Mass spectrometer having a charge measurement device

Abstract

The mass spectrometer may have an ion source region including an ion generator configured to generate ions from a sample, an ion detector configured to detect the ions and generate a corresponding ion detection signal, an electric field-free drift region disposed between the ion source region and the ion detector in which the generated ions drift axially toward the ion detector, a plurality of charge detection cylinders spaced apart in the drift region through which the ions drifting axially through the drift region pass, and a plurality of charge amplifiers each coupled to a different one of the plurality of charge detection cylinders and each configured to generate a charge detection signal corresponding to the magnitude of charge of one or more of the generated ions passing through a corresponding one of the plurality of charge detection cylinders.

Description

Technical Field

[0001] Cross - reference to Related Applications

[0001] This application claims the benefits and priority of U.S. Provisional Patent Application No. 62 / 949,554, filed on December 18, 2019, the disclosure of which is hereby expressly incorporated by reference in its entirety.

[0002]

[0002] The present disclosure generally relates to mass spectrometers, and more particularly to mass spectrometers configured to simultaneously measure ion mass - to - charge ratio and ion charge.

Background Art

[0003]

[0003] Conventional mass spectrometers and mass analyzers attempt to identify the chemical composition of a substance by measuring the mass - to - charge ratio of gas - phase ions generated from the substance. Since conventional mass spectrometers and mass analyzers lack the function of measuring particle charge, the spectral information generated by such instruments is limited to mass - to - charge ratio information.

Summary of the Invention

Means for Solving the Problems

[0004]

[0004] This disclosure may include one or more of the features recited in the appended claims, and / or one or more of the following features and combinations thereof. In one aspect, a mass spectrometer includes an ion source region including an ion generator configured to generate ions from a sample, an ion detector configured to detect ions and generate a corresponding ion detection signal, an electric field-free drift region disposed between the ion source region and the ion detector through which the generated ions axially drift toward the ion detector, a plurality of charge detection cylinders disposed apart from the drift region through which the ions axially drifting through the drift region pass, and a plurality of charge amplifiers each coupled to a different one of the plurality of charge detection cylinders and configured to generate a charge detection signal corresponding to the magnitude of the charge of one or more of the ions of the generated ions passing through the corresponding one of the plurality of charge detection cylinders.

Brief Description of the Drawings

[0005]

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DETAILED DESCRIPTION OF THE INVENTION

[0006]

[0031] For the purpose of facilitating understanding of the principles of the present disclosure, many exemplary embodiments shown in the accompanying drawings are referred to below and specific expressions are used to describe them.

[0007]

[0032] The present disclosure relates to an apparatus and technique for measuring the mass-to-charge ratio of charged particles, and further for measuring the magnitude or charge state of a charge as a charged particle moves through a drift region, and further to an apparatus and technique for determining the mass of a charged particle in accordance with the measured mass-to-charge ratio and the measured magnitude or charge state of the charge. For the purposes of this document, the terms "charged particle" and "ion" may be used interchangeably, and both terms are intended to refer to particles having a net positive or negative charge.

[0008]

[0033] Referring now to FIG. 1, there is shown a diagram of a mass spectrometer 10 configured to measure the mass-to-charge ratio of charged particles and further to measure the magnitude or charge state of the charge of the charged particles. In the illustrated embodiment, the mass spectrometer 10 includes an ion source region 12 coupled to an ion inlet A1 of an ion processing region 14, and an ion outlet A2 of the ion processing region 14 is coupled to one end of a drift region 16. An ion detector 18 is disposed at an opposite end of the drift region 16. In one embodiment, the ion detector 18 is a conventional microchannel plate detector having a detection surface 18A facing the drift region 16, but in other embodiments, the ion detector 18 may be a conventional detector configured and operable to generate a signal in response to detection of ions moving through the drift region 16 at that time. Examples of other conventional instruments and devices that may be implemented as the ion detector may include, but are not limited to, an ion-photon conversion detector, a Faraday cup detector, an electron multiplier detector, any solid state detector, any detector having a high voltage collision dynode, or the like.

[0009]

[0034] In the embodiment illustrated in FIG. 1, the drift region 16 is a linear drift region defined within an elongated drift tube 16A. The drift region 16 has a length DRL between the exit A2 of the ion processing region 14 and the ion detection surface 18A of the ion detector 18, and the longitudinal axis 34 extends through the center of the drift region 16 and further through the centers of the inlet A1 and the exit A2 of the ion processing region 14, respectively. Although the drift region 16 is illustrated in FIG. 1 in the form of a linear drift region, it will be understood that in alternative embodiments, the drift region 16 may be non-linear, either in whole or in part. As a non-limiting example, the drift region 16 may be provided in the form of a circular drift region including a conventional ion inlet (i.e., an inlet port) and an ion exit (i.e., an outlet port) structure. Those skilled in the art will envision other examples of at least partially non-linear drift regions, and it will be understood that such alternative configurations are intended to be within the scope of the present disclosure.

[0010]

[0035] As will be described in detail below, the ion source 12 illustratively includes any conventional device or apparatus 20 for generating ions from the sample 22, and one or more devices and / or instruments 24 for separating, collecting, and / or filtering ions according to one or more molecular characteristics and / or for dissociating, e.g., fragmenting, the ions 1 ~24 F and may further include. As a non-limiting example, by no means should it be considered limiting, the ion generator 20 may include a conventional electrospray ionization (ESI) source, a matrix-assisted laser desorption ionization (MALDI) source, or other conventional ion generators configured to generate ions from the sample 22. The sample 22 from which ions are generated may be any biological or other material.

[0011]

[0036] The voltage source 26 is electrically connected to the ion source or ion source region 12 via J signal paths and to the ion processing region 14 via K signal paths, where J and K may each be any positive integer. In some embodiments, the voltage source 26 may be implemented in the form of a single voltage source, and in other embodiments, the voltage source 26 may include any number of individual voltage sources. In some embodiments, the voltage source 26 may be configured or controlled to generate and supply one or more time-invariant (i.e., DC) voltages of selectable magnitude. Alternatively or additionally, the voltage source 26 may be configured or controlled to generate and supply one or more switchable time-invariant voltages, i.e., one or more switchable DC voltages. Alternatively or additionally, the voltage source 26 may be configured to generate and supply one or more time-varying signals of selectable shape, duty cycle, maximum amplitude, and / or frequency, or may be controllable. As a specific example of the latter embodiment, and not to be considered limiting in any way, the voltage source 26 may be configured to generate and supply one or more time-varying voltages in the form of one or more sinusoidal (or other shaped) voltages in the radio frequency (RF) range, or may be controllable.

[0012]

[0037] The voltage source 26 is illustratively shown as being electrically connected to a conventional processor 28 by M signal paths, where M may be any positive integer. The ion detector 18 is also electrically connected to the processor 28 via at least one signal path. The processor 28 is illustratively conventional and may comprise a single processing circuit or multiple processing circuits. The processor 28 illustratively comprises, or is coupled to, a memory 30 in which instructions are stored, which, when executed by the processor 28, cause the processor 28 to control the voltage source 26 to generate one or more output voltages for selectively controlling the operation of the ion source region 12 and one or more output voltages for selectively controlling the operation of the ion processing region 14. The instructions stored in the memory 30 further illustratively include instructions for processing the ion detection signals generated by the ion detector 18 to determine ion mass-to-charge ratio values in a conventional manner. In some embodiments, the processor 28 may be implemented in the form of one or more conventional microprocessors or controllers, and in such embodiments, the memory 30 may be implemented in the form of one or more conventional memory units that store instructions in the form of one or more microprocessor-executable instructions or instruction sets. In other embodiments, the processor 28 may alternatively or additionally be implemented in the form of a field programmable gate array (FPGA) or similar circuitry, and in such embodiments, the memory 30 may be implemented in the form of programmable logic blocks included within and / or external to the FPGA in which the instructions are programmed and stored. In still other embodiments, the processor 28 and / or the memory 30 may be implemented in the form of one or more application specific integrated circuits (ASICs). Those skilled in the art will recognize other forms in which the processor 28 and / or the memory 30 may be implemented, and it will be understood that such other forms of implementation are contemplated by the present disclosure and are intended to be within the scope of the present disclosure. In some alternative embodiments, the voltage source 26 itself may be programmable to selectively generate one or more constant and / or time-varying output voltages.

[0013]

[0038] Processor 28 is further illustratively coupled to one or more peripheral devices 32 (PD) via P signal paths, where P may be any positive integer. The one or more peripheral devices 32 may include one or more devices for providing signal inputs to processor 28 and / or one or more devices to which processor 28 provides signal outputs. In some embodiments, the peripheral device 32 includes at least one of a conventional display monitor, a printer, and / or other output devices, and in such embodiments, the memory 30 stores instructions that, when executed by processor 28, cause the one or more output peripheral devices 32 to be controlled to display and / or record the analysis of the digitized charge detection signal stored therein by processor 28.

[0014]

[0039] In the illustrated embodiment, the ion source or ion source region 12 illustratively comprises at least one ion generator 20 coupled to a voltage source 26. The processor 28 is illustratively programmed to control the voltage source 26 to generate one or more voltages to cause the ion generator 20 to generate ions from the sample 22, for example, by instructions stored in the memory 30. In some embodiments, the ion generator 20 and the sample 22 are disposed within the ion source region 12, in other embodiments, both the ion generator 20 and the sample 22 are disposed outside the ion source region 12, and in still other embodiments, the sample 22 is disposed outside the ion source region 12 and the ion generator 20 is disposed within the ion source region 12, but is operatively coupled to the sample 22 in a flowing or other manner, as illustrated by the dashed line representation in FIG. 1. In one embodiment, the ion generator 20 is a conventional electrospray ionization (ESI) source configured to generate ions from the sample in the form of a mist of charged droplets. In an alternative embodiment, the ion generator 20 may be or may comprise a conventional matrix-assisted laser desorption ionization (MALDI) source. It will be understood that ESI and MALDI are merely representative of two conventional ion generators, and the ion generator 20 may alternatively be provided in the form of any conventional device or apparatus for generating ions from a sample.

[0015]

[0040] In some embodiments, the ion source or ion source region 12 may further comprise one or more ion processing stages 24 1 ~24 F where F may be any positive integer. In such embodiments, the processor 28 is illustratively programmed to control the voltage source 26 to generate one or more voltages to control the operation of the one or more ion processing stages 24 1 ~24 F Such ion processing stages 24 1 ~24 FExamples may include, but are not limited to, one or more devices and / or instruments for separating, collecting, and / or filtering charged particles according to one or more molecular characteristics, and / or one or more devices and / or instruments for dissociating, e.g., fragmenting, charged particles, in any order and / or combination. Examples of one or more devices and / or instruments for separating charged particles according to one or more molecular characteristics include, but are not limited to, one or more mass spectrometers or mass analyzers, one or more ion mobility analyzers, one or more gas chromatographs and liquid chromatographs, and the like. Examples of mass spectrometers or mass analyzers include, but are not limited to, in embodiments of ion source 12 comprising one or more mass spectrometers or mass analyzers, time-of-flight (TOF) mass spectrometers, reflectron mass spectrometers, Fourier transform ion cyclotron resonance (FTICR) mass spectrometers, quadrupole mass spectrometers, triple quadrupole mass spectrometers, magnetic sector mass spectrometers, or the like. Examples of ion mobility analyzers include, but are not limited to, in embodiments of ion source 12 comprising one or more ion mobility analyzers, single-tube linear ion mobility analyzers, multi-tube linear ion mobility analyzers, circular tube ion mobility analyzers, or the like. Examples of one or more devices and / or instruments for collecting charged particles include, but are not limited to, quadrupole ion traps, hexapole ion traps, or the like. Examples of one or more devices and / or instruments for filtering charged particles include, but are not limited to, one or more devices or instruments for filtering charged particles according to mass-to-charge ratio, one or more devices or instruments for filtering charged particles according to particle mobility, and the like. Examples of one or more devices and / or instruments for dissociating charged particles include, but are not limited to, one or more devices or instruments for dissociating charged particles by collision-induced dissociation (CID), surface-induced dissociation (SID), electron capture dissociation (ECD) and / or photo-induced dissociation (PID), or the like. Ion processing stage 24 1 ~24F may include one or any combination of any of the above-described conventional ion separation apparatuses and / or ion processing apparatuses in any order, and it will be understood that some embodiments may include a plurality of adjacent or spaced-apart apparatuses among any of the above-described conventional ion separation apparatuses and / or ion processing apparatuses.

[0016]

[0041] The charge detector array 40 is illustratively disposed inside or integrated with the drift region 16. In the embodiment illustrated in FIG. 1, the charge detector array 40 illustratively includes a plurality of N spaced-apart series-connected charge detection cylinders 40 1 ~40 N where N may be any positive integer greater than 2. In one exemplary embodiment that should in no way be considered limiting, N may be approximately 100, but in other embodiments, N may be less than 100 or greater than 100. In any case, the charge detection cylinders 40 1 ~40 N each define a bore throughout to allow ions to pass through each cylinder. In the illustrated embodiment, the charge detection cylinders 40 1 ~40 N are arranged end-to-end such that the central longitudinal axis 34 of the drift region 16 passes through the center of each. In the illustrated embodiment, each charge detection cylinder 40 1 ~40 N defines a length CDL between the ion inlet end and the ion outlet end, but in alternative embodiments, one or more of the charge detection cylinders 40 1 ~40 N may have a length longer or shorter than CDL. The shortest CDL is illustratively physically recognizable and generates an electrically detectable signal response to one or more ions passing therethrough. There is theoretically no upper limit to CDL, but practical considerations such as available space and the operating conditions of the apparatus usually limit the longest useful CDL in a particular application.

[0017]

[0042] In the illustrated embodiment, a plurality of ground rings 42 1 ~42 N-1 each are disposed within a space defined between each adjacent pair of the charge detection cylinders 40 1 ~40 N-1 and another ground ring 42 N is disposed adjacent to the ion exit of the last charge detection cylinder 40 N . Each ground ring 42 1 ~42 N exemplarily defines a through-ring opening RA with its longitudinal axis 34 passing through its center, where RA is, exemplarily, equal to or less than the inner diameter of the charge detection cylinders 40 1 ~40 N . In the illustrated embodiment, the charge detection cylinders 40 1 ~40 N are axially separated from each other by a space length SL. In the illustrated embodiment, each of the ground rings 42 1 ~42 N-1 is arranged such that the distance between each respective ground ring 42 1 ~42 N and each adjacent charge detection cylinder of the charge detection cylinders 40 1 ~40 N is SL / 2, and is arranged to radially bisect the space SL between the ion inlet and the ion outlet of each adjacent charge detection cylinder of the charge detection cylinders 40 2 ~40 N . The ground ring 42 N is arranged to bisect the space SL between the ion exit of the charge detection cylinder 40 N and the detection surface 18A of the ion detector 18 such that the distance from each respective ground ring 42 N is SL / 2. In some embodiments, one or more of the ground rings 42 1 ~42 N may be omitted.

[0018]

[0043] In an exemplary embodiment, the drift tube 16A is illustratively coupled to ground potential (shown in FIG. 1) or another reference potential, and a plurality of charge detection cylinders 40 1 ~40 N are provided in the form of conductive cylinders properly mounted therein. In the above embodiment including one or more ground rings 42 1 ~42 N such one or more ground rings may be electrically and mechanically coupled to the inner surface of the conductive cylinder, or the conductive cylinder and one or more ground rings 42 1 ~42 N may be integrally formed with the conductive cylinder such that they have a single structure. In other exemplary embodiments, the drift tube 16A includes a series of interconnected alternating conductive or electrically insulating spacers, and a plurality of charge detection cylinders 40 1 ~40 N and a plurality of ground rings 42 1 ~42 N to which the plurality of charge detection cylinders 40 can be properly mounted. In still other exemplary embodiments, the drift tube 16A is provided in the form of a rollable sheet of flexible or semi-flexible electrical insulating material, such as a flexible circuit board, to which a plurality of spaced-apart parallel conductive strips are attached, or a plurality of spaced-apart parallel conductive strips are formed by conventional techniques, such as using conventional metal mold deposition techniques. Non-limiting examples of this embodiment are illustrated in FIGS. 13 - 15 and will be described in detail below. Those skilled in the art will recognize other forms in which the drift tube 16A and / or the charge detection cylinders 40 1 ~40 N and / or one or more ground rings 42 1 ~42 N (in embodiments including them) can be provided, and it is understood that such other forms are intended to be within the scope of the present disclosure.

[0019]

[0044] Each charge detection cylinder 40 1 ~40 Nis electrically connected to the signal inputs of the corresponding charge amplifiers of N charge amplifiers CA1 to CAN, and the signal outputs of each of the charge amplifiers CA1 to CAN are electrically connected to the processor 28. When charged particles enter the drift tube 16A from the ion exit A2 of the ion processing region 14, the entering charged particles move axially through the drift region 16 and enter the detection surface 18A of the ion detector 18. When the charged particles move axially through the drift tube 16A, each of such charged particles passes through a plurality of charge detection cylinders 40 1 ~40 N sequentially. When each of such charged particles passes through each of the successive charge detection cylinders 40 1 ~40 N , charge is induced by the charged particle, and the induced charge has a magnitude proportional to the magnitude of the charge of the particle. The charge amplifiers CA1 to CAN are each illustratively conventional and respond to the charge induced by the charged particle on each of the charge detectors 40 1 ~40 N to generate the corresponding respective charge detection signals at their outputs. The charge detection signals generated by the charge amplifiers CA1 to CAN are supplied to the processor 28. The magnitude of the charge detection signals generated by the charge amplifiers CA1 to CAN is, at any given time, (i) in the case of a single charged particle passing through each of the corresponding ones of the charge detection cylinders 40 1 ~40 N , the magnitude of the charge of the single charged particle, or (ii) in the case of a plurality of charged particles passing through each of the corresponding ones of the charge detection cylinders 40 1 ~40 N simultaneously, proportional to the magnitude of the combined charge of those plurality of charged particles. The processor 28 then receives and digitizes the charge detection signals generated by each of the charge amplifiers CA1 to CAN and is illustratively operable to store the digitized charge detection signals in a memory 30 coupled to the processor 28 or one or more other memory units otherwise accessible by the processor 28.

[0020]

[0045] The drift region 16 of the mass spectrometer 10 is a field-free drift region (i.e., a non-electric field), and charged particle ions that enter the drift tube 16A at an initial velocity through the ion exit A2 of the ion processing region 14 drift toward the detection surface 18A of the ion detector 18 at a substantially constant velocity. In this regard, the ion source 12 and / or the ion processing region 14 typically provide the driving force for passing ions into the drift tube 16A at an initial velocity. The driving force may be illustratively provided in any one form or any combination of several different forms, examples of which may include, but are not limited to, one or more ion acceleration electric fields, one or more magnetic fields, a pressure difference between the external environment and the ion source 12 and / or a pressure difference between the ion source 12 and the drift tube 16A, and the like. In any case, when charged particles drift through the field-free drift region 16, the charged particles separate in time according to the mass-to-charge ratio, and charged particles having a lower mass-to-charge ratio reach the ion detector 18 faster than charged particles having a higher mass-to-charge ratio.

[0021]

[0046] As briefly described above, the memory 30 illustratively includes instructions executable by the processor 28 to: (a) cause the ion generator 20 to generate charged particles and cause the processor 28 to cause a predetermined group or set of the charged particles, or all of the generated charged particles, to pass from the ion processing region 14 to the drift region 16, and to control the voltage source 26 in a conventional manner so that the charged particles each move axially through the drift region 16 with a constant energy toward the ion detector 18; and (b) process the detection signals generated by the ion detector 18 in a conventional manner to determine the mass-to-charge ratio of the charged particles reaching the detector 18. In the embodiment of the mass spectrometer 10 illustrated in FIG. 1, the memory 30 further illustratively includes instructions executable by the processor 28 to determine the magnitude and / or charge state of the respective charges of the charged particles that have moved axially through the drift region 16, and then to determine the particle mass based on the measured particle mass-to-charge ratio and the magnitude or charge state of the measured particle charge, by processing the detection signals generated by the ion detector 18 and the detection signals generated by each or at least some of the charge amplifiers CA1 - CAN. In some embodiments, for example, if the ion source 12 and / or the ion processing region 14 generate multiple ions and are configured to supply them simultaneously from the ion exit A2 of the ion processing region 14 to the drift region 16, as illustrated by way of example in FIG. 1, between the ion exit A2 of the ion processing region 14 and the ion inlet end of the first charge detection cylinder 16 1 of the drift region 16 (or between the ion exit A2 of the ion processing region 14 and the ion inlet end of the first charge detection cylinder 16 1It may be desirable to configure the drift tube 16A to include an array pre-space of length PRL between the ion exit A2 and the ion inlet of a ground ring that can be disposed in front of the ion inlet end thereof. Thereby, charged particles moving axially through the drift region 16 are enabled to undergo some amount of temporal axial separation (depending on the mass-to-charge ratio in the field-free region 16) prior to performing charge measurement by the charge detector array 16, thereby enhancing the quality and usefulness of the charge detection signals generated by the first one or more of the charge amplifiers CA1 to CAN. The length PRL of the array pre-space 16B may be exemplarily selected based on the application, and in some embodiments, the array pre-space 16B may be entirely omitted.

[0022]

[0047] Referring now to FIG. 2, an embodiment of the ion processing region 14 implemented in the form of an ion acceleration region 14' is shown. In the embodiment illustrated in FIG. 2, the ion acceleration region 14' includes a conductive gate 36 that defines an ion inlet A1 and another conductive gate 38 that defines an ion exit A2. The gates 36, 38 are axially spaced apart from each other, with the gate 36 disposed adjacent to the ion source region 12 and the gate 38 disposed adjacent to the inlet end of the drift tube 16A. In one embodiment, the gates 36, 38 are exemplarily provided in the form of conductive plates or rings that define their respective inlets A1 / exits A2. In some such embodiments, the ion acceleration region 14' may comprise one or more conventional radiation focusing structures or devices configured and / or controlled in a conventional manner by the processor 28, for example, to direct charged particles by the ion exit A2. In some alternative embodiments, one or both of the gates 36, 38 may be provided in the form of a conductive grid or other conventional conductive gate structure. In any case, the voltage output VS1 of the voltage source 26 is electrically connected to the conductive gate 36, and the other voltage output VS2 of the voltage source 26 is electrically connected to the conductive gate 38.

[0023]

[0048] The operation of the ion acceleration region 14’ is conventional in that when one or more generated ions enter the ion acceleration region 14’ through the ion inlet A1, the processor 28 is operable to control the voltage source 26 to generate an electric field E between the gates 36, 38 oriented to accelerate the ions to enter the inlet end of the drift tube 16A through the ion outlet A2. For positively charged particles, the voltages VS1 and VS2 are selected to generate an electric field E between the gates 36, 38 in the direction illustrated in FIG. 2, and for negatively charged particles, the voltages VS1 and VS2 are selected to generate an electric field between the gates 36, 38 in a direction opposite to that illustrated in FIG. 2. In either case, the generated electric field E operates to accelerate one or more generated ions included in the ion acceleration region 14’ into the drift region 16, and through the drift region 16, one or more generated ions axially drift towards the ion detector 18 with constant energy respectively. When the ion processing region 14 is implemented as the ion acceleration region 14’ as illustrated by way of example in FIG. 2, the mass spectrometer 10 is a time-of-flight (TOF) mass spectrometer that structurally has a charge detector array 40 disposed axially in, or as part of, or defining the field-free drift tube 16A.

[0024]

[0049] Referring now to FIG. 3, a simplified flowchart is shown illustrating an exemplary process 100 for operating the TOF mass spectrometer of FIGS. 1 and 2 (i.e., the mass spectrometer 10 of FIG. 1 having the ion acceleration region 14' of FIG. 2 implemented as the ion processing region 14) to measure ion mass-to-charge ratio, ion charge (magnitude and / or charge state), and ion mass. Process 100 is stored in memory 30, illustratively, in the form of instructions executable by a processor 28 that performs measurements of particle mass-to-charge ratio, particle charge, and particle mass. Process 100 illustratively begins when one or more charged particles generated by ion generator 20 are present within ion acceleration region 14', i.e., between gates 36, 38. Prior to process 100, processor 28 controls voltage source 26 in a conventional manner to cause ion generator 20 to generate a plurality of ions. In embodiments where ion source 12 does not include any of ion processing stages 24 (see FIG. 1), most but not all of the plurality of generated ions pass through inlet A1 and are present in ion acceleration region 14', and in some cases, voltage source 26 is controlled to assist in controlling one or both of output voltages VS1, VS2, if present, with respect to the voltage applied to ion generator 20. 1 ~24 F In embodiments that do not include any of ion processing stages 24 (see FIG. 1), most but not all of the plurality of generated ions pass through inlet A1 and are present in ion acceleration region 14', and in some cases, voltage source 26 is controlled to assist in controlling one or both of output voltages VS1, VS2, if present, with respect to the voltage applied to ion generator 20.

[0025]

[0050] In alternative embodiments where ion source 12 includes one or more of ion processing stages 24 (see FIG. 1), processor 28 is operable to control voltage source 26 to supply a subset of the plurality of generated ions to ion acceleration region 14' and / or to supply a modified set of the plurality of generated ions to ion acceleration region 14' by controlling one or more ion processing stages 24 1 ~24 F (see FIG. 1) in a conventional manner or otherwise operate them. In an exemplary embodiment, without being considered limiting in any way, one or more ion processing stages 24 1 ~24 F In alternative embodiments where ion source 12 includes one or more of ion processing stages 24 (see FIG. 1), processor 28 is operable to control voltage source 26 to supply a subset of the plurality of generated ions to ion acceleration region 14' and / or to supply a modified set of the plurality of generated ions to ion acceleration region 14' by controlling one or more ion processing stages 24 1 ~24 Fmay be implemented in the form of a conventional mass-to-charge ratio filter, such as a quadrupole filter. In this exemplary embodiment, the processor 28 may be operable to control the voltage source 26 to pass a subset of the plurality of generated ions having a mass-to-charge ratio above a threshold mass-to-charge ratio value, or below the threshold mass-to-charge ratio value, or within a predetermined range of mass-to-charge ratio values, to the ion acceleration region 14'. In other exemplary embodiments, which should in no way be considered limiting, one or more ion processing stages 24 1 ~24 F alternatively or additionally, may include a dissociation stage operable or controllable by the processor 28 to dissociate, e.g., fragment, a plurality of the generated ions or subsets thereof, in which case a modified set of the plurality of charged particles generated is passed to the ion acceleration region 14'. In yet other exemplary embodiments, which should in no way be considered limiting, one or more ion processing stages 24 1 ~24 F may include an ion mobility analyzer controllable by the processor 28 to pass a subset of the plurality of generated ions having an ion mobility value above a threshold ion mobility value, or below the threshold ion mobility value, or within a predetermined range of ion mobility values, to the ion acceleration region 14'. Those skilled in the art will recognize other apparatuses or stages, and combinations of apparatuses or stages, that may be implemented as one or more ion processing stages 24 1 ~24 F and it is understood that any such other apparatuses or stages and / or combinations of apparatuses or stages are intended to be within the scope of the present disclosure. Overall, one or more ion processing stages 24 1 ~24 F are one or more ion processing stages 24 1 ~24 FIn an embodiment of the ion source 12 comprising, it may be implemented in the form of one or more instruments or stages configured to separate, collect and / or filter ions according to one or more molecular characteristics and / or to dissociate ions, for example fragment them, and / or various combinations thereof.

[0026]

[0051] Referring again to FIG. 3, process 100 illustratively begins at step 102 where processor 28 is operable to store at least a portion of the dimensional information (DI) of drift region 16 in memory 30. In some embodiments, step 102 is partially executed by processor 28, for example, manually by inputting the dimensional information into memory 30 using a peripheral device 32 coupled to processor 28, and in other embodiments, processor 28 may execute step 102 entirely, for example, by reading the DI from a file stored in an external memory device readable by memory 30 or a peripheral device 32 coupled to processor 28. In one embodiment, the DI illustratively includes at least the total length DRL between the ion exit A2 of the drift region 16, i.e., the ion acceleration region 14', and the ion detection surface 18A of the ion detector 18, a plurality of charge detection cylinders 40 1 ~40 N the length CDL of, the length SL of the space between adjacent charge detection cylinders 40 1 ~40 N the total number N of charge detection cylinders 40 1 ~40 N if present, the length PRL before the array, and, if different from SL, the distance between the ion exit end of the last charge detection cylinder 40 N and the ion detection surface 18A of the ion detector. The dimensional information (DI) illustratively includes each charged particle passing axially through the drift region 16 such that the charged particle passes axially through each of the charge detection cylinders 40 1 ~40 N respectively, or the charge detection cylinders 40 1 ~40 NIt is stored for the purpose of matching with corresponding times passing through at least a subset of

[0027]

[0052] After step 102, process 100 proceeds to step 104, and processor 28 causes voltage source 26 to generate voltages VS1 and VS2 such that each of the charged particles drifts axially through drift region 16 at its respective constant velocity, or switches voltages VS1 and VS2 to values that construct an ion acceleration electric field in ion acceleration region 14' oriented to accelerate charged particles present in ion acceleration region 14' through ion exit A2 into drift region 16, and is operable to control voltage source 26 at reference time RT. For the purpose of explaining process 100, it is assumed that at RT, M charged particles are accelerated from ion acceleration region 14' into drift region 16, where M may be any positive integer.

[0028]

[0053] After step 104, process 100 proceeds to step 106, and processor 28 is operable to record, i.e., store, the charge detection signals generated by each of charge amplifiers CA1 - CAN, or at least a subset thereof, in relation to RT at which the M charged particles accelerated into drift region 16 drift axially toward ion detector 18. In one embodiment, processor 28 is operable in step 106 to sample the charge detection signals generated by charge amplifiers CA1 - CAN at a selected sampling rate. In some embodiments, processor 28 may be operable to continuously stop sampling of each charge detection signal after the charge detection signal has ceased activity, i.e., after all of the charged particles accelerated into drift region 16 in step 104 have passed through their respective charge detection cylinders 40 1 ~40 N After passing through. In other embodiments, processor 28 may be operable to stop sampling after detection of the last charged particle among the charged particles at ion detector 18.

[0029]

[0054] In any case, the process proceeds from step 106 to step 108, and the processor 28 determines that each of the M charged particles has reached the detection surface 18A of the ion detector 18, and based on the detected reference time RT, the detection time DT 1 ~DT M is recordable, i.e., operable to be stored in the memory 30. Then, at step 110, the processor 28 determines that each of the reference time RT and the stored detection time DT 1 ~DT M corresponding detection time, for example, TOF 1-M =(DT 1-M -RT), and is operable to calculate the time of flight (TOF) of the M charged particles and store it in the memory 30. Thereby, after the detection of the M-th charged particle by the ion detector 18, the memory 30 stores the M time-of-flight values TOF 1-M in itself.

[0030]

[0055] After step 110, the process 100 proceeds to step 112, and the processor 28 determines, for example, CH 1-M =F(DI,TOF 1-M ,CA1~CAN), etc., based on the stored dimension information DI, each stored time of flight TOF 1-M , and the stored charge detection signals generated by all or at least a subset of the charge amplifiers CA1~CAN, or as a function thereof, and is operable to calculate the magnitude or charge state (CH) of the charges of the M charged particles and store it in the memory 30.

[0031]

[0056] After step 112, the process 100 proceeds to step 114, and the processor 28 determines, for example, m / z 1-M =F(TOF 1-M ,DRL,U), etc., based on each time of flight TOF 1-M, as a known function of the potential U related to the length DRL of the drift region 16 and the magnitudes of the voltages VS1 and VS2 for accelerating charged particles from the ion acceleration region 14' to the drift region 16, it is operable to calculate the mass-to-charge ratio (m / z) of M charged particles by a conventional method and store it in the memory 30 as a known function.

[0032]

[0057] After step 114, the process 100 proceeds to step 116, and the processor 28, for example, m 1-M = m / z 1-M * CH 1-M and so on, for example, as the product of m / z and CH, it is operable to calculate the mass values (m) of M charged particles by a conventional method and store them in the memory 30.

[0033]

[0058] Assuming that a new set or subset of charged particles is present in the ion acceleration region 14' at any time after the last charged particle M reaches the ion detector 18, it will be understood that the process 100 can return to step 104. Thereby, the process 100 may return to step 104 after any of steps 108 - 116, as illustrated by the dashed line representation in FIG. 3, and the remaining steps 110 - 116 after the loop can be executed separately from the controlled operation of the mass spectrometer 10.

[0034]

[0059] The processor 28 can, by way of example, use various different processes or algorithms to execute step 112 of the process 100. An example of such a process 200 for the execution of step 112 of the process 100 is illustrated in FIG. 8 and will be described in detail below. However, before describing this process, a simplified example of two charged particles P1 and P2 having different mass-to-charge ratios moving axially through a simplified drift region 16 including three axially arranged charge detection cylinders 40 1 ~40 3 will be described with reference to FIGS. 4A - 7, and this example is used to demonstrate the operation of the process 200 illustrated in FIG. 8.

[0035]

[0060] Referring now to FIGS. 4A through 4L, three charge detection cylinders 40 axially disposed in the drift region 16 between the ion exit A2 of the gate 38 of the ion acceleration region 14' and the ion detection surface 18A of the ion detector 18 1 ~40 3 are shown as part of a simplified example of the TOF mass spectrometer 10 of FIGS. 1 and 2. Using this simplified mass spectrometer, FIGS. 4A through 4L illustrate two charged particles P1, P2 that are accelerated into the drift region 16 and that successively drift through each of the three charge detection cylinders 40 1 ~40 3 as a function of time, where P1 has a lower mass-to-charge ratio than P2. FIG. 5 illustrates an exemplary charge detection signal generated by the first charge amplifier CA1 as the charged particles pass through, and FIGS. 6 and 7 illustrate exemplary charge detection signals generated by the second charge amplifier CA2 and the third charge amplifier CA3, respectively

[0036]

[0061] As shown in FIG. 4A, the charged particles P1 and P2 are accelerated from the ion acceleration region 14' into the drift region 16 at a reference time T = T0. In this example, it is understood that both charged particles P1 and P2 pass through the ion exit A2 of the ion acceleration region 14' at T = T0 and begin an axial drift through the drift region at T = T0. As described above with respect to step 104 of process 100, the processor 28 is operable to record the reference time RT as RT = T0

[0037]

[0062] At a subsequent time T1 > T0, both the first charged particle P1 and the second charged particle P2 enter the first charge detection cylinder 40 1 as also shown in FIG. 1. As shown in FIG. 4B, the charged particle P1 exits the charge detection cylinder 40 1 at a time T2 > T1, and as shown in FIG. 4D, the charged particle P2 exits the charge detection cylinder 40 1 at a time T4 > T2. As shown in FIG. 5, as both charged particles P1 and P2 pass through the charge detection cylinder 40 1Between T1 and T2 moving through, between charged particles P1 and P2, both induce a charge of magnitude C1 on the charge detection cylinder 40 1 Similarly as illustrated in FIG. 5, thereafter, between T2 and T4, only particle P2 continues to move through the charge detection cylinder 40 1 and induces a charge of magnitude C2 on the charge detection cylinder 40 1 as shown in FIG. 5.

[0038]

[0063] As illustrated in FIGS. 4C to 4H, charged particles P1 and P2 enter the second charge detection cylinder 40 2 at times T3 and T5 respectively, where T5 > T4 > T3. At time T6 > T5, charged particle P1 exits the charge detection cylinder 40 2 and at time T8 > T6, charged particle P2 exits the charge detection cylinder 40 2 As shown in FIG. 6, when only particle P1 moves through the charge detection cylinder 40 2 between T3 and T5, charged particle P1 induces a charge of magnitude C3 on the charge detection cylinder 40 2 Similarly as shown in FIG. 6, between T5 and T6 when both charged particles P1 and P2 move through the charge detection cylinder 40 2 both charged particles P1 and P2 induce a charge of magnitude C4 > C3 on the charge detection cylinder 40 2 and when only charged particle P2 moves through the charge detection cylinder 40 2 between T6 and T8, charged particle P2 induces a charge of C5 < C3 on the charge detection cylinder 40 2 as shown in FIG. 6.

[0039]

[0064] As illustrated in FIGS. 4G to 4L, charged particles P1 and P2 enter the third charge detection cylinder 40 3 at times T7 and T9 respectively, where T9 > T8 > T7. At time T10 > T9, charged particle P1 exits the charge detection cylinder 40 3Exiting, at time T11 > T10, charged particle P1 contacts the detection surface 18A of ion detector 18. As described above with respect to step 108 of process 100, ion detector 18 generates a detection signal upon detection of charged particle P1 at T = T11, and processor 28 is operable to record the detection time DT P1 of charged particle P1 P1 as DT

[0040]

[0065] At time T12 > T11, charged particle P2 exits charge detection cylinder 40 3 and, at time T13 > T12, charged particle P2 contacts the detection surface 18A of ion detector 18. As described above with respect to step 108 of process 100, ion detector 18 generates a detection signal upon detection of charged particle P2 at T = T13, and processor 28 is operable to record the detection time DT P2 of charged particle P2 P2 as DT

[0041]

[0066] As shown in FIG. 7, between T7 and T9, only charged particle P1 moving through third charge detection cylinder 40 3 induces a charge of magnitude C6 on charge detection cylinder 40 3 . Between T9 and T10, when both charged particles P1 and P2 move through charge detection cylinder 40 3 , both charged particles P1 and P2 induce a charge of magnitude C7 > C6 on charge detection cylinder 40 3 , and between T10 and T12, when only charged particle P2 moves through charge detection cylinder 40 3 , charged particle P2 induces a charge of C8 < C6 on charge detection cylinder 40 3 .

[0042]

[0067] Referring now to FIG. 8, there is shown a simplified flowchart illustrating an exemplary process 200 for performing step 112 of process 100 illustrated and described above with reference to FIG. 3. Process 200 is stored in memory 30 in the form of instructions executable by a processor 28 that, illustratively, performs a measurement of the magnitude or charge state of a charge particle moving through the drift region 16 of the time-of-flight mass spectrometer 10 illustrated in FIGS. 1 and 2. Process 200 illustratively begins at step 202 where the processor 28 is operable to set a counter i to 1 or some other constant. Thereafter, at step 204, the processor 28 illustratively processes, for example, the flight time value TOF i,1-N = F(DI, TOF i ) etc. of the i-th charged particle as part of process 100 to determine the time or time window TW 1 ~40 N at which the i-th charged particle passes through each of the N charge detection cylinders 40 i,1-N and stores it in memory 30, together with the dimensional information DI, for the i-th charged particle out of the total M charged particles that passed through the drift region 16 as determined in step 110 of process 100 (in accordance with the process 100 illustrated in FIG. 3). i

[0043]

[0068] In one embodiment, the processor 28 is operable to perform step 204 by first determining the (constant) velocity v i = DRL / TOF i of the i-th charged particle in the drift region 16 in accordance with the relationship. Here, if the v i of the i-th charged particle is known, the processor 28 is based on a known position within the drift region, the velocity v i of the i-th charged particle, and one or both of a reference time RT and the detection time DT i of the i-th charged particle, based on the distance between the ion inlet and / or outlet ends of the charge detection cylinders 40 i ~40 1 to determine the N time windows TW N i,1-Nis operable to determine. As an example, the time window TW corresponding to the time window during which the i-th charged particle passes through the first charge detection cylinder 40 1 is given by the relationship TW i,1 =PRL / v i,1 from (PRL+CDL) / v i to (PRL+CDL) / v i and can be determined by the processor 28 with reference to the reference time RT. The time window TW corresponding to the time window during which the i-th charged particle passes through the second charge detection cylinder 40 2 is similarly given by the relationship TW i,2 =(PRL+CDL+SL) / v i,2 from (PRL+2CDL+SL) / v i to (PRL+2CDL+SL) / v i and can be determined by the processor 28 with reference to the reference time RT. As another example, the time window TW i,1 is given by the relationship TW i,1 =[DT i -N(CDL+SL) / v i from {DT i -[(N - 1)(CDL)+(N)(SL)] / v i} and can be determined by the processor 28 with reference to the reference time RT using the detection time DT i of the i-th charged particle. In other embodiments, the processor 28 may be operable to calculate the time window TW i in relation to the detection time DT i or with reference to the time between RT and DT i,1-N . In any case, when each of the time windows TW 1 ~40 N corresponding to the time windows during which the i-th charged particle passes through each of the N charge detection cylinders 40 i is determined in step 204, the process 200 proceeds to steps 206 and 208, increments the counter i by 1, and determines the time windows TW i,1-N for all M charged particles among the charged particles 1-M,1-NStep 204 is re-executed until it is determined. After completion of steps 204 to 208, the memory 30 stores in itself an M×N matrix of the time window TW 1-M,1-N where each of the M rows contains the time window data of the corresponding one of the M charged particles, and each of the N columns contains the time window data of the corresponding one of the N charge detection cylinders 40 1 ~40 N respectively.

[0044]

[0069] After the YES branch in step 206, the processor 28 is operable, by way of example, in step 210 to reset the counter i to 1 or some other constant. Thereafter, in step 212, the processor 28 is operable, by way of example, to process the magnitude of the charge detection generated by the i-th charge amplifier CAi in each time window of the i-th column of the time window matrix so as to match the magnitude of the different charges generated by the corresponding charged particle among the M charged particles in each time window. For example, during the time window TW i through which the first of the M charged particles passes, the first charged particle induces on the i-th charge detection cylinder 40 1,i the charge captured by the charge detection signal generated by the i-th charge amplifier CAi during that time window TW 1,i . Similarly, during the time window TW i through which the second of the M charged particles passes, the second charged particle induces on the i-th charge detection cylinder 40 i the charge captured by the charge detection signal generated by the i-th charge amplifier CAi during that time window TW 2,i . Further, during the time windows TW 2,i and TW i through which both the first and second of the M charged particles pass, on the i-th charge detection cylinder 40 i the first and second charged particles induce the charges captured by the charge detection signals generated by the i-th charge amplifier CAi during those time windows TW 1,i and TW 2,iDuring the overlap between them, both the first and second charged particles induce a combined charge on the i-th charge amplifier CAi, such as during the overlap of their time windows. Thus, by processing the charge detection signal generated by the i-th charge amplifier CAi during the time window of the i-th column of the time window matrix, a set of equations is generated that map each of the M charged particles and / or their various combinations to corresponding charge magnitude values. After step 212, process 200 proceeds to steps 214 and 216, increments counter i by 1, and re-executes step 212 until the magnitudes of the charge detection signals generated by each of the N charge amplifiers CA1 to CAN are mapped to the corresponding charged particles and / or various combinations among the M charged particles. After completion of steps 212 - 216, memory 30 stores a set of simultaneous equations that relate each of the M charged particles and / or their various combinations to their respective charge magnitude values. After step 216, processor 28 proceeds to step 218, solves the set of simultaneous equations or at least a subset thereof, and determines the charge magnitude CH 1-M of each of the M charged particles, or determines the charge magnitudes of at least a subset of the M charged particles. In some embodiments, processor 28, in step 218, further operates to convert one or more of the determined charge magnitude values CH i =CH i / e according to, for example, the relationship CS 1-M to charge state values CS 1-M , where e is the elementary charge (a constant).

[0045]

[0070] Referring again to the simplified examples illustrated in FIGS. 4A - 7, to further illustrate the operation of each process by application to a simplified set of charged particles and a simplified mass spectrometer structure, here the steps of processes 100 and 200 are applied to that example. In this simplified example, M = 2 (two charged particles P1 and P2) and N = 3 (three charge detection cylinders 40 1 ~40 3and each of the charge amplifiers CA1 to CA3). In the following description, the time window is, by way of example, determined with reference to the reference time RT as described above. However, it will be understood that the time window may be determined with reference to one or more other time events associated with the operation of the mass spectrometer 10 for which several non-limiting examples have been described above.

[0046]

[0071] In step 104, the processor 28 is operable to control the voltage source 26 to accelerate P1 and P2 into the drift region 16 at the reference time RT = T0. Thereafter, in step 106, the processor 28 is operable to store in the memory samples of the charge detection signals generated by each of the three charge amplifiers CA1 to CA3 when the charged particles P1 and P2 drift into and enter the ion detector 18 as illustrated in FIGS. 4A to 4L. In step 108, the processor 28 determines the detection time DT P1 of the charged particle P1 by the ion detector 18 P1 as DT P2 = T11 and stores it in the memory 30 (see FIG. 4K), and the detection time DT P2 of the charged particle P2 of the ion detector 18 P1 as DT P1 = T13 (see FIG. 4L) and stores it in the memory 30. Thereafter, in step 110, the processor 28 calculates the time of flight TOF P1 of the first charged particle P1 as TOF P2 = (DT P2 - RT), and calculates the time of flight TOF P2 of the second charged particle P2 as TOF

[0047]

[0072] When i = 1 in step 204 of process 200, the processor 28 calculates the (constant) velocity v 1 of the first charged particle P1 passing through the drift region 16 according to the relationship v P1 = DRL / TOF 1is operable to first determine. Thereafter, processor 28, at step 204, determines TW 1,1 as, as illustrated in FIGS. 4A and 4B, PRL / v 1 = T1 to (PRL + CDL) / v 1 = T2 or from T1 to T2, or, using a simplified notation, is operable to determine as T1 - T2. Processor 28 then, at step 204, determines TW 1,2 as, as illustrated in FIGS. 4C - 4F, (PRL + CDL + SL) / v 1 = T3 to (PRL + 2CDL + SL) / v 1 = T6, or is operable to determine as T3 - T6. Finally, processor 28, at step 204, determines TW 1,3 as, as illustrated in FIGS. 4G - 4J, (PRL + 2CDL + 2SL) / v 1 = T7 to (PRL + 3CDL + 2SL) / v 1 = T10, or is operable to determine as T7 - T10. Thereafter, process 200 executes a loop through step 206, increments i to i = 2 at step 208, and re - executes step 204 with i = 2. According to the relationship v 2 = DRL / TOF P2 the (constant) velocity v of the second charged particle P2 in the drift region 16 determined by processor 28, in the case of 2 processor 28 proceeds to determine subsequent time windows TW 2,1 = T1 - T4, TW 2,2 = T5 - T8, and TW 2,3 = T9 - T12 as illustrated in FIGS. 4A - 4D, FIGS. 4E - 4H, and FIGS. 4I - 4L respectively. When i = 2 = M is satisfied at step 206, process 200 proceeds to steps 210 - 216 using the following 2×3 (i.e., M×N) time window matrix TW:

Number

[0048]

[0073] When i = 1 in step 212 of process 200, the processor 28 is operable to process CA1 against the time window of column 1 of TW to align or map the magnitude of CA1 to the contributions made individually and / or collectively by P1 and P2. Referring to FIG. 5, from the two column 1 time windows TW 1,1 =(T1 - T2) and TW 2,1 =(T1 - T4), it is clear that the magnitude C1 of the charge detection signal CA1 between T1 and T2 is the result of P1 and P2 both inducing a combined charge on the charge detection cylinder 40 1 such that CH P1 + CH P2 = C1 is obtained, where CH P1 is the magnitude of the charge of charged particle P1 and CH P2 is the magnitude of the charge of charged particle P2. From the time windows TW 1,1 and TW 2,1 it is further clear that the magnitude of the charge detection signal CA1 between T2 and T4 is the result of only P2 inducing a charge on the charge detection cylinder 40 1 such that CH P2 = C2 is obtained.

[0049]

[0074] Process 200 executes a loop through steps 214 and 216, incrementing the counter i to i = 2, and the processor 28 is then, in step 212, operable to process CA2 against the time window of column 2 of the TW matrix to align or map the magnitude of CA2 to the contributions made individually and / or collectively by P1 and P2. Referring to FIG. 6, from the two column 2 time windows TW 1,2 =(T3 - T6) and TW 2,2 =(T5 - T8), it is clear that the magnitude C3 of the charge detection signal CA1 between T3 and T5 is the result of only P1 inducing its charge on the charge detection cylinder 40 2 such that CH P1 = C3 is obtained. TW 1,2 and TW 2,2From this, the magnitude C4 of the charge detection signal CA2 between T5 and T6 is such that P1 and P2 both induce a combined charge on the charge detection cylinder 40 2 thereby inducing a combined charge, resulting in CH P1 +CH P2 =C4. Finally, from TW 1,2 and TW 2,2 it is clear that the magnitude C5 of the charge detection signal CA2 between T6 and T8 is the result of only P2 inducing a charge on the charge detection cylinder 40 2 thereby resulting in CH P2 =C5.

[0050]

[0075] Process 200 again executes a loop through steps 214 and 216, increments the counter i to i = 3, and the processor 28 then, at step 212, is operable to process CA3 with respect to the time window of column 3 of the TW matrix in order to align or map the magnitude of CA3 to the contributions made individually and / or collectively by P1 and P2. Referring to FIG. 7, in a manner similar to the operation of step 212 with respect to CA2, three magnitudes C6, C7, and C8 of CA3 result in CH P1 =C6, CH P1 +CH P2 =C7, and CH P2 =C8. Thereby, after the YES branch of step 214, process 200 proceeds to step 218 using the following system of equations.

[0051]

[0076] C1 = CH P1 +CH P2

[0077] C2 = CH P2

[0078] C3 = CH P1

[0079] C4 + CH P1 +CH P2

[0080] C5 = CH P2

[0081] C6=CH P1

[0082] C7=CH P1 +CH P2

[0083] C8=CH P2

[0052]

[0084] In step 218, the processor 28 is operable to solve the foregoing system of simultaneous equations for CH P1 and CH P2 . The processor 28 may be programmed to solve the foregoing system of simultaneous equations using any conventional mathematical method. As an example, the processor 28 may calculate CH P1 and CH P2 each as the algebraic mean of the individual measurement results, and then, if necessary, modify one or both of those values to satisfy the combined measurement result along with the individual measurement results, and may be programmed to solve the system of simultaneous equations in the examples of FIGS. 4A - 7. Thus, for example, in step 218, the processor 28 may determine CH P1 =(C3 + C6) / 2 and CH P2 =(C2, + C5 + C8) / 3 according to this example, and then CH P1 and CH P2 for this example, and then operate to modify CH P1 and / or CH P2 to satisfy the equation CH P1 + CH P2 =(C1 + C4 + C7) / 3 together with the above two equations. In an alternative embodiment, the processor 28 may include, but is not limited to, one or more regression analysis techniques such as, by way of example, the least squares method or other regression techniques, one or more iterative techniques such as the Runge - Kutta method or other iterative techniques, or the like, and may be programmed to perform step 218 by using any one or combination of conventional mathematical equation - solving methods and / or by using any one or combination of conventional data - fitting techniques to solve the system of simultaneous equations obtained as a result of steps 210 - 216.

[0053]

[0085] To complete this example, return again to process 100 of FIG. 3, and at step 114, processor 28 determines the mass-to-charge ratio of each of the two charged particles P1 and P2 as m / z P1 =F(TOF P1 , DRL, U) and m / z P2 =F(TOF P2 , DRL, U), etc., as a conventional function of the measured time-of-flight TOF P1 and TOF P2 of each length DRL of drift region 16, and the potential U related to the magnitudes of the voltages VS1, VS2 that accelerate the charged particles from ion acceleration region 14' to drift region 16. Thereafter, at step 16, processor 28 is operable to calculate the mass m P1 =(m / z P1 )(CH P1 ) and m P2 =(m / z P2 )(CH P2 ) according to the mass m P1 and m P2 of each of the charged particles P1 and P2, respectively.

[0054]

[0086] The examples illustrated in FIGS. 4A-7 are provided only for the purpose of explaining exemplary operation of a simplified time-of-flight mass spectrometer of the type illustrated in FIGS. 1 and 2 and are not intended to be limiting in any way. Those skilled in the art will understand that the processes described above or variations thereof can be directly applied to the determination of the mass-to-charge ratio, charge magnitude and / or charge state, and mass values of many charged particles, such as hundreds, thousands, or more. Alternatively, those skilled in the art will recognize other techniques for determining the magnitude and / or charge state of multiple charged particles based on one or more of the charge detection signals generated by charge amplifiers CA1-CAN, and it is intended that such other techniques fall within the scope of the present disclosure.

[0055]

[0087] In the mass spectrometer 10 illustrated in FIG. 1, it will be further understood that not all of the charge detection signals need to be used to determine the particle charge value. In some embodiments where charged particles exit the ion processing region 14 in a mass, for example, the charge detection signals generated by the first one or several charge amplifiers may be ignored by the processor 28. Alternatively or additionally, as described above, the drift tube 16A may be configured to include a pre-array space 16B having any desired length that can at least initiate the axial separation of the drift region 16 before such a mass of particles passes through the first one of the plurality of charge detection cylinders 40 1 ~40 N and having an array of any desired length that can at least initiate the axial separation of the drift region 16 before such a mass of particles passes through the first one of the plurality of charge detection cylinders 40.

[0056]

[0088] Referring now to FIG. 9, another embodiment 14” of the ion processing region 14 implemented in the form of a conventional mass-to-charge ratio filter (m / z filter) 60 downstream of the conventional ion trap 62 is shown. In the embodiment illustrated in FIG. 9, one end of the mass-to-charge ratio filter 60 defines the ion inlet A1 of the ion processing region 14”, and the ion exit end of the ion trap 62 defines the ion exit A2 of the ion processing region 14”. The mass-to-charge ratio (m / z) filter 60 is conventional and may be implemented, for example, in the form of a quadrupole or other device operably coupled to the voltage source 26. In the illustrated embodiment, for example, the output voltage VS1 of the voltage source 26 is operably coupled to the m / z filter 60 via K signal paths, where K may be any positive integer, and another output voltage VS2 of the voltage source 26 is similarly operably coupled to the m / z filter 60 via L signal paths, where L may be any positive integer. In some embodiments, VS1 is, for example, a time-varying voltage signal of selectable frequency and maximum amplitude supplied to the m / z filter 60 in the form of a pair of antiphase voltages that are 180 degrees out of phase with each other, and VS2 is a constant voltage of selectable amplitude, for example, a DC voltage. In such embodiments, the processor 28 is programmed, or is programmable, to control the output voltages VS1 and VS2 in a conventional manner to create the electric field conditions within the selected m / z filter 60 such that only ions having a mass-to-charge ratio of the selected mass-to-charge ratio, or ions having a mass-to-charge ratio within a selected range of mass-to-charge ratios, pass through the m / z filter 60. In some alternative embodiments, only VS1 is applied to the m / z filter 60, and the processor 28 controls the creation of the electric field conditions within the selected m / z filter 60 such that only ions having a mass-to-charge ratio above a threshold mass-to-charge ratio pass through the m / z filter 60.

[0057]

[0089] In the embodiment illustrated in FIG. 9, the ion trap 62 is similarly conventional and may be implemented, for example, in the form of a quadrupole, hexapole or other device having an inlet gate 64, for example, in the form of a conventional end cap defining the ion inlet A2' and the outlet gate 66 of the ion trap 62, for example, in the form of another conventional end cap defining the ion outlet A2 of the ion processing region 14". In the illustrated embodiment, the output voltage VS3 of the voltage source 26 is operably coupled to the inlet end cap 64, the output voltage VS4 of the voltage source 26 is operably coupled to the outlet end cap 66, and the output voltage VS5 is operably coupled to the body of the ion trap 62 via J signal paths, where J may be any positive integer. In some embodiments, VS3 and VS4 are switchable DC voltages having selectable amplitudes, and VS5 is a time-varying voltage signal of selectable frequency and maximum amplitude supplied to the ion trap 62, for example, in the form of a pair of out-of-phase voltages that are 180 degrees out of phase with each other. In such embodiments, the processor 28 is programmed or programmable to control the output voltages VS3-VS5 in a conventional manner to selectively pass charged particles through the ion trap 62 via the ion inlet A2', confine the charged particles within the ion trap 62, and selectively release the confined ions from the ion trap 62 through the ion outlet A2. In some alternative embodiments, the m / z filter 60 and the ion trap 62 may be integrated into a single device, for example, in the form of a conventional quadrupole mass-to-charge ratio filter having end caps. In any case, the resulting mass spectrometer 10 is controllable, for example, to operate as a single mass-to-charge ratio mass spectrometer, a single range of mass-to-charge ratio mass spectrometers, and / or a mass-to-charge ratio scanning mass spectrometer. However, in any operating mode, the mass spectrometer 10 is configured to determine the particle mass-to-charge ratio, the magnitude or charge state of the particle charge, and the particle mass value.

[0058]

[0090] Referring now to FIG. 10, a simplified flowchart is shown illustrating an exemplary process 300 for operating the mass spectrometers of FIGS. 1 and 9 (i.e., the mass spectrometer 10 of FIG. 1 having the ion processing region 14” of FIG. 9 implemented as the ion processing region 14) so as to measure an ion mass-to-charge ratio, an ion charge (magnitude and / or charge state), and an ion mass. Process 300 is stored in memory 30, illustratively, in the form of instructions executable by a processor 28 that performs measurements of, illustratively, a particle mass-to-charge ratio, a particle charge, and a particle mass. Process 300 illustratively begins when one or more charged particles are generated by an ion generator 20 and travel through an ion acceleration structure and / or pressure differential conditions constructed in or a portion of the ion source region 12 toward the ion processing region 14”. Process 300 illustratively includes many of the steps of process 100, and thus similar steps are identified by similar numbers, and the operation of the processor 28 during such steps is as described above with respect to FIG. 3.

[0059]

[0091] Process 300 illustratively begins with step 102 of process 100, where drift region dimension information (DI) is stored in memory 30. Thereafter, at step 302, the processor 28 is operable to set a counter i = 1 or some other constant. Thereafter, at step 304, the processor 28 illustratively determines a first selected mass-to-charge ratio m / z iThe voltage source 26 is operable to be controlled so as to configure the m / z filter 60 such that only ions having [it] or only ions having a mass-to-charge ratio within a first selected range i of the mass-to-charge ratio pass through. Thereafter, in step 306, the processor 28 is operable to control the voltage source 26 so as to control or configure the ion trap 62 to collect and capture charged particles exiting the m / z filter 60. Exemplarily, the processor 28 is operable to maintain the above control of the ion trap 62 for a predefined period in order to collect a plurality of charged particles in the ion trap 62. The predefined period may vary depending on different applications and / or different samples 22. In any case, after the expiration of the predefined time for which the processor 28 is operable to maintain the above control of the ion trap 62, the process 300 proceeds to step 308, and the processor 28 is operable to control the voltage source 26 to accelerate the captured charged particles from the ion trap 62. Such control is realized, for example, by appropriately switching the DC voltage applied to one or both of the gates 64, 66, and in any case, a reference time RT is set at which the charged particles released from the ion trap 62 start to drift through the drift region 16 of the mass spectrometer 10. After step 308, the processor 28 is operable to execute steps 106 to 116 of the process 100 illustrated in FIG. 3 in order to determine the mass-to-charge ratio, the magnitude or charge state of the charge, and the mass value of the charged particles drifting through the drift region 16, all as described above.

[0060]

[0092] In some embodiments where the m / z filter 60 is controlled to selectively pass charged particles of a selected mass-to-charge ratio or charged particles having a mass-to-charge ratio within a very narrow range of mass-to-charge ratio values, the mass-to-charge ratio of the charged particles drifting through the drift region 16 is known and need not be calculated in step 114 such that step 114 can be omitted. However, in some such embodiments, step 114 may be included, for example, to provide additional mass-to-charge ratio information used when calibrating the m / z filter 60 and / or to achieve an improvement in mass-to-charge ratio resolution. In any case, process 300 proceeds from step 116 to step 310, and processor 28 is operable to compare counter i to count value Q. If i < Q, process 300 proceeds to step 312, where counter i is incremented, and returns to step 304 to the second selected mass-to-charge ratio m / z i The voltage source 26 is controlled to configure the m / z filter 60 such that only ions having or only ions having a mass-to-charge ratio within a second predetermined range i of the mass-to-charge ratio pass through. The second selected mass-to-charge ratio or the second selected range of mass-to-charge ratio is incrementally different from the first selected mass-to-charge ratio or the first selected range of mass-to-charge ratio, for example, greater than or less than it. At step 310, if i = Q, the range of mass-to-charge ratio is scanned and processed, and process 300 ends. The value Q and the gradually increasing step size in the selected mass-to-charge ratio or the selected range of mass-to-charge ratio may be optionally selected, for example, to scan any desired range of mass-to-charge ratio values.

[0061]

[0093] In an alternative embodiment where the m / z filter 60 and the ion trap 62 are coupled to be a single instrument as described above, process 300 accordingly combines steps 304 and 306 such that processor 28 m / z ia single step operable to control voltage source 26 to configure an instrument coupled to capture only ions of m / z i or steps 306 and 308 can be combined and modified to be a single step operable to control voltage source 26 so that only ions of m / z are emitted from the coupled instrument. In some alternative embodiments, the ion trap 62 may be omitted so that charged particles exiting the m / z filter 60 enter the drift region 16 directly. However, in such embodiments, the ion acceleration region is included in the ion source region 12 to set the reference time RT, and in such embodiments, the m / z filter 60 becomes part of the drift region, so the dimension information DI includes at least the dimension information of the m / z filter 60 in the axial direction.

[0062]

[0094] Referring now to FIG. 11, another embodiment 14”’ of the ion processing region 14 is shown in the form of two conventional mass-to-charge ratio filters (m / z filters) 70, 74 with a dissociation stage 72 disposed therebetween. In the embodiment illustrated in FIG. 11, one end of the mass-to-charge ratio filter 70 defines the ion inlet A1 of the ion processing region 14”’, and the ion exit end of the mass-to-charge ratio filter 74 defines the ion exit A2 of the ion processing region 14”’. The mass-to-charge ratio (m / z) filters 70, 74 are conventional and each may be implemented, by way of example, in the form of a quadrupole or other instrument operably coupled to the voltage source 26, and the dissociation stage 72 is likewise conventional and is operably coupled to the voltage source 26 in the illustrated embodiment.

[0063]

[0095] In the illustrated embodiment, the output voltage VS1 of the voltage source 26 is operably coupled to the m / z filter 70 via H signal paths, where H may be any positive integer, and another output voltage VS2 of the voltage source 26 is similarly operably coupled to the m / z filter 70 via I signal paths, where I may be any positive integer. Another output voltage VS3 of the voltage source 26 is operably coupled to the m / z filter 74 via L signal paths, where L may be any positive integer, and another output voltage VS4 of the voltage source 26 is similarly operably coupled to the m / z filter 74 via R signal paths, where R may be any positive integer. In some embodiments, VS1 and VS3 are, for example, time-varying voltage signals of selectable frequencies and maximum amplitudes supplied to the m / z filters 70, 74 respectively in the form of a pair of inverted-phase voltages that are 180 degrees out of phase with each other, and VS2 and V4 are invariant voltages of selectable amplitudes, for example, DC voltages. In such embodiments, the processor 28 is programmed, or is programmable, to control VS1 - VS4 in a conventional manner to create the electric field conditions within the selected m / z filters 70, 74 such that only ions having a mass-to-charge ratio of the selected mass-to-charge ratios, or only ions having a mass-to-charge ratio within a selected range of mass-to-charge ratios, pass through the m / z filters 70, 74. In some alternative embodiments, only VS1 is applied to the m / z filter 70 and is controlled by the processor 28 to create the electric field conditions within the selected m / z filter 70 such that only ions having a mass-to-charge ratio above a threshold mass-to-charge ratio pass through the m / z filter 70. Alternatively or additionally, only VS3 is applied to the m / z filter 74 and is controlled by the processor 28 to create the electric field conditions within the selected m / z filter 74 such that only ions having a mass-to-charge ratio above a threshold mass-to-charge ratio pass through the m / z filter 74.

[0064]

[0096] In the embodiment illustrated in FIG. 11, voltage source 26 is shown as being operably coupled to dissociation stage 72 via two voltage outputs VS5 and VS6. It will be understood that such a voltage source connection is only included in embodiments implemented in the form of a device or instrument in which dissociation stage 72 is controllable by one or more voltage signals to dissociate charged particles, e.g., fragment them. In such embodiments, VS5 may be a time-varying voltage signal having a selectable frequency and maximum amplitude, and VS6 may be a constant voltage having a selectable amplitude, e.g., a DC voltage. In some such embodiments, voltage source 26 may generate only VS5, and in other embodiments, voltage source 26 may generate only VS6. In other embodiments, dissociation stage 72 may not be connected to voltage source 26 at all, and instead may be coupled only to one or more gas sources (not shown), and dissociation stage 72 may be operable to dissociate charged particles, e.g., fragment them, by collision with one or more gases provided by the one or more gas sources. In any case, the resulting mass spectrometer 10 is illustratively controllable to operate as a single mass-to-charge ratio mass spectrometer, a single range of mass-to-charge ratio mass spectrometer, a single mass-to-charge ratio scanning mass spectrometer (e.g., scanning a range of mass-to-charge ratios with m / z filter 70 or m / z filter 74) and / or a double mass-to-charge ratio scanning mass spectrometer (e.g., scanning a range of mass-to-charge ratios with both m / z filter 70 and m / z filter 74). However, in any operating mode, mass spectrometer 10 is configured to determine particle mass-to-charge ratio, particle charge magnitude or charge state, and particle mass value.

[0065]

[0097] Referring now to FIG. 12, a simplified flowchart is shown that illustrates an exemplary process 400 for operating the mass spectrometers of FIGS. 1 and 11 (i.e., the mass spectrometer 10 of FIG. 1 having the ion processing region 14”’ of FIG. 11 implemented as the ion processing region 14) to measure an ion mass-to-charge ratio, an ion charge (magnitude and / or charge state), and an ion mass. Process 400 is stored in memory 30, illustratively, in the form of instructions executable by a processor 28 that performs measurements of a particle mass-to-charge ratio, a particle charge, and a particle mass. Similar to process 300, process 400 illustratively begins when one or more charged particles are generated by an ion generator 20 and travel through an ion acceleration structure and / or pressure differential conditions constructed in or part of the ion source region 12 towards the ion processing region 14”’. Process 400 illustratively includes many of the steps of process 100, and thus similar steps are identified by similar numbers, and the operation of the processor 28 during such steps is as described above with respect to FIG. 3.

[0066]

[0098] Process 400 illustratively begins with step 102 of process 100, where drift region dimension information (DI) is stored in memory 30. Thereafter, at step 402, the processor 28 is operable to set two counters i = 1 and j = 1, or some other constant. Thereafter, at step 404, the processor 28 illustratively determines a first selected mass-to-charge ratio m / z iThe processor 28 is then operable to control the voltage source 26 to configure the m / z filter 70 to pass only ions having a first selected mass to charge ratio m / z or only ions having a mass to charge ratio within a first selected range of mass to charge ratios. Thereafter, in step 406, the processor 28 is illustratively operable to control the voltage source 26 to configure a dissociation stage 72 to dissociate, e.g., fragment, the charged particles exiting the m / z filter 70. In embodiments in which the voltage source 26 is not operable to control the dissociation stage 72, step 406 may be omitted or replaced by a suitable control step controlling gas flow or other control features of the dissociation region 72. Thereafter, in step 408, the processor 28 illustratively determines the first selected mass to charge ratio m / z of the dissociated ions exiting the dissociation stage 72 to pass only ions having a first selected mass to charge ratio m / z j The m / z filter 74 is operable to control the voltage source 26 to configure the m / z filter 74 to pass only ions having a mass to charge ratio of, or within a first selected range j of mass to charge ratios.

[0067]

[0099] In some embodiments, the m / z filter 74 may be configured in a conventional manner to have an ion capture function, as described above with respect to the m / z filter 60 of FIG. 9. In such embodiments, the processor 28, at step 408, controls the voltage source 26 to collect and capture charged particles within the m / z filter 74 for some period of time, and then further operates to control the voltage source 26 to accelerate the captured charged particles from the m / z filter 74 to set a reference time RT at which the charged particles released from the m / z filter 74 begin to drift through the drift region 16 of the mass spectrometer 10. In embodiments of the m / z filter 74 that do not have the ion capture function as described above, the ion acceleration region is included in the ion source region 12 to set the reference time RT, and in such embodiments, the m / z filters 70, 74 and the dissociation stage 72 form part of the drift region 16, so the dimension information DI includes at least the dimension information of the m / z filters 70, 74 and the dissociation stage 72 in the axial direction. In other such embodiments, an ion acceleration stage in the form of, for example, a conventional ion trap or other ion acceleration stage may be provided as part of the dissociation stage 72, or may be inserted into the mass spectrometer 10 between the dissociation stage 72 and the m / z filter 74 for the purpose of collecting a plurality of charged particles and setting the reference time RT. In yet other such embodiments, a conventional ion trap or other ion acceleration stage may be inserted into the mass spectrometer 10 between the m / z filter 74 and the drift region 16 for the purpose of collecting a plurality of charged particles and setting the reference time RT, as illustrated by way of example in the embodiment of the ion processing region 14' shown in FIG. 9.

[0068]

[0100] After step 408, the processor 28 is operable to perform steps 106-116 of process 100 illustrated in FIG. 3 to determine, for example, as described above in full, the mass-to-charge ratio, the magnitude or charge state of the charge, and the mass value of the charged particles drifting through the drift region 16. In some embodiments where the m / z filter 74 is controlled to selectively pass charged particles of the selected mass-to-charge ratio or to pass charged particles having a mass-to-charge ratio within a very narrow range of mass-to-charge ratio values, the mass-to-charge ratio of the charged particles drifting through the drift region 16 is known and step 114 need not be calculated at step 114 so that it can be omitted. However, in some such embodiments, step 114 may be included, for example, to provide additional mass-to-charge ratio information used when calibrating the m / z filter 74 and / or to achieve an improvement in mass-to-charge ratio resolution. In any case, process 400 proceeds from step 116 to step 410, and the processor 28 is operable to compare counter j to count value R. If j < R, process 400 proceeds to step 412, where counter j is incremented at step 412 and returns to step 408 for a second selected mass-to-charge ratio m / z j The voltage source 26 is controlled to configure the m / z filter 74 such that only ions having j or only ions having a mass-to-charge ratio within a second predetermined range j of the mass-to-charge ratio pass, and the second selected mass-to-charge ratio or the second selected range of mass-to-charge ratios is incrementally different from the first selected mass-to-charge ratio or the first selected range of mass-to-charge ratios, for example, greater than or less than it.

[0069]

[0101] At step 410, if j = R, the range of mass-to-charge ratios is scanned and processed by the m / z filter 74, and process 400 proceeds to step 414, where the processor 28 is operable to compare counter i to count value Q. If i < Q, process 400 proceeds to step 416, where counter i is incremented at step 416 and returns to step 404 for a second selected mass-to-charge ratio m / z iVoltage source 26 is controlled to configure m / z filter 74 to pass only ions having mass to charge ratios Q, or ions having mass to charge ratios within a second predetermined range i of mass to charge ratios, the second selected mass to charge ratio or second selected range of mass to charge ratios being incrementally different, e.g., greater than or less than, the first selected mass to charge ratio or first selected range of mass to charge ratios. In step 414, if i=Q, the range of mass to charge ratios has been scanned and processed by m / z filter 70 and process 400 ends. The increasing step sizes, along with the values ​​R and Q in the selected mass to charge ratio or selected range of mass to charge ratios, may illustratively be selected to scan any desired range of mass to charge ratio values.

[0070]

[0102] 13-15, there is shown an embodiment of the drift region 16 of a mass spectrometer 10 that may be implemented in any of the mass spectrometer configurations described above. In the illustrated embodiment, the drift tube 16A may be provided in the form of an elongated sheet of flexible or semi-flexible electrically insulating material, such as, for example, a flexible circuit board material, having a plurality of spaced apart parallel conductive strips attached thereto or formed in a conventional manner, for example, using conventional metal mold deposition techniques. In this embodiment, the plurality of spaced apart parallel conductive strips form a plurality of charge detection cylinders 40 when opposite sides of the flexible or semi-flexible sheet are joined together to form an elongated cylinder, for example as illustrated in FIG. 14. 1 ~40 N and one or more ground rings 42 1 ~42 N In some alternative embodiments, the conductive strips are illustratively oriented to form a ground ring 42. 1 ~42 N One or more or all of the drift tube 16A and / or the charge detection cylinder 40 may be omitted. 1 ~40 N and / or one or more ground rings 421 ~42 N It will be understood that other forms may be recognized (in embodiments including them) that can be provided, and that such other forms are intended to be within the scope of the present disclosure.

[0071]

[0103] Although the present disclosure has been illustrated and described in detail in the above drawings and description, these disclosures should be considered exemplary and not limiting in their features, and it is understood that only exemplary embodiments thereof have been shown and described, and that all changes and modifications within the spirit of the present disclosure are desired to be protected. For example, some structures are shown in the accompanying drawings and described herein as being controllable and / or configurable to build one or more electric fields in the specification that are configured and oriented to accelerate charged particles and / or otherwise act on charged particles. One of ordinary skill in the art will recognize that the acceleration of charged particles and / or other actions on charged particles can, in some cases, be alternatively or additionally realized by one or more magnetic fields. Accordingly, it will be understood that any conventional structure and / or mechanism that replaces or improves one or more of the electric fields described herein with one or more appropriate magnetic fields is intended to be within the scope of the present disclosure. As another example, various embodiments of the drift tube 16A are shown in the accompanying drawings and described herein as having an overall linear structure, i.e., a linear drift tube, but the concepts described herein are directly applicable to drift tubes of other shapes and configurations, examples of which include, but are not limited to, V-shaped drift tubes as conventionally implemented in reflectron time-of-flight mass spectrometers, W-shaped drift tubes as conventionally implemented in multi-reflectron time-of-flight mass spectrometers, L-shaped drift tubes, or the like. It is not intended, and should never be inferred, that there are any limitations with respect to the shape of the drift tube 16A.

Claims

1. an ion source region comprising an ion generator configured to generate a plurality of ions from a sample, an ion detector configured to detect ions and generate a corresponding ion detection signal, an electric field-free drift region disposed between the ion source region and the ion detector, through which the generated plurality of ions drift axially toward the ion detector, a plurality of charge detection cylinders disposed apart from the field-free drift region through which the plurality of ions drifting axially through the field-free drift region pass, a plurality of charge amplifiers each coupled to a different one of the plurality of charge detection cylinders and configured to generate a charge detection signal corresponding to the magnitude of the charge of one or more of the plurality of ions passing through the corresponding one of the plurality of charge detection cylinders, at least one processor operably coupled to the ion detector and each of the plurality of charge amplifiers, at least one memory storing instructions executable by the at least one processor to determine, based on the ion detection signal, a mass-to-charge ratio of each of the plurality of ions drifting through the field-free drift region and to process the charge detection signal generated by each of the plurality of charge amplifiers to determine the magnitude of the charge of each of the plurality of ions drifting through the field-free drift region, a mass spectrometer comprising the same.

2. an ion region or instrument disposed between the ion source region and the field-free drift region, at least one voltage source electrically connected to the ion region or instrument and configured to selectively generate at least one voltage to construct an electric field within the ion region or instrument oriented to accelerate the generated plurality of ions into the field-free drift region The mass spectrometer according to claim 1, further comprising the same.

3. The at least one memory stores The mass spectrometer according to claim 2, wherein instructions executable by the processor are stored to control the at least one voltage source that generates the at least one voltage to construct the electric field in the ion region or the instrument.

4. The instructions stored in the at least one memory are (a) controlling the at least one voltage source that generates the at least one voltage to construct the electric field in the ion region at a reference time RT to accelerate the generated plurality of ions into the field-free drift region; (b) storing samples of the charge detection signals generated by each of the plurality of charge amplifiers in the at least one memory when the accelerated plurality of ions axially drift through the field-free drift region toward the ion detector; (c) monitoring the ion detector and storing a detection time (DT) by the ion detector when each of the accelerated plurality of ions reaches the ion detector; (d) determining the time-of-flight (TOF) of each of the plurality of ions accelerated through the field-free drift region based on each detection time DT of the detection time DT with respect to RT; (e) further including instructions executable by the processor to determine the magnitude or charge state of the charge of each of the plurality of accelerated ions based on the magnitude of the stored samples of the charge detection signals generated by the plurality of charge amplifiers based on each of the TOFs, and based on the field-free drift region, each of the plurality of charge detection cylinders, and the axial length of the gap therebetween. The mass spectrometer according to claim 3.

5. The instructions stored in the at least one memory are (i) determining the speed of each of the plurality of accelerated ions based on each of the TOFs and the axial length of the field-free drift region; (ii) For each of the plurality of accelerated ions, a plurality of time windows are determined based on the determined velocity of the ions, the field-free drift region, each of the plurality of charge detection cylinders, and the axial length of the gap therebetween, and each of the plurality of time windows corresponds to a time window during which the ion passes through a different one of the plurality of charge detection cylinders, with reference to the RT or DT of the ion. (iii) For each of the plurality of charge amplifiers, the samples of the charge detection signals generated by the charge amplifier during each of the respective time windows for each of the plurality of accelerated ions are processed to determine a set of equations that relate the magnitude of the charge detection signal to the magnitude of the charge of the plurality of accelerated ions. (iv) Solving a plurality of sets of equations to determine the magnitude or charge state of the charge of each of the plurality of accelerated ions. The mass spectrometer according to claim 4, further comprising executable instructions by the processor for determining the magnitude or charge state of the charge of each of the plurality of accelerated ions thereby.

6. The ion region or apparatus comprises an ion acceleration region having first and second gates disposed apart, the first gate being adjacent to the ion source region and the second gate being adjacent to the field-free drift region. The at least one voltage source is electrically connected to the first and second gates and is configured to selectively control the voltage applied by the voltage source to at least one of the first and second gates to construct the electric field within the ion acceleration region. The mass spectrometer according to any one of claims 2 to 5.

7. The ion region or apparatus comprises an ion trap. The at least one voltage source is electrically connected to the ion trap and is configured to selectively control the voltage applied to the ion trap to construct the electric field within the ion trap. The mass spectrometer according to any one of claims 2 to 5.

8. The ion region or apparatus comprises a mass-to-charge ratio filter. The at least one voltage source is electrically connected to the mass-to-charge ratio filter and is configured to selectively control the voltage applied to the mass-to-charge ratio filter to construct the electric field within the mass-to-charge ratio filter, the mass spectrometer according to any one of claims 2 to 5.

9. The mass spectrometer further comprises a mass-to-charge ratio filter disposed between the ion source region and the ion region or the instrument, The ion region or the instrument comprises an ion trap, The at least one voltage source is electrically connected to the mass-to-charge ratio filter and the ion trap, and the at least one voltage source selectively generates at least a first voltage that configures the mass-to-charge ratio filter such that only ions having a selected mass-to-charge ratio or only ions having a mass-to-charge ratio within a selected range of mass-to-charge ratios pass through, and generates at least a second voltage that selectively constructs the electric field within the ion trap, the mass spectrometer according to any one of claims 2 to 5.

10. The mass spectrometer, A first mass-to-charge ratio filter disposed between the ion source region and the ion region or the instrument, A dissociation stage disposed between the first mass-to-charge ratio filter and the ion region or the instrument and configured to dissociate the passing ions, And a second mass-to-charge ratio filter disposed between the ion source region and the ion region or the instrument, The at least one voltage source is electrically connected to each of the first and second mass-to-charge ratio filters, and the at least one voltage source selectively generates at least a first voltage that configures the first mass-to-charge ratio filter such that only ions having a first selected mass-to-charge ratio or only ions having a mass-to-charge ratio within a first selected range of mass-to-charge ratios pass through, and selectively generates at least a second voltage that configures the second mass-to-charge ratio filter such that only ions having a selected second mass-to-charge ratio or only ions having a mass-to-charge ratio within a selected range of the second mass-to-charge ratios pass through, the mass spectrometer according to any one of claims 2 to 5.

11. The instructions stored in the at least one memory further include instructions executable by the processor to determine, based on each of the respective TOFs and the axial length of the field-free drift region, each of the mass-to-charge ratios of the plurality of accelerated ions, for the mass spectrometer according to claim 4 or 5.

12. The instructions stored in the at least one memory further include instructions executable by the processor to determine, based on each of the determined mass-to-charge ratios and each of the determined magnitudes or charge states of the charges, each of the mass values of the plurality of accelerated ions, for the mass spectrometer according to claim 11.

13. The ion detector comprises a microchannel plate detector, for the mass spectrometer according to any one of claims 1 to 12.

14. The ion detector comprises an ion-photon conversion detector, for the mass spectrometer according to any one of claims 1 to 12.

15. The ion detector comprises a Faraday cup detector, for the mass spectrometer according to any one of claims 1 to 12.

16. The ion detector comprises an electron multiplier detector, for the mass spectrometer according to any one of claims 1 to 12.

17. Both the ion generator and the sample are disposed within the ion source region, for the mass spectrometer according to any one of claims 1 to 16.

18. The ion generator and the sample are disposed outside the ion source region, The ion generator is configured to generate ions from the sample and supply the generated ions to the ion source region, for the mass spectrometer according to any one of claims 1 to 16.

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