EP4670203A1 - ELECTRON CAPTURE DISSOCIATION CELL - Google Patents

ELECTRON CAPTURE DISSOCIATION CELL

Info

Publication number
EP4670203A1
EP4670203A1 EP23924460.1A EP23924460A EP4670203A1 EP 4670203 A1 EP4670203 A1 EP 4670203A1 EP 23924460 A EP23924460 A EP 23924460A EP 4670203 A1 EP4670203 A1 EP 4670203A1
Authority
EP
European Patent Office
Prior art keywords
lenses
ecd
lens
ecd cell
disposed
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP23924460.1A
Other languages
German (de)
French (fr)
Inventor
Martin BREITENLECHNER
Maozi Liu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Agilent Technologies Inc
Original Assignee
Agilent Technologies Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Agilent Technologies Inc filed Critical Agilent Technologies Inc
Publication of EP4670203A1 publication Critical patent/EP4670203A1/en
Pending legal-status Critical Current

Links

Classifications

    • HELECTRICITY
    • H01ELECTRIC ELEMENTS
    • H01JELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00Particle spectrometers or separator tubes
    • H01J49/004Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn
    • H01J49/0045Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn characterised by the fragmentation or other specific reaction
    • H01J49/0054Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn characterised by the fragmentation or other specific reaction by an electron beam, e.g. electron impact dissociation, electron capture dissociation
    • HELECTRICITY
    • H01ELECTRIC ELEMENTS
    • H01JELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00Particle spectrometers or separator tubes
    • H01J49/02Details
    • H01J49/06Electron- or ion-optical arrangements
    • H01J49/067Ion lenses, apertures, skimmers

Definitions

  • ECD electron-capture dissociation
  • CID collision induced dissociation
  • Figure 1A is an isometric cutout view of an asymmetric ECD cell, in accordance with an example of the present disclosure
  • Figure 1 B is a schematic view of the asymmetric ECD cell of Figure 1 A, in accordance with an example of the present disclosure
  • Figure 1 C illustrates centerline potential with increasing electron emission for an ECD mode of operation of the asymmetric ECD cell of Figure 1 A, in accordance with an example of the present disclosure
  • Figure 2 illustrates centerline potential with increasing electron emission for operation with filament OFF for the asymmetric ECD cell of Figure 1 A, in accordance with an example of the present disclosure
  • Figure 3 illustrates centerline potential with increasing electron emission for operation with filament ON for the asymmetric ECD cell of Figure 1 A, in accordance with an example of the present disclosure
  • Figure 4 is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure.
  • Figure 5 is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure.
  • Figure 6 is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure.
  • Figure 7 is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure.
  • Figure 8 is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure.
  • Figure 9 is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure.
  • Figure 10 is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure.
  • Figure 11 is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure.
  • Figure 12A is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure.
  • Figure 12B illustrates centerline potential with increasing electron emission for the asymmetric ECD cell of Figure 12A, in accordance with an example of the present disclosure.
  • Figure 13 is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure. DETAILED DESCRIPTION
  • the terms “a” and “an” are intended to denote at least one of a particular element.
  • the term “includes” means includes but not limited to, and the term “including” means including but not limited to.
  • the term “based on” means based at least in part on.
  • An electron-capture dissociation (ECD) cell may include a filament that emits electrons and other components to confine the emitted electrons, thus forming a dense electron cloud.
  • the confinement may be achieved by ring magnets and electrostatic lenses (e.g., also denoted as electrodes).
  • electrons may orbit around magnetic field lines produced by the ring magnets, which may be approximately parallel to an ECD cell symmetry axis.
  • the magnetic field may be produced by two permanent ring magnets, located on both sides of the filament.
  • electrostatic lenses e.g., denoted L1 , L2, L3 ... Lx, etc.
  • the electrostatic lenses may include L1 , L2, L3 ... L7.
  • High purity Nitrogen (N2) may be introduced to the ECD cell to prevent filament burnout (e.g., by excluding oxygen).
  • the N2 gas may also act as a buffer gas to collisionally thermalize electron energies after their emission to maximize a cross section with the positive ions.
  • Electron energies may represent an important parameter that determines the ECD cell’s fragmentation efficiency. In this regard, even moderately energetic electrons with a kinetic energy of 1 eV may include a thousand fold lower capture cross section compared to truly thermal electrons with typical kinetic energies in the order of 0.1 eV.
  • ECD efficiency may be defined by a ratio of total abundance of fragment ions to a total abundance of precursor ions in the absence of an electron cloud. In existing ECD cells, ECD efficiency may range, for example, from 10% to 20%.
  • two ring magnets may create a magnetic field with field lines that are approximately parallel to an axis of the ECD cell.
  • Lenses L1 and L7 may be set to optimize transmission to and from other functional elements of the instrument.
  • Intermediate lenses L2 and L6 may be used to create valleys in the electric potential, confining electrons axially.
  • lenses L3 and L5 may include permanent ring magnets with non-magnetic inserts.
  • electrons may be negatively charged, thus being attracted to positively charged electrodes (e.g., positive relative to the electrons current potential).
  • positively charged electrodes e.g., positive relative to the electrons current potential.
  • lenses L3 and L5 may have to be positively biased relative to the filament and lens L4.
  • Several collisions with the nitrogen buffer gas may occur, sequentially reducing the initial kinetic energy given to the electrons by the potential differences between the filament and lenses L3 and L5, respectively.
  • Lenses L2 and L6 may be used to prevent the electrons from leaving the ECD cell axially.
  • the electron cloud may create a potential by itself, which may be denoted a space-charge potential. As the electron density becomes higher, the electric potential may increasingly deviate from the original potential created by the electrostatic lenses.
  • the space-charge effect may facilitate transmission of ions through the ECD cell since the space-charge creates an attractive potential for positive ions along most of the length of the ECD cell around its axis.
  • an ECD cell may generate two electron clouds, one on each side of the filament. While this theoretically maximizes overall ECD efficiency using a single filament, this symmetric design may include various drawbacks.
  • the ECD cell may be tuned to transmit ions in an acceptable abundance, but the transmission efficiency is relatively sensitive to minute changes to any potentials on lenses L4 through L6, while transmission efficiency is less sensitive to comparable voltage changes on lenses L1 through L4.
  • Figure 1 A is an isometric cutout view of an asymmetric ECD cell 100, in accordance with an example of the present disclosure.
  • Figure 1 B is a schematic view of the asymmetric ECD cell 100, in accordance with an example of the present disclosure.
  • Figure 1 C illustrates centerline potential with increasing electron emission for an ECD mode of operation of the asymmetric ECD cell 100, in accordance with an example of the present disclosure.
  • the ECD mode of operation is similarly applicable to the asymmetric ECD cells disclosed herein with reference to Figures 4 -13.
  • ECD cell 100 may include lenses (e.g., electrodes) L1 , L2, L3, L6, and L7 configured as shown, and magnets M1 and M2 configured as shown.
  • the lenses and magnets of ECD cell 100 may be formed in a ring configuration about central axis 102, and include an ion passage 104.
  • a filament 106 may be disposed between lenses L3 and L6 as shown.
  • the ECD cell 100 may include a plurality of lenses, where at least one lens (e.g., lens L3 in the example of Figures 1A-1 C, lenses L3, L4, or L5 in the example of Figure 4, lenses L3 or L4 in the example of Figure 5, and other lenses as shown in the examples of Figures 6-11 ) of the plurality of lenses may be asymmetrically arranged about an axis 120 that is orthogonal to the central axis 102 of the ECD cell and intersects a center-point 122 along a length 124 of the ECD cell defined along the central axis.
  • at least one lens e.g., lens L3 in the example of Figures 1A-1 C, lenses L3, L4, or L5 in the example of Figure 4, lenses L3 or L4 in the example of Figure 5, and other lenses as shown in the examples of Figures 6-11 .
  • the at least one lens of the plurality of lenses may be asymmetrically arranged in the ECD cell 100 such that a centerline potential (e.g., as shown in Figures 1 B-3), and with increasing electron emission includes a predetermined gradient.
  • at least one magnet e.g., magnets M1 or M2 in the example of Figures 1A-1 C
  • the filament 106 may be disposed between the at least one lens (e.g., lens L3 in the example of Figures 1A-1 C) and a further lens (e.g., lens L6 in the example of Figures 1 A-1 C) of the plurality of lenses.
  • At least two further lenses may include first and second further lenses disposed at opposite ends of the ECD cell. Further, at least two further lenses (e.g., lenses L2 and L6 in the example of Figures 1A-1 C, lenses L2 and L6 of Figure 4, etc.) may include third and fourth further lenses disposed between the first and second further lenses and the at least one lens. Magnets (e.g., M1 and M2 in the example of Figures 1A-1C) may be disposed between the first and second further lenses.
  • the magnets may be configured such that electrons emitted from the filament are radially confined.
  • the magnets may be placed in such a way that the magnetic field lines are approximately parallel to the ECD cell axis in the region between lenses L2 and L7.
  • the magnetic field lines may need to be approximately parallel between lens L2 and the filament.
  • the magnetic field lines are also approximately parallel between the filament and lens L7.
  • the magnets may also be denoted as electromagnets.
  • lenses L2 and L6 may represent electrostatic lenses that axially confine electrons. Lenses L1 and L7 may optionally interface to the instrument. Further, lenses L3 and L5 may shape the electron cloud between lens L2 and the filament.
  • one goal of the ECD cell 100 may include creating an electron cloud between lens L2 and filament 106. Electrons may need to be confined long enough, such that a significant number of electrons have kinetic energies below 1eV, preferably below 0.1 eV, and generally preferably kinetic energies close to thermal kinetic energies. Electron densities may need to be as high as possible, preferably close to the space-charge limit. In this regard, a high density of low energy electrons may lead to electron capture and subsequent dissociation.
  • F defined as 0 Volts lens L6: lower than F: Electrons repelled from lens L6, towards lens L3 lens L3: higher than F; attract electrons away from F lens L2: lower than F; prevent initial electrons from exiting towards lens L1 lens L1 : provides reference interface potential (upstream) lens L7: provides reference interface potential (downstream)
  • ECD cell 100 As shown at 108, the presence of electrons may lower the centerline potential to the point where electrons emitted by the filament are no longer effectively extracted into the region including lens L3.
  • the centerline potential without electrons is shown at 110, and the centerline potential with electrons is shown at 112.
  • Figure 2 illustrates centerline potential with increasing electron emission for an MS1 mode of operation and/or MS2 mode of operation (with fragmentation such as CID) with filament 106 OFF for the asymmetric ECD cell 100, in accordance with an example of the present disclosure.
  • This MS1 mode of operation and/or MS2 mode of operation (with fragmentation such as CID) is similarly applicable to the asymmetric ECD cells disclosed herein with reference to Figures 4-13.
  • Typical electrostatic lens settings to achieve MS1 with filament 106 OFF may include the following specifications:
  • lens L6 defined as 0 Volts lens L6: lower than F: positive ions attracted towards exit (lens L7)
  • lens L3 set between lens L2 and filament F (continuous gradient toward exit)
  • lens L2 set between lens L1 and lens L3 (continuous gradient toward exit)
  • lens L1 provides reference interface potential (upstream)
  • lens L7 provides reference interface potential (downstream)
  • all lenses may be set to achieve a negative gradient throughout the ECD cell 100 in order to guide positive ions toward the exit.
  • FIG 3 illustrates centerline potential with increasing electron emission for an MS1 mode of operation and/or MS2 mode of operation (with fragmentation such as CID) with filament 106 ON for the asymmetric ECD cell 100, in accordance with an example of the present disclosure.
  • This MS1 mode of operation and/or MS2 mode of operation (with fragmentation such as CID) is similarly applicable to the asymmetric ECD cells disclosed herein with reference to Figures 4-13.
  • the MS1 mode of operation and/or MS2 mode of operation with filament 106 ON, electrons are present in the ECD cell 100, but no electron capture is desired.
  • a goal of the MS1 mode may include transmitting ions with minimal loss with the filament ON.
  • ECD may depend on kinetic energy of electrons (e.g., lower is more efficient) and electron density. This mode may ensure that the electron cloud is limited to presence between lens L6 and lens L7, with a high kinetic energy and low density (e.g., due to short lifetime). This mode may enable relatively quick switching between MS1 (and/or MS2) and ECD mode, since the warm-up time of the filament 106 is not needed.
  • Typical electrostatic lens settings to achieve MS1 with filament 106 ON may include the following specifications:
  • F defined as 0 Volts lens L6: Higher than F: positive ions attracted towards this lens.
  • ECD lens L3 set lower than F - repel electrons towards lens L6
  • lens L2 set between lens L1 and lens L3 (continuous gradient toward) exit lens
  • L1 provides reference interface potential (upstream)
  • lens L7 provides reference interface potential (downstream)
  • electron cloud 116 may result in a decreased centerline potential at 118.
  • all lenses may be set to achieve a negative gradient throughout the ECD cell 100, in order to guide positive ions toward the exit, except lens L6.
  • Ions may include sufficient kinetic energy (e.g., sourced from lens L1 and lens L2) to overcome the hump.
  • the distances between filament F and lens L6, and between lens L6 and lens L7 are relatively short.
  • ECD cell 100 may thus avoid the aforementioned polarity conflict, as illustrated in Figure 1 B.
  • ECD efficiency, as well as ease-of-use and transmission efficiency may be achieved, for example, in use cases where ECD is not desired (e.g., single stage mass spectrometry, MS1 , or collision induced dissociation mode).
  • tuning of the ECD cell 100 may be relatively efficient since there is no tradeoff between ion transmission (e.g., from left to right) and electron trapping is needed.
  • the ECD cell 100 may also include a robust operation in that the optimum voltage setting combination is less sensitive to potential contamination and other (unknown) changes.
  • FIG. 4 is a schematic view of another asymmetric ECD cell 400, in accordance with an example of the present disclosure.
  • ECD cell 400 may include lenses (e.g., electrodes) L1 , L2, L3, L4, L5, L6, and L7 configured as shown, and magnet M1 configured as shown.
  • the lenses and magnets of ECD cell 400 may be formed in a ring configuration about central axis 402, and include an ion passage 404.
  • a filament 406 may be disposed between lenses L5 and L6 as shown.
  • the filament 406 may be disposed between lenses L2 and L3 (not shown).
  • Figure 5 is a schematic view of another asymmetric ECD cell 500, in accordance with an example of the present disclosure.
  • ECD cell 500 may include lenses (e.g., electrodes) L1 , L2, L3, L4, L6, and L7 configured as shown, and magnet M1 configured as shown.
  • the lenses and magnets of ECD cell 500 may be formed in a ring configuration about central axis 502, and include an ion passage 504.
  • a filament 506 may be disposed between lenses L4 and L6 as shown.
  • the filament 506 may be disposed between lenses L2 and L3 (not shown).
  • FIG. 6 is a schematic view of another asymmetric ECD cell 600, in accordance with an example of the present disclosure.
  • ECD cell 600 may include lenses (e.g., electrodes) L1 , L2, L3, L6, and L7 configured as shown, and magnet M1 configured as shown.
  • the lenses and magnets of ECD cell 600 may be formed in a ring configuration about central axis 602, and include an ion passage 604.
  • a filament 606 may be disposed between lenses L3 and L6 as shown. Alternatively, the filament 606 may be disposed between lenses L2 and L3 (not shown).
  • Figure 7 is a schematic view of another asymmetric ECD cell 700, in accordance with an example of the present disclosure.
  • ECD cell 700 may include lenses (e.g., electrodes) L1 , L2, L3, L4, L5, L6, and L7 configured as shown, and magnets M1 and M2 configured as shown.
  • the lenses and magnets of ECD cell 700 may be formed in a ring configuration about central axis 702, and include an ion passage 704.
  • a filament 706 may be disposed between lenses L5 and L6 as shown.
  • magnets e.g., M1 and M2 of Figure 7
  • the filament 706 may be disposed between lenses L2 and L3 (not shown).
  • FIG 8 is a schematic view of another asymmetric ECD cell 800, in accordance with an example of the present disclosure.
  • ECD cell 800 may include lenses (e.g., electrodes) L1 , L2, L3, L4, L6, and L7 configured as shown, and magnets M1 and M2 configured as shown.
  • the lenses and magnets of ECD cell 800 may be formed in a ring configuration about central axis 802, and include an ion passage 804.
  • a filament 806 may be disposed between lenses L4 and L6 as shown. Alternatively, the filament 806 may be disposed between lenses L2 and L3 (not shown).
  • Figure 9 is a schematic view of another asymmetric ECD cell 900, in accordance with an example of the present disclosure.
  • ECD cell 900 may include lenses (e.g., electrodes) L1 , L2, L3, L6, and L7 configured as shown, and magnets M1 and M2 configured as shown.
  • the lenses and magnets of ECD cell 900 may be formed in a ring configuration about central axis 902, and include an ion passage 904.
  • a filament 906 may be disposed between lenses L3 and L6 as shown.
  • the filament 906 may be disposed between lenses L2 and L3 (not shown).
  • Figure 10 is a schematic view of another asymmetric ECD cell 1000, in accordance with an example of the present disclosure.
  • ECD cell 1000 may include lenses (e.g., electrodes) L1 , L2, L3, L4, L5, L6, and L7 configured as shown, and magnets M1 and M2 configured as shown.
  • the lenses and magnets of ECD cell 1000 may be formed in a ring configuration about central axis 1002, and include an ion passage 1004.
  • a filament 1006 may be disposed between lenses L5 and L6 as shown.
  • the filament 1006 may be disposed between lenses L2 and L3 (not shown).
  • magnets e.g., M1 and M2
  • magnets may be disposed at opposite ends of the ECD cell.
  • Figure 11 is a schematic view of another asymmetric ECD cell 1100, in accordance with an example of the present disclosure.
  • ECD cell 1100 may include lenses (e.g. , electrodes) L1 , L2, L3, L4, L6, and L7 configured as shown, and magnets M1 , M2, and M3 configured as shown.
  • the lenses and magnets of ECD cell 1100 may be formed in a ring configuration about central axis 1102, and include an ion passage 1104.
  • a filament 1106 may be disposed between lenses L4 and L6 as shown.
  • the filament 1106 may be disposed between lenses L1 and L2 (not shown).
  • Figure 12A is a schematic view of another asymmetric ECD cell 1200, in accordance with an example of the present disclosure.
  • Figure 12B illustrates centerline potential with increasing electron emission for the asymmetric ECD cell 1200, in accordance with an example of the present disclosure.
  • ECD cell 1200 may include lenses
  • the lenses and magnets of ECD cell 1200 may be formed in a ring configuration about central axis 1202, and include an ion passage 1204.
  • a filament 1206 may be disposed primarily within lens L5 as shown.
  • the filament 1206 may be disposed within a cavity 1208 of the at least one lens (e.g., lens L5).
  • at least one magnet e.g., M2 including the at least one lens (e.g., lens L5) may be disposed adjacent to the at least one magnet.
  • Figure 13 is a schematic view of another asymmetric ECD cell 1300, in accordance with an example of the present disclosure.
  • ECD cell 1300 may include lenses (e.g., electrodes) L1 , L2, L3, L4, L5, L6, and L7 configured as shown, and magnet M1 configured as shown.
  • the lenses and magnets of ECD cell 1300 may be formed in a ring configuration about central axis 1302, and include an ion passage 1304.
  • a filament 1306 may be disposed between lenses L2 and L3 as shown.

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  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electron Sources, Ion Sources (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)

Abstract

In some examples, an electron capture dissociation (ECD) cell may include a plurality of lenses. At least one lens of the plurality of lenses may be asymmetrically arranged about an axis that is orthogonal to a central axis of the ECD cell and intersects a center-point along a length of the ECD cell defined along the central axis.

Description

ELECTRON CAPTURE DISSOCIATION (ECD) CELL
BACKGROUND
[0001] With respect to tandem mass spectrometry, electron-capture dissociation (ECD) may be implemented to fragment positively charged ions for structural analysis by capturing low energy electrons. ECD may be utilized to analyze and sequence the structure of proteins and peptides. In collision induced dissociation (CID), ion activation and dissociation may be obtained by collisions between ions and neutral buffer gas molecules. ECD and CID may be both implemented in mass spectrometry.
BRIEF DESCRIPTION OF DRAWINGS
[0002] Features of the present disclosure are illustrated by way of example and not limited in the following figure(s), in which like numerals indicate like elements, in which:
[0003] Figure 1A is an isometric cutout view of an asymmetric ECD cell, in accordance with an example of the present disclosure;
[0004] Figure 1 B is a schematic view of the asymmetric ECD cell of Figure 1 A, in accordance with an example of the present disclosure;
[0005] Figure 1 C illustrates centerline potential with increasing electron emission for an ECD mode of operation of the asymmetric ECD cell of Figure 1 A, in accordance with an example of the present disclosure;
[0006] Figure 2 illustrates centerline potential with increasing electron emission for operation with filament OFF for the asymmetric ECD cell of Figure 1 A, in accordance with an example of the present disclosure;
[0007] Figure 3 illustrates centerline potential with increasing electron emission for operation with filament ON for the asymmetric ECD cell of Figure 1 A, in accordance with an example of the present disclosure;
[0008] Figure 4 is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure;
[0009] Figure 5 is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure; [0010] Figure 6 is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure;
[0011] Figure 7 is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure;
[0012] Figure 8 is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure;
[0013] Figure 9 is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure;
[0014] Figure 10 is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure;
[0015] Figure 11 is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure;
[0016] Figure 12A is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure;
[0017] Figure 12B illustrates centerline potential with increasing electron emission for the asymmetric ECD cell of Figure 12A, in accordance with an example of the present disclosure; and
[0018] Figure 13 is a schematic view of another asymmetric ECD cell, in accordance with an example of the present disclosure. DETAILED DESCRIPTION
[0019] For simplicity and illustrative purposes, the present disclosure is described by referring mainly to examples. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present disclosure. It will be readily apparent however, that the present disclosure may be practiced without limitation to these specific details. In other instances, some methods and structures have not been described in detail so as not to unnecessarily obscure the present disclosure.
[0020] Throughout the present disclosure, the terms "a" and "an" are intended to denote at least one of a particular element. As used herein, the term "includes" means includes but not limited to, and the term "including" means including but not limited to. The term "based on" means based at least in part on.
[0021] An electron-capture dissociation (ECD) cell may include a filament that emits electrons and other components to confine the emitted electrons, thus forming a dense electron cloud. The confinement may be achieved by ring magnets and electrostatic lenses (e.g., also denoted as electrodes). In this regard, electrons may orbit around magnetic field lines produced by the ring magnets, which may be approximately parallel to an ECD cell symmetry axis. In one example, the magnetic field may be produced by two permanent ring magnets, located on both sides of the filament. Axially, electrons may be confined by a set of electrostatic lenses (e.g., denoted L1 , L2, L3 ... Lx, etc.) at appropriate electric potentials. In one example, the electrostatic lenses may include L1 , L2, L3 ... L7. High purity Nitrogen (N2) may be introduced to the ECD cell to prevent filament burnout (e.g., by excluding oxygen). The N2 gas may also act as a buffer gas to collisionally thermalize electron energies after their emission to maximize a cross section with the positive ions. Electron energies may represent an important parameter that determines the ECD cell’s fragmentation efficiency. In this regard, even moderately energetic electrons with a kinetic energy of 1 eV may include a thousand fold lower capture cross section compared to truly thermal electrons with typical kinetic energies in the order of 0.1 eV. ECD efficiency may be defined by a ratio of total abundance of fragment ions to a total abundance of precursor ions in the absence of an electron cloud. In existing ECD cells, ECD efficiency may range, for example, from 10% to 20%.
[0022] In one example of a symmetrical ECD cell that includes electrostatic lenses L1 , L2, L3 ... L7, two ring magnets may create a magnetic field with field lines that are approximately parallel to an axis of the ECD cell. Lenses L1 and L7 may be set to optimize transmission to and from other functional elements of the instrument. Intermediate lenses L2 and L6 may be used to create valleys in the electric potential, confining electrons axially. Further, lenses L3 and L5 may include permanent ring magnets with non-magnetic inserts.
[0023] With respect to operation of an ECD cell generally, electrons may be negatively charged, thus being attracted to positively charged electrodes (e.g., positive relative to the electrons current potential). In order to bring the electron cloud away from a filament and into a magnet region, lenses L3 and L5 may have to be positively biased relative to the filament and lens L4. Several collisions with the nitrogen buffer gas may occur, sequentially reducing the initial kinetic energy given to the electrons by the potential differences between the filament and lenses L3 and L5, respectively. Lenses L2 and L6 may be used to prevent the electrons from leaving the ECD cell axially.
[0024] The electron cloud may create a potential by itself, which may be denoted a space-charge potential. As the electron density becomes higher, the electric potential may increasingly deviate from the original potential created by the electrostatic lenses. The space-charge effect may facilitate transmission of ions through the ECD cell since the space-charge creates an attractive potential for positive ions along most of the length of the ECD cell around its axis.
[0025] In one example, an ECD cell may generate two electron clouds, one on each side of the filament. While this theoretically maximizes overall ECD efficiency using a single filament, this symmetric design may include various drawbacks.
While electrons may be considered as high-potential-seekers, positive ions behave the opposite way and are therefore attracted to negative potentials. There is no conflict of these properties on one side (e.g., left side including lenses L1 through L4 and filament) of the ECD cell. In this regard, positive ions may follow the overall gradient “downhill” the centerline potential, thereby overcoming the “valley” created by lens L2 and ultimately flying towards the filament. In one drawback of the symmetric ECD cell, ions pass the filament but now they have to overcome a second, wider potential wall between the filament and lens L5. The ECD cell may be tuned to transmit ions in an acceptable abundance, but the transmission efficiency is relatively sensitive to minute changes to any potentials on lenses L4 through L6, while transmission efficiency is less sensitive to comparable voltage changes on lenses L1 through L4.
[0026] Figure 1 A is an isometric cutout view of an asymmetric ECD cell 100, in accordance with an example of the present disclosure. Figure 1 B is a schematic view of the asymmetric ECD cell 100, in accordance with an example of the present disclosure. Figure 1 C illustrates centerline potential with increasing electron emission for an ECD mode of operation of the asymmetric ECD cell 100, in accordance with an example of the present disclosure. The ECD mode of operation is similarly applicable to the asymmetric ECD cells disclosed herein with reference to Figures 4 -13.
[0027] Referring to Figures 1A-1 C, ECD cell 100 may include lenses (e.g., electrodes) L1 , L2, L3, L6, and L7 configured as shown, and magnets M1 and M2 configured as shown. In a similar manner as shown for ECD cell 1200 of Figure 12A, the lenses and magnets of ECD cell 100 may be formed in a ring configuration about central axis 102, and include an ion passage 104. A filament 106 may be disposed between lenses L3 and L6 as shown.
[0028] Generally, the ECD cell 100 may include a plurality of lenses, where at least one lens (e.g., lens L3 in the example of Figures 1A-1 C, lenses L3, L4, or L5 in the example of Figure 4, lenses L3 or L4 in the example of Figure 5, and other lenses as shown in the examples of Figures 6-11 ) of the plurality of lenses may be asymmetrically arranged about an axis 120 that is orthogonal to the central axis 102 of the ECD cell and intersects a center-point 122 along a length 124 of the ECD cell defined along the central axis. In this regard, the at least one lens of the plurality of lenses may be asymmetrically arranged in the ECD cell 100 such that a centerline potential (e.g., as shown in Figures 1 B-3), and with increasing electron emission includes a predetermined gradient. Further, at least one magnet (e.g., magnets M1 or M2 in the example of Figures 1A-1 C) including the at least one lens may be at least partially disposed between the central axis and the at least one magnet. The filament 106 may be disposed between the at least one lens (e.g., lens L3 in the example of Figures 1A-1 C) and a further lens (e.g., lens L6 in the example of Figures 1 A-1 C) of the plurality of lenses.
[0029] At least two further lenses (e.g., lenses L1 and L7 in the example of Figures 1A-1 C, lenses L1 and L7 of Figure 4, etc.) may include first and second further lenses disposed at opposite ends of the ECD cell. Further, at least two further lenses (e.g., lenses L2 and L6 in the example of Figures 1A-1 C, lenses L2 and L6 of Figure 4, etc.) may include third and fourth further lenses disposed between the first and second further lenses and the at least one lens. Magnets (e.g., M1 and M2 in the example of Figures 1A-1C) may be disposed between the first and second further lenses.
[0030] For the ECD cell 100, the magnets may be configured such that electrons emitted from the filament are radially confined. The magnets may be placed in such a way that the magnetic field lines are approximately parallel to the ECD cell axis in the region between lenses L2 and L7. In this regard, the magnetic field lines may need to be approximately parallel between lens L2 and the filament. However, in the example of Figures 1 A-1 C, the magnetic field lines are also approximately parallel between the filament and lens L7. The magnets may also be denoted as electromagnets.
[0031] For the ECD cell 100, lenses L2 and L6 may represent electrostatic lenses that axially confine electrons. Lenses L1 and L7 may optionally interface to the instrument. Further, lenses L3 and L5 may shape the electron cloud between lens L2 and the filament.
[0032] In the ECD mode, one goal of the ECD cell 100 may include creating an electron cloud between lens L2 and filament 106. Electrons may need to be confined long enough, such that a significant number of electrons have kinetic energies below 1eV, preferably below 0.1 eV, and generally preferably kinetic energies close to thermal kinetic energies. Electron densities may need to be as high as possible, preferably close to the space-charge limit. In this regard, a high density of low energy electrons may lead to electron capture and subsequent dissociation.
[0033] An example of electrostatic lens settings to achieve ECD mode is specified as follows:
F: defined as 0 Volts lens L6: lower than F: Electrons repelled from lens L6, towards lens L3 lens L3: higher than F; attract electrons away from F lens L2: lower than F; prevent initial electrons from exiting towards lens L1 lens L1 : provides reference interface potential (upstream) lens L7: provides reference interface potential (downstream)
[0034] With respect to ECD cell 100, as shown at 108, the presence of electrons may lower the centerline potential to the point where electrons emitted by the filament are no longer effectively extracted into the region including lens L3. In this regard, the centerline potential without electrons is shown at 110, and the centerline potential with electrons is shown at 112.
[0035] Figure 2 illustrates centerline potential with increasing electron emission for an MS1 mode of operation and/or MS2 mode of operation (with fragmentation such as CID) with filament 106 OFF for the asymmetric ECD cell 100, in accordance with an example of the present disclosure. This MS1 mode of operation and/or MS2 mode of operation (with fragmentation such as CID) is similarly applicable to the asymmetric ECD cells disclosed herein with reference to Figures 4-13.
[0036] With respect to the MS1 mode of operation and/or MS2 mode of operation (with fragmentation such as CID), with filament 106 OFF, no electrons are present in the ECD cell 100. A goal of the ECD cell 100 may include transmitting ions with minimal loss. With the filament 106 OFF, the chance of having unwanted ECD in this mode may be eliminated. However, filament warmup may take some time (e.g., many seconds to minutes).
[0037] Typical electrostatic lens settings to achieve MS1 with filament 106 OFF (e.g., denoted herein as mode 2A) may include the following specifications:
F: defined as 0 Volts lens L6: lower than F: positive ions attracted towards exit (lens L7) lens L3: set between lens L2 and filament F (continuous gradient toward exit) lens L2: set between lens L1 and lens L3 (continuous gradient toward exit) lens L1 : provides reference interface potential (upstream) lens L7: provides reference interface potential (downstream)
[0038] As shown at 114, all lenses may be set to achieve a negative gradient throughout the ECD cell 100 in order to guide positive ions toward the exit.
[0039] Figure 3 illustrates centerline potential with increasing electron emission for an MS1 mode of operation and/or MS2 mode of operation (with fragmentation such as CID) with filament 106 ON for the asymmetric ECD cell 100, in accordance with an example of the present disclosure. This MS1 mode of operation and/or MS2 mode of operation (with fragmentation such as CID) is similarly applicable to the asymmetric ECD cells disclosed herein with reference to Figures 4-13. [0040] With respect to the MS1 mode of operation and/or MS2 mode of operation (with fragmentation such as CID), with filament 106 ON, electrons are present in the ECD cell 100, but no electron capture is desired. A goal of the MS1 mode may include transmitting ions with minimal loss with the filament ON. In this regard, ECD may depend on kinetic energy of electrons (e.g., lower is more efficient) and electron density. This mode may ensure that the electron cloud is limited to presence between lens L6 and lens L7, with a high kinetic energy and low density (e.g., due to short lifetime). This mode may enable relatively quick switching between MS1 (and/or MS2) and ECD mode, since the warm-up time of the filament 106 is not needed.
[0041] Typical electrostatic lens settings to achieve MS1 with filament 106 ON (e.g., denoted herein as mode 2B) may include the following specifications:
F: defined as 0 Volts lens L6: Higher than F: positive ions attracted towards this lens.
Electrons hit lens L6, lifetime and therefore density is short
— minimized ECD lens L3: set lower than F - repel electrons towards lens L6 lens L2: set between lens L1 and lens L3 (continuous gradient toward) exit lens L1 : provides reference interface potential (upstream) lens L7: provides reference interface potential (downstream)
[0042] For the example of Figure 3, electron cloud 116 may result in a decreased centerline potential at 118.
[0043] For the example of Figures 1 A-3, all lenses may be set to achieve a negative gradient throughout the ECD cell 100, in order to guide positive ions toward the exit, except lens L6. Ions may include sufficient kinetic energy (e.g., sourced from lens L1 and lens L2) to overcome the hump. Thus, the distances between filament F and lens L6, and between lens L6 and lens L7 are relatively short.
[0044] The asymmetric design of ECD cell 100 may thus avoid the aforementioned polarity conflict, as illustrated in Figure 1 B. Thus, ECD efficiency, as well as ease-of-use and transmission efficiency may be achieved, for example, in use cases where ECD is not desired (e.g., single stage mass spectrometry, MS1 , or collision induced dissociation mode). With the avoidance of the aforementioned polarity conflict, tuning of the ECD cell 100 may be relatively efficient since there is no tradeoff between ion transmission (e.g., from left to right) and electron trapping is needed. The ECD cell 100 may also include a robust operation in that the optimum voltage setting combination is less sensitive to potential contamination and other (unknown) changes. Thus, the ECD cell 100 may be operated close to optimum settings with less intermittent retuning procedures, and a possible re-tune procedure (e.g., automated or done by the user) may be efficiently implemented and/or performed. [0045] Figure 4 is a schematic view of another asymmetric ECD cell 400, in accordance with an example of the present disclosure.
[0046] Referring to Figure 4, ECD cell 400 may include lenses (e.g., electrodes) L1 , L2, L3, L4, L5, L6, and L7 configured as shown, and magnet M1 configured as shown. In a similar manner as shown for ECD cell 1200 of Figure 12A, the lenses and magnets of ECD cell 400 may be formed in a ring configuration about central axis 402, and include an ion passage 404. A filament 406 may be disposed between lenses L5 and L6 as shown. Alternatively, the filament 406 may be disposed between lenses L2 and L3 (not shown).
[0047] Figure 5 is a schematic view of another asymmetric ECD cell 500, in accordance with an example of the present disclosure.
[0048] Referring to Figure 5, ECD cell 500 may include lenses (e.g., electrodes) L1 , L2, L3, L4, L6, and L7 configured as shown, and magnet M1 configured as shown. In a similar manner as shown for ECD cell 1200 of Figure 12A, the lenses and magnets of ECD cell 500 may be formed in a ring configuration about central axis 502, and include an ion passage 504. A filament 506 may be disposed between lenses L4 and L6 as shown. Alternatively, the filament 506 may be disposed between lenses L2 and L3 (not shown).
[0049] Figure 6 is a schematic view of another asymmetric ECD cell 600, in accordance with an example of the present disclosure. [0050] Referring to Figure 6, ECD cell 600 may include lenses (e.g., electrodes) L1 , L2, L3, L6, and L7 configured as shown, and magnet M1 configured as shown. In a similar manner as shown for ECD cell 1200 of Figure 12A, the lenses and magnets of ECD cell 600 may be formed in a ring configuration about central axis 602, and include an ion passage 604. A filament 606 may be disposed between lenses L3 and L6 as shown. Alternatively, the filament 606 may be disposed between lenses L2 and L3 (not shown).
[0051] Figure 7 is a schematic view of another asymmetric ECD cell 700, in accordance with an example of the present disclosure.
[0052] Referring to Figure 7, ECD cell 700 may include lenses (e.g., electrodes) L1 , L2, L3, L4, L5, L6, and L7 configured as shown, and magnets M1 and M2 configured as shown. In a similar manner as shown for ECD cell 1200 of Figure 12A, the lenses and magnets of ECD cell 700 may be formed in a ring configuration about central axis 702, and include an ion passage 704. A filament 706 may be disposed between lenses L5 and L6 as shown. With respect to the first and second lenses disclosed herein, magnets (e.g., M1 and M2 of Figure 7) may be disposed between the third and fourth further lenses (e.g., lenses L2 and L6 of Figure 7). Alternatively, the filament 706 may be disposed between lenses L2 and L3 (not shown).
[0053] Figure 8 is a schematic view of another asymmetric ECD cell 800, in accordance with an example of the present disclosure. [0054] Referring to Figure 8, ECD cell 800 may include lenses (e.g., electrodes) L1 , L2, L3, L4, L6, and L7 configured as shown, and magnets M1 and M2 configured as shown. In a similar manner as shown for ECD cell 1200 of Figure 12A, the lenses and magnets of ECD cell 800 may be formed in a ring configuration about central axis 802, and include an ion passage 804. A filament 806 may be disposed between lenses L4 and L6 as shown. Alternatively, the filament 806 may be disposed between lenses L2 and L3 (not shown).
[0055] Figure 9 is a schematic view of another asymmetric ECD cell 900, in accordance with an example of the present disclosure.
[0056] Referring to Figure 9, ECD cell 900 may include lenses (e.g., electrodes) L1 , L2, L3, L6, and L7 configured as shown, and magnets M1 and M2 configured as shown. In a similar manner as shown for ECD cell 1200 of Figure 12A, the lenses and magnets of ECD cell 900 may be formed in a ring configuration about central axis 902, and include an ion passage 904. A filament 906 may be disposed between lenses L3 and L6 as shown. Alternatively, the filament 906 may be disposed between lenses L2 and L3 (not shown).
[0057] Figure 10 is a schematic view of another asymmetric ECD cell 1000, in accordance with an example of the present disclosure.
[0058] Referring to Figure 10, ECD cell 1000 may include lenses (e.g., electrodes) L1 , L2, L3, L4, L5, L6, and L7 configured as shown, and magnets M1 and M2 configured as shown. In a similar manner as shown for ECD cell 1200 of Figure 12A, the lenses and magnets of ECD cell 1000 may be formed in a ring configuration about central axis 1002, and include an ion passage 1004. A filament 1006 may be disposed between lenses L5 and L6 as shown. Alternatively, the filament 1006 may be disposed between lenses L2 and L3 (not shown). For the example of Figure 10, magnets (e.g., M1 and M2) may be disposed at opposite ends of the ECD cell.
[0059] Figure 11 is a schematic view of another asymmetric ECD cell 1100, in accordance with an example of the present disclosure.
[0060] Referring to Figure 11 , ECD cell 1100 may include lenses (e.g. , electrodes) L1 , L2, L3, L4, L6, and L7 configured as shown, and magnets M1 , M2, and M3 configured as shown. In a similar manner as shown for ECD cell 1200 of Figure 12A, the lenses and magnets of ECD cell 1100 may be formed in a ring configuration about central axis 1102, and include an ion passage 1104. A filament 1106 may be disposed between lenses L4 and L6 as shown. Alternatively, the filament 1106 may be disposed between lenses L1 and L2 (not shown).
[0061] Figure 12A is a schematic view of another asymmetric ECD cell 1200, in accordance with an example of the present disclosure. Figure 12B illustrates centerline potential with increasing electron emission for the asymmetric ECD cell 1200, in accordance with an example of the present disclosure.
[0062] Referring to Figures 12A and 12B, ECD cell 1200 may include lenses
(e.g., electrodes) L1 , L2, L3, L4, L5, and L6 configured as shown, and magnets M1 and M2 configured as shown. The lenses and magnets of ECD cell 1200 may be formed in a ring configuration about central axis 1202, and include an ion passage 1204. A filament 1206 may be disposed primarily within lens L5 as shown. For example, the filament 1206 may be disposed within a cavity 1208 of the at least one lens (e.g., lens L5). As shown in Figure 12A, at least one magnet (e.g., M2) including the at least one lens (e.g., lens L5) may be disposed adjacent to the at least one magnet.
[0063] Referring to Figures 1 B and 12A, compared to the ECD cell 1200 that includes no gaps (e.g., at 1210) between the magnets and the lenses, whereas the ECD cell 100 that includes gaps (e.g., at 126) between the magnets and lenses, these gaps may or may not be present. For example, in the example of Figure 12A, lenses L3 and L4 line up with the magnets surrounding them and may be press-fit together such that the electrical connection may be provided from outside of the ECD cell 1200. In the ECD cell 100 of Figure 1 B (as well as the EDC cells of Figures 4-11 ), the gap may be included to prevent an electrical short between the lenses and the magnets.
[0064] Figure 13 is a schematic view of another asymmetric ECD cell 1300, in accordance with an example of the present disclosure.
[0065] Referring to Figure 13, ECD cell 1300 may include lenses (e.g., electrodes) L1 , L2, L3, L4, L5, L6, and L7 configured as shown, and magnet M1 configured as shown. In a similar manner as shown for ECD cell 1200 of Figure 12A, the lenses and magnets of ECD cell 1300 may be formed in a ring configuration about central axis 1302, and include an ion passage 1304. A filament 1306 may be disposed between lenses L2 and L3 as shown. [0066] What has been described and illustrated herein is an example along with some of its variations. The terms, descriptions and figures used herein are set forth by way of illustration only and are not meant as limitations. Many variations are possible within the spirit and scope of the subject matter, which is intended to be defined by the following claims -and their equivalents- in which all terms are meant in their broadest reasonable sense unless otherwise indicated.

Claims

What is claimed is:
1 . An electron capture dissociation (ECD) cell comprising: a plurality of lenses, wherein at least one lens of the plurality of lenses is asymmetrically arranged about an axis that is orthogonal to a central axis of the ECD cell and intersects a center-point along a length of the ECD cell defined along the central axis.
2. The ECD cell according to claim 1 , further comprising: at least one magnet including the at least one lens at least partially disposed between the central axis and the at least one magnet.
3. The ECD cell according to claim 1 , further comprising: at least one magnet including the at least one lens disposed adjacent to the at least one magnet.
4. The ECD cell according to claim 1 , further comprising: a filament disposed between the at least one lens and a further lens of the plurality of lenses.
5. The ECD cell according to claim 1 , further comprising: a filament disposed within a cavity of the at least one lens.
6. The ECD cell according to claim 1 , wherein the plurality of lenses comprises: at least two further lenses including first and second further lenses disposed at opposite ends of the ECD cell.
7. The ECD cell according to claim 6, wherein the plurality of lenses comprises: at least two further lenses including third and fourth further lenses disposed between the first and second further lenses and the at least one lens.
8. The ECD cell according to claim 7, further comprising: magnets disposed between the third and fourth further lenses.
9. The ECD cell according to claim 6, further comprising: magnets disposed between the first and second further lenses.
10. The ECD cell according to claim 1 , further comprising: magnets disposed at opposite ends of the ECD cell.
11. An electron capture dissociation (ECD) cell comprising: a plurality of lenses, wherein at least one lens of the plurality of lenses is asymmetrically arranged along a length of the ECD cell defined along a central axis.
12. The ECD cell according to claim 11 , further comprising: at least one magnet including the at least one lens at least partially disposed between the central axis and the at least one magnet.
13. The ECD cell according to claim 11 , further comprising: a filament disposed between the at least one lens and a further lens of the plurality of lenses.
14. An electron capture dissociation (ECD) cell comprising: a plurality of lenses, wherein at least one lens of the plurality of lenses is asymmetrically arranged in the ECD cell such that a centerline potential with increasing electron emission includes a predetermined gradient.
15. The ECD cell according to claim 14, further comprising: at least one magnet including the at least one lens at least partially disposed between a central axis of the ECD cell and the at least one magnet.
16. The ECD cell according to claim 14, wherein the plurality of lenses comprises: at least two further lenses including first and second further lenses disposed at opposite ends of the ECD cell.
17. The ECD cell according to claim 16, wherein the plurality of lenses comprises: at least two further lenses including third and fourth further lenses disposed between the first and second further lenses and the at least one lens.
18. The ECD cell according to claim 17, further comprising: magnets disposed between the third and fourth further lenses.
19. The ECD cell according to claim 16, further comprising: magnets disposed between the first and second further lenses.
20. The ECD cell according to claim 14, further comprising: magnets disposed at opposite ends of the ECD cell.
EP23924460.1A 2023-02-24 2023-12-19 ELECTRON CAPTURE DISSOCIATION CELL Pending EP4670203A1 (en)

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US202363448105P 2023-02-24 2023-02-24
PCT/US2023/084910 WO2024177714A1 (en) 2023-02-24 2023-12-19 Electron capture dissociation (ecd) cell

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US20070221862A1 (en) * 2006-03-22 2007-09-27 Wayne State University Coupled Electrostatic Ion and Electron Traps for Electron Capture Dissociation - Tandem Mass Spectrometry
JP5111123B2 (en) * 2008-01-16 2012-12-26 株式会社日立製作所 Mass spectrometer and mass spectrometry method
US8519353B2 (en) * 2010-12-29 2013-08-27 Varian Semiconductor Equipment Associates, Inc. Method and apparatus for controlling an asymmetric electrostatic lens about a central ray trajectory of an ion beam
JP5637299B2 (en) * 2011-03-25 2014-12-10 株式会社島津製作所 Time-of-flight mass spectrometer
KR101286561B1 (en) * 2011-10-13 2013-07-22 한국기초과학지원연구원 Lens for electron capture dissociation, fourier transform ion cyclotron resonance mass spectrometer comprising the same and method for improving signal of fourier transform ion cyclotron resonance mass spectrometer

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