Mass spectrometer with a charge measurement arrangement

Abstract

A mass spectrometer can have 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, a field-free drift region disposed between the ion source region and the ion detector through which the generated ions axially drift towards the ion detector, a plurality of spaced-apart charge detection cylinders through which the ions that are axially drifting through the drift region pass, and a plurality of charge amplifiers, each charge amplifier being coupled to a different one of the plurality of charge detection cylinders and each being configured to generate a charge detection signal that corresponds to the magnitude of the charge of one or more of the generated ions passing through the corresponding one of the plurality of charge detection cylinders.

Description

[0001] Cross - reference to related applications

[0002] This patent application claims the benefit and priority of U.S. Provisional Patent Application Serial No. 62 / 949,554, filed on December 18, 2019, the disclosure of which is hereby expressly incorporated by reference in its entirety. Technical Field

[0003] This disclosure generally relates to mass spectrometers, and more particularly to mass spectrometers configured to simultaneously measure the mass - to - charge ratio and the ion charge of ions. Background Art

[0004] Conventional mass spectrometers and mass analyzers provide an identification of the chemical composition of a substance by measuring the mass - to - charge ratio of gas - phase ions generated from the substance. The spectral information generated by conventional mass spectrometers and mass analyzers is limited to mass - to - charge ratio information because such instruments lack the ability to measure the charge of particles. Summary of the Invention

[0005] 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 may include 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 spaced - apart charge - detection cylinders disposed in the drift region through which the ions axially drifting through the drift region pass, and a plurality of charge amplifiers, each charge amplifier being coupled to a different one of the plurality of charge - detection cylinders and each being configured to generate a charge - detection signal corresponding to the magnitude of the charge of one or more of the generated ions passing through the corresponding one of the plurality of charge - detection cylinders. Brief Description of the Drawings

[0006] Figure 1 is a simplified diagram of a mass spectrometer configured to separate and measure ions according to their mass - to - charge ratio and measure the magnitude of the ion charge or charge state as they are separated.

[0007] Figure 2 is a Figure 1 form of an ion acceleration region embodying an embodiment of configuring the Figure 1 spectrometer as a time - of - flight (TOF) mass spectrometer of a simplified diagram of an ion processing region of the spectrometer.

[0008] Figure 3 is a flow chart showing an embodiment of a simplified process for operating Figure 1 and Figure 2 a TOF mass spectrometer to separate and measure ions as a function of their mass-to-charge ratio and to measure the charge value or charge state of the ions as they are separated.

[0009] Figure 4A is Figure 1 and Figure 2 a simplified diagram that is part of an illustrative example of a spectrometer including three charge detection cylinders axially arranged in a field-free drift region, and showing two example charged particles of different mass-to-charge ratios entering the field-free drift region at time T1 after being accelerated from the acceleration region of the spectrometer at time T0 < T1.

[0010] Figure 4B is similar to Figure 4A showing the corresponding positions of two example charged particles in the field-free drift region at time T2 > T1.

[0011] Figure 4C is similar to Figure 4A and 4B showing the corresponding positions of two example charged particles in the field-free drift region at time T3 > T2.

[0012] Figure 4D is similar to Figures 4A - 4C showing the corresponding positions of two example charged particles in the field-free drift region at time T4 > T3.

[0013] Figure 4E is similar to Figures 4A - 4D showing the corresponding positions of two example charged particles in the field-free drift region at time T5 > T4.

[0014] Figure 4F is similar to Figures 4A - 4E showing the corresponding positions of two example charged particles in the field-free drift region at time T6 > T5.

[0015] Figure 4G is similar to Figures 4A - 4F showing the corresponding positions of two example charged particles in the field-free drift region at time T7 > T6.

[0016] Figure 4H is similar to Figures 4A - 4G showing the corresponding positions of two example charged particles in the field-free drift region at time T8 > T7.

[0017] Figure 4I is a simplified diagram similar to Figures 4A - 4H and shows the respective positions of two example charged particles in the field-free drift region at time T9 > T8.

[0018] Figure 4J is a simplified diagram similar to Figures 4A - 4I and shows the respective positions of two example charged particles in the field-free drift region at time T10 > T9.

[0019] Figure 4K is a simplified diagram similar to Figures 4A - 4J and shows the position of charged particle P2 in the field-free drift region and shows charged particle P1 that reaches the detector at time T11 > T10.

[0020] Figure 4L is a simplified diagram similar to Figures 4A - 4J and shows the position of charged particle P2 in the field-free drift region at time T12 > T11 and also shows charged particle P2 that subsequently reaches the detector at time T13 > T12.

[0021] Figure 5 is a plot of charge quantity value vs. time and shows an example output of charge amplifier CA1 during the time window T1–T4 (relative to T0) depicted in Figures 4A - 4D when two example charged particles pass through the first charge detection cylinder disposed in the drift region adjacent to the exit of the acceleration region.

[0022] Figure 6 is a plot of charge quantity value vs. time and shows an example output of charge amplifier CA2 during the time window T3–T8 (relative to T0) depicted in Figures 4C - 4H when two example charged particles pass through the second charge detection cylinder disposed in the drift region between the first and third charge detection cylinders.

[0023] Figure 7 is a plot of charge quantity value vs. time and shows an example output of charge amplifier CA3 during the time window T7–T12 (relative to T0) depicted in Figures 4G - 4L when two example charged particles pass through the third charge detection cylinder disposed in the drift region adjacent to the second charge detection cylinder and adjacent to the ion detector.

[0024] Figure 8 is a flowchart of an embodiment showing a part of the process shown in Figure 3 for determining the charge values of ions axially separated in time through the drift region.

[0025] Figure 9 is embodied as a mass-to-charge ratio filter (filter) of an embodiment in which a spectrometer of Figure 1 is configured as a mass-to-charge ratio scanable mass spectrometer and optionally in the form of an ion trap Figure 1 A simplified diagram of the ion processing region of the spectrometer of

[0026] Figure 10 is a flowchart of an embodiment showing a simplification process for operating Figure 1 and 9 a mass-to-charge ratio scanable mass spectrometer of

[0027] Figure 11 is embodied as two mass-to-charge ratio filters separated in the ion dissociation region of a spectrometer of Figure 1 which is configured as another embodiment of a mass-to-charge ratio scanable mass spectrometer Figure 1 A simplified diagram of the ion processing region of the spectrometer of

[0028] Figure 12 is a flowchart of an embodiment showing a simplification process for operating Figure 1 and 11 a mass-to-charge ratio scanable mass spectrometer of

[0029] Figure 13 is in the form of an elongated electrically insulating sheet having a plurality of spaced conductive strips formed on one surface thereof Figure 1 A perspective view of an embodiment of the field-free drift region of

[0030] Figure 14 is shown having a sheet that joins opposite sides of a field-free drift region in the form of a field-free drift tube Figure 13 A perspective view of the sheet of

[0031] Figure 15 is a cross-sectional view of a field-free drift tube of Figure 14 as viewed along section line 15-15 of Figure 13 and 14 A cross-sectional view of the field-free drift tube of Detailed Description

[0032] To facilitate understanding of the principles of the present disclosure, reference will now be made to the several illustrative embodiments shown in the drawings and specific language will be used to describe them.

[0033] The present disclosure relates to apparatus and techniques for measuring the mass-to-charge ratio of charged particles and also for measuring the charge quantity value or charge state of charged particles as they move through a drift region and for determining the mass of the charged particles as a function of the measured mass-to-charge ratio and the measured charge quantity value or charge state. For the purposes of this document, the terms "charged particle" and "ion" may be used interchangeably, and both terms are intended to refer to any particle having a net positive or negative charge.

[0034] Now referring to Figure 1 , a schematic view of a mass spectrometer 10 is shown, which is configured to measure the mass-to-charge ratio of charged particles and also to measure the charge quantity value or charge state of 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 located at the 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, although in other embodiments the ion detector 18 can be any conventional detector that is configured and operable to generate a signal in response to detecting ions moving through the drift region 16 thereat. Examples of other conventional instruments and devices that can be implemented as ion detectors can include, but are not limited to, ion-to-photon detectors, Faraday cup detectors, electron multiplier detectors, any solid-state detector, any detector having a high-voltage collision dynode, or the like.

[0035] In Figure 1 the illustrated embodiment, the drift region 16 is a linear drift region defined within an elongate drift tube 16A. The drift region 16 has a length DRL between the outlet A2 of the ion processing region 14 and the ion detection surface 18A of the ion detector 18, and a longitudinal axis 34 extends centrally through the drift region 16 and centrally through each of the inlets and outlets A1, A2 of the ion processing region 14, respectively. It will be understood that although the drift region 16 is shown in Figure 1 in the form of a linear drift region, in alternative embodiments the drift region 16 can be wholly or partially non-linear. As a non-limiting example, the drift region 16 can be provided in the form of a circular drift region including a conventional ion inlet (i.e., entry port) and ion outlet (i.e., exit port) structure. Those skilled in the art will envision other examples of at least partially non-linear drift regions and will understand that any such alternative configurations are intended to fall within the scope of the present disclosure.

[0036] As will be described in more detail below, the ion source 12 illustratively includes any conventional device or apparatus 20 for generating ions from a sample 22, and may further include one or more devices and / or instruments 24 for separating, collecting, and / or filtering ions and / or for fragmenting, e.g., fragmenting ions, based on one or more molecular properties 1 -24 F . As an illustrative example that should not be construed as limiting in any way, 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

[0037] A voltage source 26 is electrically connected to the ion source or source region 12 via a number J of signal paths and to the ion processing region 14 via a number K of signal paths, where each of J and K may 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 magnitudes. 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 or controllable to generate and supply one or more time-varying signals of selectable shape, duty cycle, peak magnitude, and / or frequency. As a specific example of the latter embodiment that should not be construed as limiting in any way, the voltage source 26 may be configured or controllable 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

[0038] The voltage source 26 is illustratively shown as being electrically connected to a conventional processor 28 via a number M of signal paths, where M can 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 can include a single processing circuit or multiple processing circuits. The processor 28 illustratively includes or is coupled to a memory 30 in which instructions are stored that, 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 processor 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 ratios in a conventional manner. In some embodiments, the processor 28 can be implemented in the form of one or more conventional microprocessors or controllers, and in such embodiments, the memory 30 can be implemented in the form of one or more conventional memory units having instructions stored therein in the form of one or more microprocessor-executable instructions or instruction sets. In other embodiments, the processor 28 can 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 can be implemented in the form of programmable logic blocks included within and / or external to the FPGA in which instructions can be programmed and stored. In yet another embodiment, the processor 28 and / or the memory 30 can 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 can be implemented and will understand that any such other form of implementation is contemplated by the present disclosure and is intended to fall within the scope of the present disclosure. In some alternative embodiments, the voltage source 26 itself can be programmable to selectively generate one or more constant and / or time-varying output voltages.

[0039] The processor 28 is further illustratively coupled to one or more peripheral devices 32 (PD) via a number P of signal paths, where P can be any positive integer. The one or more peripheral devices 32 can include one or more devices for providing (one or more) signal inputs to the processor 28 and / or one or more devices to which the processor 28 provides (one or more) signal outputs. In some embodiments, the peripheral devices 32 include at least one of a conventional display monitor, a printer, and / or other output devices, and in such embodiments, the memory 30 has instructions stored therein that, when executed by the processor 28, cause the processor 28 to control one or more such output peripheral devices 32 to display and / or record an analysis of the stored digitized charge detection signals.

[0040] In the illustrated embodiment, the ion source or source region 12 illustratively includes at least one ion generator 20 coupled to a voltage source 26. The processor 28 is illustratively programmed, for example via instructions stored in the memory 30, 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. In some embodiments, the ion generator 20 and the sample 22 are located within the ion source region 12, in other embodiments both the ion generator 20 and the sample 22 are located external to the ion source region 12, and in yet other embodiments, the sample 22 is located external to the ion source region 12 and the ion generator 20 is located within the ion source region 12 but is fluidly or otherwise operatively coupled to the sample 22, as Figure 2 represented by the dashed lines shown in. 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 fine mist of charged droplets. In alternative embodiments, the ion generator 20 may be or include a conventional matrix-assisted laser desorption ionization (MALDI) source. It will be understood that ESI and MALDI represent only 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.

[0041] In some embodiments, the ion source or source region 12 may further include one or more ion processing stages 24 1 -24 F , where F can 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 one or more ion processing stages 24 1 -24 F . Such ion processing stages 24 1 -24 FExamples can include, but are not limited to, any sequence and / or combination of devices and / or instruments for separating, collecting, and / or filtering charged particles according to one or more molecular properties, and / or one or more devices and / or instruments for decomposing, such as fragmenting, charged particles. Examples of devices and / or instruments for separating charged particles according to one or more molecular properties include, but are not limited to, one or more mass spectrometers or mass analyzers, one or more ion mobility spectrometers, one or more gas or liquid chromatographs, and the like. In embodiments including one or more of ion source 12, examples of mass spectrometers or mass analyzers include, but are not limited to, 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. In embodiments including one or more of ion source 12, examples of ion mobility spectrometers include, but are not limited to, single-tube linear ion mobility spectrometers, multi-tube linear ion mobility spectrometers, circular-tube ion mobility spectrometers, 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, and 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 decomposing charged particles include, but are not limited to, one or more devices or instruments for decomposing charged particles by collision-induced dissociation (CID), surface-induced dissociation (SID), electron capture dissociation (ECD), and / or photo-induced dissociation (PID), or the like. It will be understood that (one or more) ion processing stage 24 1 -24 F can include any one or any combination in any sequence of any such conventional ion separation instruments and / or ion processing instruments, and some embodiments can include multiple adjacent or spaced-apart instruments of any such conventional ion separation instruments and / or ion processing instruments.

[0042] The charge detector array 40 is illustratively disposed within or integrated with the drift region 16. In as Figure 1In the embodiment shown, the charge detector array 40 illustratively includes a plurality, i.e., N, of spaced-apart cascaded charge detection cylinders 40 1 -40 N , where N can be any positive integer greater than 2. In one exemplary embodiment, which should not be considered limiting in any way, N can be approximately 100, although in other embodiments N can be less than 100 or greater than 100. In any case, each of the charge detection cylinders 40 1 -40 N defines a hole therethrough to allow ions to pass through the respective cylinder, and in the embodiment shown, the charge detection cylinders 40 1 -40 N are arranged end-to-end such that the longitudinal axis 34 of the drift region 16 passes through the center of each cylinder. In the embodiment shown, each charge detection cylinder 40 1 -40 N defines a length CDL between its ion inlet and ion outlet ends, although in alternative embodiments, one or more of the charge detection cylinders 40 1 -40 N can have a length greater than or less than the length CDL. The minimum CDL is illustratively physically achievable and will produce an electrically detectable signal response to one or more ions passing therethrough. Although there is no theoretical upper limit to the CDL, practical considerations such as available space and instrument operating conditions will typically limit the maximum useful CDL in any particular application.

[0043] In the embodiment shown, a plurality of ground rings 42 1 -42 N-1 are each located within the space defined between each adjacent pair of the charge detection cylinders 40 1 -40 N , and another ground ring 42 N is positioned adjacent to the ion outlet of the last charge detection cylinder 40 N . Each ground ring 42 1 -42 N illustratively defines a ring aperture RA therethrough and the longitudinal axis 34 passes through the center of the ring aperture RA, where RA is illustratively less than or equal to the inner diameter of the charge detection cylinders 40 1 -40 N . In the embodiment shown, the charge detection cylinders 40 1 -40 N are axially spaced apart from each other by a space length SL. In the embodiment shown, the ground rings 42 1 -42 N-1Each in is positioned to radially bisect the charge detection cylinder 40 2 -40 N in the space SL between the ion inlet and the ion outlet of the corresponding adjacent charge detection cylinder in such a way that each ground ring 42 1 -42 N is spaced from the charge detection cylinder 40 1 -40 N by a distance of SL / 2 from the corresponding adjacent cylinder, and the ground ring 42 N is positioned to bisect the space SL between the ion outlet of the charge detection cylinder 40 N and the detection surface 18A of the ion detector 18 such that the distance from the ground ring 42 N to each is SL / 2. In some embodiments, one or more of the ground rings 42 1 -42 N may be omitted.

[0044] In one exemplary embodiment, the drift tube 16A is provided in the form of a conductive cylinder which is illustratively coupled to ground potential (as shown in Figure 1 ) or to another reference potential, and in which a plurality of charge detection cylinders 40 1 –40 N are suitably mounted. In such embodiments which include 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 may be integrally formed with the conductive cylinder such that the conductive cylinder and one or more ground rings 42 1 -42 N are a single construction. In another exemplary embodiment, the drift tube 16A may be formed by a series of interconnected alternating conductive or electrically insulating spacers and the corresponding ground rings among a plurality of ground rings 42 1 -42 N and in which a plurality of charge detection cylinders 40 1 -40 N may be suitably mounted. In yet another exemplary embodiment, the drift tube 16A may be provided in the form of a rollable sheet of flexible or semi-flexible electrically insulating material, such as a flexible circuit board, to which or on which a plurality of spaced parallel conductive strips are attached or formed in a conventional manner, such as using conventional metal pattern deposition techniques. A non-limiting example of this embodiment is shown in Figures 13 - 15 and will be described in detail below. Those skilled in the art will recognize that the drift tube 16A and / or the charge detection cylinders 40 1 -40 Nand / or one or more ground rings 42 1 -42 N (in embodiments that include them) and other forms, and it will be understood that any such other forms are intended to fall within the scope of the present disclosure.

[0045] Each charge detection cylinder 40 1 -40 N is electrically connected to the signal input of a corresponding one of the N charge sensitive amplifiers CA1 - CAN, and the signal output of each of the charge amplifiers CA1 - CAN is electrically connected to the processor 28. As 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 towards and into the sensing surface 18A of the ion detector 18. As the charged particles move axially through the drift tube 16A, each such charged particle sequentially passes through a plurality of charge detection cylinders 40 1 -40 N . As each such charged particle passes through each successive charge detection cylinder 40 1 -40 N , a charge is induced on it by the charged particle, where the induced charge has a magnitude proportional to the magnitude of the charge of that particle. Each of the charge amplifiers CA1 - CAN is illustratively conventional and responsive to the charge induced on the corresponding one of the charge detectors 40 1 -40 N to generate a corresponding and respective charge detection signal at its output. The charge detection signals generated by the charge amplifiers CA1 - CAN are supplied to the processor 28. The magnitude of the charge detection signals generated by the charge amplifiers CA1 - CAN is at any point in time proportional to: (i) the magnitude of the charge of a single charged particle in the case where a single charged particle passes through the corresponding one of the charge detection cylinders 40 1 -40 N , or (ii) the combined magnitude of the charges of a plurality of charged particles in the case where a plurality of charged particles pass through the corresponding one of the charge detection cylinders 40 1 -40 N . The processor 28 is then illustratively operable to receive and digitize the charge detection signals generated by each of the charge amplifiers CA1 - CAN and store the digitized charge detection signals in the memory 30 or in one or more other storage units coupled to or otherwise accessible by the processor 28.

[0046] The drift region 16 of the mass spectrometer 10 is a field-free drift region (i.e., no electric field), and charged particle ions that enter the drift tube 16A at an initial rate via the ion exit A2 of the ion processing region 14 drift toward and enter the detection surface 18A of the ion detector 18 at a substantially constant rate. At this point, the ion source 12 and / or the ion processing region 14 generally provide the motive force for the ions to enter the drift tube 16A at the initial rate. The motive force can be illustratively provided in any one or combination of several different forms, examples of which can 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 or the like. In any case, as the charged particles drift through the field-free drift region 16, they will separate in time according to the mass-to-charge ratio, where the charged particles with a lower mass-to-charge ratio reach the ion detector 18 faster than the charged particles with a higher mass-to-charge ratio.

[0047] As described above, the memory 30 illustratively includes instructions executable by the processor 28 to (a) cause the processor 28 to control the voltage source 26 in a conventional manner to (i) cause the ion generator 20 to generate charged particles, and (ii) cause a single charged particle among the charged particles, a specified group or set of charged particles, or all the generated charged particles to pass through, and they enter the drift region 16 through which the charged particles move from the ion processing region 14, each having a constant energy axially toward and enter the ion detector 18, and (b) process the detection signal 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 Figure 1 the embodiment of the mass spectrometer 10 shown, the memory 30 further illustratively includes instructions executable by the processor 28 to process the detection signal generated by the ion detector 18 and the detection signals generated by each or at least some of the charge amplifiers CA1 - CAN to determine the charge quantity value and / or charge state of each charged particle that has axially moved through the drift region 16, and then determine the particle mass based on the measured particle mass-to-charge ratio and the measured particle charge quantity value or charge state. In some embodiments, such as when the ion source 12 and / or the ion processing region 14 are configured to simultaneously generate multiple ions from the ion exit A2 of the ion processing region 14 and supply them into the drift region 16, for example, it may be desirable to configure the drift tube 16A to include between the ion exit A2 of the ion processing region 14 and the ion inlet end of the first charge detection cylinder 16 1 or between the ion exit A2 and the first charge detection cylinder 16 that can be placed 1the length PRL of the pre-array space between the ion inlet of the front ground ring at the ion inlet end), as Figure 1 shown in the example in. This will allow charged particles moving axially through the drift region 16 to experience some amount of axial separation in time (as a function of the mass-to-charge ratio in the field-free region 16) before charge measurement with the charge detector array 16, and thereby the quality and usefulness of the charge detection signals generated by the first one or more of the charge amplifiers CA1-CAN can be increased. The length PRL of the pre-array space 16B can be illustratively selected based on the application, and in some embodiments, the pre-array space 16B can be omitted entirely.

[0048] Now referring to Figure 2 , an embodiment of the ion processing region 14 is shown as being implemented in the form of an ion acceleration region 14'. In Figure 2 the embodiment shown in, the ion acceleration region 14' includes a conductive gate 36 defining an ion inlet A1 and another conductive gate 38 defining an ion outlet A2. The gates 36, 38 are axially spaced apart from each other, the gate 36 is positioned adjacent to the ion source region 12 and the gate 38 is positioned adjacent to the inlet end of the drift tube 16A. In one embodiment, each of the gates 36, 38 is illustratively provided in the form of a conductive plate or ring that defines the respective inlet / outlet A1, A2 therethrough. In some such embodiments, the ion acceleration region 14' can include one or more conventional radial focusing structures or devices, e.g., configured and / or controlled in a conventional manner by the processor 28 to direct charged particles through the ion outlet A2. In some alternative embodiments, one or both of the gates 36, 38 can 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 another voltage output VS2 of the voltage source 26 is electrically connected to the conductive gate 38.

[0049] The operation of the ion acceleration region 14' is conventional in that, in the case where one or more generated ions have entered the ion acceleration region 14' via the ion inlet A1, the processor 28 is operable to control the voltage source 26 to create an electric field E between the gates 36, 38, which electric field E is oriented to accelerate the ions through the ion outlet A2 and into the inlet end of the drift tube 16A. In the case of positively charged particles, the voltages VS1 and VS2 are selected to create the electric field E between the gates 36, 38 in the direction depicted in Figure 2 and, in the case of negatively charged particles, the voltages VS1 and VS2 will be selected to be in the opposite direction to that depicted in Figure 2An electric field is created between gates 36, 38 in directions opposite to the depicted direction. In either case, the generated electric field E operates to accelerate one or more generated ions contained in the ion acceleration region 14' into the drift region 16, through which each of them drifts axially towards the ion detector 18 with a constant energy. In the case where the ion processing region 14, as shown in the example of Figure 2 is implemented as the ion acceleration region 14', the mass spectrometer 10 is structurally a time-of-flight (TOF) mass spectrometer having a charge detector array 40 axially arranged in, as part of, or defining a field-free drift tube 16A.

[0050] Now referring to Figure 3 , a simplified flowchart depicting an example process 100 is shown, the example process 100 for operating Figure 1 and Figure 2 's TOF mass spectrometer (i.e., Figure 1 's mass spectrometer 10, having an ion acceleration region 14' implemented as the ion processing region 14 of Figure 2 ) to measure ion mass-to-charge ratio, ion charge (magnitude and / or charge state), and ion mass. The process 100 is illustratively stored in the memory 30 in the form of instructions executable by the processor 28 to perform measurements of particle mass-to-charge ratio, particle charge, and particle mass. The process 100 illustratively begins with one or more charged particles generated by the ion generator 20 residing within the ion acceleration region 14', i.e., at a point between the gates 36, 38. Prior to the process 100, the processor 28 will control the voltage source 26 in a conventional manner to cause the ion generator 20 to generate a plurality of ions. In embodiments where the ion source 12 does not include any ion processing stages 24 1 -24 F (see Figure 1 ), most, if not all, of the plurality of generated ions will pass through the inlet A1 and reside in the ion acceleration region 14', in some cases assisted by controlling one or both of the output voltages VS1, VS2 relative to the voltage applied to the ion generator 20, if any, through the control of the voltage source 26.

[0051] In alternative embodiments where the ion source 12 includes one or more ion processing stages 24 1 -24 F (see Figure 1 ), the processor 28 is operable to control the voltage source 26 to control in a conventional manner or otherwise operate one or more ion processing stages 24 1 -24 F, to supply a subset of the plurality of generated ions to the ion acceleration region 14' and / or to supply a modified set of the plurality of generated ions to the ion acceleration region 14'. In one exemplary embodiment, which should not be considered limiting in any way, one or more ion processing stages 24 1 -24 F may be implemented in the form of a conventional mass-to-charge ratio filter, such as a quadrupole filter, and the processor 28 is operable in this exemplary embodiment to control the voltage source 26 to deliver a subset of the plurality of generated ions to the ion acceleration region 14', the subset of the plurality of generated ions having a mass-to-charge ratio that is higher or lower than a threshold mass-to-charge ratio or having a mass-to-charge ratio within a specified range of mass-to-charge ratios. In another exemplary embodiment, which should also not be considered limiting in any way, one or more ion processing stages 24 1 -24 F Alternatively or additionally include a dissociation stage that may be operated or controlled by the processor 28 to dissociate, e.g., fragment, the plurality of generated ions or a subset thereof, in which case a modified set of the plurality of charged particles is delivered to the ion acceleration region 14'. In yet another exemplary embodiment, which should not be considered limiting in any way, one or more ion processing stages 24 1 -24 F may include an ion mobility spectrometer controllable by the processor 28 to deliver a subset of the plurality of generated ions having an ion mobility value that is higher or lower than a threshold ion mobility value or having an ion mobility value within a specified range of ion mobility values to the ion acceleration region 14'. Those skilled in the art will recognize other instruments or stages that may be implemented as one or more ion processing stages 24 1 -24 F and combinations of instruments or stages, and will understand that any such other instruments or stages and / or combinations of instruments or stages are intended to fall within the scope of the present disclosure. Generally, in embodiments of the ion source 12 that include one or more ion processing stages 24 1 -24 F the one or more ion processing stages 24 1 -24 F may be implemented in the form of one or more instruments or stages and / or various combinations thereof, the one or more instruments or stages and / or various combinations thereof being configured to separate, collect, and / or filter ions and / or dissociate, e.g., fragment, ions according to one or more molecular properties.

[0052] Referring again to as Figure 3, Process 100 illustratively begins at step 102, where processor 28 is illustratively operable to store at least some dimensional information (DI) of drift region 16 in memory 30. In some embodiments, step 102 is performed partly by processor 28 and partly manually, e.g., by typing the dimensional information into memory 30 using a peripheral device 32 coupled to processor 28, and in other embodiments, processor 28 can perform step 102 entirely, e.g., by reading from a file on an external memory device that is readable from memory 30 or a peripheral device 32 coupled to processor 28. In one embodiment, DI illustratively includes at least the total length DRL of drift region 16, i.e., between the ion exit A2 of ion acceleration region 14' and the ion detection surface 18A of ion detector 18, the length CDL of a plurality of charge detection cylinders 40 1 -40 N of, the space length SL between adjacent charge detection cylinders 40 1 -40 N , the total number N of charge detection cylinders 40 1 -40 N , the pre-array length PRL, if any, and 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, if different from SL. The dimensional information (DI) is illustratively stored for the purpose of matching each charged particle axially traversing drift region 16 with a corresponding time during which the charged particle axially travels through each charge detection cylinder 40 1 -40 N or at least through a subset of charge detection cylinders 40 1 -40 N .

[0053] After step 102, process 100 proceeds to step 104, where processor 28 is operable to control voltage source 26 at a reference time RT to cause voltage source 26 to generate or switch voltages VS1 and VS2 to values that establish an ion acceleration electric field in the oriented ion acceleration region 14' to accelerate charged particles resident in ion acceleration region 14' through its ion exit A2 and into drift region 16 such that the charged particles axially drift through drift region 16, each with a corresponding constant rate. For purposes of describing process 100, it will be assumed that at RT, a number M of charged particles are accelerated from ion acceleration region 14' into drift region 16, where M can be any positive integer.

[0054] After step 104, process 100 proceeds to step 106, where processor 28 is operable to record, i.e., store, charge detection signals generated by each or at least a subset of charge amplifiers CA1 - CAN as M charged particles accelerating axially into drift region 16 towards ion detector 18 drift relative to RT. In one embodiment, processor 28 is operable at 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 cease activity as the charge detection signals stop, i.e., all charged particles accelerating into drift region 16 at step 104 have passed through respective charge detection cylinders 40 1 –40 N After that, sampling of each such charge detection signal is discontinued continuously. In other embodiments, processor 28 may be operable to stop sampling after the last charged particle among the charged particles is detected at ion detector 18.

[0055] In any case, the process proceeds from step 106 to step 108, where processor 28 is operable to record, i.e., store in memory 30, detection times DT relative to reference time RT as each of the M charged particles reaches detection surface 18A of ion detector 18 and is detected by detection surface 18A of ion detector 18 1 -DT M Thereafter at step 110, processor 28 is operable to calculate the time of flight (TOF) of each of the M charged particles as a function of the respective reference time RT and the stored detection time DT 1 –DT M For example, , and store it in memory 30. Thus, after the Mth charged particle is detected at ion detector 18, memory 30 has stored M time of flight values TOF 1-M .

[0056] After step 110, process 100 proceeds to step 112, where processor 28 is operable to calculate charge quantity values or charge states (CH) of the M charged particles based on the stored dimension information DI, the respective stored time of flight TOF 1-M , and the stored charge detection signals generated by all or at least one subset of charge amplifiers CA1 – CAN or as a function thereof, for example, , and store them in memory 30.

[0057] After step 112, process 100 proceeds to step 114, where processor 28 is operable as the respective time of flight TOF 1-M, the known function of the potential U related to the length DRL of the drift region 16 and the magnitude of the voltage VS1, VS2 (one or more) that accelerates charged particles from the ion acceleration region 14' into the drift region 16 calculates the mass-to-charge ratio (m / z) of M charged particles in a conventional manner. For example, , and stores it in the memory 30.

[0058] After step 114, the process 100 proceeds to step 116, where the processor 28 is operable to calculate the mass value (m) of M charged particles in a conventional manner. For example, as the product of m / z and CH. For example, , and stores it in the memory 30.

[0059] It will be understood that the process 100 can loop back to step 104, assuming that at any time after the last charged particle M has reached the ion detector 18, a new set or subset of charged particles resides in the ion acceleration region 14'. In this way, the process 100 can loop back to step 104 after any of the steps 108 - 116, as Figure 3 depicted by the dashed line in, and the remainder of steps 110 - 116 after the loop can be performed separately from the controlled operation of the mass spectrometer 10.

[0060] The processor 28 can illustratively use various different processes or algorithms to perform step 112 of the process 100. An example of one such process 200 for performing step 112 of the process 100 is shown in Figure 8 , and will be described in detail below. However, before describing this process, reference will be made to Figures 4A - 7 to describe a simplified example of two charged particles P1 and P2 of different mass-to-charge ratios axially moving through a simplified drift region 16 including three axially arranged charge detection cylinders 40 1 -40 3 , and this example will be used to demonstrate Figure 8 the operation of the process 200 shown in.

[0061] Now referring to Figures 4A - 4L , a simplified example of a part of the TOF mass spectrometer 10 is shown, which includes three charge detection cylinders 40 Figure 1 and 2 axially arranged between the ion exit A2 of the gate 38 in the ion acceleration region 14' and the ion detection surface 18A of the ion detector 18 in the drift region 16. 1 -40 3 . For this simplified mass spectrometer, Figures 4A - 4L depicts, as a function of time, the acceleration into the drift region 16 and the successive drift through the three charge detection cylinders 40 1 -403 Each of the two charged particles P1, P2 therein, where P1 has a lower mass-to-charge ratio than P2. Figure 5 Depicts an example charge detection signal generated by the first charge amplifier CA1 when the charged particle passes through the first charge amplifier CA1, and Figure 6 and 7 The same thing is depicted for the second and third charge amplifiers CA2 and CA3 respectively.

[0062] As Figure 4A shown, the charged particles P1 and P2 are accelerated from the ion acceleration region 14' into the drift region 16 at the reference time T = T0. In this example, both charged particles P1 and P2 pass through the ion exit A2 of the ion acceleration region 14' at T = T0 and are understood to start axially drifting through the drift region at T = T0. As described above regarding step 104 of process 100, the processor 28 is operable to record the reference time RT as RT = T0.

[0063] At a subsequent time T1 > T0, both the first and second charged particles P1, P2 enter the first charge detection cylinder 40 1 , also as Figure 1 depicted. At time T2 > T1, the charged particle P1 leaves the charge detection cylinder 40 1 , as Figure 4B shown, and at time T4 > T2, the charged particle P2 leaves the charge detection cylinder 40 1 , as Figure 4D shown. Between T2 and T1 when both charged particles P1 and P2 move through the charge detection cylinder 40 1 , the charged particles P1 and P2 together induce a charge of magnitude C1 on the charge detection cylinder 40 1 , as Figure 5 depicted. Thereafter between T2 and T4, the particle P2 alone continues to move through the charge detection cylinder 40 1 and induces a charge of magnitude C2 on the charge detection cylinder 40 1 , also as Figure 5 depicted.

[0064] As Figures 4C - 4H shown, the charged particles P1 and P2 enter the second charge detection cylinder 40 at times T3 and T5 respectively 2 , where T5 > T4 > T3. At time T6 > T5, the charged particle P1 leaves the charge detection cylinder 40 2 , and at time T8 > T6, the charged particle P2 leaves the charge detection cylinder 40 2 . While the particle P1 moves through the charge detection cylinder 40 alone between T3 and T52 In the case where, charged particle P1 induces a charge with a magnitude of C3 on the charge detection cylinder 40 2 as depicted in Figure 6 . When both charged particles P1 and P2 move through between T5 and T6 of the charge detection cylinder 40 2 , charged particles P1 and P2 together induce a charge with a magnitude of C4 > C3 on the charge detection cylinder 40 2 , and when only charged particle P2 passes through between T8 and T6 of the charge detection cylinder 40 2 , charged particle P2 induces a charge of C5 < C3 on the charge detection cylinder 40 2 as also depicted in Figure 6 .

[0065] As Figures 4G - 4L shown, charged particles P1 and P2 enter the third charge detection cylinder 40 at times T7 and T9 respectively 3 , where T9 > T8 > T7. At time T10 > T9, charged particle P1 leaves the charge detection cylinder 40 3 , and at time T11 > T10, charged particle P1 contacts the detection surface 18A of the ion detector 18. As described above regarding step 108 of process 100, the ion detector 18 generates a detection signal when detecting charged particle P1 at T = T11, and the processor 28 is operable to record the detection time DT P1 of charged particle P1 as DT P1 = T11.

[0066] At time T12 > T11, charged particle P2 leaves the charge detection cylinder 40 3 , and at time T13 > T12, charged particle P2 contacts the detection surface 18A of the ion detector 18. As described above regarding step 108 of process 100, the ion detector 18 generates a detection signal when detecting charged particle P2 at T = T13, and the processor 28 is operable to record the detection time DT P2 of charged particle P2 as DT P2 = T13.

[0067] Between T7 and T9, charged particle P1 moving alone through the third charge detection cylinder 40 3 induces a charge with a magnitude of C6 on the charge detection cylinder 40 3 as depicted in Figure 7 . When both charged particles P1 and P2 move through between T9 and T10 of the charge detection cylinder 40 3 , charged particles P1 and P2 together 3A charge with a magnitude C7 > C6 is induced thereon, and during this period only the charged particle P2 moves through the charge detection cylinder 40 3 Between T10 and T12 of, the charged particle P2 is on the charge detection cylinder 40 3 A charge of C8 < C6 is induced.

[0068] Now refer to Figure 8 , which shows a simplified flowchart of an example process 200 for performing Figure 3 The step 112 of the process 100 shown and described above. The process 200 is illustratively stored in the memory 30 in the form of instructions executable by the processor 28 to perform measurements on the charge magnitude or charge state of charged particles moving through Figure 1 and 2 The drift region 16 of the time-of-flight mass spectrometer 10 shown in. The 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 is illustratively operable to process the time-of-flight value TOF of the i-th charged particle (out of a total of M charged particles determined to have passed through the drift region 16 according to the process 100 shown in Figure 3 ) determined at step 110 of the process 100 i Together with the dimension information DI to determine and store in the memory 30 the time or time window TW during which the i-th charged particle passed through each of the N charge detection cylinders 40 1 -40 N As part of the process 100; for example, TW i,1-N ; for example, TW i,1-N = F(DI, TOF i ).

[0069] In one embodiment, the processor 28 is operable to perform step 204 by first determining the (constant) rate v of the i-th charged particle passing through the drift region 16 according to the relationship v i = DRL / TOF i . With the v of the i-th charged particle now known, the processor 28 is operable to determine the N time windows TW based on the distance between the ion inlet and / or outlet ends of the charge detection cylinders 40 i -40 i relative to a known position within the drift region, the rate v of the i-th charged particle 1 -40 N And one or both of the reference time RT and detection time DT of the i-th charged particle i To determine the N time windows TW i In i,1-NAs an example, the period corresponding to the i-th charged particle passing through the first charge detection cylinder 40 1 The time window TW i,1 The processor 28 can be used according to the relationship TW i,1 =PRL / v i to (PRL+CDL) / v i Determined relative to the reference time RT. Corresponding to the period during which the i-th charged particle passes through the second charge detection cylinder 40 2 The time window TW i,2 Similarly, the processor 28 can be configured according to the relationship TW i,2 =(PRL+CDL+SL) / v i to (PRL+2CDL+SL) / v i is determined relative to a reference time RT, and so on. As another example, the time window TW i,1 The processor 28 can be used according to the relationship TW i,1 =[DT i –N(CDL+SL) / v i ] to {DT i –[(N-1)(CDL)+(N)(SL)] / v i}Use the i-th charged particle DT i The detection time of DT is determined relative to the reference time RT, and so on. In other embodiments, the processor 28 may be operable to calculate the detection time DT relative to the reference time RT. i Or relative to RT and DT i The time window TW i,1-N In any case, for the period during which the i-th charged particle passes through the N charge detection cylinders 40 determined at step 204, 1 -40 N Each of the relative RT, DT i or a time window TW corresponding to a time window of a certain reference time between them i,1-N Each time window TW of all M charged particles has been determined, process 200 proceeds to steps 206 and 208 to increment counter i by 1 and re-execute step 204. 1-M,1-N After completing steps 204-208, the memory 30 has stored therein the time window TW 1-M,1-N An M×N matrix, wherein each of the M rows contains time window data for a corresponding one of the M charged particles and each of the N columns contains time window data for N charge detection cylinders 40 1 -40 N The time window data of the corresponding one in .

[0070] After the (YES) branch of step 206, the processor 28 is illustratively operable at step 210 to reset the counter i to 1 or some other constant. Thereafter at step 212, the processor 28 is illustratively operable to process the charge detection measurements generated by the ith charge amplifier CAi during each time window in the ith column of the time window matrix to match the different charge quantities generated by the ith charge amplifier CAi with the contributions made thereto by the corresponding charged particles among the M charged particles during the corresponding time windows. For example, during the time window TW i in which the first of the M charged particles passes through the ith charge detection cylinder 40 1,i the first charged particle induces a charge on the ith charge detection cylinder 40 i which is captured in the charge detection signal generated by the ith charge amplifier CAi during the time window TW 1,i Similarly, during the time window TW i in which the second of the M charged particles passes through the ith charge detection cylinder 40 2,i the second charged particle induces a charge on the ith charge detection cylinder 40 i which is captured in the charge detection signal generated by the ith charge amplifier CAi during this time window TW 2,i Furthermore, during any overlap between the time windows TW i in which the first and second of the M charged particles both pass through the ith charge detection cylinder 40 1,i and TW 2,i the first and second charged particles together induce a combined charge on the ith charge amplifier CAi during this time window overlap, and so on. Processing the charge detection signals generated by the ith charge amplifier CAi during the time windows in the ith column of the time window matrix thus results in a set of equations that map each of the M charged particles and / or their various combinations to the corresponding charge quantity values. After step 212, process 200 advances to steps 214 and 216 to increment the counter i by 1 and re-execute step 212 until the measurements of the charge detection signals generated by each of the N charge amplifiers CA1 - CAN have been mapped to the corresponding charged particles and / or various combinations among the M charged particles. After completing steps 212 - 216, the memory 30 has stored therein a system of equations relating each of the M charged particles and / or their various combinations to the corresponding charge quantity values. After step 216, the processor 28 advances to step 218 to solve the system of equations or at least a subset thereof to determine the charge quantity values CH of each of the M charged particles1-M or determine the charge quantity values of at least a subset of the M charged particles. In some embodiments, the processor 28 is further operable at step 218 to convert the determined charge quantity values CH 1-M of one or more of them into charge state values CS 1-M , for example, according to the relationship CS i = CH i / e, where e is the elementary charge (constant).

[0071] Referring again to Figures 4A - 7 the simplified example shown in

[0072] Figures 4A - 4L the steps of processes 100 and 200 are now applied to this example to further illustrate the operation of each process via its application to the simplified set of charged particles and the simplified mass spectrometer configuration. In this simplified example, M = 2 (two charged particles P1 and P2) and N = 3 (three charge detection cylinders 40 1 -40 3 and corresponding charge amplifiers CA1 - CA3). In the following description, the time window will be illustratively determined relative to a reference time RT, as described above, although it will be understood that the time window can be determined relative to one or more other time events associated with the operation of the mass spectrometer 10, some non - limiting examples of which were described above.

[0072] At 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 at step 106, the processor 28 is operable to store in the memory a sample of the charge detection signals generated by each of the three charge amplifiers CA1 - CA3 when the charged particles P1 and P2 drift towards and enter the ion detector 18 as shown in Figures 4A - 4L . At step 108, the processor 28 is operable to store in the memory 30 the detection time DT P1 of the ion detector 18 for the charged particle P1 as DT P1 = T11 (see Figure 4K ), and store in the memory 30 the detection time DT P2 of the ion detector 18 for the charged particle P2 as DT P2 = T13 (see Figure 4L ). Thereafter at step 110, the processor 28 is operable to calculate the time - of - flight TOF P1 of the first charged particle P1 as TOF P1 =(DT P1 - RT), and calculate the time - of - flight TOF P2 of the second charged particle P2 as TOF P2 =(DT P2-RT). Thereafter, at step 112, process 200 is executed by processor 28.

[0073] In the case where i = 1 at step 204 of process 200, processor 28 is operable to determine, according to the relationship v 1 = DRL / TOF P1 the (constant) rate v of the first charged particle Pl passing through the drift region 16. 1 Thereafter, processor 28 is operable at step 204 to determine TW 1,1 to be: PRL / v 1 = T1 to (PRL + CDL) / v 1 = T2, or T1 - T2, or using the shorthand notation T1 - T2, as Figure 4A and 4B depicted. Processor 28 is thereafter operable at step 204 to determine TW 1,2 to be: (PRL + CDL + SL) / v 1 = T3 to (PRL + 2CDL + SL) / v 1 = T6, or T3 - T6, as Figures 4C - 4F depicted. Finally, processor 28 is operable at step 204 to determine TW 1,3 to be: (PRL + 2CDL + 2SL) / v 1 = T7 to (PRL + 3CDL + 2SL) / v 1 = T10, or T7 - T10, as Figures 4G - 4J depicted. Thereafter, process 200 loops through step 206, increments i to i = 2 at step 208 and re - executes step 204 for i = 2. In the case where processor 28 determines, according to the relationship v 2 = DRL / TOF P2 the (constant) rate v of the second charged particle P2 passing through the drift region 16, processor 28 continues to determine the following time windows TW 2 = T1 - T4, TW 2,1 = T5 - T8 and TW 2,2 = T9 - T12, as 2,3 depicted in Figures 4A - 4D 4E - 4H and 4I - 4L respectively. In the case where i = 2 = M is satisfied at step 206, process 200 proceeds to steps 210 - 216, with the following 2x3 (i.e., MxN) time window matrix TW:

[0074]

[0075] When i = 1 at step 212 of process 200, the processor 28 is operable to process CA1 for the time windows of the first column of TW to match or map the magnitude(s) of CA1 to the contribution(s) made by P1 and P2 individually and / or collectively. Refer to Figure 5 , from the two first column 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 together inducing a combined charge on the charge detection cylinder 40 1 which produces CH P1 +CH P2 = C1, where CH P1 is the charge magnitude of the charged particle P1 and CH P2 is the charge magnitude of the 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 P2 alone inducing its charge on the charge detection cylinder 40 1 which produces CH P2 = C2.

[0076] Process 200 loops through steps 214 and 216 to increment the counter i to i = 2, and the processor 28 is then operable at step 212 to process CA2 for the time windows of the second column of the TW matrix to match or map the magnitude(s) of CA2 to the contribution(s) made by P1 and P2 individually and / or collectively. Refer to Figure 6 , from the two second column 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 P1 alone inducing its charge on the charge detection cylinder 40 2 which produces CH P1 = C3. From TW 1,2 and TW 2,2 it is further clear that the magnitude C4 of the charge detection signal CA2 between T5 and T6 is the result of P1 and P2 together inducing a combined charge on the charge detection cylinder 40 2 which produces 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 P2 alone inducing its charge on the charge detection cylinder 40 2 which produces CHP2 =C5.

[0077] The process 200 loops again through steps 214 and 216 to increment the counter i to i=3 and the processor 28 is then operable at step 212 to process CA3 for the time window of column 3 of the TW matrix to match or map the magnitude(s) of CA3 to the contributions made thereto by P1 and P2 individually and / or collectively. Figure 7 It is clear that the three values ​​C6, C7 and C8 of CA3 produce the result CH in a similar manner to the operation of step 212 with respect to CA2. P1 =C6, CH P1 +CH P2 =C7 and CH P2 = C8. Therefore, after the yes branch at step 214, process 200 proceeds to step 218 using the following set of equations:

[0078]

[0079] At step 218, the processor 28 is operable to solve for CH P1 and CH P2 The processor 28 may be programmed to solve the above system of equations using any conventional mathematical technique. As an example, the processor 28 may be programmed to solve the above system of equations by calculating CH P1 and CH P2 as the algebraic mean of their individual measurements, and then modifying one or both of these values ​​(if any) to satisfy the individual measurements as well as the combined measurement to solve Figures 4A - 7 Thus, for example, the processor 28 at step 218 may be operable to calculate the equations according to the relationship CH P1 = (C3 + C6) / 2 and CH P2 =(C2,+C5+C8) / 3 to determine CH in the example P1 and CH P2 , and then modify CH P1 and / or CH P2 To satisfy these two equations and equation CH P1 +CH P2 = (C1 + C4 + C7) / 3. It will be appreciated that in alternative embodiments, processor 28 may be programmed to perform step 218 by solving the system of equations resulting from steps 210-216 using any one or combination of conventional mathematical equation solving techniques and / or using any one or combination of conventional data fitting techniques, examples of which may include but are not limited to one or more regression analysis techniques, such as least squares or other regression techniques, one or more iterative techniques, such as Runge-Kutta or other iterative techniques, or the like.

[0080] Return to Figure 3 To complete the example of process 100, processor 28 is operable at step 114 to use the TOF as the time of flight of the two charged particles P1 and P2 as the corresponding measurement. P1 and TOF P2 , the length DRL of the drift region 16, and the potential U related to the magnitude of the voltages VS1, VS2 that accelerate the charged particles from the ion acceleration region 14' into the drift region 16 to calculate the mass-to-charge ratio of each of the two charged particles P1 and P2, so that m / z P1 =F(TOF P1 ,DRL,U) and m / z P2 =F(TOF P2 ,DRL,U). Thereafter, at step 16, the processor 28 may be operable to calculate the P1 =(m / z P1 )(CH P1 ) and m P2 =(m / z P2 )(CH P2 ) Calculate the masses m of charged particles P1 and P2 respectively P1 and m P2 .

[0081] It will be understood that for the purpose of description only Figure 1 and Figure 2 For the purpose of providing an example operation of a simplified time-of-flight mass spectrometer of the type shown in Figures 4A - 7 The examples shown in , and are not intended to be limiting in any way. Those skilled in the art will appreciate that the above process or variations thereof may be directly applied to determine the mass-to-charge ratio, charge magnitude, and / or charge state and mass value of many charged particles, such as hundreds or thousands or more charged particles. 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 charge detection signals generated by the charge amplifier CA1-CAN, and will appreciate that any such other techniques are intended to fall within the scope of the present disclosure.

[0082] It will be further understood that Figure 1 In the mass spectrometer 10 shown in FIG. 1 , not all charge detection signals may be used to determine particle charge values. For example, in some embodiments where charged particles may bunch together leaving the ion processing region 14, the processor 28 may ignore the charge detection signals generated by the first one or more charge amplifiers. Alternatively or additionally, the drift tube 16A may be configured to include a pre-array space 16B of any desired length to allow such bunched particles to be dispersed while passing through the plurality of charge detection cylinders 40.1 -40 N separated from each other by at least the first one of 1 in the axial direction of the drift region 16, as described above.

[0083] Now referring to Figure 9 , another embodiment 14'' of the ion processing region 14 is shown as being implemented in the form of a conventional mass-to-charge ratio filter (m / z filter) 60 following a conventional ion trap 62. In the embodiment shown in Figure 9 , one end of the mass-to-charge ratio filter 60 defines an ion inlet A1 of the ion processing region 14'' and the ion exit end of the ion trap 62 defines an ion outlet A2 of the ion processing region 14''. The mass-to-charge ratio (m / z) filter 60 is conventional and may illustratively be implemented in the form of a quadrupole or other instrument operatively coupled to a voltage source 26. In the embodiment shown, for example, the output voltage VS1 of the voltage source 26 is operatively coupled to the m / z filter 60 via a number K of signal paths, where K can be any positive integer, and another output voltage VS2 of the voltage source 26 is likewise operatively coupled to the m / z filter 60 via a number L of signal paths, where L can be any positive integer. In some embodiments, VS1 is a time-varying voltage signal of an optional frequency and peak magnitude supplied to the m / z filter 60 in the form of a pair of opposite-phase voltages, opposite-phase being, for example, 180 degrees out of phase with each other, and VS2 is a constant, for example, a DC voltage of an optional magnitude. In such an embodiment, the processor 28 is illustratively programmed or programmable to control the output voltages VS1 and VS2 in a conventional manner to create field conditions within the m / z filter 60 that are selected to allow only ions having a selected mass-to-charge ratio or mass-to-charge ratios within a selected range of mass-to-charge ratios to pass through the m / z filter 60. In some alternative embodiments, only VS1 is applied to the m / z filter 60 and controlled by the processor 28 to create field conditions within the m / z filter 60 that are selected to allow only ions having a mass-to-charge ratio above a threshold mass-to-charge ratio to pass through the m / z filter 60.

[0084] In Figure 9In the illustrated embodiment, the ion trap 62 is likewise conventional and may illustratively be implemented in the form of a quadrupole, hexapole, or other instrument with an entrance gate 64, e.g., in the form of a conventional end cap, defining an ion entrance A2' of the ion trap 62 and an exit gate 66, e.g., in the form of another conventional end cap, defining an ion exit A2 of the ion processing region 14''. In the illustrated embodiment, the output voltage VS3 of the voltage source 26 is operatively coupled to the entrance end cap 64, the output voltage VS4 of the voltage source 26 is operatively coupled to the exit end cap 66 and the output voltage VS5 is operatively coupled to the body of the ion trap 62 via a number J of signal paths, where J can be any positive integer. In some embodiments, VS3 and VS4 are switchable DC voltages with selectable magnitudes, and VS5 is a time-varying voltage signal of selectable frequency and peak magnitude supplied to the ion trap 62 in the form of a pair of out-of-phase voltages, out-of-phase, e.g., 180 degrees out of phase with each other. In such embodiments, the processor 28 is illustratively programmed or programmable to control the output voltages VS3 - VS5 in a conventional manner to selectively transfer charged particles into the ion trap 62 via the ion entrance A2', to confine the charged particles within the ion trap 62 and to selectively eject the confined ions from the ion trap 62 through the ion exit A2. In some alternative embodiments, the m / z filter 60 and the ion trap 62 may be incorporated into a single instrument, e.g., in the form of a conventional quadrupole mass-to-charge filter with end caps. In any case, the resulting mass spectrometer 10 is illustratively controllable to operate as a single mass-to-charge mass spectrometer, a single range of mass-to-charge mass spectrometers, and / or a mass-to-charge scanning mass spectrometer. However, in any mode of operation, the mass spectrometer 10 is configured to determine the particle mass-to-charge ratio, the particle charge magnitude or charge state, and the particle mass value.

[0085] Now referring to Figure 10 , a simplified flowchart is shown that depicts an example process 300 for operating Figure 1 and 9 a mass spectrometer (i.e., having an ion processing region 14'' that is implemented as an ion processing region 14 of Figure 9 Figure 1of the mass spectrometer 10) to measure the ion mass-to-charge ratio, ion charge (magnitude and / or charge state), and ion mass. Process 300 is illustratively stored in memory 30 in the form of instructions executable by processor 28 to perform measurements of particle mass-to-charge ratio, particle charge, and particle mass. Process 300 illustratively begins at a point where one or more charged particles have been generated by ion generator 20 and advanced toward and through ion processing region 14'' via pressure differential conditions established in or as part of ion source region 12 and / or an ion acceleration structure. Process 300 illustratively includes many of the steps of process 100, and thus the same steps are identified by the same numbers, and the operation of processor 28 during such steps will be as described above with respect to Figure 3 as described.

[0086] Process 300 illustratively begins step 102 of process 100, where drift region size information (DI) is stored in memory 30. Thereafter, at step 302, processor 28 is operable to set counter i = 1 or some other constant. Thereafter, at step 304, processor 28 is illustratively operable to control voltage source 26 to configure m / z filter 60 to allow only ions having a first selected mass-to-charge ratio m / z i or having a mass-to-charge ratio within a first selected range i of mass-to-charge ratios to pass therethrough. Thereafter, at step 306, processor 28 is illustratively operable to control voltage source 26 to control or configure ion trap 62 to collect and capture therein charged particles exiting m / z filter 60. Illustratively, processor 28 is operable to maintain such control of ion trap 62 for a predefined period of time in order to collect a plurality of charged particles therein. The predefined period of time may vary for different applications and / or for different samples 22. In any case, after the predefined period of time during which processor 28 is operable to maintain such control of ion trap 62 has expired, process 300 advances to step 308, where processor 28 is operable to control voltage source 26 to accelerate the captured charged particles from ion trap 62. Such control is illustratively accomplished by appropriately switching the (one or more) DC voltages applied to one or both of gates 64, 66, and in any case establishing a reference time RT from which the charged particles released from ion trap 62 begin to drift through drift region 16 of mass spectrometer 10. After step 308, processor 28 is illustratively operable to perform Figure 3 steps 106 - 116 of process 100 as shown in to determine the mass-to-charge ratio, charge magnitude or charge state, and mass value of the charged particles drifting through drift region 16, all as described above.

[0087] 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 ratios, the mass-to-charge ratio of the charged particles drifting through the drift region 16 will be known and need not be calculated at step 114, such that step 114 can be omitted. However, in some such embodiments, step 114 may be included to provide additional mass-to-charge ratio information, e.g., for use in calibrating the m / z filter 60 and / or providing improved mass-to-charge ratio resolution. In any case, process 300 proceeds from step 116 to step 310, where the processor 28 is operable to compare the counter i to the count value Q. If i < Q, process 300 proceeds to step 312 to increment the counter i at step 312 and loop back to step 304 to control the voltage source 26 to configure the m / z filter 60 to pass only ions having a second selected mass-to-charge ratio m / z i or having a mass-to-charge ratio within a second specified range i of mass-to-charge ratios, where the second selected mass-to-charge ratio or the second selected range of mass-to-charge ratios is incrementally different, e.g., greater than or less than the first. If at step 310 i = Q, the range of mass-to-charge ratios has been scanned and processed, and process 300 is complete. The values Q and the incremental step in the selected mass-to-charge ratio or the selected range of mass-to-charge ratios can be illustratively selected such that any desired range of mass-to-charge ratio values is scanned.

[0088] In alternative embodiments where the m / z filter 60 and the ion trap 62 are combined into a single instrument as described above, process 300 can be correspondingly modified to combine step 304 and step 306 into a single step, where the processor 28 is operable to control the voltage source 26 to configure the combined instrument to capture only ions therein having an m / z i or to combine step 306 and 308 into a single step, where the processor 28 is operable to control the voltage source 26 to expel only ions having an m / z i from the combined instrument. In some alternative embodiments, the ion trap 62 can be omitted such that the charged particles leaving the m / z filter 60 enter directly into the drift region 16. However, in such embodiments, an ion acceleration region will be included in the ion source region 12 to establish the reference time RT, and the dimension information DI will include dimension information of the m / z filter 60 in at least the axial direction, since in such embodiments the m / z filter 60 will become part of the drift region.

[0089] Now referring to Figure 11 , another embodiment 14''' of the ion processing region 14 is shown implemented in the form of two conventional mass-to-charge ratio filters (m / z filters) 70, 74 having a decomposition stage 72 disposed therebetween. In Figure 11In the illustrated embodiment, one end of the mass-to-charge ratio filter 70 defines an ion inlet A1 of the ion processing region 14''', and the ion outlet end of the mass-to-charge ratio filter 74 defines an ion outlet A2 of the ion processing region 14'''. The mass-to-charge ratio (m / z) filters 70, 74 are conventional and each may illustratively be implemented in the form of a quadrupole or other instrument operatively coupled to a voltage source 26, and the decomposition stage 72 is likewise conventional and, in the illustrated embodiment, operatively coupled to the voltage source 26.

[0090] In the illustrated embodiment, the output voltage VS1 of the voltage source 26 is operatively coupled to the m / z filter 70 via a number H of signal paths, where H can be any positive integer, and another output voltage VS2 of the voltage source 26 is likewise operatively coupled to the m / z filter 70 via a number I of signal paths, where I can be any positive integer. Another output voltage VS3 of the voltage source 26 is operatively coupled to the m / z filter 74 via a number L of signal paths, where L can be any positive integer, and another output voltage VS4 of the voltage source 26 is likewise operatively coupled to the m / z filter 74 via a number R of signal paths, where R can be any positive integer. In some embodiments, VS1 and VS3 are time-varying voltage signals of selectable frequencies and peak magnitudes supplied to the m / z filters 70 and 74 respectively in the form of a pair of anti-phase voltages, anti-phase being, for example, 180 degrees out of phase with each other, and VS2 and VS4 are constants, for example, DC voltages of selectable magnitudes. In such embodiments, the processor 28 is illustratively programmed or programmable to control the output voltages VS1-VS4 in a conventional manner to create field conditions within the m / z filters 70, 74 that are selected to allow only ions having a selected mass-to-charge ratio or mass-to-charge ratios within a selected range of mass-to-charge ratios to pass through the m / z filters 70, 74. In some alternative embodiments, only VS1 is applied to the m / z filter 70 and controlled by the processor 28 to create field conditions within the m / z filter 70 that are selected to allow only ions having a mass-to-charge ratio above a threshold mass-to-charge ratio to pass through the m / z filter 70. Alternatively or additionally, only VS3 may be applied to the m / z filter 74 and controlled by the processor 28 to create field conditions within the m / z filter 74 that are selected to allow only ions having a mass-to-charge ratio above a threshold mass-to-charge ratio to pass through the m / z filter 74.

[0091] In Figure 11In the embodiment shown in , the voltage source 26 is shown as being operatively coupled to the decomposition stage 72 via two voltage outputs VS5 and VS6. It will be understood that such a voltage source connection is only included in embodiments where the decomposition stage 72 is implemented in the form of a device or instrument that can be controlled by one or more voltage signals to decompose, such as fragmenting, charged particles. In such embodiments, VS5 can be a time-varying voltage signal of selectable frequency and peak magnitude, and VS6 can be a constant, such as a DC voltage of selectable magnitude. In some such embodiments, the voltage source 26 can only generate VS5, and in other embodiments, the voltage source 26 can only generate VS6. In other embodiments, the decomposition stage 72 may not be connected to the voltage source 26 at all and instead may be coupled only to one or more gas sources (not shown), wherein the decomposition stage 72 is operable to decompose, such as fragmenting, charged particles via 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 operation (e.g., scanning a range of mass-to-charge ratios with either m / z filter 70 or m / z filter 74), and / or a dual mass-to-charge ratio scanning mass spectrometer (e.g., scanning a range of mass-to-charge ratios with both m / z filter 70 or m / z filter 74). However, in any operating mode, the mass spectrometer 10 is configured to determine particle mass-to-charge ratios, particle charge magnitudes or charge states, and particle mass values.

[0092] Reference now Figure 12 , a simplified flowchart is shown, which depicts an example process 400 for operating Figure 1 and 11 A mass spectrometer (i.e., having an ion processing region 14 implemented as Figure 11 The ion treatment area 14''' Figure 1 The mass spectrometer 10 of the present invention measures ion mass-to-charge ratio, ion charge (magnitude and / or charge state), and ion mass. Process 400 is illustratively stored in memory 30 in the form of instructions executable by processor 28 to perform measurements of particle mass-to-charge ratio, particle charge, and particle mass. Similar to process 300, process 400 illustratively begins at a point where one or more charged particles have been generated by ion generator 20 and proceed toward and through ion processing region 14''' via pressure differential conditions and / or ion acceleration structures established in or as part of ion source region 12. Process 400 illustratively includes many of the steps of process 100, and thus like steps are identified with like numbers, and the operation of processor 28 during such steps will be as described above with respect to Figure 3 Just as described.

[0093] Process 400 illustratively begins with step 102 of process 100, where the drift region size information (DI) is stored in memory 30. Thereafter, at step 402, processor 28 is operable to set two counters i = 1 and j = 1 or some other constant(s). Thereafter, at step 404, processor 28 is illustratively operable to control voltage source 26 to configure m / z filter 70 to allow only ions having a first selected mass-to-charge ratio m / z i or having a mass-to-charge ratio within a range of the first selected mass-to-charge ratio to pass therethrough. Thereafter, at step 406, processor 28 is illustratively operable to control voltage source 26 to configure dissociation stage 72 to dissociate, e.g., fragment, the charged particles exiting m / z filter 70. In embodiments where voltage source 26 is not operable to control dissociation stage 72, step 406 may be omitted or replaced by a suitable control step for controlling the gas flow or other control features of dissociation region 72. Thereafter, at step 408, processor 28 is illustratively operable to control voltage source 26 to configure m / z filter 74 to allow only those of the dissociated ions exiting dissociation stage having a first selected mass-to-charge ratio m / z j or having a mass-to-charge ratio within a range j of the first selected mass-to-charge ratio to pass therethrough.

[0094] In some embodiments, m / z filter 74 may be configured in a conventional manner to include ion trapping features as described above with respect to Figure 9 m / z filter 60, and in such embodiments, processor 28 may further operate at step 408 to control voltage source 26 to collect and trap charged particles within m / z filter 74 for a certain period of time, and then control voltage source 26 to accelerate the trapped charged particles from m / z filter 74, which establishes a reference time RT at which the charged particles released from m / z filter 74 begin to drift through drift region 16 of mass spectrometer 10. In embodiments of m / z filter 74 that do not include such ion trapping features, an ion acceleration region will be included in ion source region 12 to establish reference time RT, and the size information DI will include the size information of m / z filters 70, 74, and dissociation stage 72 in at least the axial direction, since m / z filters 70, 74, and dissociation stage 72 will form part of drift region 16 in such embodiments. In other such embodiments, an ion acceleration stage, e.g., in the form of a conventional ion trap or other ion acceleration stage, may be included as part of dissociation stage 72 or inserted into mass spectrometer 10 between dissociation stage 72 and m / z filter 74 for the purpose of collecting multiple charged particles and establishing reference time RT. In yet some other such embodiments, a conventional ion trap or other ion acceleration stage may be inserted into mass spectrometer 10 between m / z filter 74 and drift region 16, as Figure 9As shown by way of example in the embodiment of the ion processing region 14' depicted, for the purpose of collecting a plurality of charged particles and establishing a reference time RT.

[0095] After step 408, the processor 28 is illustratively operable to perform Figure 3 Steps 106 - 116 of the process 100 shown in to determine the mass-to-charge ratio, charge quantity value or charge state, and mass value of the charged particles drifting through the drift region 16, all as described above. In some embodiments where the m / z filter 74 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 will be known and need not be calculated at step 114, such that step 114 can be omitted. However, in some such embodiments, step 114 can be included to provide additional mass-to-charge ratio information, e.g., for use in calibrating the m / z filter 74 and / or providing improved mass-to-charge ratio resolution. In any case, the process 400 proceeds from step 116 to step 410, where the processor 28 is operable to compare the counter j with the count value R. If j < R, the process 400 proceeds to step 412 to increment the counter j at step 412 and loop back to step 408 to control the voltage source 26 to configure the m / z filter 74 to only pass ions having a second selected mass-to-charge ratio m / z j or having a mass-to-charge ratio within a second specified range of mass-to-charge ratios j, where the second selected mass-to-charge ratio or the second selected range of mass-to-charge ratios is incrementally different, e.g., greater than or less than the first.

[0096] If j = R at step 410, the range of mass-to-charge ratios has been scanned and processed by the m / z filter 74, and the process 400 proceeds to step 414, where the processor 28 is operable to compare the counter i with the count value Q. If i < Q, the process 400 proceeds to step 416 to increment the counter i at step 416 and loop back to step 404 to control the voltage source 26 to configure the m / z filter 74 to only pass ions having a second selected mass-to-charge ratio m / z i or having a mass-to-charge ratio within a second specified range of mass-to-charge ratios i, where the second selected mass-to-charge ratio or the second selected range of mass-to-charge ratios is incrementally different, e.g., greater than or less than the first. If i = Q at step 414, the range of mass-to-charge ratios has been scanned and processed by the m / z filter 70, and the process 400 is complete. The values R and Q and the incremental step size within the selected mass-to-charge ratio or the selected range of mass-to-charge ratios can be illustratively selected such that any desired range of mass-to-charge ratio values is scanned.

[0097] Now refer to Figures 13 - 15, showing an embodiment of the drift region 16 of a mass spectrometer 10, which can be implemented in any of the forms of the mass spectrometers described above. In the illustrated embodiment, the drift tube 16A is provided in the form of an elongate sheet of flexible or semi-flexible electrical insulating material, such as flexible circuit board material, to which a plurality of spaced-apart parallel conductive strips are attached or on which a plurality of spaced-apart parallel conductive strips are formed in a conventional manner, such as using conventional metal pattern deposition techniques. In this embodiment, the conductive strips are illustratively oriented so that when the opposite sides of the flexible or semi-flexible sheet are brought together to form an elongate cylinder, for example, as shown in Figure 14 a plurality of spaced-apart parallel conductive strips form a plurality of charge detection cylinders 40 1 -40 N and one or more ground rings 42 1 -42 N . In some alternative embodiments, one or more or all of the ground rings 42 1 -42 N may be omitted. Those skilled in the art will recognize that other forms of 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 that include them) can be provided, and will understand that any such other forms are intended to fall within the scope of the present disclosure.

[0098] Although the present disclosure has been shown and described in detail in the foregoing drawings and description, it should be considered illustrative and accordingly not restrictive. It will be understood that only illustrative embodiments thereof have been shown and described and all changes and modifications within the spirit of the present disclosure are desired to be protected. For example, although several structures are shown in the drawings and described herein as being controllable and / or configurable to establish one or more electric fields therein, the one or more electric fields being configured and directed to accelerate and / or otherwise manipulate charged particles, those skilled in the art will recognize that the acceleration of charged particles and / or other manipulation of charged particles can alternatively or additionally be accomplished via one or more magnetic fields in some cases. Accordingly, it will be understood that any conventional structures and / or mechanisms for replacing or augmenting one or more of the electric fields described herein with one or more suitable magnetic fields are intended to fall within the scope of the present disclosure. As another example, although various embodiments of the drift tube 16A are shown in the drawings and described herein as being generally linear structures, i.e., linear drift tubes, it will be understood that the concepts described herein apply directly to drift tubes of other shapes and configurations, examples of which include but are not limited to V-shaped drift tubes conventionally implemented in reflector time-of-flight mass spectrometers, W-shaped drift tubes conventionally implemented in multi-reflector time-of-flight mass spectrometers, L-shaped drift tubes, or the like. It is not intended to be limiting with respect to the shape of the drift tube 16A, and no limitation should be inferred.

Claims

1. A mass spectrometer, comprising: an ion source region including an ion generator configured to generate a plurality of ions from a sample, an ion detector configured to detect ions and generate corresponding ion detection signals, a field-free drift region disposed between the ion source region and the ion detector, through which the generated plurality of ions axially drift toward the ion detector, a plurality of spaced-apart charge detection cylinders disposed in the drift region and through which the plurality of ions axially drifting through the drift region pass, 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 the charge of one or more of the generated plurality of ions passing through the corresponding one of the plurality of charge detection cylinders, at least one processor operatively coupled to the ion detector and each of the plurality of charge amplifiers, and at least one memory having instructions stored therein, the instructions executable by the at least one processor to cause the at least one processor to determine a mass-to-charge ratio of each of the plurality of ions drifting through the field-free drift region based on the ion detection signals and process the charge detection signals 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.

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

3. The mass spectrometer according to claim 2, further comprising: at least one processor, and at least one memory having instructions stored therein, the instructions executable by the processor to control the at least one voltage source to generate at least one voltage to establish an electric field within the ion region or instrument.

4. The mass spectrometer according to claim 3, wherein, the instructions stored in the at least one memory further include instructions executable by the processor to: (a) control the at least one voltage source to generate at least one voltage to establish an electric field within the ion region at a reference time RT, (b) store in the at least one memory a sample of the charge detection signals generated by each of the plurality of charge amplifiers as the accelerated ions axially drift through the field-free drift region toward the ion detector, (c) monitor the ion detector and store the detection time DT of the ion detector for each of at least a subset of the accelerated ions, (d) determine, based on the respective one of the detection times DT relative to RT, the time-of-flight TOF of each of at least a subset of the accelerated ions through the drift region, and (e) based on the respective TOF of each of at least a subset of the accelerated ions, based on the magnitude of the stored sample of the charge detection signals generated by the plurality of charge amplifiers and based on the axial lengths of the drift region, each of the plurality of charge detection cylinders, and the spacing therebetween, determine the magnitude of the charge or the charge state of each of at least a subset of the accelerated ions.

5. The mass spectrometer according to claim 4, wherein the instructions stored in at least one memory further include instructions executable by a processor to determine a charge quantity value or a charge state of each of at least a subset of the accelerated ions by: (i) determining a rate of each of at least a subset of the accelerated ions based on a respective TOF of each of at least a subset of the accelerated ions and an axial length of a drift region, (ii) for each of at least a subset of the accelerated ions, determining a plurality of time windows based on the determined rate of the ion and the axial length, each of the plurality of time windows corresponding to a time window relative to the RT or DT of the ion during which the ion has passed through a different respective one of a plurality of charge detection cylinders, (iii) for each of a plurality of charge amplifiers, processing a sample of the resulting charge detection signal for each of at least a subset of the accelerated ions during a respective time window to determine a set of equations relating the magnitude of the charge detection signal to the magnitude of at least a subset of the accelerated ions, and (iv) solving the plurality of sets of equations to determine a charge quantity value or a charge state of each of at least a subset of the accelerated ions.

6. The mass spectrometer according to any one of claims 2 to 5, wherein, the ion region or the instrument includes an ion acceleration region having spaced-apart first and second gates, a first gate adjacent to the ion source region and a second gate adjacent to the field-free drift region, and wherein at least one voltage source is electrically connected to the first and second gates and is configured to selectively control the voltage applied to at least one of the first and second gates to establish an electric field within the ion acceleration region.

7. The mass spectrometer according to any one of claims 2 to 5, wherein, the ion region or the instrument includes an ion trap, and wherein at least one voltage source is electrically connected to the ion trap and is configured to selectively control the voltage applied thereto to establish an electric field within the ion trap.

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

9. The mass spectrometer according to any one of claims 2 to 5, further comprising a mass-to-charge ratio filter disposed between the ion source region and the ion region or the instrument, wherein, the ion region or the instrument includes an ion trap, and wherein at least one voltage source is electrically connected to the mass-to-charge ratio filter and electrically connected to the ion trap, and at least one voltage source is configured to selectively generate at least a first voltage to configure the mass-to-charge ratio filter to allow only ions having a selected mass-to-charge ratio or a mass-to-charge ratio within a selected range of mass-to-charge ratios to pass therethrough, and generate at least a second voltage to selectively establish an electric field within the ion trap.

10. The mass spectrometer according to any one of claims 2 to 5, further comprising: a first mass-to-charge ratio filter disposed between the ion source region and the ion region or the instrument, A fragmentation stage, disposed between the first mass-to-charge ratio filter and the ion region or the instrument and configured to fragment ions passing therethrough, and A second mass-to-charge ratio filter, disposed between the ion source and the ion region instrument, And wherein at least one voltage source is electrically connected to each of the first and second mass-to-charge ratio filters, the at least one voltage source being configured to selectively generate at least a first voltage to configure the first mass-to-charge ratio filter to allow only ions having a first selected mass-to-charge ratio or mass-to-charge ratios within a first selected range of mass-to-charge ratios to pass therethrough, and to generate at least a second voltage to configure the second mass-to-charge ratio filter to allow only ions having a second selected mass-to-charge ratio or mass-to-charge ratios within a second selected range of mass-to-charge ratios to pass therethrough.

11. The mass spectrometer according to claim 4 or claim 5, wherein the instructions stored in the at least one memory further include instructions executable by a processor to determine the mass-to-charge ratio of each of at least a subset of the accelerated ions based on the respective TOF of each of at least a subset of the accelerated ions and the axial length of the drift region.

12. The mass spectrometer according to claim 11, Wherein, The instructions stored in the at least one memory further include instructions executable by a processor to determine the mass value of each of at least a subset of the accelerated ions based on the respective determined mass-to-charge ratio of each of at least a subset of the accelerated ions and its respective determined charge quantity value or charge state.

13. The mass spectrometer according to any one of claims 1 to 4, Wherein, The ion detector includes a microchannel plate detector.

14. The mass spectrometer according to any one of claims 1 to 4, Wherein, The ion detector includes an ion photon detector.

15. The mass spectrometer according to any one of claims 1 to 4, Wherein, The ion detector includes a Faraday cup detector.

16. The mass spectrometer according to any one of claims 1 to 4, Wherein, The ion detector includes an electron multiplier detector.

17. The mass spectrometer according to any one of claims 1 to 4, Wherein, Both the ion generator and the sample are located within the ion source region.

18. The mass spectrometer according to any one of claims 1 to 4, Wherein, The ion generator and the sample are located outside the ion source region, And wherein the ion generator is configured to generate ions from the sample and supply the generated ions to the ion source region.

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