Mass calibration device for mass analyzer and corresponding method and program product

Abstract

A calibration device for a mass analyzer comprises an ion source device and a dual-purpose electron beam generating unit. The ion source device ionizes an analyte of a sample to generate analyte ions. The dual-purpose electron beam generating unit is located between the ion source device and the mass analyzer. In a first mode, the dual-purpose electron beam generating unit is used to generate fragmentation of analyte ions of unknown mass-to-charge ratio. In a second mode, the dual-purpose electron beam generating unit is used to generate ions of a calibration compound of known mass-to-charge ratio. All ions are then transferred to the mass analyzer.

Description

[0001] Related Applications

[0002] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 860,300, filed on June 12, 2019, the contents of which are incorporated herein by reference in their entirety. Technical Field

[0003] The teachings herein relate to a calibration device for a mass analyzer of a mass spectrometer. More specifically, an electron-based dissociation (ExD) cell is located between an ion source and a mass analyzer, and the mass analyzer is used to transmit or fragment analyte ions for mass analysis and then also ionize the gas of the ExD cell to produce calibrant ions for mass analysis.

[0004] The devices described herein may be used in conjunction with a processor, controller, or computer system (e.g. Figure 1 computer systems). Background Art

[0005] Dissociation Technology Background

[0006] Electron-based dissociation (ExD) and collision-induced dissociation (CID) are often used as dissociation techniques for tandem mass spectrometry (mass spectrometry / mass spectrometry (MS / MS)). ExD may include, but is not limited to, electron capture dissociation (ECD) or electron transfer dissociation (ETD). CID is the most common technique for dissociation in tandem mass spectrometers.

[0007] Mass Analyzer Calibration Background

[0008] Mass analyzers, such as time-of-flight (TOF), Fourier transform ion cyclotron resonance (FTICR) mass analyzers, and orbi-trap mass analyzers, are capable of providing high-precision mass measurements. However, this level of precision requires a certain level of instrument stability and repeatability, which may be susceptible to fluctuations in ambient temperature, spectrometer chamber pressure, and applied voltages. To account for these fluctuations, mass is used to calibrate the mass analyzer, a process known as mass calibration.

[0009] Traditionally, known compounds, also called calibrants or lock masses, have been combined with or analyzed sequentially with samples of unknown compounds or compounds of interest (analytes). In one approach, the calibrants are mixed with the analytes in solution prior to ionization in the ion source. However, this approach can result in contamination of the transfer line at the tip of the capillary with calibrants. Calibrants can also inhibit the ionization efficiency of the analyte.

[0010] As a result, other methods of introducing calibrants into mass spectrometers or generating calibrants in mass spectrometers have been developed. For example, a calibration delivery system (CDS) can be used to simultaneously introduce two or more compounds, including a calibrant compound, into an ion source chamber. Unfortunately, however, such CDS systems require duplication of sample probes and syringes, complex ion source interfaces, and adaptations specifically for electrospray ionization (ESI) sources.

[0011] In order to generate calibrants in a mass spectrometer, a dynamic background calibration system (DBS) can be used. In DBS, the background ions present in the mass spectrometer are used as calibrants. Unfortunately, however, DBS can only be used for calibration in mass spectrometry (MS) mode. In other words, DBS cannot be used in mass spectrometry / mass spectrometry (MS / MS) mode, in which the background ions will be fragmented and thus useless for calibration.

[0012] No. 6,797,947 (hereinafter referred to as The '947 patent) describes another method for introducing a calibrant into a mass spectrometer. In this method, a dedicated lock mass source and a dedicated lock mass ionization source are positioned adjacent to ion optics located between the ion source and the mass analyzer.

[0013] Figure 2 is an exemplary schematic diagram 200 of the apparatus described in U.S. Patent No. 6,797,947. Figure 2 In FIG. 2 , a lock mass source 225 and a lock mass ionization source 235 are shown as being located adjacent to the collision cell 220. The collision cell 220 is located between the ion source 202 and the mass analyzer 240. The lock mass ionization source 235 can ionize the lock mass using photoionization, field desorption ionization, electron ionization, or thermal ionization. Unfortunately, however, as with CDS, The method of the '947 patent increases the complexity of the mass spectrometer by introducing a calibrant source and an ionization source for calibration purposes only.

[0014] Therefore, there is a need for additional equipment and methods to achieve calibration of a mass analyzer without increasing the complexity of a mass spectrometer used solely for this purpose. Summary of the invention

[0015] A device, method and computer program product for calibrating a mass analyzer are disclosed. The calibration device includes an ion source device and an electron-based dissociation (ExD) cell. The ion source device ionizes an analyte of a sample to generate analyte ions. The ExD cell is located between the ion source device and the mass analyzer.

[0016] In single mass spectrometry (MS) mode, the ExD cell is therefore used for calibration: a background gas or calibration compound of known mass-to-charge ratio is ionized using the ExD cell operated as an electron impact ionization (EII) ion source, and these ions are then introduced into the mass spectrometer. In the EII mode, the ExD cell accelerates the electrons in the ExD cell to a kinetic energy between, for example, 24 eV and 150 eV.

[0017] The background gas may be residual air (oxygen, water, nitrogen) or possibly a calibration compound may be introduced. Examples of calibration compounds include perfluorokerosene or perfluorotributylamine.

[0018] In normal operation, the ExD cell is closed to allow previously ionized analyte ions of unknown mass-to-charge ratio (ions produced by electrospray ionization in an ion source, MALDI ion source, atmospheric pressure chemical ionization, or any other type of ion source) to transmit through the ExD cell, into the collision cell, and then into the time-of-flight mass spectrometer (or any other mass spectrometer type).

[0019] During calibration, the ExD cell is switched on to produce ions of known mass-to-charge ratio present as trace amounts of background gas or as introduced calibrants.

[0020] It is desirable to use the ExD cell as a calibration device frequently enough so that there is not enough time to allow the mass calibration of the high resolution mass spectrometer to change. In this way, the mass accuracy of the mass spectrometer is always maintained at a high level.

[0021] In tandem mass spectrometry (MS / MS) mode, the ExD cell is thus used for calibration: the ExD cell is used to generate molecular ions of a background gas or a calibrant introduced using electron impact ionization (EII). In this case, it may prove advantageous to reduce the kinetic energy to increase the probability of forming a molecular ion. The molecular ions are introduced into the collision cell with a kinetic energy sufficient to cause fragmentation by collision-induced fragmentation, which is caused by collisions between the molecular ions formed by the ExD cell and the gas in the collision cell. These fragment ions are then used to calibrate a high-resolution mass spectrometer.

[0022] This may be helpful if the collision cell causes a systematic mass shift that requires different mass calibrations in MS mode and MSMS mode.

[0023] Furthermore, if ions are trapped or otherwise manipulated to produce additional advantage, any drift in the mass calibration can be tracked and corrected in this way.

[0024] These and other features of the applicant's teachings are set forth herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Those skilled in the art will appreciate that the drawings described below are for illustration purposes only and are not intended to limit the scope of the present teachings in any way.

[0026] Figure 1 is a block diagram illustrating a computer system upon which embodiments of the present teachings may be implemented.

[0027] Figure 2 is an exemplary schematic diagram 200 of the apparatus described in US Pat. No. 6,797,947.

[0028] Figure 3 is an exemplary plot of a reference spectrum of FC43 (perfluorotributylamine) produced by an electron ionization (EI) mass spectrometer operating in positive ionization mode with a beam energy of about 70 eV.

[0029] Figure 4 is an exemplary graph of a calibration spectrum of FC43 produced by ionizing FC43 using a chimera electron capture dissociation (ECD) cell operating in positive ion mode and with a beam energy of about 30 eV, according to various embodiments.

[0030] Figure 5 is an exemplary illustration of a calibration spectrum of FC43 produced by ionizing FC43 using a chimeric ECD cell operating in negative ion mode with a beam energy of about 30 eV, according to various embodiments.

[0031] Figure 6 is a schematic diagram of a chimeric ECD pool according to various embodiments.

[0032] Figure 7 is a schematic diagram of a mass spectrometry system including a chimeric ECD cell according to various embodiments.

[0033] Figure 8 is a cutaway three-dimensional perspective view of a chimeric ECD cell and CID collision cell according to various embodiments.

[0034] Fig. 9 is an exemplary flow chart showing a method for calibrating a mass analyzer according to various embodiments.

[0035] Fig.10 is a schematic diagram of a system including one or more different software modules that execute a method for calibrating a mass analyzer according to various embodiments.

[0036] Before describing one or more embodiments of the present invention in detail, those skilled in the art will understand that the present teachings are not limited in their application to the construction details, component arrangements, and step arrangements set forth in the following detailed description or shown in the accompanying drawings. Moreover, it should be understood that the words and terms used herein are for descriptive purposes and should not be considered as limiting. DETAILED DESCRIPTION

[0037] Computer-implemented systems

[0038] Figure 1 1 is a block diagram illustrating a computer system 100 upon which embodiments of the present teachings may be implemented. The computer system 100 includes a bus 102 or other communication mechanism for communicating information, and a processor 104 coupled to the bus 102 for processing information. The computer system 100 also includes a memory 106, which may be a random access memory (RAM) or other dynamic storage device, coupled to the bus 102 for storing instructions to be executed by the processor 104. The memory 106 may also be used to store temporary variables or other intermediate information during the execution of instructions to be executed by the processor 104. The computer system 100 also includes a read-only memory (ROM) 108 or other static storage device, which is coupled to the bus 102 for storing static information and instructions for the processor 104. A storage device 110, such as a magnetic disk or optical disk, is provided and coupled to the bus 102 for storing information and instructions.

[0039] The computer system 100 may be coupled to a display 112, such as a cathode ray tube (CRT) or a liquid crystal display (LCD), via the bus 102 for displaying information to a computer user. An input device 114, including alphanumeric and other keys, is coupled to the bus 102 for communicating information and command selections to the processor 104. Another type of user input device is a cursor controller 116, such as a mouse, trackball, or cursor direction keys, for communicating direction information and command selections to the processor 104 and for controlling cursor movement on the display 112. The input device typically has two degrees of freedom in two axes, a first axis (i.e., x) and a second axis (i.e., y), which allows the device to specify a position in a plane.

[0040] The computer system 100 can perform the present teaching. According to certain embodiments of the present teaching, the computer system 100 provides a result in response to the processor 104 executing one or more sequences of one or more instructions contained in the memory 106. These instructions can be read into the memory 106 from another computer-readable medium such as the storage device 110. The execution of the sequence of instructions contained in the memory 106 causes the processor 104 to perform the process described herein. Alternatively, hard-wired circuits can be used instead of software instructions or in combination with software instructions to implement the present teaching. Therefore, the embodiments of the present teaching are not limited to any specific combination of hardware circuits and software.

[0041] The term "computer-readable medium" as used herein refers to any medium that participates in providing instructions to processor 104 for execution. Such media may take many forms, including but not limited to non-volatile media, volatile media, and transmission media. Non-volatile media include, for example, optical or magnetic disks, such as storage device 110. Volatile media include dynamic memory, such as memory 106. Transmission media include coaxial cables, copper wire, and fiber optics, including the wires that comprise bus 102.

[0042] Common forms of computer readable media include, for example, floppy disks, flexible disks, hard disks, magnetic tapes or any other magnetic media, CD-ROMs, Digital Video Disks (DVDs), Blu-ray Discs, any other optical media, thumb drives, memory cards, RAM, PROMs and EPROMs, FLASH-EPROMs, and any other memory chip or cartridge, or any other tangible medium from which a computer can read.

[0043] Various forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to processor 104 for execution. For example, the instructions may initially be carried on a disk of a remote computer. The remote computer may load the instructions into its dynamic memory and send the instructions over a telephone line using a modem. A modem local to computer system 100 may receive the data on the telephone line and convert the data into an infrared signal using an infrared transmitter. An infrared detector coupled to bus 102 may receive the data carried in the infrared signal and place the data on bus 102. Bus 102 transfers the data to memory 106, from which processor 104 retrieves and executes the instructions. The instructions received by memory 106 may optionally be stored on storage device 110 before or after execution by processor 104.

[0044] According to various embodiments, instructions configured to be executed by a processor to perform a method are stored on a computer readable medium. A computer readable medium may be a device for storing digital information. For example, a computer readable medium includes a compact disc read-only memory (CD-ROM) known in the art for storing software. The computer readable medium is accessed by a processor adapted to execute instructions configured to be executed.

[0045] For the purpose of illustration and description, the following description of various embodiments of the present teaching has been presented. It is not exhaustive and does not limit the present teaching to the precise form disclosed. Modifications and variations are possible in accordance with the above teachings, or may be obtained from the practice of the present teachings. In addition, the described embodiments include software, but the present teachings may be implemented as a combination of hardware and software or may be implemented in hardware alone. The present teachings may be implemented with object-oriented and non-object-oriented programming systems.

[0046] Calibration equipment and methods

[0047] High-precision mass analyzers such as time-of-flight (TOF), Fourier transform ion cyclotron resonance (FTICR) mass analyzers, and orbitrap mass analyzers require mass calibration in order to cope with fluctuations in ambient temperature, spectrometer chamber pressure, and applied voltage. Traditionally, known compounds, also called calibrants or lock masses, have been combined with or analyzed sequentially with samples of unknown compounds or compounds of interest (analytes). More recently, other methods of introducing calibrants into or generating calibrants in a mass spectrometer have been developed.

[0048] For example, The '947 patent describes a method for introducing a calibrant into a mass spectrometer in which a dedicated lock mass source and a dedicated lock mass ionization source are positioned adjacent to ion optics located between the ion source and the mass analyzer. Unfortunately, however, The approach of the '947 patent increases the complexity of the mass spectrometer by introducing a calibration source and an ionization source that are used only for calibration purposes.

[0049] As a result, additional equipment and methods are needed to achieve calibration of the mass analyzer without adding complexity to the mass spectrometer solely for this purpose.

[0050] In various embodiments, the ExD cell is located between the ion source and the mass analyzer and is additionally selectively operated as an electron ionization source to produce calibrant ions in the ExD cell. The ExD cell is conventionally operated as an ion guide in MS mode to transfer analyte ions to the mass analyzer. In MS / MS mode, the ExD cell is typically used to fragment analyte ions or transfer them to another type of collision cell. The use of the ExD cell is now expanded to ionize gases in the ExD cell to produce calibrant ions for mass calibration.

[0051] The ExD cell may be an electron capture dissociation (ECD) device or an electron transfer dissociation (ETD) device. In a preferred embodiment, the ExD cell is an ECD cell.

[0052] ExD cells are not traditionally considered to be good devices for ionization. Although ExD cells use electron beams to dissociate ions, the electron beams are usually composed of low-energy electrons with kinetic energy on the order of 1 eV. On the contrary, it is understood by those of ordinary skill in the art that electron ionization sources usually use electron beams composed of high-energy electrons with kinetic energy on the order of 70 eV.

[0053] As a result, in various embodiments, the ExD cell is modified to selectively produce an electron beam having low energy electrons or high energy electrons. The modification may include, for example, providing a switchable power source for the ExD cell.

[0054] Exemplary ExD cell is the chimeric ECD cell of SCIEX.In order to determine whether the ExD cell is suitable for electron ionization, the chimeric ECD cell is used to perform experiments.FC43 (perfluorotributylamine), a standard compound for calibration of electron ionization (EI) mass spectrometer, is commonly used in gas chromatography-mass spectrometry (GC-MS), is leaked into the ion channel of the mass spectrometer including the chimeric ECD cell.When the wire of the chimeric ECD cell is connected, FC43 is leaked into the ion channel, and the ion beam energy is set to about 30eV.The result is a large amount of ions suitable for calibration mass spectrometers in positive ion mode.

[0055] Figure 3 is an exemplary graph 300 of a reference spectrum of FC43 produced by an EI mass spectrometer operating in positive ion mode with a beam energy of about 70 eV.

[0056] Figure 4 is an exemplary graph 400 of a calibration spectrum of FC43 produced by ionizing FC43 using a chimeric ECD cell operating in positive ion mode with a beam energy of about 30 eV, according to various embodiments. Figure 3 The reference spectrum and Figure 4 Comparison of the calibration spectra of shows that the chimeric ECD cell operated at about 30 eV can produce a significant number of ions suitable for calibration.

[0057] Figure 5 is an exemplary graph 500 of a calibration spectrum of FC43 produced by ionizing FC43 using a chimeric ECD cell operating in negative ion mode with a beam energy of about 30 eV according to various embodiments. Figure 5 Only a single FC43 ion was produced in the calibration spectrum of . This appropriately demonstrates that if a suitable compound is identified, this method will likely produce a spectrum that can be used to calibrate the mass analyser in negative mode.

[0058] In conclusion, Figure 4 and 5 It is shown that ions that can be used for calibration can be generated using an ECD cell in positive and negative ion modes.

[0059] Figure 6 is a schematic diagram 600 of a chimeric ECD cell according to various embodiments. The chimeric ECD cell includes an electron emitter or filament 610 and an electron grid 620. Electrons are emitted perpendicular to the direction of the ion flow 630 and parallel to the magnetic field 640.

[0060] Figure 7is a schematic diagram of a mass spectrometry system 700 including a chimeric ECD cell according to various embodiments. The system 700 includes a mass spectrometer 710 and a processor 720. The processor 720 controls the mass spectrometer 710 and is used to analyze measurement data received from the mass spectrometer 710. The processor 720 controls the mass spectrometer 710, for example, by controlling one or more voltage sources, one or more valves, and one or more pumps (not shown) of the mass spectrometer 710.

[0061] The mass spectrometer 710 includes an ion source device 711, an ion guide 712, a mass filter 713, a chimeric ECD cell 714, a CID collision cell 715 and a mass analyzer 716. Traditionally, the chimeric ECD cell 714 operates in one of two modes. For MS analysis of analyte ions and for MS / MS analysis of analyte ions with CID, the chimeric ECD cell 714 operates as an ion guide. In other words, it simply receives analyte ions from the mass filter 713 and transmits them to the CID collision cell 715. For MS analysis of analyte ions, analyte precursor ions are mass analyzed by the mass analyzer 716. For MS / MS analysis of analyte ions with CID, analyte precursor ions are fragmented by the CID collision cell 715, and the resulting product ions are mass analyzed by the mass analyzer 716.

[0062] For MS / MS analysis of analyte ions using ECD or electron impact excitation of ions from organic matter (EIEIO), the chimeric ECD cell 714 operates as a collision cell. Using a low electron beam energy of approximately 1 eV, the analyte ions are fragmented by the chimeric ECD cell 714. The resulting analyte product ions are transmitted through a CID collision cell 715 and onto a mass analyzer 716 for mass analysis.

[0063] Figure 8 is a cross-sectional three-dimensional perspective view 800 of a chimeric ECD cell and CID collision cell according to various embodiments. Figure 8 It is shown that fragmentation of the analyte ion can be performed selectively at position 811 in the chimeric ECD cell 814 or at position 812 in the CID collision cell 815.

[0064] Back to Figure 7 In various embodiments, the chimeric ECD cell 714 is modified to include a selectable third calibration operating mode. In this third calibration mode, analyte ions are blocked from entering the chimeric ECD cell 714. The ECD cell 714 is then operated to ionize the gas in the ECD cell 714 using a high electron beam energy of about 30 eV. In one embodiment, the gas can be a background gas, such as a component of air or pump oil. In another embodiment, the gas can be a calibration gas introduced into the chimeric ECD cell 714 from a calibrant source 717.

[0065] After the calibration gas is ionized, the calibrant ions are cooled, just like the analyte ions, in the back of the chimeric ECD cell 714 or in the CID collision cell 715. The calibrant ions can be stored in the CID collision cell 715 along with previously received analyte ions or analyte product ions. These stored ions are then mass analyzed using the mass analyzer 716 and used to calibrate the mass analyzer 716 measurements.

[0066] Because the calibrant ions are ionized separately from the analyte ions, this calibration mode can be used in both MS or MS / MS analysis modes. Figure 7 As a result, this calibration mode can be used for TOF-MS or TOF-MS / MS analysis mode.

[0067] The TOF mass analyzer may include an ion guide for focusing ion packets prior to mass analysis. When ion packets are focused so that heavier and lighter ions with the same energy meet substantially simultaneously in the extraction region of the TOF mass analyzer, this is referred to as a Zeno pulse. The calibration mode of the chimeric ECD cell 714 may be used to provide calibrant ions both when the Zeno pulse of the TOF mass analyzer is on and when it is off.

[0068] For example, U.S. Pat. No. 7,456,388, issued on November 25, 2008 (hereinafter "the '388 patent"), which is incorporated herein by reference, describes an ion guide for focusing ion packets. The '388 patent provides an apparatus and method that allows, for example, ions to be analyzed over a wide m / z range with virtually no transmission losses. The ejection of ions from the ion guide is affected by creating conditions under which all ions (regardless of m / z) can be caused to arrive at a designated point in space, such as an extraction region or accelerator of a TOF mass analyzer, in a desired order or at a desired time and with approximately the same energy. The ions bunched in this manner can then be manipulated as a group, such as by extraction using a TOF extraction pulse, and propelled along a desired path so as to arrive at the same point on a TOF detector.

[0069] In order to be able to operate in calibration mode, the chimeric ECD cell 714 is modified to produce an electron beam with higher kinetic energy. As described above, this can include providing a switchable power source for the chimeric ECD cell 714. The chimeric ECD cell 714 is also modified to include a tool for controlling the injection of calibration gas from the calibration source 717 into the chimeric ECD cell 714 and for quickly clearing the calibration from the chimeric ECD cell 714 after calibration. These tools can include, but are not limited to, electronically controlled pumps and valves.

[0070] Although the chimeric ECD cell 714 is modified for calibration mode, the same electron source used for fragmentation is also used for ionization. The additional complexity required for calibration is reduced compared to the device of the '947 patent. The simplest chimeric ECD cell 714 serves a dual purpose rather than being used solely for calibration.

[0071] Calibration equipment for mass analyzers

[0072] Refer again Figure 7 , the calibration equipment for mass analyzer 716 includes ion source device 711 and dual-purpose electron beam generating unit 714. Mass analyzer 716 can include but is not limited to time of flight (TOF) device, quadrupole, ion trap, linear ion trap, orbital trap, magnetic four-sector mass analyzer, hybrid quadrupole time of flight (Q-TOF) mass analyzer or Fourier transform mass analyzer. In a preferred embodiment, mass analyzer 716 is a TOF device.

[0073] The analyte of the ion source device 711 ionization sample produces analyte ions. The ion source device 711 of the mass spectrometer 710 can be any ion source device known in the art. In various embodiments, suitable ion sources can include but are not limited to electrospray ionization source (ESI), electron impact source and fast atom bombardment source, atmospheric pressure chemical ionization source (APCI), atmospheric pressure photoionization (APPI) source or matrix assisted laser desorption source (MALDI). In a preferred embodiment, electrospray ionization is used.

[0074] The dual-purpose electron beam generating unit 714 of the mass spectrometer 710 is positioned between the mass analyzer 716 and the ion source device 711 of the mass spectrometer 710. In a first mode, when the mass spectrometer 710 is in the MS mode, the dual-purpose electron beam generating unit 714 transmits analyte ions to the mass analyzer 716 directly or through one or more other units of the mass spectrometer 710 for mass analysis.

[0075] Alternatively, in the first mode, when the mass spectrometer 710 is in the MS / MS mode, the dual-purpose electron beam generating unit 714 fragments the analyte ions into product ions and transmits the product ions directly or through one or more other units to the mass analyzer 716 for mass analysis, or transmits the analyte ions to the collision cell 715 of the mass spectrometer 710 for fragmentation, and then transmits the resulting product ions to the mass analyzer 716 for mass analysis.

[0076] In the second mode, the dual-purpose electron beam generating unit 714 generates ions of the calibration compound and transmits the calibration ions directly or through one or more other units to the mass analyzer 716 for mass analysis. Note that one or more other units of the mass spectrometer 710 may include a collision cell 715.

[0077] The dual-purpose electron beam generating unit 714 can switch back and forth between the first mode and the second mode. For example, the dual-purpose electron beam generating unit 714 can switch back and forth between the first mode and the second mode multiple times during a chromatography experiment.

[0078] In various embodiments, the dual-purpose electron beam generating unit 714 is an ExD cell. The ExD cell 714 can be an ECD cell or an ETD cell. In a preferred embodiment, the ExD cell 714 is an ECD cell. Thus, in a first mode, when the mass spectrometer 710 is in MS / MS mode, the ExD cell 714 receives analyte ions, fragments the analyte ions using an electron beam, generates product ions, and transmits the product ions directly or through one or more other units to a mass analyzer 716 for mass analysis. In a second mode, the ExD cell 714 ionizes the gas of the ExD cell 714 using an electron beam, generates calibrant ions, and transmits the calibrant ions directly or through one or more other units to a mass analyzer 716 for mass analysis.

[0079] In various embodiments, the dual-purpose electron beam generating unit 714 is an ExD cell, and the collision cell 714 is a CID collision cell positioned between the ExD cell 714 and the mass analyzer 716. Thus, in a first mode, when the mass spectrometer 710 is in the MS mode, the ExD cell 714 transmits analyte ions to the mass analyzer 716 through the CID collision cell 715 for mass analysis. In a second mode, the ExD cell 714 generates ions of calibration compounds, and transmits the calibration ions to the mass analyzer 716 through the CID collision cell 715 for mass analysis.

[0080] Similarly, in the first mode, when the mass spectrometer 710 is in the MS / MS mode, the ExD cell 714 transmits the analyte ions to the CID collision cell 715, which in turn transmits the resulting product ions to the mass analyzer 716 for mass analysis. In the second mode, the ExD cell 714 generates ions of the calibration compound and transmits the calibration ions to the mass analyzer 716 through the CID collision cell 715 for mass analysis.

[0081] In various embodiments, the calibrant compound comprises a background gas.

[0082] The background gas may include air components or vacuum pump oil components.

[0083] In various embodiments, the mass spectrometer 710 further includes a gas source 717 fluidly coupled to the dual-purpose electron beam generating unit 714. The gas source 717 provides a calibration compound to the dual-purpose electron beam generating unit 714 as a gas calibrant.

[0084] In various embodiments, in the second mode, the dual-purpose electron beam generation unit 714 ionizes the gas calibrant by applying an electron beam having a kinetic energy between 24 eV and 150 eV.

[0085] In various embodiments, the dual-purpose electron beam generation unit 714 fragments the analyte ions by applying an electron beam having a kinetic energy less than 2 eV.

[0086] In various embodiments, the calibration device further includes a processor 720 for controlling the ion source device 711, the ExD cell 714, the gas source 717, the CID collision cell 715, and the mass analyzer 716. The processor 720 can be, but is not limited to, a controller, a computer, a microprocessor, Figure 1 A computer system, or any device capable of sending control signals and data to components of mass spectrometer 710 and receiving control signals and data from them and processing the data.

[0087] Method for calibrating a mass analyzer

[0088] Fig. 9 is an exemplary flow chart illustrating a method 900 for calibrating a mass analyzer according to various embodiments.

[0089] In step 910 of method 900 , using a processor, an ion source assembly of a mass spectrometer is directed to ionize an analyte of a sample to produce analyte ions.

[0090] In step 920, using a processor, when the mass spectrometer is in MS mode, in a first mode, a dual-purpose electron beam generating unit of the mass spectrometer located between a mass analyzer and an ion source device of the mass spectrometer is instructed to transmit analyte ions to the mass analyzer directly or through one or more other units of the mass spectrometer for mass analysis.

[0091] In step 930, using a processor, when the mass spectrometer is in MS / MS mode, in a first mode, the dual-purpose electron beam generating unit is instructed to fragment analyte ions into product ions and transmit the product ions directly or through one or more of the other units to the mass analyzer for mass analysis, or to transmit the analyte ions to a collision cell of the mass spectrometer for fragmentation, and then transmit the resulting product ions to the mass analyzer for mass analysis.

[0092] In step 940, using the processor, in a second mode, the dual-purpose electron beam generating unit is directed to generate ions of the calibration compound and transmit the calibration ions to the mass analyzer for mass analysis, either directly or through the one or more other units.

[0093] Computer program product for calibrating a mass analyser

[0094] In various embodiments, a computer program product includes a non-transitory tangible computer readable storage medium, the contents of which include a program with instructions that are executed on a processor to perform a method for calibrating a mass analyzer. The method is performed by a system including one or more different software modules.

[0095] Fig.10 is a schematic diagram of a system 1000 including one or more different software modules that perform a method for calibrating a mass analyzer according to various embodiments. The system 1000 includes a control module 1010 .

[0096] The control module 1010 instructs the ion source device of the mass spectrometer to ionize the analyte of the sample to generate analyte ions.

[0097] When the mass spectrometer is in MS mode, in a first mode, the control module 1010 instructs a dual-purpose electron beam generating unit of the mass spectrometer located between a mass analyzer and an ion source device of the mass spectrometer to transmit analyte ions to the mass analyzer directly or through one or more other units of the mass spectrometer for mass analysis.

[0098] When the mass spectrometer is in MS / MS mode, in the first mode, the control module 1010 instructs the dual-purpose electron beam generating unit to fragment the analyte ions into product ions, and transmit the product ions directly or through the one or more other units to the mass analyzer for mass analysis, or transmits the analyte ions to the collision cell of the mass spectrometer for fragmentation, and then transmits the resulting product ions to the mass analyzer for mass analysis.

[0099] In the second mode, the control module 1010 instructs the dual-purpose electron beam generating unit to generate ions of the calibration compound and transmit the calibration ions directly or through the one or more other units to the mass analyzer for mass analysis using the control module.

[0100] Although the present teachings are described in conjunction with various embodiments, the present teachings are not intended to be limited to these embodiments. On the contrary, the present teachings encompass various alternatives, modifications and equivalents, as will be understood by those skilled in the art.

[0101] In addition, when describing various embodiments, this specification may have presented method and / or process as a specific sequence of steps. However, to the extent that method or process does not rely on the specific order of steps stated herein, method or process should not be limited to the described specific sequence of steps. As will be understood by those of ordinary skill in the art, other sequences of steps are also possible. Therefore, the specific order of the steps set forth in the specification should not be interpreted as limiting the scope of protection. In addition, the scope of protection for method and / or process should not be limited to performing its steps in the order written, and those skilled in the art can easily understand that the order can be changed and still remain within the spirit and scope of the various embodiments.

Claims

1. A mass calibration device for a mass analyzer, comprising: An ion source device of a mass spectrometer, used to ionize analytes in a sample and generate analyte ions; as well as The dual-purpose electron beam generating unit of the mass spectrometer is located between the ion source device and the mass analyzer of the mass spectrometer, wherein the dual-purpose electron beam generating unit is based on the electron dissociation ExD cell, In a first mode, when the mass spectrometer is in a mass spectrometer (MS) mode, the analyte ions are transmitted directly or through one or more other units of the mass spectrometer to a mass analyzer for mass analysis, or when the mass spectrometer is in a mass spectrometer (MS / MS) mode, the analyte ions are fragmented into product ions and the product ions are transmitted directly or through the one or more other units to a mass analyzer for mass analysis, or the analyte ions are transmitted to a collision cell of a mass spectrometer for fragmentation, and the resulting product ions are transmitted to a mass analyzer for mass analysis, and, In a second mode, ions of the calibration compound are generated and transmitted, either directly or through the one or more other cells, to the mass analyser for mass analysis.

2. An apparatus according to claim 1, wherein in a first mode, when the mass spectrometer is in MS / MS mode, the ExD cell receives analyte ions, fragments the analyte ions using an electron beam, generates product ions, and transmits the product ions directly or through the one or more other units to the mass analyzer for mass analysis, and in a second mode, the ExD cell ionizes the gas of the ExD cell using an electron beam, generates calibrant ions, and transmits the calibrant ions directly or through the one or more other units to the mass analyzer for mass analysis.

3. The apparatus of claim 1, wherein the collision cell comprises a collision induced dissociation (CID) collision cell located between the ExD cell and the mass analyzer.

4. The device according to claim 3, wherein: In the first mode, when the mass spectrometer is in MS mode, the ExD cell transmits analyte ions through the CID collision cell to the mass analyzer for mass analysis, and in the second mode, the ExD cell generates ions of calibration compounds and transmits the calibration ions through the CID collision cell to the mass analyzer for mass analysis.

5. The device according to claim 3, wherein: In the first mode, when the mass spectrometer is in MS / MS mode, the ExD cell transmits analyte ions to the CID collision cell, which in turn transmits the resulting product ions to the mass analyzer for mass analysis, and in the second mode, the ExD cell generates ions of calibration compounds and transmits the calibration ions to the mass analyzer via the CID collision cell for mass analysis.

6. The apparatus of claim 1, wherein the calibrant compound comprises a background gas.

7. The apparatus of claim 6, wherein the background gas comprises a component of air or a component of vacuum pump oil.

8. The apparatus of claim 1, wherein the apparatus further comprises a gas source fluidly coupled to the ExD collision cell, and wherein the gas source provides the calibrant compound to the ExD cell as a gas calibrant.

9. The device according to claim 8, wherein: The ExD cell ionizes the gas calibrant by applying an electron beam with a kinetic energy between 24 eV and 150 eV.

10. The device according to claim 2, wherein: The ExD cell ionizes the calibration compounds by applying an electron beam with a kinetic energy between 24 eV and 150 eV.

11. The apparatus of claim 2, wherein the ExD cell fragments the analyte ions by applying an electron beam having a kinetic energy less than 2 eV.

12. The apparatus of claim 1, wherein the ExD cell comprises an electron capture dissociation (ECD) cell or an electron transfer dissociation (ETD) cell.

13. The apparatus of claim 8, further comprising a processor for controlling the ion source assembly, the ExD cell, the gas source, the CID collision cell, and the mass analyzer.

14. A method for calibrating a mass analyzer, comprising: Using a processor to instruct an ion source device to ionize an analyte of the sample to produce analyte ions, Using a processor, in a first mode, when the mass spectrometer is in a mass spectrometry (MS) mode, instructing a dual-purpose electron beam generating unit of the mass spectrometer located between an ion source device and a mass analyzer of the mass spectrometer to transmit analyte ions to the mass analyzer directly or through one or more other units of the mass spectrometer for mass analysis, wherein the dual-purpose electron beam generating unit is an electron-based dissociation (ExD) cell, Using the processor, in a first mode, when the mass spectrometer is in a mass spectrometry / mass spectrometry (MS / MS) mode, instructing the dual-purpose electron beam generating unit to fragment analyte ions into product ions and transmit the product ions directly or through the one or more other units to the mass analyzer for mass analysis, or to transmit the analyte ions to a collision cell of the mass spectrometer for fragmentation, and then transmit the resulting product ions to the mass analyzer for mass analysis, and Using the processor, in a second mode, the dual-purpose electron beam generating unit is instructed to generate ions of the calibration compound and transmit the calibration ions to the mass analyzer directly or through the one or more other units for mass analysis.

15. A computer program product comprising a non-transitory tangible computer readable storage medium, the contents of which include a program having instructions that are executed on a processor to implement a method for calibrating a mass analyzer, the method comprising: Providing a system, wherein the system comprises one or more different software modules, and wherein the different software modules comprise a control module; Using the control module to instruct the ion source device to ionize the analyte of the sample to generate analyte ions, Using the control module, in a first mode, when the mass spectrometer is in a mass spectrometry (MS) mode, instructing a dual-purpose electron beam generating unit of the mass spectrometer located between an ion source device and a mass analyzer of the mass spectrometer to transmit analyte ions to the mass analyzer directly or through one or more other units of the mass spectrometer for mass analysis, wherein the dual-purpose electron beam generating unit is an electron-based dissociation (ExD) cell, Using the control module, in a first mode, when the mass spectrometer is in a mass spectrometry / mass spectrometry (MS / MS) mode, instructing the dual-purpose electron beam generating unit to fragment analyte ions into product ions and transmit the product ions directly or through the one or more other units to the mass analyzer for mass analysis, or to transmit the analyte ions to a collision cell of the mass spectrometer for fragmentation, and then transmit the resulting product ions to the mass analyzer for mass analysis, and Using the control module, in a second mode, the dual-purpose electron beam generating unit is instructed to generate ions of the calibration compound and transmit the calibration ions to the mass analyzer directly or through the one or more other units for mass analysis.

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