIG2 , among the four metal plates 101A to 101D of the first set of differential quadrupoles 101 , two metal plates disposed opposite to each other are applied with the same voltage, that is, the voltage U1 applied to the first set of differential quadrupoles 101 includes U1 + and U1 - , referred to as U1 + / - .

[0050] In one embodiment, a voltage U1 may be applied to the metal plates 101A and 101C. + = U1 + V1cosωt, and opposite voltages U1 are applied to the other two oppositely disposed metal plates 101B and 101D. - =-U1-V1cosωt. At voltage U1 + / - The voltage components are composed of DC and RF voltages, where U1 is the DC voltage coefficient and V1 is the RF voltage coefficient, and the two voltages are in opposite phases. Under the independent control of the digital drive circuit, the values ​​of U1 and V1 can be set arbitrarily.

[0051] In another embodiment, the same voltage can be applied to the two pairs of metal plates, that is, U1 + =U1 -. For example, by applying the same first DC voltage to a group of differential quadrupoles near the front end and applying the same second DC voltage to another group of differential quadrupoles near the end, a modulated electric field distributed along the axial direction can be formed between the two groups of differential quadrupoles. When the first DC voltage is greater than the second DC voltage, a deceleration electric field is formed, and the ions are decelerated when passing through; conversely, when the second DC voltage is greater than the first DC voltage, an acceleration electric field is formed, and the ions are accelerated when passing through. This is beneficial for forming an ion drift tube and further realizing the function of ion mobility separation. The direction and / or intensity and / or axial length of the modulated electric field can be changed by an independently controlled digital drive circuit. It is also possible to form multiple modulated electric fields distributed along the axial direction on the differential quadrupole array, and their directions and / or intensities and / or axial lengths can be independently set by the digital drive circuit, and can be set to be the same or different.

[0052] The above voltage application method is also applicable to other differential quadrupoles 102 to 108 .

[0053] For example, applying a DC increasing voltage or a DC decreasing voltage to two pairs of metal plates of multiple sets of differential quadrupoles can also form an accelerating electric field or a decelerating electric field between the multiple sets of differential quadrupoles to achieve the function of ion acceleration / deceleration.

[0054] Alternatively, by controlling the digital drive circuit to apply, for example, a pulse voltage to two pairs of metal plates of one or more sets of differential quadrupoles, the one or more sets of differential quadrupoles can be configured as an ion gate. When the pulse voltage has the same polarity as the ions, the ions cannot pass through the one or more sets of differential quadrupoles, causing the ion gate to be closed. When the pulse voltage is, for example, zero or opposite in polarity to the ions, the ions can pass through the one or more sets of differential quadrupoles, causing the ion gate to be open.

[0055] Different voltages applied to each metal plate create different electric fields across the plates, particularly at their radially inner edges. This allows the differential quadrupole array to perform its various functions in any axial segment, including ion acceleration / deceleration, ion convergence / divergence, ion selection, ion collisions, linear ion trapping, and ion mobility separation. This is illustrated below with specific examples.

[0056] In the first embodiment of FIG1 , a DC voltage and a radio frequency voltage DC / RF are applied to the differential quadrupoles 101 to 108, causing the differential quadrupole array 10 as a whole to operate in a selected ion monitoring (SIM) mode. In this mode, ions with a mass-to-charge ratio that meets the requirements move along the ion motion path 200 around the axis L in the ion transmission channel 110, ultimately passing through the differential quadrupole array 10 and reaching the ion detector 30; while ions with a mass-to-charge ratio that does not meet the requirements move along the ion motion path 210, collide with the differential quadrupoles, and ultimately fail to reach the ion detector 30. In this way, through a separately controlled digital drive circuit, the differential quadrupole array 10 can be configured as a single quadrupole to achieve the function of ion selection.

[0057] Optionally, by adjusting the voltage applied to each differential quadrupole 101 to 108 through a digital driving circuit, the differential quadrupole array 10 as a whole can be operated in a total passage of ions (TTI) mode or a scanning mode.

[0058] In the second embodiment of FIG. 3 , unlike the first embodiment, only a radio frequency (RF) voltage is applied to the differential quadrupoles 101 to 104, rather than a DC voltage, and the RF voltage coefficient gradually increases. In this case, as ions pass through this axial section, their radial motion radius gradually decreases due to the influence of the gradually increasing electric field, gradually transitioning from a path 200 with a larger motion radius to a path 220 with a smaller motion radius. Thus, through a separately controlled digital drive circuit, the differential quadrupole array 10 is used as a pre-quadrupole in the axial section of the differential quadrupoles 101 to 104, achieving an ion convergence effect. Conversely, if the RF voltage coefficient is adjusted to gradually decrease through the digital drive circuit, an ion divergence effect can be achieved.

[0059] In this embodiment, a DC voltage and a radio frequency voltage DC / RF are applied to the differential quadrupoles 105 to 108, causing the entire differential quadrupole array 10 to operate in SIM mode. Thus, through individually controlled digital drive circuits, the differential quadrupole array 10 is configured as a combination of pre-quadrupoles and single quadrupoles.

[0060] In the third embodiment shown in FIG. 4, different from the first embodiment, a first DC voltage and a first RF voltage DC / RF are applied to the differential quadrupoles 101 and 102, so that the differential quadrupole array 10 operates in the SIM mode in the axial section where the differential quadrupoles 101 to 102 are located and selects precursor ions having a first mass-to-charge ratio to pass through; no DC voltage is applied to the differential quadrupoles 103 and 104, and only an RF voltage RF is applied, so that the differential quadrupole array 10 operates in the TTI mode in the axial section where the differential quadrupoles 103 to 104 are located. Preferably, the RF alternating voltage RF applied to the differential quadrupoles 103 and 104 is increasing, that is, its RF voltage component V3 < V4, so that the ions are accelerated when passing through the differential quadrupoles 103 and 104. On the one hand, ion acceleration can compensate for the kinetic energy loss caused by ion collisions. On the other hand, the smooth progress of ion collisions requires the ions to have a certain initial velocity. At the same time, the first gas inlet 120 releases an inert gas, and the distribution of the inert gas is maintained within, for example, the axial section where the differential quadrupoles 103 to 104 are located to form a gas space with the inert gas. Thus, a collision cell is formed within the axial section where the differential quadrupoles 103 to 104 are located. The precursor ions enter the collision cell with a certain initial velocity and collide with the inert gas molecules in the collision cell, thereby dissociating into multiple fragment ions. Thereafter, a second DC voltage and a second RF voltage DC / RF are applied to the differential quadrupoles 105 to 108, so that the differential quadrupole array 10 operates in the SIM mode in the axial section where the differential quadrupoles 105 to 108 are located and selects fragment ions having a second mass-to-charge ratio to pass through and reach the ion detector 30; ions / fragment ions with inconsistent mass-to-charge ratios hit the metal plate along the ion movement path 230 and cannot reach the ion detector 30. Thus, the differential quadrupole array 10 is configured as a triple tandem quadrupole through a digital drive circuit to implement the functions of ion collision and ion selection.

[0061] Optionally, by adjusting the voltage applied to the differential quadrupoles 105 to 108 through the digital drive circuit, the differential quadrupole array 10 can also operate in the TTI mode or the scanning mode in the axial section of the differential quadrupoles 105 to 108.

[0062] In the fourth embodiment of FIG5 , unlike the third embodiment, the axial segment in which differential quadrupoles 101 to 104 are located is configured as the first quadrupole in a triple tandem quadrupole arrangement, the axial segment in which differential quadrupoles 105 to 106 are located is configured as the second quadrupole in a triple tandem quadrupole arrangement, and the axial segment in which differential quadrupoles 107 to 108 are located is configured as the third quadrupole in a triple tandem quadrupole arrangement. Simultaneously, second gas inlet 122 located on second radial plane S2 is enabled, while first gas inlet 120 located on first radial plane S1 is disabled, thereby forming the aforementioned gas space or collision cell in the axial segment including second radial plane S2. This increases the number of differential quadrupoles used to select precursor ions having a first mass-to-charge ratio, thereby lengthening the path that the precursor ions travel when selected in the first quadrupole. This can, in some cases, increase the accuracy of ion selection for the precursor ions. Accordingly, in this embodiment, the path of the fragment ions in the differential quadrupole is shortened. When the axial section where the differential quadrupoles 107 to 108 are located operates in TTI mode, appropriately shortening the path of the fragment ions in the differential quadrupole will not produce adverse effects.

[0063] This means that by individually controlling the voltages applied to the differential quadrupoles, the lengths of the various functional regions formed by the limited-length differential quadrupole array 10 can be rationally allocated. Furthermore, the lack of radially extending spacers between the differential quadrupoles 101 to 108 also facilitates the length allocation of the various functional regions.

[0064] In the fifth embodiment of FIG6 , unlike the first embodiment, a DC voltage with a polarity opposite to that of the ions is applied to the differential quadrupoles 103 and 106 to form an axial confinement field. The ions are confined in the axial confinement field, thereby configuring the differential quadrupole array 10 as a linear ion trap, thereby achieving the functions of a linear ion trap or ion confinement. Alternatively, the axial confinement field may be generated by other means, including radio frequency alternating voltage or a combination of radio frequency alternating voltage and DC voltage.

[0065] Furthermore, instead of applying a DC voltage to differential quadrupoles 104 and 105, only a radio frequency voltage (RF) is applied, allowing differential quadrupole array 10 to operate in a TTI mode in the axial segment where differential quadrupoles 104 and 105 are located. Simultaneously, gas can be released through first gas inlet 120 and / or second gas inlet 122 to form the aforementioned gas space or collision cell within the axial segment between differential quadrupoles 103 and 106. As trapped ions travel back and forth along ion motion path 250 between differential quadrupoles 103 and 106, they collide with gas molecules within the collision cell and dissociate, thereby achieving the ion collision function.

[0066] After a predetermined time has passed, the trapped ions shuttle back and forth several times within the axial section of the differential quadrupoles 103 to 106 and undergo multiple collisions and dissociations. At this point, the digital drive circuit can stop applying the DC voltage and / or RF alternating voltage to the terminal differential quadrupole 106, causing the fragment ions to reach the ion detector 30 along the ion motion path 260. In this case, the digital drive circuit can also adjust the voltage applied to the differential quadrupoles 106 to 108, causing the differential quadrupole array 10 to operate in the TTI mode (as shown in FIG6 ), scanning mode, or SIM mode on the axial section of the differential quadrupoles 106 to 108.

[0067] In the sixth embodiment of Figure 7, different from the first embodiment, a first DC voltage and a first radio frequency voltage DC / RF are applied to the differential quadrupoles 101 and 102, so that the differential quadrupole array 10 operates in the SIM mode in the axial segment where the differential quadrupoles 101 to 102 are located and selects precursor ions with a first mass-to-charge ratio to pass through; a first DC voltage DC is applied to the differential quadrupole 103, and a second DC voltage DC greater than the first DC voltage is applied to the differential quadrupole 106, thereby forming an axial accelerating electric field (similar to an ion drift tube) between the differential quadrupoles 103 and 106; no DC voltage is applied to the differential quadrupoles 104 and 105, but only a radio frequency voltage RF is applied, so that the differential quadrupole array 10 operates in the TTI mode in the axial segment where the differential quadrupoles 104 to 105 are located. Simultaneously, second gas inlet 122 releases buffer gas, which forms a gas space within the axial section where differential quadrupoles 103 to 106 are located, and forms a countercurrent in the central region that is opposite to the axial direction of the ions' motion. Although the precursor ions have the same mass-to-charge ratio, their structures may differ, resulting in different ion mobilities. As a result, during interaction with the buffer gas, the relative positions of the ions change based on their ion mobilities, separating ions of different structures and achieving ion mobility separation. For example, in Figure 7, ions with more compact structures move along ion motion path 270, while ions with more relaxed structures move along ion motion path 280.

[0068] Alternatively, a DC increasing voltage may be applied to the differential quadrupoles 103 to 106 in the gas space to achieve the functions of ion acceleration and ion mobility separation in the gas space.

[0069] Additionally, a differential quadrupole located at the front end of the gas space, for example, the differential quadrupole 103 , may be configured as the aforementioned ion gate in order to introduce ions into the gas space in batches.

[0070] Furthermore, appropriate voltages can be applied to the differential quadrupoles 107 to 108 as needed to cause their axial sections to operate in, for example, a TTI mode. Thus, by controlling the digital drive circuit, a portion of the differential quadrupole array 10 is configured as an ion drift tube, thereby achieving ion mobility separation.

[0071] Based on the above embodiments, appropriate voltages can be applied to the differential quadrupole in any axial segment as needed to achieve the above functions and their combinations in any order, including ion acceleration / deceleration, ion convergence / divergence, ion selection, ion collision, linear ion trap and ion mobility separation.

[0072] In the above embodiment, only a differential quadrupole array 10 consisting of eight groups of differential quadrupoles 101-108 is shown. However, the differential quadrupole array 10 may include more groups of differential quadrupoles. In addition, the thickness of the metal plates of each group of differential quadrupoles is preferably the same and is within the range of 0.1-2 mm, and the axial spacing between adjacent differential quadrupoles is preferably the same and is within the range of 0.1-2 mm. A metal plate with a certain thickness can form a desired electric field at the radial inner edge, however, a metal plate that is too thick is not conducive to forming by stamping or laser cutting. If the spacing between the metal plates is too narrow, there is a risk of voltage breakdown; if the spacing between the metal plates is too wide, the combined electric field formed will be too different from the electric field formed by ordinary quadrupoles, affecting the functional realization of each functional area of ​​the differential quadrupole array, for example, reducing the accuracy of ion selection.

[0073] In one embodiment, the differential quadrupole array includes 1024 groups of differential quadrupoles, each group of differential quadrupoles includes four metal plates with a thickness of 0.1 mm, and the radial inner profile of the metal plates is a hyperbola. The 1024 groups of differential quadrupoles are arranged at intervals of 0.1 mm in the axial direction, and all differential quadrupoles are individually controlled by a digital drive circuit.

[0074] In another embodiment, the differential quadrupole array includes 256 groups of differential quadrupoles, each group of differential quadrupoles includes four metal plates with a thickness of 2 mm, the radial inner profile of the metal plates is a hyperbola, and the 256 groups of differential quadrupoles are arranged at intervals of 2 mm in the axial direction. All differential quadrupoles are individually controlled by a digital drive circuit.

[0075] FIG8 shows another embodiment of the differential quadrupole array of the present invention, which differs from the above embodiment in that an insulating structure 109 is provided between the metal plates of adjacent differential quadrupoles. For example, the insulating structure 109 can be an insulating coating applied on the axial end surface of the metal plate, or an insulating sheet provided between adjacent metal plates. Such an insulating structure 109 can effectively prevent the metal plates from being broken down by voltage, so the axial spacing between adjacent differential quadrupoles can be less than 2 mm, and in particular, less than 0.1 mm. The smaller the spacing between adjacent differential quadrupoles, the closer the combined electric field formed by the superposition of the sub-electric fields of each group of differential quadrupoles is to the electric field formed by an ordinary differential quadrupole, thereby, for example, improving the accuracy of ion selection.

[0076] In addition, as mentioned above, ions with a mass-to-charge ratio that meets the requirements will pass through the differential quadrupole, while ions with a mass-to-charge ratio that does not meet the requirements will collide with the metal plate of the differential quadrupole. In order to prevent these ions with a mass-to-charge ratio that does not meet the requirements and the neutral molecules that may be doped therein from accumulating on the metal plate of the differential quadrupole and forming contamination, a heating device and a temperature sensor can be provided in the mass spectrometer. The heating device heats the metal plate of the differential quadrupole, and the temperature is controlled at, for example, 100 degrees Celsius by the temperature sensor. The thermal motion of the metal atoms on the surface of the heated metal plate is more intense, making it impossible for ions and neutral molecules to adhere to and accumulate thereon.

[0077] The above description of various embodiments of the present invention is provided for the purpose of description to one of ordinary skill in the relevant art. It is not intended to exclude or limit the present invention to a single disclosed embodiment. As above, a person of ordinary skill in the art will understand the various substitutions and variations of the present invention. Therefore, although some alternative embodiments are specifically described, a person of ordinary skill in the art will understand or relatively easily develop other embodiments. The present invention is intended to include all substitutions, modifications and variations of the present invention described herein, as well as other embodiments that fall within the spirit and scope of the present invention described above.

[0078] Description of the Reference Numerals: 1 mass spectrometer 10 differential quadrupole array 20 ion source 30 ion detector 40 housing 50 , 60 spacers 101 - 108 differential quadrupoles 101A - 101D metal plate 109 insulating structure 110 ion transmission channel 120 first gas inlet 122 second gas inlet 130 gas extraction port 200 ion movement path 210 ion movement path 220 ion movement path 230 ion movement path 240 ion movement path 250 ion movement path 260 ion movement path 270 ion movement path 280 ion movement path L axis S1 first radial plane S2 second radial plane DC direct current voltage RF radio frequency voltage DC / RF direct current voltage superimposed radio frequency voltage U1 - U8 voltage U1 applied to each group of differential quadrupoles + A pair of voltages U1 applied to the first set of differential quadrupoles - Another pair of voltages applied to the first set of differential quadrupoles

Claims

1. A differential quadrupole array, comprising a plurality of groups of differential quadrupoles, each group of differential quadrupoles comprising four metal plates extending on a radial plane of the differential quadrupole array and having the same contour line, the four metal plates being arranged rotationally symmetrically in the radial plane, the plurality of groups of differential quadrupoles being arranged in sequence and aligned along an axial direction and forming an ion transmission channel extending along the axial direction, characterized in that: Each set of differential quadrupoles is individually controlled by a digital drive circuit.

2. The differential quadrupole array according to claim 1, characterized in that: By controlling the digital drive circuit, the differential quadrupole array is configured into a pre-quadrupole, a single quadrupole, a tandem quadrupole, a linear ion trap, an ion drift tube and a combination thereof, so as to realize the functions of ion convergence / divergence, ion selection, ion collision, linear ion trap and / or ion mobility separation, and the order of the above functions can be defined as needed.

3. The differential quadrupole array according to claim 1, characterized in that: At least one modulatable electric field distributed along the axial direction is formed on the differential quadrupole array by controlling the digital driving circuit, and the direction and / or intensity and / or axial length of the modulatable electric field can be changed by the digital driving circuit.

4. The differential quadrupole array according to claim 3, characterized in that: The modulatable electric field is a plurality of electric fields with different directions, intensities and / or axial lengths.

5. The differential quadrupole array according to claim 1, characterized in that: One or more groups of differential quadrupoles at any position of the differential quadrupole array are configured as ion gates by controlling the digital driving circuit.

6. The differential quadrupole array according to claim 1, characterized in that: The radial inner profile of the metal plate is a hyperbola.

7. The differential quadrupole array according to claim 1, characterized in that: The metal plate is formed by precision punching or laser cutting on a metal plate or a printed circuit board.

8. The differential quadrupole array according to claim 1, characterized in that: The thickness of the metal plates is 0.1-2 mm, and the axial spacing between the metal plates in the axial direction is 0.1-2 mm.

9. The differential quadrupole array according to claim 1, characterized in that: An insulating structure is arranged between the metal plates, and the insulating structure is an insulating coating coated on the axial end surface of the metal plate or an insulating sheet arranged between adjacent metal plates. Preferably, the axial spacing between the metal plates in the axial direction is less than 2 mm, and more preferably less than 0.1 mm.

10. The differential quadrupole array according to claim 1, characterized in that: The metal plate is kept at a constant temperature in a working state by a heating device and a temperature sensor.

11. A mass spectrometer, comprising a housing, an ion source and an ion detector installed in the housing, characterized in that: The mass spectrometer is provided with a differential quadrupole array according to any one of claims 1 to 10 between the ion source and the ion detector.

12. The mass spectrometer according to claim 11, characterized in that One or more gas inlets are arranged on the inner wall of the mass spectrometer, and the gas inlets are configured to release gas into the differential quadrupole array to form a gas space corresponding to the position of the gas inlets.

13. The mass spectrometer according to claim 12, characterized in that A radio frequency alternating voltage is applied to the differential quadrupole in the gas space by the digital driving circuit to realize the functions of ion acceleration and ion collision in the gas space. Preferably, the radio frequency alternating voltage applied to the differential quadrupole in the gas space is increasing.

14. The mass spectrometer according to claim 12, characterized in that A direct current voltage and / or a radio frequency alternating voltage is applied to the differential quadrupoles at both ends of the gas space by the digital driving circuit, so as to realize the function of a linear ion trap in the gas space.

15. The mass spectrometer according to claim 14, characterized in that After a predetermined time has passed, the digital drive circuit stops applying the DC voltage and / or the RF alternating voltage to the differential quadrupole at the end of the gas space.

16. The mass spectrometer according to claim 12, characterized in that A DC voltage is applied to the differential quadrupoles at both ends of the gas space or a DC increasing voltage is applied to the differential quadrupoles in the gas space by the digital driving circuit, so as to realize the functions of ion acceleration and ion mobility separation in the gas space.

17. The mass spectrometer according to claim 11, characterized in that There are no radially extending spacers between the multiple groups of differential quadrupoles to form isolated chambers.

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