Charge filter device and its applications

Abstract

The charge filter apparatus includes a field-free drift region, a plurality of charge detection cylinders in the drift region through which axially drifting ions pass, a plurality of charge amplifiers each coupled to at least one charge detection cylinder and configured to generate a charge detection signal corresponding to the charge of one or more of the passing ions, a single-inlet and single-exit charge deflector or a single-inlet-multiple-exit charge drive device coupled to the exit end of the drift region, means for determining the charge magnitude or charge state of the ions drifting axially through the drift region based on the charge detection signal, and means for controlling the charge deflector or charge drive device to allow only ions having a predetermined charge magnitude or charge state to pass through the single exit or a predetermined one of the multiple exits.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 62 / 949,555, filed December 18, 2019, the disclosure of which is expressly incorporated by reference in its entirety into this specification.

[0002]

[0002] The present disclosure relates generally to instruments configured to measure particle charge and selectively filter particles based on their charge, and further to particle measurement devices or systems in which such instruments may be implemented. [Background technology]

[0003]

[0003] Spectrometry devices attempt to identify the chemical components of a substance by measuring one or more molecular characteristics of the substance. Some such instruments are configured to analyze substances in solution, while others are configured to analyze charged particles in gas phase substances. The molecular information generated by many such charged particle measurement instruments is limited because they lack the ability to measure particle charge or to process particles based on their charge. Summary of the Invention [Means for solving the problem]

[0004]

[0004] The present disclosure includes 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 charge filter apparatus may comprise: an electric field free drift region having an entrance end and an exit end opposite the entrance end, the entrance end configured to be coupled to an ion source to receive ions drifting axially through the drift region from the entrance end to the exit end; a plurality of spaced apart charge detection cylinders disposed in the drift region through which ions drifting axially through the drift region pass; a plurality of charge amplifiers each coupled to at least one of the plurality of charge detection cylinders and each configured to generate a charge detection signal corresponding to a charge magnitude of one or more of the ions passing through at least one respective one of the plurality of charge detection cylinders; one of a charge deflector having a single entrance single exit and a charge drive device having a single entrance multiple exit and coupled to the exit end of the drift region; means for determining a charge magnitude or charge state of ions drifting axially through the drift region based on the charge detection signals generated by at least some of the plurality of charge amplifiers; and means for controlling one of the charge deflector and the charge drive device to pass only ions having a predetermined charge magnitude or charge state through a corresponding one of the single exit and a predetermined one of the multiple exits.

[0005]

[0005] In another aspect, an ion filter apparatus includes an electric field free drift region having an entrance end and an exit end opposite the entrance end, the entrance end being configured to be coupled to an ion source to receive ions drifting axially from the entrance end through the drift region to the exit end, a plurality of spaced apart charge detection cylinders disposed in the drift region through which the ions drifting axially through the drift region pass, a plurality of charge amplifiers each coupled to at least one of the plurality of charge detection cylinders and each configured to generate a charge detection signal corresponding to a magnitude of charge of one or more of the ions passing through a respective at least one of the plurality of charge detection cylinders, one of a charge deflector having a single inlet and single outlet, and a charge drive device having a single inlet and multiple outlets and coupled to the exit end of the drift region, and a charge deflector operably coupled to one of the charge deflector and the charge drive device. and at least one memory having instructions stored thereon executable by the at least one processor, the instructions causing the at least one processor to (a) monitor charge detection signals generated by at least some of the plurality of charge amplifiers as ions drift axially through the field-free drift region toward an exit end thereof, (b) determine a charge magnitude or charge state of ions drifting axially through the field-free drift region based on the monitored charge detection signals, and (c) control at least one of a charge deflector and a charge drive device to cause only ions having a predetermined charge magnitude or charge state to pass through the single exit and a corresponding predetermined exit of the multiple exits. [Brief description of the drawings]

[0006] [Figure 1]FIG. 1 is a simplified schematic diagram of a charge filter device configured to filter ions according to ion charge by selectively passing ions having a predetermined charge or by selectively driving ions having different predetermined charges along different respective ion migration paths. [Figure 2A] FIG. 2A is a simplified diagram of a portion of an illustrative example of the charge filter device of FIG. 1 having three charge detection cylinders arranged axially in a field-free drift region, showing an example in which a charged particle P enters the first charge detection cylinder at time T1 and exits the first charge detection cylinder at time T2>T1. [Figure 2B] FIG. 2B is a simplified diagram similar to FIG. 2A, illustrating an example of an exemplary charged particle P entering the second charge detection cylinder at time T3>T2 and exiting the second charge detection cylinder at time T4>T3. [Figure 2C] FIG. 2C is a simplified diagram similar to FIGS. 2A and 2B, illustrating an example of an exemplary charged particle P entering the third charge detection cylinder at time T5>T4 and exiting the third charge detection cylinder at time T6>T5. [Figure 2D] FIG. 2D is a simplified diagram similar to FIGS. 2A-2C illustrating an example of an exemplary charged particle P entering the charge deflection or charge drive region of the charge filter device at time T7>T6. [Diagram 3] 2A-2D are plots of charge magnitude versus time showing exemplary outputs of charge amplifiers CA1-CA3 as an exemplary charged particle P passes through the respective first, second, and third charge detection cylinders. [Figure 4A] FIG. 2B is a simplified diagram of the exemplary charge filter apparatus shown in FIGS. 2A-2D, illustrating two exemplary charged particles P1 and P2 of slightly different mass-to-charge ratios moving along a field-free drift region, with one charged particle P1 shown entering a first charge detection cylinder at time T1 and the other charged particle P2 lagging behind P1. [Figure 4B]4B is a simplified diagram similar to FIG. 4A showing the respective positions of two exemplary charged particles P1 and P2 in the field-free drift region at times T2>T1. [Figure 4C] 4A and 4B, showing the respective positions of two exemplary charged particles P1 and P2 in the field-free drift region at times T3>T2. [Figure 4D] 4A-4C are simplified diagrams similar to those of FIGS. 4A-4C, showing the respective positions of two exemplary charged particles P1 and P2 in the field-free drift region at times T4>T3. [Figure 4E] 4A-4D are simplified diagrams similar to those of FIGS. 4A-4D, showing the respective positions of two exemplary charged particles P1 and P2 in the field-free drift region at times T5>T4. [Figure 4F] 4A-4E are simplified diagrams similar to those of FIGS. 4A-4E showing the respective positions of two exemplary charged particles P1 and P2 in the field-free drift region at times T6>T5. [Figure 4G] 4A-4F are simplified diagrams similar to those of FIGS. 4A-4F, showing the respective positions of two exemplary charged particles P1 and P2 in the field-free drift region at times T7>T6. [Figure 4H] 4A-4G are simplified diagrams similar to those of FIGS. 4A-4G, showing the respective positions of two exemplary charged particles P1 and P2 in the field-free drift region at times T8>T9. [Figure 4I] 4A-4H are simplified diagrams similar to those of FIGS. 4A-4H, showing the respective positions of two exemplary charged particles P1 and P2 in the field-free drift region at times T9>T8. [Figure 4J] 4A-4I are simplified diagrams similar to those of FIGS. 4A-4I showing the respective positions of two exemplary charged particles P1 and P2 in the field-free drift region at times T10>T9. [Figure 4K] 4A-4J are simplified diagrams similar to those of FIGS. 4A-4J illustrating the respective positions of two exemplary charged particles P1 and P2 in the field-free drift region at times T11>T10. [Figure 4L] 4A-4K are simplified diagrams showing the position of charged particle P2 in the field-free drift region and showing charged particle P1 entering the charge deflection or charge drive region of the charge filter device at time T12>T11. [Figure 4M] 4A-4L are simplified diagrams similar to those shown in FIG. 4A, showing the position of a charged particle P2 in the field-free drift region at times T13>T12. [Figure 4N] 4A-4M are simplified diagrams similar to those of FIGS. 4A-4M, showing charged particle P2 entering the charge deflection or charge drive region of the charge filter device at time T14>T13. [Diagram 5] A plot of charge magnitude versus time showing exemplary outputs of charge amplifier CA1 as two exemplary charged particles P1 and P2 pass through a first charge detection cylinder during time windows T1-T5, as shown in Figures 4A-4E. [Figure 6] A plot of charge magnitude versus time showing exemplary outputs of charge amplifier CA2 as two exemplary charged particles P1 and P2 pass through the second charge detection cylinder during time windows T4-T9, as illustrated in Figures 4D-4I. [Figure 7] A plot of charge magnitude versus time showing exemplary outputs of charge amplifier CA3 as two exemplary charged particles P1 and P2 pass through the third charge detection cylinder during time windows T8-T13, as shown in Figures 4H-4M. [Figure 8] 2 is a simplified diagram of the charge deflection or drive regions of the charge filter device of FIG. 1 shown in the form of an embodiment of a controllable charge deflector; [Figure 9A] FIG. 9A is a simplified diagram of the charge deflection or drive regions of the charge filter device of FIG. 1 shown in the form of another embodiment of a controllable charge deflector. [Figure 9B] FIG. 9B is a cross-sectional view of the charge deflector of FIG. 9A taken along section line 9B-9B. [Figure 10A]FIG. 10A is a simplified diagram of the charge deflection or drive regions of the charge filter device of FIG. 1 shown in the form of an embodiment of a controllable single-inlet multiple-outlet charge drive structure. [Figure 10B] FIG. 10B is a cross-sectional view of the charge driven structure of FIG. 10A taken along section line 10B-10B. [Figure 11] 2 is a simplified schematic diagram of the charge deflection or drive regions of the charge filter device of FIG. 1 shown in the form of another embodiment of a controllable single-inlet multiple-outlet charge drive structure. [Figure 12] FIG. 2 is a simplified diagram of an embodiment of a particle measurement instrument including the charge filter arrangement of FIG. 1, where a charge deflection or drive region is implemented in the form of a charge deflector and is interposed between an ion source region and an ion measurement stage. [Figure 13] FIG. 2 is a simplified diagram of another embodiment of a particle measurement instrument including the charge filter apparatus of FIG. 1, where a charge deflection or drive region is implemented in the form of a single-inlet multiple-outlet charge drive device and is interposed between the ion source region and each of a plurality of ion measurement stages. [Figure 14] FIG. 2 is a simplified diagram of yet another embodiment of a particle measurement instrument including the charge filter apparatus of FIG. 1, in which the charge deflection or drive region is implemented in the form of an ion drive structure including a plurality of single-inlet multiple-exit ion drive devices and is interposed between the ion source region and a single ion measurement stage. [Figure 15] 15 is a simplified diagram of an embodiment of an ion source region that may be implemented with any of the charged particle measurement instruments of FIGS. 12-14. [Figure 16] FIG. 15 is a simplified diagram of an embodiment of an ion measurement stage that may be implemented with any of the charged particle measurement devices of FIGS. 12-14. [Figure 17] FIG. 2 is a simplified diagram of yet another embodiment of a particle measurement instrument including two series implementations of the charge filter device of FIG. 1 with an ion processing region disposed therebetween, the combined charge filter device being interposed between an ion source region and an ion measurement stage. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0007]

[0041] For the purposes of promoting an understanding of the principles of the present disclosure, reference will now be made to a number of exemplary embodiments illustrated in the accompanying drawings, and specific language will be used to describe the same.

[0008]

[0042] The present disclosure relates to apparatus and techniques for determining the charge or charge state of charged particles moving through a drift region and filtering the charged particles according to their charge value or charge state by selectively passing those of the charged particles having a predetermined charge value or charge state or by selectively driving those of the charged particles having different predetermined charge values ​​or charge states along different respective paths of movement. For the purposes of this document, the terms "charged particles" and "ions" may be used interchangeably and both terms are intended to refer to particles having a net positive or negative charge.

[0009]

[0043] Referring now to FIG. 1, a diagram of a charge filter apparatus 10 configured to filter ions according to ion charge by selectively passing ions having a predetermined charge or selectively driving ions having different predetermined charges along different respective ion migration paths is shown. In the illustrated embodiment, the charge filter apparatus 10 includes a drift region 12 having an ion inlet A1 at one end and an ion outlet A2 at its opposite end. In the embodiment illustrated in FIG. 1, the drift region 12 is a linear drift region defined within an elongated drift tube 12A. The drift region 12 has a length DRL between the inlet A1 and the outlet A2, with a longitudinal axis 20 extending through the center of the drift region 12 and through the center of each of the inlet A1 and the outlet A2, respectively. Although the drift region 12 is illustrated in FIG. 1 in the form of a linear drift region, it will be understood that the drift region 12 may be nonlinear in whole or in part in alternative embodiments. As one non-limiting example, the drift region 12 may be provided in the form of a circular drift region including conventional ion inlet (i.e., inlet) and ion outlet (i.e., outlet) structures. It will be understood that other examples of at least partially non-linear drift regions will occur to those skilled in the art, and such alternative configurations are intended to be within the scope of the present disclosure.

[0010]

[0044] The charge deflection or drive region 14 is coupled to or otherwise disposed at the exit end of the drift region 12. In the illustrated embodiment, the charge deflection or drive region 14 has an ion entrance A3 defined by or disposed adjacent to the ion exit A2 of the drift region 12, and an ion exit A4. In some embodiments, the charge deflection or drive region 14 may be implemented in the form of a charge deflector controllable to selectively pass or selectively prevent the passage of ions, non-limiting exemplary embodiments of which are shown in Figures 8-9B and described in more detail below. In other embodiments, the charge deflection or drive region 14 may be implemented in the form of one or more single-entry multiple-exit charge drive devices or structures, each of which is controllable to selectively drive ions entering the single entrance through one or more of the multiple exits, some non-limiting exemplary embodiments of which are shown in Figures 10A-11 and described in more detail below.

[0011]

[0045] Voltage source VS1 is electrically connected to charge deflection or drive region 14 via K signal paths, where K may be any positive integer. In some embodiments, voltage source VS1 may be implemented in the form of a single voltage source, while in other embodiments, voltage source VS1 may include any number of individual voltage sources. In some embodiments, voltage source VS1 may be configured or controlled to generate and supply one or more time-invariant (i.e., DC) voltages of selectable magnitude. Alternatively or additionally, voltage source VS1 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, voltage source VS1 may be configured or controllable to generate and supply one or more time-varying signals of selectable shape, duty cycle, maximum amplitude and / or frequency. As a particular example of the latter embodiment, which should in no way be considered limiting, voltage source VS1 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.

[0012]

[0046] Voltage source VS1 is illustratively shown as electrically connected to a conventional processor 24 by J signal paths, where J may be any positive integer. Processor 24 is illustratively conventional and may comprise a single processing circuit or multiple processing circuits. Processor 24 illustratively comprises or is coupled to a memory 26 having instructions stored therein that, when executed by processor 24, cause processor 24 to control voltage source VS1 to generate one or more output voltages to selectively control the charge deflection or operation of drive region 14. In some embodiments, processor 24 may be embodied in the form of one or more conventional microprocessors or controllers, and in such embodiments, memory 26 may be embodied in the form of one or more conventional memory units that store instructions in the form of one or more microprocessor-executable instructions or instruction sets. In other embodiments, processor 24 may alternatively or additionally be embodied in the form of a field programmable gate array (FPGA) or similar circuitry, and in such embodiments, memory 26 may be embodied in the form of programmable logic blocks contained within and / or external to the FPGA within which instructions are programmed and stored. In still other embodiments, processor 24 and / or memory 26 may be implemented in the form of one or more application specific integrated circuits (ASICs). Those skilled in the art will recognize other forms in which processor 24 and / or memory 26 may be implemented, and it will be understood that such other forms of implementation are contemplated by and intended to be within the scope of this disclosure. In some alternative embodiments, voltage source VS1 may itself be programmable to selectively generate one or more constant and / or time-varying output voltages.

[0013]

[0047] Charge detector array 16 is illustratively disposed within or integrated with drift region 12. In the embodiment illustrated in FIG. 1, charge detector array 16 illustratively comprises a plurality of N spaced apart charge detector cylinders 161-16 in series. N where N is any positive integer greater than 2. In one exemplary embodiment, which should not be considered limiting in any way, N may be approximately 100, but in other embodiments, N may be less than 100 or greater than 100. In any case, the charge detection cylinders 161-16 N Each defines a bore therethrough to allow ions to pass through the respective cylinder, and in the illustrated embodiment, the charge detection cylinders 161-16 N are arranged end to end such that the central longitudinal axis 20 of the drift region 12 passes through the center of each. In the illustrated embodiment, each charge detection cylinder 161-16 N defines the length CDL between the ion entrance end and the ion exit end, but in an alternative embodiment, the charge detection cylinders 161-16 N One or more of the CDLs may have a length longer or shorter than the CDL. The shortest CDL is illustratively one that is physically recognizable and produces an electrically detectable signal response to one or more ions passing therethrough. While there is no theoretical upper limit to the CDL, practical considerations such as available space and instrument operating conditions typically limit the longest useful CDL in a particular application.

[0014]

[0048] In the illustrated embodiment, a plurality of ground rings 182-18 N-1 Each of the charge detection cylinders 161 to 16 N one other ground ring 181 is disposed adjacent the ion inlet of the first charge detection cylinder 161, and one other ground ring 18 N The last charge detection cylinder 16 NThe ground rings 181 to 18 are arranged adjacent to the ion outlets of the respective N 1 illustratively defines a through ring aperture RA through which longitudinal axis 20 passes, where RA illustratively defines the charge detection cylinders 161-16 N In the illustrated embodiment, the charge detection cylinders 161-16 N are axially separated from each other by a spatial length SL. N Ion inlet and ground ring 181-18 N-1 The distances between the corresponding ground rings of the charge detection cylinders 161 to 16 are approximately equal to each other. N Ion outlet and ground ring 182~18 N The distances between the corresponding ground rings of the charge detection cylinders 161 to 16 are approximately equal to each other. N Ion inlet and ground ring 181-18 N-1 The distance between the corresponding charge detection cylinders 161 to 16 N Ion outlet and ground ring 182~18 N The ground rings 181 to 18 are spaced apart from each other so that the distance between the corresponding ground rings is approximately equal to the distance between the corresponding ground rings. N In some embodiments, the ground rings 181 to 18 are disposed on the ground rings 181 to 182. N One or more of may be omitted.

[0015]

[0049] In one exemplary embodiment, drift tube 12A is illustratively coupled to ground potential (shown in FIG. 1) or other reference potential and has a plurality of charge detection cylinders 161-16 disposed therein. N are provided in the form of appropriately mounted conductive cylinders. One or more ground rings 181-18 N In the above embodiments including, such one or more ground rings may be electrically and mechanically coupled to the inner surface of the conductive cylinder, or alternatively, the conductive cylinder and one or more ground rings 181-18 may be electrically and mechanically coupled to the inner surface of the conductive cylinder. NIn another exemplary embodiment, the drift tube 12A may be formed integrally with the conductive cylinder such that the spacers 161-162 are of unitary construction. In another exemplary embodiment, the drift tube 12A may be formed integrally with the conductive cylinder such that the spacers 161-162 are of unitary construction. N A plurality of ground rings 181 to 18 on which the N In yet another exemplary embodiment, drift tube 12A may be provided in the form of a sheet of flexible or semi-flexible electrically insulating material, such as, for example, a flexible circuit board, to which a plurality of spaced apart parallel conductive strips are attached or formed in a conventional manner, such as, for example, using conventional metal pattern deposition techniques. In this embodiment, the plurality of spaced apart parallel conductive strips are attached to a plurality of charge detection cylinders and one or more ground rings 181-18 when opposite ends of each of the flexible or semi-flexible sheets are joined to form an elongated cylinder. N The conductive strips are illustratively oriented to form a. N and / or one or more ground rings 181-18 N It will be understood that other forms in which the present invention (including embodiments thereof) may be provided will be recognized, and that such other forms are intended to be within the scope of the present disclosure.

[0016]

[0050] In the illustrated embodiment, each of the charge detection cylinders 161-16 Nare electrically connected to signal inputs of a corresponding one of the N charge amplifiers CA1-CAN, and a signal output of each charge amplifier CA1-CAN is electrically connected to the processor 24. In alternative embodiments, any, some, or all of the charge amplifiers may be electrically connected to multiple charge detection cylinders, and in such embodiments, the number of charge amplifiers is accordingly less than the number of charge detection cylinders. As a charged particle entering the ion inlet A1 travels axially through the drift region 12 towards and through the ion outlet A2, each such charged particle is coupled to one of the multiple charge detection cylinders 161-16. N Each such charged particle passes through the charge detection cylinders 161-16. N When passing through the charge detection cylinder 161~16 N The charge induced thereby has a magnitude proportional to the magnitude of the charge on the particle. The charge amplifiers CA1-CAN are illustratively conventional and include charge detectors 161-16C for generating corresponding charge detection signals at their outputs and for providing the charge detection signals to processor 24. N The magnitude of the charge detection signal generated by the charge amplifiers CA1 to CACAN at any one time is: (i) the charge detection cylinders 161 to 16 N In the case of a single charged particle passing through each of the corresponding charge detection cylinders 161-16, the magnitude of the charge of that single charged particle, or (ii) N For multiple charged particles passing through corresponding respective ones of simultaneously, the magnitude of the combined charge of the multiple charged particles is proportional to . Processor 24 is then illustratively operable to receive and digitize the charge detection signals generated by each of charge amplifiers CA1-CAN and store the digitized charge detection signals in memory 26 or one or more other memory units coupled to or otherwise accessible by processor 24.

[0017]

[0051] Processor 24 is further illustratively coupled to one or more peripheral devices 28 (PD) via P signal paths, where P may be any positive integer. One or more peripheral devices 28 may include one or more devices for providing signal inputs to processor 24 and / or one or more devices to which processor 24 provides signal outputs. In some embodiments, peripheral device 28 includes at least one of a conventional display monitor, a printer, and / or other output device, and in such embodiments, memory 26 has stored thereon instructions that, when executed by processor 24, cause processor 24 to control one or more of such output peripheral devices 28 to display and / or record an analysis of the stored digitized charge detection signals.

[0018]

[0052] 1, the ion entrance end of the drift tube 12A, i.e., the end where the ion entrance A1 is located, is illustratively configured to be coupled to the ion exit end of the ion source 30, i.e., the end of the ion source 30 where the ion exit A5 is located. In an embodiment in which the ion source 30 is coupled to the charge filter apparatus 10, the second voltage source VS2 is illustratively connected to the ion source 30 via H signal paths, where H may be any positive integer, and the second voltage source VS2 is further connected to the processor 24 via G signal paths, where G may be any positive integer. VS2 may illustratively have any of the forms described above with respect to VS1, such that VS2 may be configured or controlled to generate any number of time-invariant, e.g., invariant, and / or time-varying output voltages to selectively control one or more aspects of the ion source 30.

[0019]

[0053] As described in more detail below with respect to Figure 15, the ion source 30 illustratively includes any conventional device or apparatus for generating ions from a sample and may further include one or more devices and / or instruments for separating, collecting, and / or filtering the ions according to one or more molecular characteristics and / or for dissociating, e.g., fragmenting, the ions. As an illustrative example, which should not be considered limiting in any way, the ion source 30 may include a conventional electrospray ionization source, a matrix-assisted laser desorption ionization (MALDI) source, or other conventional ion generator configured to generate ions from a sample. The sample from which ions are generated may be any biological or other material.

[0020]

[0054] The drift region 12 of the charge filter apparatus 10 is a field-free drift region (i.e., no electric field) such that ions entering the entrance A1 of the drift tube 12A from the ion source 30 with an initial velocity drift toward and therethrough to the ion outlet A2 with a nearly constant velocity. In this regard, the ion source 30 typically provides a motive force for passing the ions into the drift tube 12A with an initial velocity. The motive force may illustratively be provided in any one form or any combination of several different forms, examples of which may include, but are not limited to, one or more ion accelerating electric fields, one or more magnetic fields, a pressure difference between the external environment and the ion source 30 and / or a pressure difference between the ion source 30 and the drift tube 12A, and the like. In either case, as the charged particles drift through the field-free drift region 12, the charged particles separate in time according to their mass-to-charge ratio, with charged particles having a lower mass-to-charge ratio reaching the ion outlet A2 sooner than charged particles having a higher mass-to-charge ratio.

[0021]

[0055] 4A-7, memory 26 illustratively stores instructions executable by processor 24 to cause processor 24 to process charge detection signals generated by at least some of charge amplifiers CA1-CAN to determine the charge magnitude and / or charge state of the charged particles as they separate along the length of drift region 12, whereby the charge magnitude and / or charge state of each charged particle is known before it passes through ion outlet A2 of drift tube 12A. In some embodiments, memory 26 further illustratively stores instructions executable by processor 24 to cause processor 24 to control voltage source VS1 to selectively pass through charge deflection or drive region 14 only charged particles having a selected charge magnitude, or only charged particles having a charge magnitude within a selected range of charge magnitudes, or only charged particles having a selected charge state. In other embodiments, memory 26 further illustratively stores instructions executable by processor 24 to cause processor 24 to control voltage source VS1 to cause charge deflection or drive region 14 to selectively drive charged particles having different charge magnitudes, or within different ranges of charge magnitudes, along different ion movement paths, or to selectively drive charged particles having different charge states along different ion movement paths. In some embodiments, it may be desirable to determine the velocity of the charged particles moving through drift region 12, so that in controlling voltage source VS1 to selectively pass or drive the charged particles through charge deflection or drive region 14, the future position of the charged particles within charge deflection or drive region 14 can be accurately estimated.

[0022]

[0056] 1, the ion outlet end of the ion deflection or drive region 14, i.e., the end where the ion outlet A4 is located, is illustratively configured to be coupled to the ion inlet end of the ion storage, drive and / or measurement stage 32, i.e., the end where the ion inlet A6 is located, of the ion storage, drive and / or measurement stage 32. In an embodiment where the ion storage, drive and / or measurement stage 32 is coupled to the charge filter apparatus 10, the third voltage source VS3 is illustratively connected to the ion storage, drive and / or measurement stage 32 via M signal paths, where M may be any positive integer, and the third voltage source VS3 is further connected to the processor 24 via L signal paths, where L may be any positive integer. VS3 may illustratively have any of the forms described above with respect to VS1, such that VS3 may be configured or controlled to generate any number of time-invariant, e.g., invariant, and / or time-varying output voltages to selectively control one or more aspects of the ion storage, drive and / or measurement stage 32.

[0023]

[0057] 12-14 and 16, the ion storage, drive and / or measurement stage 32 may comprise any conventional device or apparatus for ion storage, ion measurement, ion processing after or before the measurement, and / or ion drive between one or more devices. The one or more ion measurement instruments, devices, apparatus or stages are illustratively connected to the processor 24 via Q signal paths, where Q may be any positive integer.

[0024]

[0058] As briefly described above, memory 26 illustratively includes instructions executable by processor 24 to cause processor 24 to determine a charge magnitude and / or charge state of each of the charged particles moving through drift region 12, and then control voltage source VS1 to selectively pass or drive the charged particles through charge deflection or drive region 14 based on those charge magnitudes or charge states. In some embodiments, for example, when ion source 30 is configured to generate and simultaneously deliver multiple ions, for example to ion inlet A1 of drift tube 12A, it may be desirable to configure drift tube 12A to include a pre-array space 12B of length PRL between ion inlet A1 of drift tube 12A and first ground ring 181 (or the ion inlet end of first charge detection cylinder 161 in embodiments in which first ground ring 181 is omitted), as illustrated by way of example in FIG. This allows charged particles moving axially through the drift region 12 to be axially separated for some amount of time (depending on the mass-to-charge ratio in the field-free region 12) before performing a charge measurement with the charge detector array 16, thereby improving the quality and usefulness of the charge detection signal generated by the first one or more of the charge amplifiers CA1-CAN. The length PRL of the pre-array space 12B may be illustratively selected based on the application, and in some embodiments the pre-array space 12B may be omitted entirely. Alternatively or additionally, in some embodiments, a final ground ring 18 may be provided, as further illustrated by way of example in FIG. N (or the last ground ring 18 N The last charge detection cylinder 16 in the embodiment where N It may be desirable to configure the drift tube 12A to include a post-array space 12C of length POL between the drift tube 12A and the charge deflection or drive array 14 (the ion exit end of the charge deflection or drive array 14). In some such embodiments, some or all of the length POL of the post-array space 12C may be provided adjacent to the front end, i.e., ion entrance A3, of the charge deflection or drive array 14. In any case, the post-array space 12C in embodiments that include a post-array space 12C may be provided adjacent to the front end, i.e., ion entrance A3, of the final charge detection cylinder 16.N , thereby easing the determination and control timing and / or switching speed requirements of the charge deflection or drive region 14. The length POL of the post-array space 12C may illustratively be selected depending on the application, and in some embodiments the post-array space 12C may be omitted in its entirety.

[0025]

[0059] 2A-2D, a simplified example of the charge filter apparatus 10 of FIG. 1 is shown, including three charge detection cylinders 161-163 axially arranged between the ion inlet A1 of the drift tube 12A and the charge deflection or drive region 14. With this simplified apparatus 10, FIGS. 2A-2D illustrate a single charge particle P drifting successively through each of the three charge detection cylinders 161-163 as a function of time, and FIG. 3 illustrates exemplary charge detection signals generated by the three respective charge amplifiers CA1-CA3 as the charged particle passes through. As illustrated in FIGS. 2A and 3, the charged particle P enters the first charge detection cylinder 161 at time T1 and subsequently exits the charge detection cylinder 161 at time T2, while inside the charge detection cylinders 161, the charged particle induces a charge of magnitude C1 on the charge detection cylinder 161. In some embodiments, time T1 may be a time associated with an ion generation or acceleration event controlled by the ion source 30 at a previous time T0. In an alternative embodiment, the output signal generated by CA1 may be monitored after the ion generation or acceleration event, and T1 may simply be the time when the first (in this example only) particle P is detected, for example by a rising edge of the charge detection signal output generated by CA1 when it enters the first charge detection cylinder 161 after the ion generation or acceleration event. In either case, as illustrated in FIG. 2B, at time T3>T2, the charged particle P exiting the first charge detection cylinder 161 then enters the second charge detection cylinder 162, and the charged particle P then exits the charge detection cylinder 162 at a subsequent time T4. As illustrated in FIG. 3, within the charge detection cylinder 162, the charged particle induces a charge of magnitude C2 on the charge detection cylinder 162. 2C, at time T5>T4, the charged particle P exits the second charge detection cylinder 162 and then enters the third and final charge detection cylinder 163, where the charged particle P then exits the charge detection cylinder 163 at a subsequent time T6. As shown in FIG. 3, within the charge detection cylinder 163, the charged particle induces a charge of magnitude C1 on the charge detection cylinder 163.

[0026]

[0060] As illustrated by way of example in FIGS. 2A-2C, as the charged particle P moves successively through the charge detection cylinders 161-163, the processor 24 is illustratively operable to determine the magnitude and / or charge state of the charged particle P based on the charge detection signals generated by the charge amplifiers CA1-CA3 according to execution of corresponding instructions stored in the memory 26. In one embodiment, the processor 24 is operable to make the above determination based on the charge detection signal generated by the first charge amplifier CA1, and thereafter to successively update the charge determination based on the charge detection signals generated by the remaining charge amplifiers CA2 and CA3 after the charged particle has passed through the respective charge detection cylinders 161 and 162. In some embodiments, the processor 24 is further operable to similarly determine the velocity of the charged particle P based on the charge detection signal generated by the first charge amplifier CA1 according to execution of corresponding instructions stored in the memory 26, and thereafter to update the velocity determination based on the charge detection signals generated by the remaining charge amplifiers CA2 and CA3 after the charged particle has passed through the respective charge detection cylinders 161 and 162.

[0027]

[0061] Using this exemplary model, the processor 24 is illustratively operable to determine an initial magnitude of charge CH of the particle P after the particle P leaves the first charge detection cylinder 161 as shown, for example, at the falling edge of CA1, as the magnitude CH=C1 generated by the charge amplifier CA1 between the rising edge of CA1 at time T1 and the falling edge of CA1 at time T2. In some embodiments, the processor 24 further determines the initial velocity of the charged particle as Vel PAfter detecting the falling edge of CA2 at time T4, processor 24 is operable to determine an updated magnitude of the charge of particle P as CH=(CH+C2) based on the magnitude C2 generated by charge amplifier CA2 between the rising edge of CA2 at time T3 and the falling edge of CA2 at time T4. In some embodiments, processor 24 determines an updated velocity of the charged particle as Vel P =Vel P After detecting the falling edge of CA3 at time T6, processor 24 is operable to determine a final updated magnitude of the charge of particle P as CH=CH+C3 based on the magnitude C1 generated by charge amplifier CA3 between the rising edge of CA3 at time T5 and the falling edge of CA3 at time T6. In some embodiments, processor 24 determines the updated velocity of the charged particle as Vel P =Vel P After the ions have traveled through all of the charge detectors, the average charge is calculated from CH = CH / N, where N is the number of measurements (in this case, 3), and the average velocity is Vel P =Vel P Calculated from / N.

[0028]

[0062] Shortly after T6, the processor 24 determines the magnitude CH of the charge of the particle P and, in some embodiments, the velocity Vel based on the average of the charge detection signals generated by the charge amplifiers CA1-CA3. P In some embodiments, the processor 24 determines, for example, an elementary charge constant e (e.g., 1.602716634×10 -19The processor 24 may be operable to convert the charge magnitude to a charge state by dividing CH by the charge magnitude (Coulombs) or to calculate the initial and updated charge values ​​as charge state values ​​rather than charge magnitudes. In either case, if the determined charge magnitude or charge state CH is equal to or within a predetermined range of a predetermined or target charge magnitude or charge state value, the processor 24 is operable to control the voltage source VS1 to apply one or more voltage values ​​to the charge deflection or drive region 14, thereby causing the charge deflection or drive region 14 to pass the charged particle P. Otherwise, the processor 24 is operable to control the voltage source VS2 to apply one or more voltage values ​​to the charge deflection or drive region 14, thereby causing the charge deflection or drive region 14 to prevent the passage of the charged particle P or to drive the charged particle P away from the region 14. In some embodiments of charge deflection or drive region 14, such control of voltage source VS1 must occur before charged particle P enters region 14 at time T7>T6, while in other embodiments, such control of voltage source VS1 may occur after charged particle P has entered region 14 but before charged particle P has left region 14. In either case, when processor 24 determines that Vel P In the embodiment for determining the velocity Vel, the determined velocity Vel is used to estimate the future position of the charged particle P entering, within, and / or moving through the region 14 for purposes of determining the timing of the control of the voltage source VS1 to pass, prevent, or drive the charged particle P through the region 14. P may be used along with dimensional information of the drift region 12 and / or the charge deflection or drive region 14. In an alternative embodiment, the processor 24 may use the determined velocity Vel of the charged particle approaching the region 14. P The timing of the control of voltage source VS1 may be based solely on this.

[0029]

[0063] Those skilled in the art will recognize other techniques for determining the size and / or charge state and / or velocity of charged particle P based on one or more of the charge detection signals generated by charge amplifiers CA1 to CAN, and / or other techniques for determining the timing of control of voltage source VS1 for passing, preventing passing, or driving charged particle P through region 14. It will be understood that such other techniques are intended to be within the scope of the present disclosure.

[0030]

[0064] Referring now to FIGS. 4A-4N, another simplified example of the charge filter apparatus 10 of FIG. 1 is shown, including three charge detection cylinders 161-163 axially disposed between the ion inlet A1 of the drift tube 12A and the charge deflection or drive region 14. Using this simplified apparatus 10, FIGS. 4A-4N illustrate two charged particles P1, P2 continuously drifting through each of the three charge detection cylinders 161-163 over time, where P1 has a slightly lower mass-to-charge ratio than P2. FIG. 5 illustrates an exemplary charge detection signal generated by the first charge amplifier CA1 when the charged particle passes through, and FIGS. 6 and 7 illustrate exemplary charge detection signals generated by the second charge amplifier CA2 and the third charge amplifier CA3, respectively. As shown in FIGS. 4A-4E, charged particles P1 and P2 enter the first charge detection cylinder 161 at respective times T1 and T2, where T2>T1. At time T3>T2, charged particle P1 exits the charge detection cylinder 161, and at time T5>T3, charged particle P2 exits the charge detection cylinder 161. As shown in FIG. 5, only particle P1 moves within the charge detection cylinder 161 between T1 and T2, and charged particle P1 induces a charge of magnitude C1 on the charge detection cylinder 161. Between T2 and T3 when both charged particles P1 and P2 are moving through the charge detection cylinder 161, both charged particles P1 and P2 induce a charge of magnitude C2>C1 on the charge detection cylinder 161, and between T3 and T5 when only charged particle P2 is moving through the charge detection cylinder 161, charged particle P2 induces a charge of C3<C1 on the charge detection cylinder 161.

[0031]

[0065] A plurality of charged particles pass axially through the drift region 12 and thus through successive charge detection cylinders 161-16. N 2A-3 may be used to track ion charge and velocity based on detection by processor 24 of rising and falling edges of charge detection signals generated by successive ones of charge amplifiers CA1-CAN as a single charged particle drifts axially through charge detection cylinders 161-16. In particular, instructions stored in memory 26 illustratively monitor the charge detection signals generated by charge amplifiers CA1-CAN and detect when a single charged particle drifts axially through charge detection cylinders 161-16. N Count each rising edge of the charge detection signal when a single charged particle enters each of the charge detection cylinders 161 to 16 N the charge detection signal as it exits the charged particle detector 22, and may include instructions executable by the processor 24 to count the falling edges of each of the charge detection signals as they exit the charged particle detector 22, record the various magnitudes of the charge detection signals as magnitudes of single charged particles and combinations of charged particles, and record the velocities of each of the plurality of charged particles based on the rising and falling edges of the charge detection signals.

[0032]

[0066] Using the charge detection signal generated by CA1, for example, the first rising edge is counted as a first charged particle having a charge magnitude equal to the magnitude of the charge detection signal between the first rising edge and the next rising edge or falling edge. If the next edge event is a falling edge, the velocity of the first charged particle is equal to the ratio of the length CDL of the charge detection cylinder 161 and the time difference between the rising edge and the falling edge. If the next edge event is instead another rising edge, the second rising edge is counted as a second charged particle having a composite charge magnitude equal to the magnitude of the charge detection signal between the second rising edge and the next rising edge or falling edge. This process continues with each rising edge. Upon detecting the first falling edge, this is counted as a first charged particle exiting the charge detection cylinder 161, the velocity of the first charged particle is equal to the ratio of the length CDL of the charge detection cylinder 161 to the time difference between the first rising edge and the first falling edge, and the magnitude of the charge detection signal generated by CA1 after the first falling edge is the magnitude of the combined charge of the charged particles remaining in the charge detection cylinder 161. This process continues until the last falling edge of the charge detection signal generated by CA1, and an identical process is performed with respect to the charge detection signals generated by each of the remaining charge amplifiers CA1 through CAN.

[0033]

[0067] Referring again to FIG. 5, the processor 24 executing the above-described process calculates the charge CH of the first charged particle P1 between T1 and T2. P1 is C1, and the combined charge CH of charged particles P1 and P2 between T2 and T3 is P1P2 is C2, and the charge CH of the second charged particle P2 between T3 and T5 P2 In an embodiment in which the velocity of the charged particles passing through the charge detection cylinder 161 is determined by the processor 24 as part of the process described above, the processor 24 determines the velocity of the first charged particle P1 as Vel P1is determined as = CDL / (T3 - T1), and the velocity of the second charged particle P2 is Vel P2 is operable to be determined as = CDL / (T5 - T2). In some embodiments, the processor 24 is CH P1 and CH P2 such that the measured relationship CH P1 + CH P2 = C2 is further satisfied, CH P1 and CH P2 may be operable to be modified. In alternative embodiments, after processing the charge detection signals generated by one or more or all of the downstream charge amplifiers CA2 to CAN, CH P1 and CH P2 the above modification of is incorporated into the magnitude values of the charges CH P1 and CH P2 .

[0034]

[0068] As shown in FIGS. 4D to 4I, the charged particles P1 and P2 enter the second charge detection cylinder 162 at times T4 and T6 respectively, where T6 > T4 > T3. At time T7 > T6, the charged particle P1 exits the charge detection cylinder 162, and at time T9 > T7, the charged particle P2 exits the charge detection cylinder 162. As shown in FIG. 6, only the particle P1 moves inside the charge detection cylinder 162 between T4 and T6, and the charged particle P1 induces a charge of magnitude C4 on the charge detection cylinder 162. Between T6 and T7 when both the charged particles P1 and P2 are moving through the charge detection cylinder 162, both the charged particles P1 and P2 induce a charge of magnitude C5 > C4 on the charge detection cylinder 162, and between T7 and T9 when only the charged particle P2 is moving through the charge detection cylinder 162, the charged particle P2 induces a charge of C6 < C4 on the charge detection cylinder 162. Also in this case, using the process described above, the processor 24 updates the charge CH P1 of the first charged particle P1 to CH P1 = CH P1 + C4, and the charge CH P2 of the second charged particle P2 to CH P2 = CH P2+ C6, and the combined charge CH of charged particles P1 and P2 between T6 and T7 P1P2 In an embodiment in which the velocity of the charged particles passing through the charge detection cylinder 162 is determined by the processor 24 as part of the process described above, the processor 24 determines the velocity of the first charged particle P1 as Vel P1 =Vel P1 +CDL / (T7-T4), and update the velocity of the second charged particle P2 to Vel P2 =Vel P2 +CDL / (T9-T6). In some embodiments, the processor 24 is operable to update the CH P1 and C.H. P2 is the measured relationship CH P1 +CH P2 =C5 to further satisfy CH P1 and C.H. P2 In an alternative embodiment, after processing of the charge detection signals generated by one or more or all of the downstream charge amplifiers CA3-CAN, P1 and C.H. P2 The above corrections are made to the charge magnitude value CH P1 and C.H. P2 is woven into the fabric.

[0035]

[0069] As shown in FIGS. 4H to 4M, charged particles P1 and P2 enter the third charge detection cylinder 163 at times T8 and T10, respectively, where T10>T8>T7. At time T11>T10, charged particle P1 exits the charge detection cylinder 163, and at time T13>T11, charged particle P2 exits the charge detection cylinder 163. At time T12, when the second charged particle P2 is still inside the third charge detection cylinder 163 such that T11<T12<T13, the first charged particle P1 enters the charge deflection or drive region 14 as shown in FIG. 4L, and at time T14>T13, the second charged particle P2 enters the charge deflection or drive region 14. As shown in FIG. 7, only particle P1 moves inside the charge detection cylinder 163 between T8 and T10, and charged particle P1 induces a charge of magnitude C7 on the charge detection cylinder 163. Between T10 and T11 when both charged particles P1 and P2 are moving through the charge detection cylinder 163, both charged particles P1 and P2 induce a charge of magnitude C8>C7 on the charge detection cylinder 163, and between T11 and T13 when only charged particle P2 is moving through the charge detection cylinder 163, charged particle P2 induces a charge of C9<C7 on the charge detection cylinder 163.

[0036]

[0070] Also in this case, using the process described above, the processor 24 is operable to update the charge CH of the first charged particle P1 between T11 and T12 as CH P1 to CH P1 =CH P1 +C7. In an embodiment where the velocity of the charged particle passing through the charge detection cylinder 163 is determined by the processor 24 as part of the process described above, the processor 24 is further operable between T11 and T12 to update the velocity of the first charged particle P1 as Vel P1 =Vel P1 +CDL / (T11-T8). Since the charge detection cylinder 163 is the last charge detection cylinder in the example shown in FIGS. 4A to 4N, CH at the time between T11 and T12 P1is the last measured value of the magnitude of the charge of the first charged particle P1, and in the embodiment including it, the value Vel P1 is the final measurement of the velocity of the first charged particle P1. Its average charge is CH P1 =CH P1 / N, where N is the number of measurements (in this case, 3), and the average velocity is Vel P1 =Vel P1 Before the first charged particle P1 enters the charge deflection or actuation region 14, the processor 24 calculates CH P1 to one or more target charge magnitude values, or P1 =CH P1 / e) charge state CS P1 Calculate CS P1 to one or more target charge states, and then P1 or C.S. P1 The processor 24 is operable to control the voltage source VS1 after T12 and before T14 to pass / block the first charged particle P1 or drive the first charged particle P1 along one of a plurality of different paths in the region 14 based on the result of a comparison of the first charged particle P1 with one or more target charge magnitudes or target charge states. In an embodiment in which particle velocity is calculated, the timing of the above control of the voltage source VS1 by the processor 24 is based on the velocity Vel P1 and / or the Vel of the charge filter device 10 relative to and / or within the charge deflection or drive region 14. P1 and may be based on, or at least take into account, an estimated future position of the charged particle P1 based on the dimensional information.

[0037]

[0071] The processor 24 then calculates the charge CH of the second charged particle P2. P2 CH P2 =CH P2 +C9. In some embodiments, the processor 24 is operable between T13 and T14 to update the measurement CH generated by the charge amplifier CA3 as P1 +CH P2=CH to fill C8 P2 In an embodiment in which the velocity of the charged particles passing through the charge detection cylinder 163 is determined by the processor 24 as part of the process described above, the processor 24 may further operate between T13 and T14 to modify the velocity of the second charged particle P2 as Ve P2 =Vel P2 +CDL / (T13-T10). Again, since charge detection cylinder 163 is the last charge detection cylinder in the example illustrated in Figures 4A-4N, the CH at times between T13 and T14 can be updated as CDL +CDL / (T13-T10). P2 is the last measured value of the magnitude of the charge of the second charged particle P2, and in embodiments including it, the value Vel P2 is the final measurement of the velocity of the second charged particle P2. Its average charge is CH P2 =CH P2 / N, where N is the number of measurements (in this case, 3), and the average velocity is Vel P2 =Vel P2 / N. After the first charged particle P1 enters the charge deflection or drive region 14 at T12, and in some embodiments after the processor 24 controls the voltage source VS1 to pass / block or drive the first charged particle P1 through the charge deflection or drive region 14, and in any case before the second charged particle P2 enters the charge deflection or drive region 14, the processor 24 controls the CH P2 or a second charged particle P2 (CS P2 =CH P2 / e) charge state CS P2 Calculate CS P2 to one or more target charge states, and then P2 or C.S. P2The processor 24 is operable to control the voltage source VS1 from T14 onwards to pass / block the second charged particle P2 or drive the second charged particle P2 along one of a number of different paths in the region 14 based on the result of a comparison of the second charged particle P2 with one or more target charge magnitudes or target charge states. In an embodiment in which particle velocity is calculated, the timing of the above control of the voltage source VS1 by the processor 24 is based on the velocity Vel P2 and / or the Vel of the charge filter device 10 relative to and / or within the charge deflection or drive region 14. P2 and may be based on, or at least take into account, an estimated future position of charged particle P2 based on dimensional information.

[0038]

[0072] It will be understood that the examples illustrated in Figures 2A-7 are provided solely for purposes of illustrating the operation of the charge filter apparatus 10 and are not intended to be limiting in any way. Those skilled in the art will appreciate that the above-described process, or variations thereof, may be directly applied to determining the magnitude, charge state, and / or velocity of the charge, and further determining the passage / blocking and / or driving of many charged particles, e.g., hundreds, thousands, or more. Alternatively, those skilled in the art will recognize other techniques for determining the magnitude and / or charge state and / or velocity of a plurality of charged particles based on one or more of the charge detection signals generated by the charge amplifiers CA1-CAN, and / or other techniques for determining the timing of the control of the voltage source VS1 to pass, prevent passage, or drive the charged particles P through the region 14, and it will be understood that such other techniques are intended to be within the scope of the present disclosure. For example, in some embodiments, the charge detection signals generated by the charge amplifiers CA1-CAN may be differentiated. Each time an ion enters the charge detection cylinder, a pulse toward the positive pole results, and each time an ion exits the charge detection cylinder, an ion toward the negative pole results. If the rise and fall times of the output signals of the charge amplifiers CA1-CAN (see, e.g., Figures 3, 5, 6, and 7) are significantly shorter than the time constants for differentiation, then the charge is given by the height of the peak. On the other hand, if the rise and fall times are significantly longer than the time constants for differentiation, then the charge is given by the area of ​​the peak. The amplitudes of the positive-going and negative-going pulses associated with a particular ion should be identical, which provides an identifier for pairing the positive-going and negative-going pulses, from which the velocity and average charge may be determined. This alternative data analysis technique may be beneficial, for example, when there is a large number of ions drifting through the drift tube 16A.

[0039]

[0073] It will be further appreciated that in the charge filter apparatus 10 illustrated in FIG. 1, not all of the charge detection signals may be used to determine particle charge value and / or particle velocity. In some embodiments where charged particles exit the ion source 30 in agglomerated form, for example, the charge detection signals generated by the first one or more charge amplifiers may be ignored by the processor 24. Alternatively or additionally, the drift tube 12A may be configured to detect such agglomerated particles in a number of charge detection cylinders 161-16. N The pre-array space 12B may be configured to have any desired length that allows the charged particles to at least begin to separate axially in the drift region 12 before passing through the first of the charge detection cylinders 16. As another example, the processor 24 may be configured to determine whether the charged particles are to separate axially in the drift region 12 before passing through the first of the charge detection cylinders 16. N or before the charged particles reach the last few charge detection cylinders 16 N-Y ~16 N , where Y may be any positive integer less than N. Alternatively or additionally, drift tube 12A may be configured to include a post-array space 12C of any desired length to ease timing requirements for control of voltage source VS1 after determination of particle charge value and / or velocity. As yet another example, processor 24 may be configured or programmed in some embodiments to determine only charge values, i.e., not particle velocity values, and to base control of voltage source VS1 solely on charge value determinations, and further, in some embodiments, solely on dimensional information of charge filter apparatus 10.

[0040]

[0074] As briefly discussed above, the charge deflection and drive region 14 is controllable, i.e., by controlling the voltage source VS1, to pass, block, or drive ions based on the charge magnitude or charge state of the ions. In this regard, ions of a particular charge magnitude, ions of a particular charge state, ions having a charge within a predetermined range of charge magnitudes, or ions having a calculated charge state within a predetermined range of one or more particular integer charge states may be analyzed and / or collected for analysis of one or more molecular features. Because all such ions have a known common charge magnitude or charge state as a result of the charge measurement information generated by the charge amplifiers CA1-CAN, the known ion charge magnitude and / or charge state of such ions may be used in such downstream analysis to determine molecular feature information not previously determinable with conventional instruments. For example, in one non-limiting application in which the charge filter instrument 10 is controlled to pass only ions having a charge state of a+1, for example, as described above, such charge information may be used to directly determine particle mass values ​​using a conventional mass spectrometer or mass analyzer that measures ion mass-to-charge ratios. As another non-limiting application example, where the charge filter instrument 10 is controlled to pass only ions having a+1 charge state, for example, as described above, such charge information can be used to directly determine particle mobility values ​​using a conventional ion mobility analyzer that measures ion mobility as a function of particle charge. As yet another non-limiting example, the charge filter instrument 10 can be configured and controlled to drive and analyze, or collect for analysis, different sets of ions, each having a different charge magnitude or state, for example, +1, +2, +3, for example, as described above. The known charge magnitude or charge state of each of said sets can then be used in conjunction with one or more molecular analysis stages to determine one or more molecular characteristics of the set, for example, particle mass, particle mobility, etc.

[0041]

[0075] Referring now to FIG. 8, there is shown an embodiment of the charge deflection or drive region 14 of the charge filter apparatus illustrated in FIGS. 1, 2A-2D, and 4A-4N. In the illustrated embodiment, the charge deflection or drive region 14 is implemented in the form of a single inlet-single outlet charge deflector 14A configured and controllable to selectively pass or block the passage of ions. The charge deflector 14A comprises a pair of conductive members 60, 62, each having a length DL, disposed apart from one another to generally define a channel 64 between a single ion inlet A3 and a single ion outlet A4, illustratively in the form of a plate, grid, or other conductive material. In the illustrated embodiment, the members 60, 62 are illustrated as flat plate-like pieces such that the channel 64 is a square or rectangular channel. In alternative embodiments, the conductive members 60, 62 may be implemented in other shapes, without limitation. In either case, a first voltage output V1 of voltage source VS1 is electrically connected to conductive member 62 and a second voltage output V2 of voltage source VS1 is electrically connected to conductive member 60. In one embodiment, voltages V1 and V2 may be switchable DC voltages, or one of voltages V1, V2 may be set to a reference potential, e.g., ground potential or other reference potential, and the other voltage V1, V2 may be a switchable DC voltage. In an alternative embodiment, voltage V1 and / or voltage V2 may be a time-varying voltage.

[0042]

[0076] In either case, the charge deflector 14A is illustratively operable to deflect the charged particle P entering the inlet A3 towards one or the other of the members 60, 62 by controlling the voltages V1 and / or V2 to generate an electric field E of sufficient magnitude to divert and accelerate the charged particle P towards the members 60, 62 as illustrated by way of example in Fig. 8. Conversely, the charge deflector 14A is illustratively operable to pass the charged particle P entering the inlet A3 towards and through the outlet A4, as illustrated by dashed line representation in Fig. 8, unless an electric field E is established between the members 60, 62, or unless an electric field E is established between the members 60, 62 but is not of sufficient magnitude to deflect the charged particle P towards one or the other of the members 60, 62. In one illustrative example, which should in no way be considered limiting, if the charged particle P has a positive charge, then V1=V2=0 volts (earth potential) will cause the charged particle P to pass through the channel 64, and V1=0 volts, V2=+Z volts will cause the charged particle P to deflect toward and into the conductive member 62, where Z is selected to establish an electric field E between the members 60, 62 that is large enough to direct and accelerate the charged particle P over the surface of the member 62 before it reaches the outlet A4, thereby blocking its passage through the charge deflector 14A. It will be understood that in alternative embodiments, the roles of V1 and V2 may be reversed. In other alternative embodiments, the electric field E may be a time-varying field established by one or more time-varying voltages V1, V2.

[0043]

[0077] 9A and 9B, there is shown another embodiment of the charge deflection or drive region 14 of the charge filter apparatus illustrated in FIGS. 1, 2A-2D, and 4A-4N. In the embodiment illustrated in FIGS. 9A and 9B, the charge deflection or drive region 14 is implemented in the form of another single inlet-single outlet charge deflector 14B configured and controllable to selectively pass or block the passage of ions. The charge deflector 14B is illustratively provided in the form of a quadrupole filter including four elongated conductive rods 70, 72, 74, 76, each having a length RL and positioned radially spaced apart from one another to define a channel 78 therethrough between a single ion inlet A3 and a single ion outlet A4. In the illustrated embodiment, the rods 70-76 are illustrated as cylindrical rods having a generally circular cross-sectional shape, although in alternative embodiments the rods 70-76 may have a cross-sectional shape other than circular. In either case, a first voltage output V1 of voltage source VS1 is electrically connected to conductive rods 70, 72 and a second voltage output V2 of voltage source VS1 is electrically connected to conductive rods 74, 76, where rod 70 is disposed radially opposite rod 72 and rod 74 is disposed radially opposite rod 76. In one embodiment, voltages V1 and V2 may include time-varying voltages, e.g., RF voltages, that are 180 degrees out of phase with each other and may further include DC voltages between rod pairs 70, 72 and 74, 76. In some alternative embodiments, V1 and V2 may include only time-varying voltages, e.g., RF voltages, and in other alternative embodiments, V1 and V2 may include only DC voltages.

[0044]

[0078] In either case, the charge deflector 14B is illustratively operable to deflect a charged particle P entering the inlet A3 to one of the rods 70-76 by controlling the voltages V1 and / or V2 in a conventional manner to generate a non-resonant electric field E between the rods 70-76 that is sufficient to block passage of the charged particle P through the charge deflector 14B by deflecting the charged particle P to one of the rods 70-76. Conversely, the charge deflector 14B is illustratively operable to cause a charged particle P entering the inlet A3 to pass toward and exit the outlet A4 by controlling the voltages V1 and / or V2 in a conventional manner to generate a resonant electric field E between the rods 70-76 that confines the charged particle P to the channel 78, thereby allowing the charged particle P entering the inlet A3 to pass axially through the channel 78 and exit through the ion outlet A4. In some alternative embodiments, charge deflector 14B may be used in combination with one or more other charge deflection or drive components to pass only ions having a mass-to-charge ratio above a threshold mass-to-charge ratio, for example by controlling V1 and V2 to supply only time-varying voltages (i.e., non-DC voltages).

[0045]

[0079] 10A and 10B, there is shown yet another embodiment of the charge deflection or drive region 14 of the charge filter apparatus illustrated in FIGS. 1, 2A-2D, and 4A-4N. In the embodiment illustrated in FIGS. 10A and 10B, the charge deflection or drive region 14 is implemented in the form of a single-inlet-multiple-exit charge drive device 14C configured and controllable to selectively drive ions entering the inlet A3 through one of a plurality of different ion outlets. The charge drive device 14C is illustratively provided in the form of a single-inlet-three-exit quadrupole charge drive device having four elongated conductive arc members 80, 82, 84, 86 spaced apart from one another to define an ion drive space 88 therebetween. Each of the conductive arcuate members 80, 82, 84, 86 has a convex surface facing the drive space 88, with the members 80, 82 positioned opposite each other on either side of the space 88, and the members 84, 86 positioned opposite each other on either side of the space 88. Each adjacent pair of arcuate members defines an ion inlet or outlet therebetween. For example, the arcuate members 80 and 84 are positioned radially apart from each other to define an ion inlet A3 of the drive device 14B therebetween, and the arcuate members 82 and 86 are similarly positioned radially apart from each other to define one ion outlet A4 axially opposite the ion inlet A3 therebetween. The arcuate members 80 and 86 are positioned axially apart from each other to define one side outlet SA1 therebetween, and the arcuate members 82 and 84 are similarly positioned axially apart from each other to define another side outlet SA2 radially opposite the side outlet SA1 therebetween.

[0046]

[0080] In the embodiment illustrated in FIG. 10B, a first voltage output V1 of the voltage source VS1 is electrically connected to the conductive members 80 and 82, and a second voltage output V2 of the voltage source VS1 is electrically connected to the conductive members 84 and 86. In one embodiment, the voltages V1 and V2 may include time-varying voltages, e.g., RF voltages, that are 180 degrees out of phase with each other, and may further include DC voltages between the rod pairs 80, 82 and 84, 86. In some alternative embodiments, V1 and V2 may include only time-varying voltages, e.g., RF voltages, and in other alternative embodiments, V1 and V2 may include only DC voltages. In one illustrative example, the voltages V1 and V2 are switchable DC voltages, and the processor 24 is illustratively operable to control V1 and V2 to the same voltage, e.g., ground potential or other potential, to cause the charged particles P that have entered the inlet A3 to pass directly through the space 88 through the ion outlet A4 along a linear axis 85, as shown by the dashed line in FIG. 10B. Alternatively, assuming that the charged particle P has a positive charge, the processor 24 may be operable to control V1 to a negative potential and V2 to an opposite positive potential to generate an electric field within the space 88 configured to drive the charged particle P that has entered the ion inlet A3 along an arcuate path 87A and out of the charge drive device 14B through the side outlet SA1 as also shown in FIG 10B. Still alternatively, again assuming that the charged particle P has a positive charge, the processor 24 may be operable to control V1 to a positive potential and V2 to an opposite negative potential to generate an electric field within the space 88 configured to drive the charged particle P that has entered the ion inlet A3 along an arcuate path 87B and out of the charge drive device 14B through the side outlet SA2 as also shown in FIG 10B.

[0047]

[0081] 11, there is shown a further embodiment of the charge deflection or drive region 14 of the charge filter apparatus illustrated in FIGS. 1, 2A-2D, and 4A-4N. In the embodiment illustrated in FIG. 11, the charge deflection or drive region 14 is implemented in the form of another single-inlet-multiple-outlet charge drive device 14D configured and controllable to selectively drive ions that have entered the inlet A3 through one of a plurality of different ion outlets. The charge drive device 14D illustratively includes a pattern of four substantially identical, spaced apart conductive pads C1-C4 formed on an inner major surface 90A of one substrate 90 having an opposite outer major surface 90B, and an identical pattern of four substantially identical, spaced apart conductive pads C1-C4 formed on an inner major surface 92A of another substrate 92 having an opposite outer major surface 92B. The spaced apart inner major surfaces 90A, 92A of the substrates 90, 92 are spaced apart in a generally parallel relationship, with the conductive pads C1-C4 of the substrate 90 juxtaposed over respective ones of the conductive pads C1-C4 of the substrate 92. The spaced apart inner major surfaces 90A and 92A of the substrates 90, 92 illustratively have a width D P In one embodiment, the width D of the channel 94 is P is approximately 5 cm, but in other embodiments, the distance D P may be greater or less than 5 cm.

[0048]

[0082] The opposing pad pairs C1, C1 and C3, C3 define an ion inlet A3 therebetween, and the opposing pad pairs C2, C2 and C4, C4 define an ion outlet A4 therebetween. The opposing pad pairs C1, C1 and C2, C2 define a side outlet SA1 therebetween, and the opposing pad pairs C3, C3 and C4, C4 define an opposite side outlet SA2, all of which are similarly described with respect to the embodiment illustrated in Figures 10A and 10B. The edges 90C, 92C of the substrates 90, 92 are illustratively aligned with one another, as are the edges 90D, 92D, the edges 90E, 92E, and the edges 90F, 92F.

[0049]

[0083] A first voltage output V1 of the voltage source VS1 is electrically connected to the conductive pad pairs C1, C1 and C4, C4, and a second voltage output V2 of the voltage source VS1 is electrically connected to the conductive pad pairs C2, C2 and C3, C3. In one embodiment, the voltages V1 and V2 may be switchable DC voltages that are controllable to selectively establish ion driving electric fields between various pad pairs of the pad pairs C1, C1, C2, C2, C3, C3, and C4, C4. In one example, the processor 24 is illustratively operable to control V1 and V2 to the same voltage, e.g., ground potential or other potential, to cause the charged particles P entering the inlet A3 to pass directly through the spatial channel 94 through the ion outlet A4 along the linear axis 96, as shown in FIG. Alternatively, assuming that the charged particle P has a positive charge, the processor 24 may be operable to control V1 to a negative potential and V2 to an opposite positive potential to generate an electric field within a channel 96 configured to drive the charged particle P that has entered the ion inlet A3 along an arcuate path 98A and exit the charge drive device 14B through a side outlet SA1 as also shown in Figure 11. Still alternatively, again assuming that the charged particle P has a positive charge, the processor 24 may be operable to control V1 to a positive potential and V2 to an opposite negative potential to generate an electric field within a channel 94 configured to drive the charged particle P that has entered the ion inlet A3 along an arcuate path and exit the charge drive device 14B through a side outlet SA2.

[0050]

[0084] 12, there is shown an embodiment of a particle measurement device 100 including an embodiment 10A of the charge filter apparatus 10 shown in FIG 1 and described above. In the embodiment shown in FIG 12, the charge filter apparatus 10A includes a drift region 12 having an ion inlet A1, and a charge detector array 16, as described above, including a plurality of charge detection cylinders 161-16 axially disposed within the drift tube 12A between the ion inlet A1 and the ion outlet A2. Nand further including a charge deflection or drive region 14 coupled to the exit end of the drift tube 12 in the form of a charge deflector. The charge deflector may be exemplarily embodied as any of the charge deflectors 14A, 14B illustrated in Figures 8 and 9A-9B, respectively, or as any of the charge drive devices 14C, 14D illustrated in Figures 10A-10B and 11, respectively. In the latter case, the charge drive device, e.g., charge drive device 14C or 14D, is exemplarily controlled to operate as a charge deflector that passes ions that have entered the ion inlet A3 towards the ion outlet A4, or blocks the passage of those ions through the ion outlet A4, e.g., by driving the ions away from the ion outlet A4 through one of the side outlets SA1, SA2. Alternatively or additionally, the charge deflector illustrated in FIG. 12 may be embodied in the form of one or more other conventional charge deflectors, charge diverters, charge driven devices, or other devices that may be controlled as described above to selectively pass ions that have entered the ion inlet A3 through to the ion outlet A4, or to selectively block ions that have entered the ion inlet A3 from passing through to the ion outlet A4, using any conventional structure and / or techniques.

[0051]

[0085] The particle measurement device 100 further includes an ion source region 30 operably coupled to the ion inlet end of the charge filter apparatus 10A. The ion source region 30 is as described above with reference to FIG. 1 and illustratively includes at least one ion generator coupled to a voltage source VS2 and configured to respond to control signals generated by the processor 24 to generate ions from a sample disposed inside or outside the ion source region 30, and further includes one or more conventional structures and / or devices for accelerating or otherwise propelling the generated ions through the ion inlet A1 into the charge filter apparatus 10A. In some embodiments, for example, the ion source region 30 may include at least one ion acceleration structure or region separate from or part of the ion generator and operably coupled to the voltage source VS2 (see FIG. 1). In this embodiment, the processor 24 may illustratively be programmed to control the voltage source VS2 to selectively establish an ion acceleration electric field with the ion acceleration structure or within the ion acceleration region, the ion acceleration structure or ion acceleration region being oriented in either case to accelerate the generated ions through the ion inlet A1 into the charge filter apparatus 10A. As another example where the sample is contained within the ion source region 30, the drift region 12 may be pressurized, e.g., by one or more conventional pumps, to a lower pressure than the ion source region 30, and in such an embodiment, the pressure differential between the ion source region 30 and the drift region 12 may propel the generated ions through the ion inlet A1 and into the charge filter apparatus 10A. As yet another example where the sample is contained outside the ion source region 30, the ion source region and / or drift region 12 may be pressurized, e.g., by one or more conventional pumps, to a lower pressure than the ambient or atmospheric pressure in which the sample is located, and in such an embodiment, the pressure differential between the ambient or atmospheric pressure outside the ion source region 30 and the lower pressure environment within the ion source region and / or drift region 12 may propel the generated ions through the ion inlet A1 and into the charge filter apparatus 10A.In yet other embodiments, a combination of a pressure differential and an ion acceleration region or structure may be used to provide the motive force to accelerate or otherwise propel the generated ions into the charge filter apparatus 10A.

[0052]

[0086] In some embodiments, the ion source region 30 may include one or more ion separation devices or stages and / or one or more ion processing devices or stages in any combination. Some examples of various compositions of the ion source region 30 are detailed below with respect to FIG.

[0053]

[0087] The particle measurement device 100 further comprises an ion storage, drive and / or measurement stage 32 operably coupled to the ion outlet end of the charge filter apparatus 10A, as illustrated in FIG. 1 and briefly described above. In the embodiment illustrated in FIG. 12, the ion storage, drive and / or measurement stage 32 is illustratively implemented in the form of an ion storage and measurement stage 32A comprising a conventional ion trap 102 operably coupled to a voltage source VS3 (see FIG. 1) and having an ion inlet coupled to an ion outlet A4 of the charge filter apparatus 10A and an ion outlet coupled to an ion inlet of the ion measurement stage 104. In some alternative embodiments, the ion trap 102 may be omitted such that the ion outlet A4 of the charge filter apparatus 10A is directly coupled to the ion inlet of the ion measurement stage 104. The ion measurement stage 104 may, in either case, illustratively comprise one or more conventional apparatus or stages for separating ions in time according to one or more molecular features. In some embodiments, the ion measurement stage 104 may further comprise one or more ion processing devices or stages in any combination with one or more ion separation devices or stages. The ion measurement stage 104 is operably coupled to a voltage source VS3 as shown in Figure 1. Some examples of various compositions of the ion measurement stage 104 are detailed below with respect to Figure 16.

[0054]

[0088] 12, ions are provided to the charge filter apparatus 10A by the ion source region 30, where the processor 24 is operable in some embodiments to determine particle charge values ​​and particle velocities as the ions drift through the drift region 12 and, as described above, to further control the voltage source VS1 to pass only ions having a target charge magnitude, a charge magnitude within a selected threshold or target charge magnitude range, a target charge state, or a charge state within a selected threshold or target charge state range (individually and collectively referred to herein as "target charge"). In one example in which the charged particle measuring device 100 includes an ion trap 102, the processor 24 is illustratively programmed, for example by instructions stored in the memory 26, to control the voltage source VS3 to collect and store in the ion trap 102 ions having a target charge and thus selected by the processor 24 for passage through the charge deflectors 14A,B,C,D into the ion trap 102. The processor 24 is illustratively configured to control the voltage source VS3 to collect and store ions within the ion trap 102 for any period of time. At some point after the ion trap 102 has operated to collect and store ions within itself, the processor 24 is operable to control the voltage source VS3 to release the collected ions into an ion inlet of the ion measurement stage 104, and the processor 24 is then operable to control the voltage source VS3 in a conventional manner to control the operation of one or more ion measurement instruments that comprise the ion measurement stage 104 to measure one or more molecular characteristics of a set of ions that all have a target charge. In an alternative embodiment that does not include an ion trap 102, ions having a target charge that exit the charge filter instrument 10A are fed directly to the ion measurement stage 104, and the processor 24 is operable to control the voltage source VS3 to measure one or more molecular characteristics of the exiting ions. In either case, the processor 24 is further operable to collect, store and analyze ion measurement information generated by the ion measurement stage 104 in a conventional manner.

[0055]

[0089] In one example of the particle measurement instrument 100, which should not be considered limiting in any way, the ion measurement stage is or comprises a conventional mass spectrometer or mass analyzer. In this example, the processor 24 is illustratively operable to control voltage source VS1 to pass only ions having a first target charge into the ion trap 102, and then control voltage source VS3 to supply the collected ions to a mass spectrometer or mass analyzer, and further control voltage source VS3 to control the mass spectrometer or mass analyzer in a conventional manner to generate a mass to charge ratio measurement of the collected ions. Because the charge magnitude or charge state of the collected ions is the same and known, the processor 24 is further operable to determine the mass of the collected ions as a simple ratio of the mass to charge ratio measurement and a target charge value. In some embodiments, the ion trap 102 may be omitted and the processor 24 may be operable to control voltage source VS3 to control the mass spectrometer or mass analyzer to generate a mass to charge ratio measurement of the charge selected ions as they exit the exit aperture A4 of the charge filter instrument 10A, as described above. In either case, the processor 24 may further be operable in a charge scanning mode in which the above-described process is repeated one or more times for a selected range of target charge values. Those skilled in the art will recognize that the ion measurement stage 104 may be or comprise other conventional ion measurement instruments or stages configured to measure one or more molecular features and / or may comprise one or more ion processing instruments or stages configured to process the ions in any conventional manner, and it will be understood that such implementations of the ion measurement stage 104 are intended to be within the scope of the present disclosure. Some non-limiting examples of various measurement and processing instruments that may be included in the ion measurement stage 104 are described below with respect to FIG. 16.

[0056]

[0090] 13, there is shown another particle measurement device 200 embodiment that includes an embodiment 10B of the charge filter apparatus 10 shown in FIG 1 and described above. In the embodiment shown in FIG 13, the charge filter apparatus 10B includes a drift region 12 having an ion inlet A1, and a charge detector array 16, as described above, including a plurality of charge detection cylinders 161-16 axially disposed within the drift tube 12A between the ion inlet A1 and the ion outlet A2. N and further including a charge deflection or drive region 14 coupled to the exit end of the drift tube 12A in the form of a single inlet-multiple outlet charge drive device. In the illustrated embodiment, the single inlet-multiple outlet charge drive device is a single inlet-three outlet charge drive device having a single ion inlet A3, an oppositely disposed ion outlet A4, and two opposite side outlets SA1, SA2, which may be exemplarily embodied as any of the charge drive devices 14C, 14D illustrated in Figures 10A-10B and 11, respectively. Alternatively, the single inlet-multiple outlet charge drive device may have the form of any conventional single inlet-multiple outlet charged particle drive device.

[0057]

[0091] The particle measurement device 200 further illustratively comprises an ion storage, drive and / or measurement stage 32 in the form of three separate ion storage and measurement stages 32A1, 32A2, 32A3, each operably coupled to a corresponding respective ion outlet A4, SA1, SA2 of the single entrance-multiple exit charge drive device 14C, 14D. In the embodiment illustrated in FIG. 13, each stage 32A1, 32A2, 32A3 is identical to the stage 32A illustrated in FIG. 12 and described above. For example, each stage 32A1, 32A2, 32A3 comprises a respective conventional ion trap 1021, 1022, 1023 operably coupled to a corresponding respective ion measurement stage 1041, 1042, 1043. In some alternative embodiments, one or more of the stages 32A1, 32A2, 32A3 may be configured differently than the rest of the stages 32A1, 32A2, 32A3. In some alternative embodiments, one or more of the ion traps 1021, 1022, 1023 may be omitted such that the ion outlets of the charge driven devices 14C,D, respectively, are directly coupled to the ion inlets of the respective ion measurement stages 1041, 1042, 1043. The ion measurement stages 1041, 1042, 1043 are similarly identical to the ion measurement stage 104 shown in FIG. 13 and described above.

[0058]

[0092] The particle measurement device 200 further includes an ion source region 30 operably coupled to the ion entrance end of the charge filter apparatus 10B. The ion source region 30 is illustratively as described above with reference to Figures 1 and 12.

[0059]

[0093] 12 and described above, in that ions are provided to the charge filter apparatus 10B by the ion source region 30, where the processor 24 is operable to determine particle charge values, and in some embodiments particle velocities, for separation of the ions as they drift through the drift region 12. However, unlike the particle measurement device 100, the particle measurement device 200 is not limited to passing particles through a single outlet of the charge deflector, but rather is configured to pass particles through any of three outlets of the charge drive devices 14C, 14D. In the case of a single entrance-three exit charge drive device 14C, 14D, the processor 24 is illustratively programmed to control the voltage source VS1 to allow only ions having a first target charge to pass through the exit A4, only ions having a second target charge different from the first target charge to pass through the second exit SA1, and only ions having a third target charge different from the first and second target charges to pass through the third exit SA2, as described above.

[0060]

[0094] In one embodiment in which the charged particle measuring device 200 comprises ion traps 1021, 1022, 1023, the processor 24, illustratively by instructions stored in the memory 26, for example, controls a voltage source VS1 to drive charged particles P having a first target charge from the ion outlet A4 of the charge drive devices 14C, 14D into the ion trap 1021 along, for example, an ion travel path 2021 as illustrated in FIG. 13 , controls a voltage source VS3 to collect and store the charged particles P having the first target charge in the ion trap 1021, and controls a voltage source VS4 to collect and store the charged particles P having a second target charge into the ion trap 1021 along, for example, an ion travel path 2021 as illustrated in FIG. 13 into the ion trap 1022, for example along an ion travel path 2022 as shown in FIG. 13, and control voltage source VS3 to collect and store the charged particles having the second target charge in the ion trap 1022, and control voltage source VS1 to drive charged particles P having a third target charge from the ion outlet SA1 of the charge drive device 14C, 14D, for example along an ion travel path 2023 as shown in FIG. 13 into the ion trap 1023, for example along an ion travel path 2024 as shown in FIG. 13, and control voltage source VS3 to collect and store the charged particles having the third target charge in the ion trap 1023. The processor 24 is then operable to control voltage source VS3 to selectively eject the collected charged particles from any or all of the ion traps 1021, 1022, 1023 into corresponding ones of the ion measurement stages 1041, 1042, 1043 for analysis thereof. The processor 24 controls the voltage source VS3 to selectively eject the collected charged particles from any or all of the ion traps 1021, 1022, 1023 into corresponding ones of the ion measurement stages 1041, 1042, 1043 for analysis thereof in a conventional manner. 2、1043. Particle measurement device 200 is thereby similar in operation to device 100 illustrated in Figure 12 and described above, but configured to collect and analyze ions having three different target charges simultaneously or for later analysis using three different ion measurement stages 1041, 1042, 1043. Those skilled in the art will appreciate that the single inlet-multiple outlet charge driven device illustrated in Figure 13 is not limited to three ion outlets and may thus be configured to include two or more ion outlets, and in such embodiments, particle measurement device 200 may accordingly include two or more ion measurement stages 1041, 1042, 1043, and in embodiments which do include them, may include two or more ion traps 1021, 1022, 1023.

[0061]

[0095] 14, there is shown yet another particle measurement device 300 embodiment that includes an embodiment 10C of the charge filter apparatus 10 shown in FIG 1 and described above. In the embodiment shown in FIG 14, the charge filter apparatus 10C includes a drift region 12 (partially shown in FIG 14) having an ion inlet A1, and a charge detector array 16 including a plurality of charge detection cylinders 161-16 axially disposed within the drift tube 12A between the ion inlet A1 and the ion outlet A2, as shown in FIG 1 and described above. NThe charge filter apparatus 10C further comprises a charge deflection or drive region 14 coupled to the outlet end of the drift tube 12A in the form of a charge drive region 14 including a circuit of two series single inlet-multiple outlet charge drive devices and corresponding drift tubes. In the illustrated embodiment, both single inlet-multiple outlet charge drive devices are single inlet-three outlet charge drive devices having a single ion inlet A3, an oppositely disposed ion outlet A4, and two opposite side outlets SA1, SA2, respectively, which may be exemplarily embodied as either of the charge drive devices 14C, 14D illustrated in Figures 10A-10B and 11, respectively. Thus, the two single inlet-three outlet charge drive devices forming part of the charge drive region 14 are illustrated in Figure 14 as 14C1, D1 and 14C2, D2, respectively. Alternatively, the single inlet-multiple outlet charge drive devices may have the form of any conventional single inlet-multiple outlet charged particle drive device.

[0062]

[0096] 14, the inlet A3 of the first charge drive device 14C1,D1 is coupled to the ion outlet A2 of the drift tube 12A, and the ion outlet A4 of the charge drive device 14C1,D1 is coupled to one end of a linear drift tube section or portion 302, the opposite end of which is coupled to the ion inlet A3 of the second charge drive device 14C2,D2. The ion outlet A4 of the charge drive device 14C2,D2 is coupled to one end of another linear drift tube section or portion 304, the opposite end of which defines the first ion outlet IO1 of the charge drive region 14. A side ion outlet SA2 of the second charge driven device 14C2,D2 is coupled to one end of an arcuate drift tube section or portion 306, the opposite end of which defines a second ion outlet IO2 of the charge driven region 14. A side ion outlet SA1 of the second charge driven device 14C2,D2 is coupled to one end of another arcuate drift tube section or portion 308, the opposite end of which defines a third ion outlet IO3 of the charge driven region 14. The side ion outlet SA2 of the first charge driven device 14C1,D1 is further coupled to one end of another arcuate drift tube section or portion 310, the opposite end of which defines a fourth ion outlet IO4 of the charge driven region 14, and the side ion outlet SA1 of the first charge driven device 14C1,D1 is further coupled to one end of another arcuate drift tube section or portion 312, the opposite end of which defines a fifth ion outlet IO5 of the charge driven region 14. In the illustrated embodiment, the arcuate drift tube sections or portions 306, 308, 310 and 312 are illustratively configured to drive ions along drift paths that redirect the axial direction of the ion drift by approximately 90 degrees.Ions exiting side outlets SA1, SA2 of charge driven devices 14C1, D1 and 14C2, D2, respectively, in a direction perpendicular to the drift direction of ions entering inlet A3 of charge driven devices 14C1, D1 and 14C2, D2 are thereby redirected by arcuate drift tube sections or portions 306, 308, 310, 312 to exit outlets IO1-IO5 in a direction parallel to the drift direction of ions entering inlet A3 and exiting outlet A4 of charge driven devices 14C1, D1 and 14C2, D2. In alternative embodiments, one or more of drift tube sections 306, 308, 310 and 312 may be other than arcuate, or may be arcuate but configured to redirect the direction of ion drift through an acute or obtuse angle.

[0063]

[0097] The particle measurement device 300 further illustratively comprises an ion storage, drive and / or measurement stage 32B in the form of a plurality, e.g. five, individual ion traps 1021-1025 each having an ion entrance coupled to an outlet IO1-IO5 of a different one of the drift tube sections or portions 304, 306, 308, 310, 312, and each having an outlet coupled via a charged particle drive circuit 32C to an entrance of a single ion measurement stage 104. The charged particle drive circuit 32C illustratively comprises a plurality, e.g. five, charge drive devices operable as ion drive devices together controllable to selectively drive charged particles from each of the ion traps 1021-1025 to the entrance of the ion measurement stage 104. In the illustrated embodiment, each of the plurality of ion drive devices is implemented as any of the charge drive devices 14C, 14D illustrated in Figures 10A-10B and 11, respectively, and some of the plurality of ion drive devices are controlled to operate as single-inlet-single-exit ion drive devices, the rest of the plurality of ion drive devices are controlled to operate as two-inlet single-exit ion drive devices, and one of the plurality of ion drive devices is controlled to operate as a three-inlet single-exit ion drive device. For example, the ion inlet A31 of the ion drive devices 14C3,D3 is coupled to the ion outlet of the ion trap 1021, the ion outlet A4 opposite the ion inlet A31 is coupled to the ion inlet of the ion measurement stage 104, and the opposite side inlets A32 and A33 adjacent to the ion inlet A31 and the ion outlet A4 are coupled to the respective ends of the two drift tube sections or portions 314 and 316, respectively. The other ion drive device 14C4,D4 has an ion inlet A31 coupled to an ion outlet of the ion trap 1022, another ion inlet A32 adjacent to inlet A31 coupled to one end of the other drift tube section or portion 318, and an ion outlet SA1 opposite the ion inlet A32 and adjacent to inlet A31 coupled to the opposite end of the drift tube section or portion 314.The ion inlet A31 of a further ion drive device 14C5, D5 is coupled to the ion outlet of the ion trap 1023, the other ion inlet A32 adjacent to the inlet A31 is coupled to one end of the further drift tube section or part 320, and the ion outlet SA2 opposite the ion inlet A32 and adjacent to the ion inlet A31 is coupled to the opposite end of the drift tube section or part 316. The ion inlet A3 of a further ion drive device 14C6, D6 is coupled to the ion outlet of the ion trap 1024, and the ion outlet SA1 adjacent to the inlet A3 is coupled to the opposite end of the drift tube section or part 318. The ion inlet A3 of a further ion drive device 14C7, D7 is coupled to the ion outlet of the ion trap 1025, and the ion outlet SA2 adjacent to the inlet A3 is coupled to the opposite end of the drift tube section or part 320.

[0064]

[0098] Particle measurement device 300 is similar in operation to device 200 shown in Figure 13 and described above, but is configured to simultaneously collect ions having five different target charges and then analyze each of the five sets using a single ion measurement stage 104. For example, ions are provided to charge filter apparatus 10C by ion source region 30 and processor 24 is operable to determine particle charge values, and in some embodiments particle velocities, as the ions separate while drifting in drift region 12 as described above. Processor 24 is illustratively programmed to control voltage source VS1, as described above, to drive ions having each of the five different target charges through charge drive devices 14C1, D1 and 14C2, D2. For example, an ion having a first target charge passing from drift tube 12A to ion inlet A3 of charge driven device 14C1, D1 is directed by processor 24 through outlet A4 of charge driven device 14C1, D1 to ion inlet A3 of charge driven device 14C2, D2 under control of voltage source VS1, and is further directed by processor 24 through outlet A4 of charge driven device 14C2, D2 under control of voltage source VS1 to a first ion trap 1021, with processor 24 further operable to control ion trap 1021 to collect and store said ion in ion trap 1021 under control of voltage source VS3. Ions passing from drift tube 12A to ion inlet A3 of charge driven device 14C1, D1 and having a second target charge are directed by processor 24 through outlet A4 of charge driven device 14C1, D1 to ion inlet A3 of charge driven device 14C2, D2 under control of voltage source VS1, and further directed by processor 24 through outlet SA2 of charge driven device 14C2, D2 under control of voltage source VS1 to a second ion trap 1022, processor 24 is further operable to control ion trap 1022 to collect and store said ions in ion trap 1022 under control of voltage source VS3.The processor 24 is similarly operable, for ions passing from the drift tube 12A to the ion inlet A3 of the charge driven device 14C1,D1 and having a third, fourth, and fifth target charge, to control voltage source VS1 to drive said ions into the third, fourth and fifth ion traps 1023-1025, respectively, and then to control voltage source VS3 to collect and store said ions in the ion traps 1023-1025.

[0065]

[0099] The processor 24 is then operable to control the voltage source VS3 to selectively, and in some embodiments sequentially, release the collected charged particles from the ion traps 1021-1025, and to control the charged particle drive circuit 32C to selectively direct the charged particles to an inlet of an ion measurement stage for analysis. For example, to release the charged particles collected in the ion trap 1021 and drive or direct the collected ions to the ion measurement stage 104, the processor 24 is operable to control the voltage source VS3 to cause the ion trap 1021 to release stored ions therefrom to an ion inlet A31 of the ion drive device 14C3,D3, and to control the voltage source VS3 to cause the ion drive device 14C3,D3 to pass ions that have entered the ion inlet A31 to its ion outlet A4 and therethrough to the ion inlet of the ion measurement stage 104. The processor 24 is then operable to control the voltage source VS3 in a conventional manner to cause the ion measurement stage 104 to measure one or more molecular characteristics of the incoming charged particles. To release the charged particles collected in the ion trap 1022 and drive or direct the collected ions to the ion measurement stage 104, the processor 24 is operable to control the voltage source VS3 to cause the ion trap 1022 to release stored ions therefrom to the ion inlet A31 of the ion drive device 14C4, D4, and to control the voltage source VS3 to cause the ion drive device 14C4, D4 to pass the ions that have entered the ion inlet A31 to its ion outlet SA1 and therethrough to one end of the drift tube section or portion 314. The processor 24 is then operable to control the voltage source VS3 to pass the charged particles that have passed through the drift tube section or portion 314 to the inlet A32 of the ion drive device 14C3,D3, and further to control the voltage source VS3 to cause the ion drive device 14C3,D3 to pass the ions that have entered the ion inlet A32 to its ion outlet A4 and therethrough to the ion inlet of the ion measurement stage 104. The processor 24 is then operable to control the voltage source VS3 in a conventional manner to cause the ion measurement stage 104 to measure one or more molecular characteristics of the charged particles entering the ion inlet of the ion measurement stage 104.The processor 24 is operable to control voltage source VS3 in a similar manner to eject charged particles from the remaining ion traps 1023-1025 and selectively direct the ejected ions to the ion inlet of the ion measurement stage 104 for analysis. It will be appreciated that while the processor 24 is controlling voltage source VS3 to eject ions from the various ion traps 1021-1025, the processor 24 may be further operable to control voltage source VS1 to fill one or more empty ion traps 1021-1025 with ions having a predetermined respective target charge. In either case, the processor 24 is further operable to collect, store and analyze all ion measurement information generated by the ion measurement stage 104 in a conventional manner.

[0066]

[0100] Those skilled in the art will recognize that while the exemplary embodiment 300 illustrated in FIG. 14 is configured to simultaneously collect ions having five different target charges and then analyze each of the five sets using a single ion measurement stage 104, the concepts illustrated in FIG. 14 can be readily extended to devices configured to simultaneously collect more or less than five sets of target charges. It will be understood that any such alternative embodiments are contemplated by the present disclosure. It will be further understood that while the exemplary embodiment 300 illustrated in FIG. 14 includes five ion traps that collect five respectively differently charged ions, alternative embodiments are contemplated in which one or more or all of the ion traps are omitted such that ions having each respective target charge can be driven directly to the ion measurement stage 104 by the ion drive circuitry 32C.

[0067]

[0101] 15, an exemplary embodiment of the ion source or ion source region 30 illustrated in FIGS. 1, 12-14 and briefly described above is shown. In the illustrated embodiment, the ion source or ion source region 30 illustratively comprises at least one ion generator 36 coupled to a voltage source VS2 and configured to respond to control signals generated by the processor 24 to generate ions from the sample S. In some embodiments, the sample S is disposed within the ion source region 30, while in other embodiments, the ion source S is disposed outside the ion source region 30, as shown in the dashed line representation in FIG. 15. In one embodiment, the ion generator 36 is a conventional electrospray ionization (ESI) source configured to generate ions from the sample in the form of a mist of charged droplets. In an alternative embodiment, the ion generator 36 may be or comprise a conventional matrix-assisted laser desorption ionization (MALDI) source. It will be understood that ESI and MALDI represent only two examples of a myriad of conventional ion generators, and that the ion generator 36 may be or include any conventional device or apparatus as described above for generating ions from a sample.

[0068]

[0102] The ion source or ion source region 30 further illustratively includes R ion processing stages IPS1 to IPS R where R may be any positive integer. R Examples of the ion generator 36 may include, but are not limited to, one or more devices and / or instruments for separating, collecting, and / or filtering the charged particles according to one or more molecular characteristics, and / or one or more devices and / or instruments for dissociating, e.g., fragmenting, the charged particles, in any order and / or combination. In some embodiments, the ion generator 36 and / or the ion processing stages IPS1-IPS2 may include, but are not limited to, one or more devices and / or instruments for separating, collecting, and / or filtering the charged particles according to one or more molecular characteristics, in any order and / or combination. RAt least one of the ion source 30 includes one or more conventional structures and / or devices for accelerating or otherwise propelling the generated ions through the ion inlet A1 and further into the charge filter instrument 10. Examples of the device or devices for separating charged particles according to one or more molecular characteristics include, but are not limited to, one or more mass spectrometers or mass analyzers, one or more ion mobility analyzers, one or more instruments for separating charged particles based on magnetic moment, one or more instruments for separating charged particles based on magnetic dipole moment, and the like. Examples of mass analyzers or mass analyzers include, but are not limited to, time-of-flight (TOF) mass analyzers, reflectron mass analyzers, Fourier transform ion cyclotron resonance (FTICR) mass analyzers, quadrupole mass analyzers, triple quadrupole mass analyzers, magnetic field mass analyzers, orbitraps, or the like, in embodiments of the ion source 30 that include one or more mass spectrometers or mass analyzers. Examples of ion mobility analyzers include, but are not limited to, single-tube linear ion mobility analyzers, multi-tube linear ion mobility analyzers, circular tube ion mobility analyzers, or the like, in embodiments of the ion source 30 that include one or more ion mobility analyzers. Examples of the one or more devices and / or instruments for collecting charged particles include, but are not limited to, quadrupole ion traps, hexapole ion traps, or the like. Examples of the 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 the one or more devices and / or instruments for dissociating charged particles include, but are not limited to, one or more devices or instruments for dissociating charged particles by collision-induced dissociation (CID), surface-induced dissociation (SID), electron capture dissociation (ECD) and / or photoinduced dissociation (PID), multiphoton dissociation (MPD), or the like.

[0069]

[0103] Ion processing stage IPS1~IPS R It will be understood that the ion processing stages IPS1-IPS2 may include one or any combination of any of the above-described conventional ion separation and / or ion processing devices in any order, and some embodiments may include a plurality of adjacent or spaced apart ones of any of the above-described conventional ion separation and / or ion processing devices. R includes a charged particle filtering device or instrument after the ion generator and a dissociation device, instrument or stage after the charged particle filtering device or instrument. In this example, the processor 24 is illustratively programmed to control the voltage source VS2 to cause the charged particle filtering device or instrument to pass only ions above or below a threshold mass to charge ratio or within a predetermined range of mass to charge ratio, and to control the voltage source VS2 to cause the dissociation device, instrument or stage to dissociate, e.g., fragment, the charged particles that exit the charged particle filtering device or instrument such that the dissociated charged particles that exit the dissociation device, instrument or stage enter the inlet A1 of the charge filter instrument 10. In some embodiments, a second charged particle filtering device or instrument may be disposed between the dissociation device, instrument or stage and the inlet A1 of the charge filter instrument 10, and the processor 24 may be operable in such embodiments to control the voltage source VS2 to cause the second charged particle filtering device or instrument to pass only dissociated ions above or below a threshold mass to charge ratio, or within a predetermined range of mass to charge ratio, to the inlet A1 of the charge filter instrument 10. One or more ion processing stages IPS1-IPS within the ion source or ion source region 30 R It will be understood that other embodiments of the present invention may be envisioned by those skilled in the art, and all such other embodiments are intended to be within the scope of the present disclosure.

[0070]

[0104] 16, there is shown an exemplary embodiment of the ion measurement stage 104 illustrated in Figures 1, 12-14 and briefly described above. In the illustrated embodiment, the ion measurement stage 104 illustratively includes one or more ion measurement instruments IMI1-IMI S where S may be any positive integer. In some embodiments, the processor 24 illustratively controls, in a conventional manner, for example by controlling a voltage source VS3, one or more of the ion measuring instruments IMI1-IMI to cause the ion measuring instruments to measure one or more molecular characteristics of charged particles contained within and / or passing through the ion measuring instruments and / or to measure and generate information therefrom one or more molecular characteristics of charged particles contained within and / or passing through the ion measuring instruments. S In any case, one or more ion measuring instruments IMI1 to IMI S The ion measurement information generated by is illustratively processed by processor 24 to generate, store and, in some embodiments, display processed molecular signature information. In other embodiments, the charge selected ions may be deposited on a suitable surface or in a matrix for collection and analysis by other methods.

[0071]

[0105] Ion measuring instruments IMI1 to IMI SExamples of the one or more devices and / or instruments may include, but are not limited to, one or more devices and / or instruments for separating charged particles in time according to one or more molecular characteristics, one or more devices and / or instruments for filtering charged particles according to one or more molecular characteristics, one or more instruments for separating charged particles based on magnetic moment, one or more instruments for separating charged particles based on magnetic dipole moment, and the like, in any order and / or combination. Examples of the one or more devices and / or instruments for separating charged particles in time according to one or more molecular characteristics include, but are not limited to, one or more mass spectrometers, one or more ion mobility spectrometers, and the like. Examples of the one or more mass spectrometers include, but are not limited to, a time-of-flight (TOF) mass spectrometer, a reflectron mass spectrometer, a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer, a quadrupole mass spectrometer, a triple quadrupole mass spectrometer, a magnetic field mass spectrometer, an orbitrap, or the like, in embodiments of the ion measurement stage 104 comprising one or more mass spectrometers. Examples of the one or more ion mobility spectrometers include, but are not limited to, in embodiments of the ion measurement stage 104 comprising one or more ion mobility spectrometers, a single-tube linear ion mobility spectrometer, a multi-tube linear ion mobility spectrometer, a circular tube ion mobility spectrometer, or the like. Examples of the 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, magnetic moment, magnetic dipole moment, and the like.Examples of one or more devices or instruments for filtering charged particles according to mass-to-charge ratio include, but are not limited to, quadrupole mass analyzers or quadrupole mass filters, quadrupole ion trap mass analyzers or mass filters, magnetic field mass analyzers, time-of-flight mass analyzers, reflectron mass analyzers, Fourier transform ion cyclotron resonance (FTICR) mass analyzers, orbitraps, or the like, in embodiments of the ion measurement stage 104 that include one or more devices or instruments. Examples of one or more devices or instruments for filtering charged particles according to particle mobility include, but are not limited to, single tube linear ion mobility analyzers, multi-tube linear ion mobility analyzers, circular tube ion mobility analyzers, or the like, in embodiments of the ion measurement stage 104 that include one or more ion mobility analyzers. It will be understood that the ion measurement stage 104 may comprise one or any combination of any of the above-described apparatus for separating charged particles in time according to one or more molecular characteristics, and / or one or more devices or apparatus for filtering charged particles according to one or more molecular characteristics or the like, in any order, and some embodiments may comprise multiple adjacent or spaced apart ones of any of the above-described apparatus or devices.

[0072]

[0106] 17, there is shown yet another embodiment of a particle measurement device 400 comprising two spaced apart charge filter apparatus 101, 102 separated by an ion processing region 402. In the illustrated embodiment, the ion source region 30 is coupled to an inlet end of a first charge filter apparatus 101 as described above, an ion outlet end of a charge deflection or drive region 14 of the first charge filter apparatus 101 is coupled to an inlet of an ion processing region 402, an ion outlet of the ion processing region 402 is coupled to an inlet end of a second charge filter apparatus 102, and an ion outlet end of the charge deflection or drive region 14 of the second charge filter apparatus 102 is coupled to an inlet of an ion storage, drive and / or measurement stage 32 as also described above. Each of the charge filter devices 101, 102 includes a drift region 12 having an ion inlet A1 and a charge detector array 16 including a plurality of charge detector cylinders 161-16 axially disposed within the drift tube 12A between the ion inlet A1 and the ion outlet A2, as shown in FIG. 1 and described above. N and further includes a charge deflection or drive region 14 coupled to the exit end of the drift tube 12A in any of the configurations shown and / or described herein.

[0073]

[0107] The ion processing region 402 of the particle measurement device 400 illustratively comprises one or more ion processing stages IS1-IS T where T may be any positive integer. TOne or more of illustratively include, but are not limited to, for example, one or more conventional instruments for separating ions according to one or more molecular characteristics (e.g., according to ion mass-to-charge ratio, ion mobility, magnetic moment, magnetic dipole moment, or the like), and / or one or more conventional ion processing instruments (e.g., one or more quadrupoles, hexapoles and / or other ion traps, etc.) for collecting and / or storing ions, one or more conventional instruments or devices for filtering ions (e.g., according to one or more molecular characteristics such as ion mass-to-charge ratio, ion mobility, magnetic moment, magnetic dipole moment, and the like), one or more instruments, devices or stages for fragmenting or otherwise dissociating ions, and the like. It will be understood that ion processing stage 402 may include one or any combination of any such instruments, devices or stages in any order, and some embodiments may include a plurality of adjacent or spaced apart ones of any such instruments, devices or stages. It will be further appreciated that any of the exemplary combinations of instruments, devices or stages described above may be implemented as or as part of ion processing stage 402. Those skilled in the art will recognize other combinations of instruments, devices or stages that may be implemented as or as part of ion processing stage 402, along with other instruments, devices and / or stages that may be included in ion processing stage 402, whether or not shown and / or described herein, and will understand that any combination of any instruments, devices and / or stages, along with such other instruments, devices and / or stages, is intended to be within the scope of the present disclosure.

[0074]

[0108] It will be appreciated that because the charge magnitude and / or charge state of any individual charged particle or any collection, set or group of charged particles passed to the ion measurement stage 104 of any of the particle measurement instruments 100, 200, 300, 400 described herein is known, i.e., as a result of the control and operation of the charge filter instrument 10 as described above, molecular characteristic information not previously obtainable from conventional ion measurement instruments can now be readily determined. As one non-limiting example, particle mass-to-charge ratio values ​​obtainable from conventional mass spectrometers and mass analyzers can be readily converted to particle mass values ​​using the known charge magnitude or charge state information. As another non-limiting example, particle mobility values ​​obtainable from conventional ion mobility analyzers can be readily converted to particle collision cross section values ​​using the known charge magnitude or charge state information. As a further non-limiting example, when the charge magnitude or charge state of a collection, group or set of charged particles is known, a conventional mass-to-charge ratio filter can be operated as an appropriate mass filter to select for passage of particles having a predetermined mass or range of masses. Other examples will occur to those of ordinary skill in the art, and any such other examples are intended to be within the scope of this disclosure.

[0075]

[0109] While the present disclosure has been illustrated and described in detail in the drawings and description above, the disclosure should be considered exemplary and not limited in character, and only exemplary embodiments thereof have been shown and described, and all modifications and variations within the scope of the present disclosure are desired to be protected. For example, some structures are illustrated in the accompanying drawings and described herein as controllable and / or configurable to establish one or more electric fields configured and oriented to accelerate and / or drive charged particles and / or otherwise act on the charged particles, and those skilled in the art will recognize that the acceleration and / or drive of charged particles and / or other actions on charged particles may, in some cases, be realized by one or more magnetic fields, alternatively or additionally. Thus, it will be understood that any conventional structure and / or mechanism that replaces or enhances one or more of the electric fields described herein with one or more suitable magnetic fields is intended to be within the scope of the present disclosure.

Claims

1. an electric field-free drift region having an entrance end and an exit end opposite the entrance end, the entrance end configured to be coupled to an ion source to receive ions drifting axially from the entrance end through the drift region to the exit end; a plurality of spaced apart charge detection cylinders disposed in the drift region through which ions drift axially through the drift region pass; a plurality of charge amplifiers, each coupled to at least one of the plurality of charge detection cylinders, each configured to generate a charge detection signal corresponding to a magnitude of charge of one or more of the ions passing through a respective at least one of the plurality of charge detection cylinders; one of a charge deflector having a single entrance and a single exit, and a charge driven device having a single entrance and multiple exits, coupled to the exit end of the drift region; means for determining a charge magnitude or charge state of ions drifting axially through the drift region based on the charge detection signals produced by at least some of the plurality of charge amplifiers; means for controlling said one of said charge deflector and said charge drive device to pass only ions having a predetermined charge magnitude or charge state that is the same as or within a predetermined range of the determined charge magnitude or charge state through a corresponding one of said single outlet and a predetermined one of said multiple outlets; 1. A charge filter device comprising:

2. 10. The charge filter apparatus of claim 1, wherein said one of said charge deflector and said charge driven device comprises said charge deflector.

3. 3. The charge filter apparatus of claim 2, further comprising at least one ion measuring instrument having an inlet coupled to said single outlet of said charge deflector, said at least one ion measuring instrument configured to measure at least one molecular characteristic of ions exiting said single outlet of said charge deflector.

4. an ion trap disposed between the single outlet of the charge deflector and the inlet of the at least one ion measurement device, the ion trap configured to trap therein ions that exit the single outlet of the charge deflector; means for controlling the ion trap to selectively release ions trapped in the ion trap into the ion inlet of the at least one ion measurement instrument; 4. The charge filter apparatus of claim 3, further comprising:

5. an ion source comprising an ion generator configured to generate ions from a sample and supply the generated ions to the inlet of the drift region such that the generated ions drift axially through the drift region towards the ion exit end of the drift region; 5. The charge filter apparatus of claim 1, wherein the ion source further comprises: (i) at least one apparatus for separating the generated ions according to at least one molecular characteristic; (ii) at least one dissociation stage configured to dissociate passing ions; and (iii) at least one ion trap configured to trap ions therein and selectively release trapped ions therefrom.

6. the one of the charge deflector and the charge driven device comprises the charge driven device; the means for controlling the charge driven device is means for controlling the charge driven device to allow only ions having a first predetermined charge magnitude or charge state to pass through a first outlet of the plurality of outlets and to allow only ions having a second predetermined charge magnitude or charge state different from the first predetermined charge magnitude or charge state to pass through a second outlet of the plurality of outlets.

2. The charge filter device of claim 1.

7. the charge filter instrument further comprises at least a first ion measurement instrument having an inlet coupled to the first outlet of the multiple outlets of the charge driven device, the at least first ion measurement instrument configured to measure at least one molecular characteristic of ions exiting the first outlet of the multiple outlets of the charge driven device; the charge filter instrument further comprising at least a second ion measurement instrument having an inlet coupled to the second outlet of the plurality of outlets of the charge driven device, the at least second ion measurement instrument configured to measure at least one molecular characteristic of ions exiting the second outlet of the plurality of outlets of the charge driven device.

7. An electric charge filter device according to claim 6.

8. the charge filter apparatus further comprising a first ion trap disposed between the first of the multiple outlets of the charge driven device and the inlet of the first ion measurement apparatus, the first ion trap configured to trap ions therein that exit the first of the multiple outlets of the charge driven device; the charge filter instrument includes means for controlling the first ion trap to selectively release ions trapped in the first ion trap into the ion inlet of the first ion measurement instrument.

8. The charge filter apparatus of claim 7, further comprising:

9. the charge filter apparatus further comprising a second ion trap disposed between the second outlet of the charge driven device and the inlet of the second ion measurement apparatus, the second ion trap configured to trap ions therein that exit the second outlet of the charge driven device; the charge filter instrument includes means for controlling the second ion trap to selectively release ions trapped in the second ion trap into the ion inlet of the second ion measurement instrument.

9. The charge filter apparatus of claim 7 or claim 8, further comprising:

10. an ion source comprising an ion generator configured to generate ions from a sample and supply the generated ions to the inlet of the drift region such that the generated ions drift axially through the drift region towards the ion exit end of the drift region; 10. The charge filter apparatus of claim 6, wherein the ion source further comprises: (i) at least one apparatus for separating the generated ions according to at least one molecular characteristic; (ii) at least one dissociation stage configured to dissociate passing ions; and (iii) at least one ion trap configured to trap ions therein and selectively release trapped ions therefrom.

11. The charge filter apparatus further comprises a first ion trap having an inlet and an outlet coupled to the first outlet of the multiple outlets of the charge driven device, the first ion trap configured to trap ions therein that exit the first outlet of the multiple outlets of the charge driven device; the charge filter apparatus further comprising a second ion trap having an inlet and an outlet coupled to the second outlet of the plurality of outlets of the charge driven device, the second ion trap configured to trap ions therein that exit the second outlet of the plurality of outlets of the charge driven device; the charge filter device having an inlet and at least one ion measurement device configured to measure at least one molecular characteristic of ions entering the inlet; an ion drive circuit having a first inlet coupled to the outlet of the first ion trap, a second inlet coupled to the outlet of the second ion trap, and an outlet coupled to the inlet of the at least one ion measurement instrument; means for controlling (i) the first ion trap selectively releasing ions trapped therein to the first ion entrance of the ion drive circuit and to the ion drive circuit, and selectively passing ions that have exited the outlet of the first ion trap to the entrance of the at least one ion measurement instrument; and (ii) the second ion trap selectively releasing ions trapped therein to the second ion entrance of the ion drive circuit and to the ion drive circuit, and selectively passing ions that have exited the outlet of the second ion trap to the entrance of the at least one ion measurement instrument; 7. The charge filter apparatus of claim 6, further comprising:

12. an ion source comprising an ion generator configured to generate ions from a sample and supply the generated ions to the inlet of the drift region such that the generated ions drift axially through the drift region towards the ion exit end of the drift region; 12. The charge filter apparatus of claim 11, wherein the ion source further comprises: (i) at least one apparatus for separating the generated ions according to at least one molecular characteristic; (ii) at least one dissociation stage configured to dissociate passing ions; and (iii) at least one ion trap configured to trap ions therein and selectively release trapped ions therefrom.

13. the electrical field free drift region is a first electrical field free drift region, the plurality of charge detection cylinders is a first plurality of charge detection cylinders, the plurality of charge amplifiers is a first plurality of charge amplifiers, the one of the charge deflector and the charge drive device is one of a first charge deflector and a first charge drive device, the means for determining a charge magnitude or charge state is a first means for determining a charge magnitude or charge state, and the means for controlling is a first means for controlling; the charge filter apparatus comprising the first electric field free drift region, the first plurality of charge detection cylinders, the first plurality of charge amplifiers, the one of the first charge deflector and the first charge driven device, the first means for determining a charge magnitude or charge state, and the first means for controlling is a first charge filter apparatus; The charge filter device comprises: a second charge filter device identical to the first charge filter device; at least one ion processing stage disposed between the single outlet, the one of the predetermined outlets of the plurality of outlets of the corresponding one of the first charge deflector and the first charge driven device, and a second entrance of a second electric field free drift region of the second charge filter apparatus.

2. The charge filter device of claim 1.

14. The at least one ion processing stage comprises at least one of: (i) at least one device for temporally separating ions according to at least one molecular characteristic; (ii) at least one ion filter configured to pass only ions having a predetermined molecular characteristic or having a molecular characteristic within a predetermined range of molecular characteristics; (iii) at least one ion trap configured to selectively trap ions therein and selectively release ions therefrom; and (iv) at least one dissociation stage configured to dissociate ions passing therethrough.

14. An electric charge filter device according to claim 13.

15. an ion source comprising an ion generator configured to generate ions from a sample and supply the generated ions to the inlet of the drift region such that the generated ions drift axially through the drift region towards the ion exit end of the drift region; 15. A charge filter apparatus according to claim 13 or claim 14, wherein the ion source further comprises: (i) at least one apparatus for separating the generated ions according to at least one molecular characteristic; (ii) at least one dissociation stage configured to dissociate passing ions; and (iii) at least one ion trap configured to trap ions therein and selectively release trapped ions therefrom.

Images