Charge filter arrangement and its application

Abstract

A charge filter instrument includes a field-free drift region, a plurality of charge detection cylinders in the drift region through which ions drift axially, a plurality of charge sensitive 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 ions passing therethrough, a single inlet, a single exit charge deflector or a single inlet, a plurality of exit charge steering devices coupled to an 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 signal, and means for controlling the charge deflector or charge steering device to cause only ions having a specified charge magnitude or charge state to pass through the single exit or through a specified one of the plurality of exits.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This patent application claims the benefit of and priority to U.S. Provisional Patent Application Serial No. 62 / 949,555, filed December 18, 2019, the disclosure of which is expressly incorporated herein by reference in its entirety. Technical Field

[0003] The present disclosure generally relates to instruments configured to measure the charge of particles and selectively filter such particles based on their charge, and further to particle measurement devices or systems in which such instruments may be implemented. Background Art

[0004] Spectroscopic instruments provide an identification of the chemical composition of a substance by measuring one or more molecular properties of the substance. Some such instruments are configured to analyze substances in solution, while others are configured to analyze charged particles of substances in the gas phase. The molecular information produced by many such charged particle measurement instruments is limited because such instruments lack the ability to measure particle charge or process particles based on their charge. Summary of the Invention

[0005] The present disclosure may include one or more of the features recited in the appended claims, and / or one or more of the following features and combinations thereof. In one aspect, a charge filter instrument may include a field-free drift region having an inlet end and an outlet end opposite the inlet end, the inlet end being configured to be coupled to an ion source to receive ions for axial drift through the drift region from the inlet end toward the outlet end, a plurality of spaced-apart charge detection cylinders disposed in the drift region and ion-passing cylinders that drift axially through the drift region, a plurality of charge sensitive amplifiers, each coupled to at least one of the plurality of charge detection cylinders and each configured to generate an electric field corresponding to one or more ions passing through a corresponding at least one of the plurality of charge detection cylinders. a charge detection signal for determining the charge magnitude or charge state of ions drifting axially through the drift region based on the charge detection signal generated by at least some of the plurality of charge sensitive amplifiers, one of a charge deflector and a charge steering device, the charge deflector having a single entrance and a single exit, the charge steering device having a single entrance and a plurality of exits, coupled to the exit end of the drift region, a device for determining the charge magnitude or charge state of ions drifting axially through the drift region based on the charge detection signal generated by at least some of the plurality of charge sensitive amplifiers, and a device for controlling one of the charge deflector and the charge steering device to allow only ions with a specified charge magnitude or charge state to pass through a corresponding one of the single exit and a specified one of the plurality of exits.

[0006] In another aspect, an ion filter instrument may include a field-free drift region having an inlet end and an outlet end opposite the inlet end, the inlet end configured to be coupled to an ion source to receive ions for axial drift through the drift region from the inlet end toward the outlet end, a plurality of spaced-apart charge detection cylinders, ions passing through the cylinders disposed in the drift region and drifting axially through the drift region, a plurality of charge sensitive 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 a charge of one or more ions passing through a corresponding at least one of the plurality of charge detection cylinders, one of a charge deflector having a single inlet and a single outlet, and a charge steering device having a single inlet and a plurality of outlets, coupled to the outlet end of the drift region, and at least one a voltage source having at least one voltage output operatively coupled to one of a charge deflector and a charge steering device, at least one processor and at least one memory, the at least one memory having instructions stored therein, the instructions executable by the at least one processor causing the at least one processor to (a) monitor charge detection signals generated by at least some of a plurality of charge sensitive amplifiers as ions drift axially through a field-free drift region toward an outlet end thereof, (b) determine a charge magnitude or charge state of the ions drifting axially through the field-free drift region based on the monitored charge detection signals, and (c) control at least one voltage output of the at least one voltage source so that one of the charge deflector and the charge steering device causes only ions having a specified charge magnitude or charge state to pass through a corresponding one of the single outlet and a specified one of the plurality of outlets. BRIEF DESCRIPTION OF THE DRAWINGS

[0007] Figure 1 is a simplified diagram of a charge filter arrangement configured to filter ions according to ion charge by selectively passing ions having a designated charge or by selectively diverting ions having different designated charges along different respective ion travel paths.

[0008] Figure 2A yes Figure 1 A simplified diagram of a portion of an illustrative example of a charge filter arrangement comprising three charge detection cylinders arranged axially in a field-free drift region, and showing an example charged particle P entering the first charge detection cylinder at time T1 and leaving the first charge detection cylinder at time T2>T1.

[0009] Figure 2B is similar to Figure 2A and shows an example charged particle P entering the second charge detection cylinder at time T3>T2 and leaving the second charge detection cylinder at time T4>T3.

[0010] Figure 2C is similar to Figure 2Aand 2B , and shows an example charged particle P entering the third charge detection cylinder at time T5>T4 and leaving the third charge detection cylinder at time T6>T5.

[0011] Figure 2D is similar to Figures 2A-2C , and shows an example charged particle P entering the charge deflection or charge diverting region of the charge filter arrangement at time T7>T6.

[0012] Figure 3 is a plot of charge magnitude vs. time, showing the behavior of an example charged particle P as it passes through a Figures 2A-2D The respective first, second, and third charge detection cylinders depicted in FIG. 5 are example outputs of the charge-sensitive amplifiers CA1 - CA3 .

[0013] Figure 4A yes Figures 2A-2D A simplified diagram of an example charge filter arrangement is depicted in Figure 1, showing two example charged particles P1 and P2 with slightly different mass-to-charge ratios moving along the field-free drift region, where one of the charged particles P1 is shown entering the first charge detection cylinder at time T1 and the other charged particle P2 lags behind P1.

[0014] Figure 4B is similar to Figure 4A , showing the corresponding positions of two example charged particles P1 and P2 in the field-free drift region at time T2>T1.

[0015] Figure 4C is similar to Figure 4A and 4B , showing the corresponding positions of two example charged particles P1 and P2 in the field-free drift region at time T3>T2.

[0016] Figure 4D is similar to Figures 4A-4C , showing the corresponding positions of two example charged particles P1 and P2 in the field-free drift region at time T4>T3.

[0017] Figure 4E is similar to Figures 4A-4D , showing the corresponding positions of two example charged particles P1 and P2 in the field-free drift region at time T5>T4.

[0018] Figure 4F is similar to Figures 4A-4E , showing the corresponding positions of two example charged particles P1 and P2 in the field-free drift region at time T6>T5.

[0019] Figure 4G is similar to Figures 4A-4F , showing the corresponding positions of two example charged particles P1 and P2 in the field-free drift region at time T7>T6.

[0020] Figure 4H is similar to Figures 4A-4G , showing the corresponding positions of two example charged particles P1 and P2 in the field-free drift region at time T8>T7.

[0021] Figure 4I is similar to Figures 4A-4H , showing the corresponding positions of two example charged particles P1 and P2 in the field-free drift region at time T9>T8.

[0022] Figure 4J is similar to Figures 4A-4I , showing the corresponding positions of two example charged particles P1 and P2 in the field-free drift region at time T10>T9.

[0023] Figure 4K is similar to Figures 4A-4J , showing the corresponding positions of two example charged particles P1 and P2 in the field-free drift region at time T11 > T10.

[0024] Figure 4L is similar to Figures 4A-4K A simplified diagram of FIG. 1 shows the position of a charged particle P2 in the field-free drift region and shows charged particle P1 entering the charge deflection or diverting region of the charge filter arrangement at time T12 > T11 .

[0025] Figure 4M is similar to Figures 4A-4L A simplified diagram of FIG1 shows the position of the charged particle P2 in the field-free drift region at time T13>T12.

[0026] Figure 4N is similar to Figures 4A-4M , showing a charged particle P2 entering the charge deflection or diverting region of the charge filter arrangement at time T14>T13.

[0027] Figure 5 is a plot of charge magnitude versus time, showing that Figures 4A-4E Example output of the charge-sensitive amplifier CA1 as two example charged particles P1 and P2 pass through the first charge detection cylinder during the time window T1-T5 depicted in FIG.

[0028] Figure 6 is a plot of charge magnitude versus time, showing that Figures 4D-4IExample output of charge-sensitive amplifier CA2 as two example charged particles P1 and P2 pass through the second charge detection cylinder during time window T4-T9 depicted in FIG.

[0029] Figure 7 is a plot of charge magnitude versus time, showing that Figures 4H-4M Example output of the charge-sensitive amplifier CA3 as two example charged particles P1 and P2 pass through the third charge detection cylinder during the time window T8–T13 depicted in FIG.

[0030] Figure 8 is shown in the form of an embodiment of a controllable charge deflector Figure 1 Simplified illustration of the charge deflection or steering area of ​​a charge filter arrangement.

[0031] Figure 9A is shown in the form of another embodiment of a controllable charge deflector Figure 1 Simplified illustration of the charge deflection or steering area of ​​a charge filter arrangement.

[0032] Figure 9B Observed along the section line 9B-9B Figure 9A Cross-sectional view of a charge deflector.

[0033] Figure 10A is shown as an embodiment of a controllable single-entry, multiple-exit charge steering structure Figure 1 Simplified illustration of the charge deflection or steering area of ​​a charge filter arrangement.

[0034] Figure 10B Observed along the section line 10B-10B Figure 10A Cross-sectional view of the charge steering structure.

[0035] Figure 11 is shown in the form of another embodiment of a controllable single-inlet, multiple-outlet charge steering device Figure 1 Simplified illustration of the charge deflection or steering area of ​​a charge filter arrangement.

[0036] Figure 12 is included Figure 1 Simplified illustration of an embodiment of a particle measuring instrument with a charge filter arrangement, wherein the charge deflection or steering region is realized in the form of a charge deflector and is inserted between the ion source region and the ion measurement stage.

[0037] Figure 13 is included Figure 1 Simplified diagram of another embodiment of a particle measurement instrument having a charge filter arrangement in which the charge deflection or steering region is implemented in the form of a single inlet, multiple outlet charge steering device interposed between the ion source region and each of a plurality of ion measurement stages.

[0038] Figure 14 is included Figure 1 Simplified illustration of another embodiment of a particle measurement instrument having a charge filter arrangement, wherein the charge deflection or steering region is implemented in the form of an ion steering structure comprising multiple single inlet, multiple outlet ion steering devices, interposed between the ion source region and the single ion measurement stage.

[0039] Figure 15 It can be used Figure 12-14 A simplified diagram of an embodiment of an ion source region of any charged particle measurement instrument implementation.

[0040] Figure 16 It can be used Figure 12-14 Simplified diagram of an embodiment of an ion measurement stage implemented in an any charged particle measurement instrument.

[0041] Figure 17 is a simplified diagram of another embodiment of a particle measuring instrument, comprising Figure 1 Two cascades of charge filter devices are implemented, with the ion processing region located between them, and a combined charge filter arrangement is inserted between the ion source region and the ion measurement stage. DETAILED DESCRIPTION

[0042] For the purposes of promoting an understanding of the principles of the present disclosure, reference will now be made to a number of illustrative embodiments shown in the drawings and specific language will be used to describe the same.

[0043] The present disclosure relates to apparatus and techniques for determining the charge or charge state of charged particles moving through a drift region, and for filtering charged particles according to charge value or charge state by selectively passing those charged particles having a specified charge value or charge state or by selectively diverting charged particles having different specified charge values ​​or charge states along different respective paths of travel. For purposes herein, the terms "charged particle" and "ion" are used interchangeably, and both terms are intended to refer to any particle having a net positive or negative charge.

[0044] Now refer to Figure 1 , shows a diagram of a charge filter instrument 10 configured to filter ions according to ion charge by selectively passing ions having a designated charge or by selectively diverting ions having different designated charges along different respective ion travel paths. In the embodiment shown, the charge filter 10 includes a drift region 12 having an ion inlet A1 at one end thereof and an ion outlet A2 at an opposite end thereof. Figure 1In the embodiment depicted in FIG, 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, and the longitudinal axis 20 extends centrally through the drift region 12 and centrally through each of the inlet and outlet A1, A2, respectively. It will be appreciated that while in the form of a linear drift region, the drift region 12 is not substantially linear. Figure 1 , but in alternative embodiments, the drift region 12 can be nonlinear in whole or in part. As a non-limiting example, the drift region 12 can be provided in the form of a circular drift region including a conventional ion inlet (i.e., entry port) and ion outlet (i.e., exit port) structure. Other examples of at least partially nonlinear drift regions will occur to those skilled in the art, and it will be understood that any such alternative configurations are intended to fall within the scope of the present disclosure.

[0045] The charge deflection or steering region 14 is coupled to or otherwise positioned at the exit end of the drift region 12. In the illustrated embodiment, the charge deflection or steering region 14 has an ion inlet A3 defined by or positioned adjacent to the ion outlet A2 of the drift region 12 and an ion outlet A4. In some embodiments, the charge deflection or steering region 14 can be implemented in the form of a charge deflector that is controllable to selectively allow or prevent the passage of ions, some non-limiting example embodiments of which are described in

[0024] Figure 8-9B In other embodiments, the charge deflection or steering region 14 may be implemented in the form of one or more single inlet, multiple outlet charge steering instruments or structures, each controllable to selectively divert ions entering the single inlet through one or more of the multiple outlets, some non-limiting example embodiments of which are described in Figure 10A-11 and will be described in detail below.

[0046] The voltage source VS1 is electrically connected to the charge deflection or steering region 14 via a signal path of number K, where K can be any positive integer. In some embodiments, the voltage source VS1 can be implemented in the form of a single voltage source, and in other embodiments, the voltage source VS1 can include any number of separate voltage sources. In some embodiments, the voltage source VS1 can be configured or controlled to generate and supply one or more time-invariant (i.e., DC) voltages of selectable magnitude. Alternatively or additionally, the voltage source VS1 can be configured or controlled to generate and supply one or more switchable time-invariant voltages, i.e., one or more switchable DC voltages. Alternatively or additionally, the voltage source VS1 can be configured or controlled to generate and supply one or more time-varying signals of selectable shape, duty cycle, peak magnitude, and / or frequency. As a specific example of the latter embodiment, which should not be considered as limiting in any way, the voltage source VS1 can be configured or controlled to generate and supply one or more time-varying voltages in the form of one or more sinusoidal (or other shaped) voltages.

[0047] Voltage source VS1 is illustratively shown electrically connected to a conventional processor 24 via a number J of signal paths, where J can be any positive integer. Processor 24 is illustratively conventional and can include a single processing circuit or multiple processing circuits. Processor 24 illustratively includes or is coupled to a memory 26 having stored therein instructions that, when executed by processor 24, cause processor 24 to control voltage source VS1 to generate one or more output voltages for selectively controlling the operation of charge deflection or steering region 14. In some embodiments, processor 24 can be implemented in the form of one or more conventional microprocessors or controllers, and in such embodiments, memory 26 can be implemented in the form of one or more conventional memory cells having stored therein instructions in the form of one or more microprocessor-executable instructions or instruction sets. In other embodiments, processor 24 can alternatively or additionally be implemented in the form of a field programmable gate array (FPGA) or similar circuitry, and in such embodiments, memory 26 can be implemented in the form of programmable logic blocks contained within and / or outside the FPGA in which instructions can be programmed and stored. In yet another embodiment, processor 24 and / or memory 26 can be implemented in the form of one or more application-specific integrated circuits (ASICs). Those skilled in the art will recognize that other forms of implementing the processor 24 and / or memory 26 may be possible, and will understand that any such other forms of implementation are contemplated by and intended to fall within the present disclosure. In some alternative embodiments, the voltage source VS1 itself may be programmable to selectively generate one or more constant and / or time-varying output voltages.

[0048] The charge detector array 16 is illustratively disposed within or integrated with the drift region 12. Figure 1In the embodiment shown in FIG, the charge detector array 16 illustratively includes a plurality, ie, N, of spaced-apart cascaded charge detection cylinders 161-16 N , where N can be any positive integer greater than 2. In one example embodiment, which should not be considered limiting in any way, N can be approximately 100, although in other embodiments N can be less than 100 or greater than 100. In any case, the charge detection cylinders 161-16 N Each of the charge detection cylinders 161-16 defines an aperture therethrough to allow ions to pass through the corresponding cylinder, and in the embodiment shown, the charge detection cylinders 161-16 N The charge detection cylinders 161-162 are arranged end-to-end so that the longitudinal axis 20 of the drift region 12 passes through each cylinder at the center. N The length CDL between its ion inlet and ion outlet ends is defined, although in alternative embodiments, one or more charge detection cylinders 161-16 N The length of the CDL may be greater or less than the length of the CDL. The smallest CDL is illustratively that which is physically achievable and will produce an electrically detectable signal response to one or more ions passing through it. Although there is no theoretical upper limit to the CDL, practical considerations such as available space and instrument operating conditions will generally limit the maximum useful CDL in any particular application.

[0049] In the illustrated embodiment, a plurality of ground rings 182-18 N-1 Each of the charge detection cylinders 161-16 N In the space defined between each adjacent pair of , another grounding ring 181 is positioned adjacent to the ion inlet of the first charge detection cylinder 161 and yet another grounding ring 18 N With the final charge detection cylinder 16 N The ion outlets are positioned adjacent to each other. N Illustratively defines a ring aperture RA therethrough and the longitudinal axis 20 centrally passes through the ring aperture RA, wherein RA is illustratively less than or equal to the charge detection cylinder 161-16 N In the embodiment shown, the charge detection cylinder 161-16 N In the embodiment shown, the grounding rings 181-18 N-1 Each of the charge detection cylinders 161-16 N Ion inlet and grounding ring 181-18 N The distances between the corresponding grounding rings in the charge detection cylinders 161-16 are substantially equal to each other. NIon outlet and grounding ring 182-18 N The distances between the corresponding ground rings in the embodiment are substantially equal to each other, and the charge detection cylinders 161-16 N Ion inlet and grounding ring 181-18 N-1 The distance between the corresponding grounding rings is substantially equal to the charge detection cylinder 161-16 N Ion outlet and grounding ring 182-18 N In some embodiments, the grounding rings 181-18 N One or more of .

[0050] In one example embodiment, the drift tube 12A is provided in the form of a conductive cylinder, which is illustratively coupled to a ground potential (e.g., Figure 1 ) or coupled to another reference potential, and wherein the plurality of charge detection cylinders 161–16 N be properly installed. Including one or more grounding rings 181-18 N In such embodiments, such one or more grounding rings may be electrically and mechanically coupled to the inner surface of the conductive cylinder or may be integrally formed with the conductive cylinder such that the conductive cylinder and the one or more grounding rings 181-18 N In another exemplary embodiment, the drift tube 12A may be formed by interconnecting a series of alternating conductive or insulating spacers and a plurality of grounding rings 181-18 N The corresponding grounding ring is formed in which multiple charge detection cylinders 161-16 N can be appropriately mounted. In yet another example embodiment, the drift tube 12A can be provided in the form of a sheet of flexible or semi-flexible electrically insulating material, such as a flexible circuit board, to which a plurality of spaced-apart parallel conductive strips are attached or formed in a conventional manner, such as using conventional metal pattern deposition techniques. In this embodiment, the conductive strips are illustratively oriented so that when the opposite ends of the flexible or semi-flexible sheet are brought together to form an elongated cylinder, the plurality of spaced-apart parallel conductive strips form a plurality of charge detection cylinders and one or more ground rings 181–18 N Those skilled in the art will recognize that drift tube 12A and / or charge detection cylinders 161-16 N and / or one or more grounding rings 181-18 N other forms (in embodiments including them), and it will be understood that any such other forms are intended to fall within the scope of the present disclosure.

[0051] In the embodiment shown, each charge detection cylinder 161-16 NThe charge sensitive amplifiers 161-162 are electrically connected to the signal input of a corresponding one of the N charge sensitive amplifiers CA1-CAN, and the signal output of each charge sensitive amplifier CA1-CAN is electrically connected to the processor 24. In alternative embodiments, any, some, or all of the charge sensitive amplifiers may be electrically connected to more than one charge detection cylinder, and in such embodiments, the number of charge sensitive amplifiers will therefore be less than the number of charge detection cylinders. As a charged particle entering the ion inlet A1 moves axially through the drift region 12 toward and through the ion outlet A2, each such charged particle sequentially passes through the plurality of charge detection cylinders 161-162. N As each such charged particle passes through the charge detection cylinder 161-16 N , whereby the charge detection cylinder 161-16 N The charge induced on the particle has a magnitude proportional to the magnitude of the charge of the particle. Each of the charge sensitive amplifiers CA1-CAN is illustratively conventional and is responsive to the charge generated by the charge detectors 161-16 N The charge-sensing amplifiers CA1-CAN generate corresponding charge detection signals at their outputs based on the charge induced by the charged particles on the corresponding one of the charge-sensing amplifiers CA1-CAN and supply the charge detection signals to the processor 24. The magnitude of the charge detection signals generated by the charge-sensing amplifiers CA1-CAN at any point in time is proportional to the following: (i) the charge detected by the charge-sensing amplifiers CA1-CAN at any point in time when a single charged particle passes through the charge detection cylinders 161-16 N In a corresponding case, the magnitude of the charge of the single charged particle, or (ii) when multiple charged particles pass through the charge detection cylinder 161-16 N The processor 24 is then illustratively operable to receive and digitize the charge detection signal generated by each of the charge-sensitive amplifiers CA1-CAN and store the digitized charge detection signal in the memory 26 or in one or more other storage units coupled to or otherwise accessible to the processor 24.

[0052] Processor 24 is further illustratively coupled to one or more peripheral devices 28 (PD) via a number P of signal paths, where P can be any positive integer. The one or more peripheral devices 28 may include one or more devices for providing signal input(s) to processor 24 and / or one or more devices to which processor 24 provides signal output(s). In some embodiments, peripheral device 28 includes at least one of a conventional display monitor, printer, and / or other output device, and in such embodiments, memory 26 has instructions stored therein that, when executed by processor 24, cause processor 24 to control one or more such output peripheral devices 28 to display and / or record an analysis of the stored digitized charge detection signal.

[0053] The ion inlet end of the drift tube 12A, ie, the end where the ion inlet A1 is located, is illustratively configured to be coupled to the ion outlet end of the ion source region 30, ie, the end where the ion outlet A5 is located, as shown. Figure 1 In an embodiment where the ion source region 30 is coupled to the charge filter instrument 10, the second voltage source VS2 is illustratively connected to the ion source region 30 via a number H of signal paths, where H can be any positive integer, and further connected to the processor 24 via a number G of signal paths, where G can be any positive integer. VS2 can illustratively take any of the forms described above with respect to VS1, such that VS2 can be configured or controlled to generate any number of time-invariant, e.g., constant, and / or time-varying output voltages to selectively control one or more aspects of the ion source region 30.

[0054] As follows about Figure 15 In more detail, the ion source region 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 ions according to one or more molecular properties and / or for dissociating, e.g., fragmenting, ions. As an illustrative example, which should not be considered limiting in any way, the ion source region 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.

[0055] The drift region 12 of the charge filter instrument 10 is a field-free drift region (i.e., no electric field) such that ions entering the inlet A1 of the drift tube 12A from the ion source region 30 at an initial velocity drift toward and through the ion outlet A2 at a substantially constant rate. In this regard, the ion source region 30 will typically provide a motive force for causing the ions to enter the drift tube 12A at an initial velocity. Power may be provided illustratively in any one or 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 region 30, and / or a pressure difference between the ion source region 30 and the drift tube 12A, or the like. In any case, as the charged particles drift through the field-free drift region 12, they will 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 faster than charged particles having a higher mass-to-charge ratio.

[0056] As will be discussed below Figure 4A-7As detailed in the example shown in , the memory 26 illustratively has instructions stored therein that are executable by the processor 24 to cause the processor 24 to process the charge detection signals generated by at least some of the charge sensitive amplifiers CA1-CAN to determine the charge magnitudes and / or charge states of the charged particles as they separate along the length of the drift region 12, such that the charge magnitude and / or charge state of each charged particle is known prior to passing through the ion outlet A2 of the drift tube 12A. In some embodiments, the memory 26 further illustratively has instructions stored therein that are executable by the processor 24 to cause the processor 24 to control the voltage source VS1 to cause the charge deflection or steering region 14 to selectively pass 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, the memory 26 further illustratively has instructions stored therein that are executable by the processor 24 to cause the processor 24 to control the voltage source VS1 to cause the charge deflection or diverting region 14 to selectively divert charged particles having different charge magnitudes or having charges within different ranges of charge magnitudes along different ion travel paths, or to selectively divert charged particles having different charge states along different ion travel paths. In some embodiments, it may be desirable to determine the velocity of charged particles traveling through the drift region 12 so that the future position of the charged particles within the charge deflection or diverting region 14 can be accurately estimated when the voltage source VS1 is controlled to selectively pass or divert charged particles passing through the charge deflection or diverting region 14.

[0057] The ion outlet end of the charge deflection or steering 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, steering and / or measurement stage 32, i.e., the end where the ion inlet A6 is located, as shown. Figure 1 . In an embodiment where the ion storage, steering, and / or measurement stage 32 is coupled to the charge filter instrument 10, the third voltage source VS3 is illustratively connected to the ion storage, steering, and / or measurement stage 32 via a number M of signal paths, where M can be any positive integer, and further connected to the processor 24 via a number L of signal paths, where L can be any positive integer. VS3 can illustratively take any of the forms described above with respect to VS1, such that VS3 can be configured or controlled to generate any number of time-invariant, e.g., constant, and / or time-varying output voltages to selectively control one or more aspects of the ion storage, steering, and / or measurement stage 32.

[0058] As will be discussed below Figure 12-14As described in more detail with reference to the example application shown in FIG16 , the ion storage, steering, and / or measurement stage 32 may include any conventional device or apparatus for storing ions, for measuring ions, for processing ions before or after their measurement, and / or for steering ions between one or more devices. The one or more ion measurement instruments, devices, apparatuses, or stages are illustratively connected to the processor 24 via a number Q of signal paths, where Q may be any positive integer.

[0059] As briefly described above, the memory 26 illustratively includes instructions executable by the processor 24 to cause the processor 24 to determine the charge magnitude and / or charge state of each charged particle moving through the drift region 12, and then control the voltage source VS1 to selectively pass or divert the charged particles passing through the charge deflection or diverting region 14 based on the charge magnitude or charge state of the charged particles. In some embodiments, such as when the ion source region 30 is configured to simultaneously generate a plurality of ions and supply a plurality of ions to the ion inlet A1 of the drift tube 12A, for example, it may be desirable to configure the drift tube 12A to include a pre-array space 12B of length PRL between the ion inlet A1 of the drift tube 12A and the first grounding ring 181 (or the ion inlet end of the first charge detection cylinder 161 in embodiments where the first grounding ring 181 is omitted), as described by Figure 1 . This will allow charged particles moving axially through the drift region 12 to experience a certain amount of axial separation in time (as a function of the mass-to-charge ratio in the field-free region) before charge measurement is made with the charge detector array 16, and thereby may increase the quality and usefulness of the charge detection signal produced by the first one or more charge sensitive amplifiers CA1-CAN. The length PRL of the array front space 12B may be illustratively selected based on the application, and in some embodiments, the array front space 12B may be omitted in its entirety. Alternatively or additionally, in some embodiments it may be desirable to configure the drift tube 12A to include a final grounding ring 18 N (or omitting the last grounding ring 18 N The final charge detection cylinder 16 in the embodiment N The length of the ion outlet end) between the array POL rear space 12C, such as Figure 1 In some such embodiments, some or all of the length POL of the post-array space 12C may be provided at the front end of the charge deflection or steering region 14, i.e., adjacent to the ion inlet A3 of the charge deflection or steering region 14. In any case, in embodiments including the post-array space 12C, the post-array space 12C will be provided at the front end of the charge particles passing through the final charge detection cylinder 16. NA certain amount of time is provided between the ion output and the subsequent ion exit A2 from the drift tube 12A, and thereby the decision and control timing and / or switching rate requirements for the charge deflection or steering region 14 can be relaxed. The length POL of the post-array space 12C can be illustratively selected based on the application, and in some embodiments, the post-array space 12C can be omitted entirely.

[0060] Now refer to Figures 2A-2D , showing Figure 1 A simplified example of a charge filter instrument 10 includes three charge detection cylinders 161-163 arranged axially between the ion inlet A1 of the drift tube 12A and the charge deflection or steering region 14. For this simplified charge filter instrument 10, Figures 2A-2D A single charged particle P drifting successively through each of the three charge detection cylinders 161-163 is depicted as a function of time, and Figure 3 Depicted are example charge detection signals generated by three corresponding charge-sensitive amplifiers CA1-CA3 when a charged particle passes through the three corresponding charge-sensitive amplifiers CA1-CA3. Figure 2A and Figure 3 As shown in , a charged particle P enters the first charge detection cylinder 161 at time T1 and leaves the charge detection cylinder 161 at a subsequent time T2, and while within the charge detection cylinder 161 the charged particle induces a charge of magnitude C1 on the charge detection cylinder 161. In some embodiments, time T1 may be the time relative to an ion generation or acceleration event controlled at the ion source region 30 at a previous time T0. In alternative embodiments, the output signal produced by CA1 may be monitored after the ion generation or acceleration event, and T1 may simply be the time at which the first (and only in this example) particle P is detected upon entering the first charge detection cylinder 161 after the ion generation or acceleration event, for example via a rising edge of the charge detection signal output produced by CA1. In any case, at time T3>T2, the charged particle P that has left the first charge detection cylinder 161 now enters the second charge detection cylinder 162, and thereafter the charged particle P leaves the charge detection cylinder 162 at a subsequent time T4, as shown in FIG. Figure 2B Although in the charge detection cylinder 162, the charged particles induce a charge of magnitude C2 on the charge detection cylinder 162, as shown in FIG. Figure 3 At time T5>T4, the charged particles P that have left the second charge detection cylinder 162 now enter the third and final charge detection cylinder 163, and the charged particles P then leave the charge detection cylinder 163 at a subsequent time T6, as shown in FIG. Figure 2C When in the charge detection cylinder 163, the charged particles induce a charge of magnitude C1 on the charge detection cylinder 163, as shown in FIG. Figure 3 As shown in .

[0061] When the charged particles P move through the charge detection cylinders 161-163 successively, as shown in FIG. Figures 2A-2C As shown in the example of , processor 24 is illustratively operable, pursuant to execution of corresponding instructions stored in memory 26, to determine the magnitude and / or charge state of a charged particle P based on the charge detection signals generated by charge-sensitive amplifiers CA1-CA3. In one embodiment, processor 24 is operable to make such a determination based on the charge detection signal generated by the first charge-sensitive amplifier CA1, and then sequentially update the charge determination based on the charge detection signals generated by the remaining charge-sensitive amplifiers CA2 and CA3 after the charged particle passes through the respective charge detection cylinders 161 and 162. In some embodiments, processor 24 is further operable, pursuant to execution of corresponding instructions stored in memory 26, to determine the velocity of the charged particle P also based on the charge detection signal generated by the first charge-sensitive amplifier CA1, and then update the velocity determination based on the charge detection signals generated by the remaining charge-sensitive amplifiers CA2 and CA3 after the charged particle passes through the respective charge detection cylinders 161 and 162.

[0062] Using this example model, processor 24 is illustratively operable to determine that the initial magnitude of the charge CH of particle P after particle P leaves first charge detection cylinder 161, as indicated by the falling edge of CA1, is the magnitude CH=C1 generated by charge sensitive amplifier CA1 between the rising edge of CA1 at time T1 and the falling edge of CA1 at time T2. In some embodiments, processor 24 is also operable to determine the initial velocity of the charged particle as Vel P =CDL / (T2-T1). After detecting the falling edge of CA2 at time T4, the processor 24 is operable to determine an updated magnitude of the charge of the particle P as CH=(CH+C2) based on the magnitude C2 generated by the charge sensitive amplifier CA2 between the rising edge of CA2 at time T3 and the falling edge of CA2 at time T4. In some embodiments, the processor 24 is further operable to determine an update rate of charged particles as Vel P =Vel P +CDL / (T4-T3). After detecting the falling edge of CA3 at time T6, the processor 24 is operable to determine the final updated magnitude of the charge of the particle P as CH=CH+C3 based on the magnitude C1 generated by the charge sensitive amplifier CA3 between the rising edge of CA3 at time T5 and the falling edge of CA3 at time T6. In some embodiments, the processor 24 is also operable to determine the update rate of the charged particles as Vel P =Vel P+ (CDL / (T6-T5)). After the ions have traveled through all charge detectors, the average charge is calculated from CH = CH / N, where N is the number of measurements (3 in this example) and the average velocity is calculated from Vel P =Vel P / N calculation.

[0063] At a point in time just after T6, processor 24 has determined the charge magnitude CH of particle P based on an average of the charge detection signals generated by charge sensitive amplifiers CA1-CA3, and in some embodiments, the velocity Vel. P In some embodiments, the processor 24 is operable to convert the charge magnitude to a charge state, for example, by dividing CH by the fundamental charge constant e (e.g., 1.602716634 x 10 -19 Coulombs), or may be operable to calculate the initial and updated charge values ​​as charge state values ​​rather than charge magnitude values. In any case, if the determined charge magnitude or charge state CH is equal to the specified or target charge magnitude or charge state value or is within its specified range, the processor 24 may be operable to control the voltage source VS1 to apply one or more voltage values ​​to the charge deflection or diversion region 14, which causes the charge deflection or diversion region 14 to cause the charged particle P to pass therethrough. Otherwise, the processor 24 may be operable to control the voltage source VS2 to apply one or more voltage values ​​to the charge deflection or diversion region 14, which causes the charge deflection or diversion region 14 to prevent the charged particle P from passing therethrough or to divert the charged particle P away from the charge deflection or diversion region 14. In some embodiments of the charge deflection or diversion region 14, such control of the voltage source VS1 should occur before the charged particle P enters the charge deflection or diversion region 14 at time T7>T6, and in other embodiments, such control of the voltage source VS1 may occur after the charged particle P has entered the charge deflection or diversion region 14 but before the charged particle P leaves the charge deflection or diversion region 14. In either case, after the processor 24 determines Vel P In the embodiment, the determined rate Vel P The information about the size of the drift region 12 and / or the charge deflection or diverting region 14 may be used together with the information about the size of the drift region 12 and / or the charge deflection or diverting region 14 to estimate the future position of a charged particle P entering, within, and / or traveling through the charge deflection or diverting region 14 for the purpose of determining the timing of controlling the voltage source VS1 to cause the charged particle P to pass through the charge deflection or diverting region 14, to prevent the charged particle P from passing through the charge deflection or diverting region 14, or to divert the charged particle P through the charge deflection or diverting region 14. In an alternative embodiment, the processor 24 may base the timing of the control of the voltage source VS1 solely on the determined velocity Vel of the charged particle approaching the charge deflection or diverting region 14. P .

[0064] Those skilled in the art will recognize other techniques for determining the magnitude and / or charge state and / or velocity of charged particle P based on one or more charge detection signals generated by charge sensitive amplifiers CA1 - CAN and / or for determining the timing of control voltage source VS1 to cause charged particle P to pass through or prevent charged particle P from passing through or deflect charged particle P through charge deflection or steering region 14. It will be understood that any such other techniques are intended to fall within the scope of this disclosure.

[0065] Now referring to Figures 4A-4N , there is shown Figure 1 another simplified example of charge filter instrument 10, which includes three charge detection cylinders 161 - 163 axially arranged between ion inlet A1 of drift tube 12A and charge deflection or steering region 14. For this simplified charge filter instrument 10, Figures 4A-4N two charged particles P1, P2 successively drifting through each of the three charge detection cylinders 161 - 163 are depicted as a function of time, where P1 has a mass - to - charge ratio slightly lower than that of P2. Figure 5 An example charge detection signal generated by first charge sensitive amplifier CA1 when a charged particle passes through first charge sensitive amplifier CA1 is depicted, and Figure 6 and 7 depict the same situation for second and third charge sensitive amplifiers CA2 and CA3 respectively. As shown in Figures 4A-4E , charged particles P1 and P2 enter first charge detection cylinder 161 at times T1 and T2 respectively, where T2 > T1. At time T3 > T2, charged particle P1 leaves charge detection cylinder 161, and at time T5 > T3, charged particle P2 leaves charge detection cylinder 161. In the case where only particle P1 moves within charge detection cylinder 161 between T1 and T2, charged particle P1 induces a charge of magnitude C1 on charge detection cylinder 161, as shown in Figure 5 . Between T2 and T3 when both charged particles P1 and P2 move through charge detection cylinder 161, charged particles P1 and P2 together induce a charge of magnitude C2 > C1 on charge detection cylinder 161, and between T3 and T5 when only charged particle P2 moves through charge detection cylinder 161, charged particle P2 induces a charge of magnitude C3 < C1 on charge detection cylinder 161.

[0066] In the case where multiple charged particles axially drift through drift region 12 and thus axially through each successive charge detection cylinder 161 - 16 N as in the case above with respect to Figure 2A-3The described process 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 amplifiers in charge sensitive amplifiers CA1-CAN. In particular, the instructions stored in memory 26 may illustratively include instructions executable by processor 24 to monitor the charge detection signals generated by charge sensitive amplifiers CA1-CAN and to detect ion charge and velocity when a single charged particle enters charge detection cylinder 161-162. N Each rising edge of the charge detection signal is counted when a single charged particle leaves the corresponding charge detection cylinder 161-16 N Each falling edge of the charge detection signal is counted to record various magnitudes of the charge detection signal as magnitudes of single charged particles and combinations of charged particles and to record the rate of each of the multiple charged particles based on the rising and falling edges of the charge detection signal.

[0067] Using the charge detection signal generated by CA1, for example, the first rising edge is counted when the first charged particle has a charge magnitude equal to the magnitude of the charge detection signal between the first rising edge and the next rising 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 to the time difference between the rising and falling edges. If, instead, the next edge event is another rising edge, the second rising edge is counted when the second charged particle has a charge magnitude equal to the combined charge magnitude of the charge detection signal between the second rising edge and the next rising or falling edge. This process continues with each rising edge. When the first falling edge is detected, the first charged particle leaves the charge detection cylinder 161, the first charged particle is counted when its velocity is equal to the ratio of the length CDL of the charge detection cylinder 161 to the time difference between the first rising and falling edges, and the magnitude of the charge detection signal generated by CA1 after the first falling edge is equal to the combined charge magnitude 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 the same process is performed with respect to the charge detection signals generated by each of the remaining charge-sensitive amplifiers CA1-CAN.

[0068] Reference again Figure 5 The processor 24 executing the above process is operable to determine the charge CH of the first charged particle P1 between T1 and T2. P1 is C1, the combined charge CH of the charged particles P1 and P2 between T2 and T3 P1P2 is C2 and the charge CH of the second charged particle P2 between T3 and T5 P2It is C3. In an embodiment where the rate of charged particles passing through the charge detection cylinder 161 is determined by the processor 24 as part of the above process, the processor 24 is operable to determine the rate of the first charged particle P1 as Vel P1 = CDL / (T3 - T1), and determine the rate of the second charged particle P2 as Vel P2 = CDL / (T5 - T2). In some embodiments, the processor 24 may be operable to modify CH P1 and CH P2 , such that CH P1 and CH P2 further satisfy the measured relationship CH P1 + CH P2 = C2. In an alternative embodiment, after processing the charge detection signals generated by one or more or all of the downstream charge sensitive amplifiers CA2 - CAN, this modification of CH P1 and CH P2 can be incorporated into the charge quantity values CH P1 and CH P2 for consideration.

[0069] As Figures 4D-4I shown, 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 leaves the charge detection cylinder 162, and at time T9 > T7, the charged particle P2 leaves the charge detection cylinder 162. In the case where the particle P1 moves alone within the charge detection cylinder 162 between T4 and T6, as Figure 6 shown, 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 move through the charge detection cylinder 162, the charged particles P1 and P2 together induce a charge of magnitude C5 > C4 on the charge detection cylinder 162, and between T7 and T9 when only the charged particle P2 passes through the charge detection cylinder 162, the charged particle P2 induces a charge of C6 < C4 on the charge detection cylinder 162. Using the above process again, the processor 24 is operable to update the charge CH P1 of the first charged particle P1 to CH P1 = CH P1 + C4, update the charge CH P2 of the second charged particle P2 to CH P2 = CH P2 + C6, and determine the combined charge CH P1P2It is C5. In an embodiment where the rate of charged particles passing through the charge detection cylinder 162 is determined by the processor 24 as part of the above process, the processor 24 is operable to update the rate of the first charged particle P1 to Vel P1 = Vel P1 + CDL / (T7 - T4), and update the rate of the second charged particle P2 to Vel P2 = Vel P2 + CDL / (T9 - T6). In some embodiments, the processor 24 may be operable to modify CH P1 and CH P2 , such that CH P1 and CH P2 further satisfy the measured relationship CH P1 + CH P2 = C5. In an alternative embodiment, after processing the charge detection signals generated by one or more or all of the downstream charge sensitive amplifiers CA3 - CAN, this modification of CH P1 and CH[[ID=2 three]] P2 can be incorporated into the charge quantity values CH P1 and CH P2 for consideration.

[0070] As Figures 4H-4M shown, the 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, the charged particle P1 leaves the charge detection cylinder 163, and at time T13 > T11, the charged particle P2 leaves the charge detection cylinder 163. At time T12, where T11 < T12 < T13, such that the second charged particle P2 is still within the third charge detection cylinder 163, as Figure 4L shown, the first charged particle P1 enters the charge deflection or turning region 14, and at T14 > T13, the second charged particle P2 enters the charge deflection or turning region 14. In the case where only the particle P1 moves within the charge detection cylinder 163 between T8 and T10, the charged particle P1 induces a charge of magnitude C7 on the charge detection cylinder 163, as Figure 7 shown. Between T10 and T11 when both charged particles P1 and P2 move through the charge detection cylinder 163, the charged particles P1 and P2 together induce a charge of magnitude C8 > C7 on the charge detection cylinder 163, and between T11 and T13 when only the charged particle P2 moves through the charge detection cylinder 163, the charged particle P2 induces a charge of C9 < C7 on the charge detection cylinder 163.

[0071] Using the above process again, the processor 24 is operable to determine the charge CH of the first charged particle P1 between T11 and T12P1 Updated to CH P1 =CH P1 In embodiments where the velocity of the charged particles passing through the charge detection cylinder 163 is determined by the processor 24 as part of the above process, the processor 24 may also operate between T11 and T12 to update the velocity of the first charged particle P1 to Vel P1 =Vel P1 +CDL / (T11-T8). Since the charge detection cylinder 163 is Figures 4A-4N The final charge detection cylinder in the example shown in FIG, so the CH at the time between T11 and T12 P1 The value of Vel is the final measured value of the charge magnitude of the first charged particle P1, and in embodiments including it, the value Vel at the time between T11 and T12 P1 is the final measured value of the velocity of the first charged particle P1. The average charge from CH P1 =CH P1 / N calculation, where N is the number of measurements (3 in this case) and the average rate is calculated from Vel P1 =Vel P1 Before the first charged particle P1 enters the charge deflection or steering region 14, the processor 24 is operable to convert CH P1 Compare with one or more target charge values, or calculate the charge state CS of the first charged particle P1 P1 (CS P1 =CH P1 / e) and CS P1 is compared with one or more target charge states and then controls the voltage source VS1 at or after T12 but before T14 to provide a voltage level based on CH P1 or CS P1 The comparison with one or more target charge magnitudes or target charge states may result in the first charged particle P1 being passed / blocked or diverted along one of a plurality of different paths through the charge deflection or diversion region 14. In embodiments where particle velocity is calculated, the timing of such control of the voltage source VS1 by the processor 24 may be based on or at least take into account the velocity Vel of the charged particle P1. P1 and / or the estimated future position of the charged particle P1, based on Vel P1 and dimensional information of the charge filter apparatus 10 relative to and / or within the charge deflection or steering region 14 .

[0072] The processor 24 may then operate between T13 and T14 to convert the charge CH of the second charged particle P2 to P2 Updated to CH P2 =CH P2+C9. In some embodiments, the processor 24 may further operate between T13 and T14 to modify CH P2 To meet the measurement CH generated by the charge sensitive amplifier CA3 P1 +CH P2 = C8. In embodiments where the velocity of the charged particles passing through the charge detection cylinder 163 is determined by the processor 24 as part of the above process, the processor 24 may further operate between T13 and T14 to update the velocity of the second charged particles P2 to Vel P2 =Vel P2 +CDL / (T13-T10). Again, since the charge detection cylinder 163 is Figures 4A-4N In the example shown in FIG, the final charge detection cylinder, CH at times between T13 and T14 P2 The value of Vel is the final measured value of the charge magnitude of the second charged particle P2, and in embodiments including it, the value Vel at the time between T13 and T14 P2 is the final measured value of the velocity of the second charged particle P2. The average charge from CH P2 =CH P2 / N calculation, where N is the number of measurements (3 in this case) and the average rate is calculated from Vel P2 =Vel P2 After the first charged particle P1 enters the charge deflection or diversion region 14 at T12, and in some embodiments, the voltage source VS1 is controlled by the processor 24 to pass / block or divert the charge deflection or diversion region 14 to the first charged particle P1, and in any case before the second charged particle P2 enters the charge deflection or diversion region 14, the processor 24 is operable to P2 Compare with one or more target charge values, or calculate the charge state CS of the second charged particle P2 P2 (CS P2 =CH P2 / e) and CS P2 is compared with one or more target charge states and then at or after T14 based on CH P2 or CS P2 The comparison with one or more target charge magnitudes or target charge states controls the voltage source VS1 to pass / block the second charged particle P2 or to divert the second charged particle P2 along one of a plurality of different paths in the charge deflection or diversion region 14. In embodiments where particle velocity is calculated, the timing of such control of the voltage source VS1 by the processor 24 may be based on or at least take into account the velocity Vel of the charged particle P2. P2 and / or the estimated future position of the charged particle P2, based on Vel P2and dimensional information of the charge filter apparatus 10 relative to and / or within the charge deflection or steering region 14 .

[0073] It will be understood that the charge filter apparatus 10 is provided for the purpose of describing the operation thereof. Figure 2A-7 In the example shown in, and is not intended to be limited in any way. Those skilled in the art will appreciate that the above process or its variants can be directly applied to determine the passage / blocking and / or steering of many charged particles such as hundreds, thousands or more. Alternatively, those skilled in the art will recognize that for determining the magnitude and / or charge state and / or speed of multiple charged particles based on one or more charge detection signals produced by charge-sensitive amplifier CA1-CAN and / or for determining the timing of control voltage source VS1 to make charged particle P pass through charge deflection or steering region 14 / prevent charged particle P from passing through charge deflection or steering region 14 or make charged particle P pass through charge deflection or steering region 14 other technologies, and will appreciate that any such other technologies are intended to fall within the scope of the present disclosure. For example, in some embodiments, the charge detection signal produced by charge-sensitive amplifier CA1-CAN can be differential (differentiated). Each time ion enters charge detection cylinder positive pulse (positive-going pulse) will produce, and each time ion leaves charge detection cylinder negative ion (negative-going ion) will produce. If the rise and fall times of the output signal of the charge sensitive amplifier CA1-CAN (see, for example, Figure 3 、 5 , 6 and 7) is much shorter than the time constant for differentiation, then the charge is given by the peak height. If on the other hand the rise and fall time is much longer than the time constant for differentiation, then the charge is given by the peak area. The amplitude of the positive and negative going pulses associated with any particular ion should be identical, and this provides an identifier to pair the positive and negative going pulses so that rate and average charge can be determined. For example, when the number of ions drifting through the drift tube 16A is large, this alternative data analysis technique may be advantageous.

[0074] It will be further understood that in Figure 1 In the charge filter instrument 10 shown in FIG. 1 , not all charge detection signals can be used to determine particle charge values ​​and / or particle velocity. In some embodiments where charged particles may aggregate together as they leave the ion source region 30, for example, the processor 24 may ignore the charge detection signals generated by the first or several charge sensitive amplifiers. Alternatively or additionally, the drift tube 12A may be configured to include a front space 12B of any desired length to allow such aggregated particles to aggregate as they pass through the plurality of charge detection cylinders 161-162. NAs another example, the processor 24 may be configured or programmed to separate the charged particles in the axial direction of the drift region 12 before the first of the charged particles reaches the last charge detection cylinder 16. N Before or after the charged particles reach the last number of charge detection cylinders 16 N-Y -16 N derive the charge value and / or particle velocity determination before, where Y can be any positive integer less than N. Alternatively or additionally, the drift tube 12A can be configured to include a post-array space 12C of any desired length to relax the timing requirements for controlling the voltage source VS1 after determining the particle charge value and / or velocity. As another example, the processor 24 can be configured or programmed in some embodiments to determine only the charge value, i.e., not the particle velocity value, and to base control of the voltage source VS solely on the charge value determination and, in some embodiments, dimensional information of the charge filter instrument 10.

[0075] As briefly described above, the charge deflection or steering region 14 is controllable, i.e., by controlling the voltage source VS1, to pass, block, or divert ions based on their charge magnitude or charge state. In this regard, ions with a specific charge magnitude, a specific charge state, a charge within a specified range of charge magnitudes, or a calculated charge state within one or more specified ranges of one or more specific integer charge states can be analyzed and / or collected for analysis of one or more molecular properties. Because all such ions will have a common charge magnitude or charge state known as a result of the charge measurement information generated by the charge-sensitive amplifiers CA1-CAN, the known ion charge magnitude and / or charge state of such ions can be used in any such downstream analysis to determine molecular property information that was previously undeterminable using conventional instruments. For example, in a non-limiting example application in which the charge filter instrument 10, such as described above, is controlled to pass only ions with an a+1 charge state, then using a conventional mass spectrometer or mass analyzer that measures the mass-to-charge ratio of the ions, such charge information can be used to directly determine the particle mass value. As another non-limiting example application in which the charge filter instrument 10 is controlled, for example as described above, to pass only ions having a+1 charge state, using a conventional ion mobility spectrometer that measures ion mobility as a function of particle charge, such charge information can be used to directly determine particle mobility values. As yet another non-limiting example, for example as described above, the charge filter instrument 10 can be configured and controlled to divert and analyze, or collect for analysis, different sets of ions each having a different charge magnitude or a different state, for example, +1, +2, +3, etc. The known charge magnitude or charge state of each such set can then be used with one or more molecular analysis stages to determine one or more molecular properties of the set, such as particle mass, particle mobility, etc.

[0076] Now refer to Figure 8 , showing Figure 1 、 2A -2D and 4A-4N are embodiments of a charge deflection or steering region 14 of a charge filter instrument. In the illustrated embodiment, the charge deflection or steering region 14 is implemented in the form of a single entrance, single exit charge deflector 14A, which is configured and controllable to selectively allow ions to pass through or prevent ions from passing through it. The charge deflector 14A includes a pair of conductive members 60, 62, each of which is DL in length and illustratively in the form of a plate, grid or (one or more) other conductive materials, spaced apart from each other to define a channel 64 passing therethrough between a single ion entrance A3 and a single ion exit A4. In the illustrated embodiment, the members 60, 62 are depicted as planar components such that the channel 64 is a square or rectangular channel. In alternative embodiments, the conductive members 60, 62 can be implemented in other shapes without limitation. In any case, the first voltage output V1 of the voltage source VS1 is electrically connected to the conductive member 62, and the second voltage output V2 of the voltage source VS1 is electrically connected to the 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, such as ground or other reference potential, and the other voltage V1, V2 may be a switchable DC voltage. In alternative embodiments, voltage V1 and / or voltage V2 may be a time-varying voltage.

[0077] In any case, charge deflector 14A is illustratively operable to deflect charged particles P entering inlet A3 into one or the other of members 60, 62 by controlling voltage(s) V1 and / or V2 to create an electric field E of a magnitude sufficient to displace and accelerate the charged particles P into members 60, 62, as shown. Figure 8 In contrast, the charge deflector 14A is illustratively operable to cause charged particles P entering inlet A3 to pass to and through outlet A4, as shown in FIG. Figure 8As shown by the dashed line in , as long as there is no electric field E established between the members 60, 62, or the electric field E is established between the members 60, 62 but does not have a magnitude sufficient to deflect the charged particles P into one or the other of the members 60, 62. In an illustrative example that should not be considered limiting in any way, where the charged particles P have a positive charge, V1=V2=0 volts (ground potential) causes the charged particles P to pass through the channel 64, and V1=0 volts, V2=+Z volts to deflect the charged particles P toward and into the conductive member 62, where Z is selected to establish an electric field E between the members 60, 62 that has a magnitude sufficient to guide and accelerate the charged particles P to the surface of the member 62 before the charged particles P reach the outlet A4, thereby preventing the charged particles P from passing through the charge deflector 14A. It should be understood that in alternative embodiments, the roles of V1 and V2 can be reversed. In other alternative embodiments, the electric field E can be a time-varying electric field established by one or more time-varying voltages V1, V2.

[0078] Now refer to Figure 9A and 9B , showing Figure 1 、 2A Another embodiment of the charge deflection or steering region 14 of the charge filter apparatus shown in FIG. Figure 9A and 9B In the embodiment shown in , the charge deflection or steering region 14 is implemented in the form of another single entrance, single exit charge deflector 14B, which is configured and controllable to selectively pass or prevent ions from passing through it. The charge deflector 14B is illustratively provided in the form of a quadrupole filter, comprising four elongated conductive rods (rods) 70, 72, 74, 76, the length of each conductive rod being RL and radially spaced apart from each other to define a channel 78 passing therethrough between a single ion entrance A3 and a single ion exit A4. In the embodiment shown, the rods 70-76 are depicted as cylindrical rods with a generally circular cross-sectional shape, although in alternative embodiments the rods 70-76 can have a non-circular cross-sectional shape. In any case, the first voltage output V1 of the voltage source VS1 is electrically connected to the conductive rods 70 and 72, and the second voltage output V2 of the voltage source VS1 is electrically connected to the conductive rods 74, 76, wherein the rod 70 is positioned radially opposite to the rod 72 and the rod 74 is positioned radially opposite to the rod 76. In one embodiment, voltages V1 and V2 may include time-varying voltages, such as 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, such as RF voltages, and in other alternative embodiments, V1 and V2 may include only DC voltages.

[0079] In any case, the charge deflector 14B is illustratively operable to deflect charged particles P entering the inlet A3 into one of the rods 70-76 by controlling the voltage(s) V1 and / or V2 in a conventional manner to generate a non-resonant electric field E between the rods 70-76 having a magnitude sufficient to transfer the charged particles P into one of the rods 70-76 to thereby prevent the charged particles P from passing through the charge deflector 14B. Conversely, the charge deflector 14B is illustratively operable to cause the charged particles P entering the inlet A3 to pass to and through the outlet A4 by controlling the voltage(s) V1 and / or V2 in a conventional manner to generate a resonant electric field E between the rods 70-76 that confines the charged particles P within the channel 78 and thereby allows the charged particles P entering the inlet A3 to pass axially through the channel 78 and exit through the ion outlet A4. In some alternative embodiments, the charge deflector 14B may be used in combination with one or more other charge deflection or steering 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 provide only time-varying voltages (i.e., no DC voltage).

[0080] Now refer to Figure 10A and 10B , showing Figure 1 、 2A - Yet another embodiment of the charge deflection or steering region 14 of the charge filter apparatus shown in FIG. Figure 10A and 10BIn the embodiment shown in , the charge deflection or steering region 14 is implemented in the form of a single-entry, multiple-exit charge steering device 14C, which is configured and controllable to selectively redirect ions entering inlet A3 through one of a plurality of different ion outlets. The charge steering device 14C is illustratively provided in the form of a single-entry, three-exit quadrupole charge steering device having four elongated conductive arcuate members 80, 82, 84, 86 spaced apart from each other to define an ion steering space 88 therebetween. Each of the conductive arcuate members 80, 82, 84, 86 has a convex surface facing the steering space 88, wherein members 80, 82 are positioned relative to each other on either side of the space 88 and members 84, 86 are also positioned relative to 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 radially spaced apart from each other to define therebetween an ion inlet A3 of the steering device, and the arcuate members 82 and 86 are likewise radially spaced apart from each other to define therebetween an ion outlet A4 axially opposite the ion inlet A3. The arcuate members 80 and 86 are axially spaced apart from each other to define therebetween a side outlet SA1, and the arcuate members 82 and 84 are likewise axially spaced apart from each other to define therebetween another side outlet SA2 axially opposite the side outlet SA1.

[0081] exist Figure 10B In the embodiment shown in , a first voltage output V1 of a 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, such as RF voltages, that are 180 degrees out of phase with each other and may also 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, such as RF voltages, and in other alternative embodiments, V1 and V2 may include only DC voltages. In one illustrative implementation, 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, such as ground or other potential, so that the charged particles P entering the inlet A3 pass directly through the space 88 along the linear axis 85 and through the ion outlet A4, as shown. Figure 10B Alternatively, assuming that the charged particle P has a positive charge, the processor 24 is operable to control V1 to a negative potential and V2 to an opposite positive potential to generate an electric field within the space 88, which is configured to cause the charged particle P entering the ion inlet A3 to be diverted along the arcuate path 87A and exit the charge diverting device through the side outlet SA1, as shown. Figure 10BStill alternatively, again assuming that the charged particles P have 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 that is configured to cause the charged particles P entering the ion inlet A3 to be diverted along the arcuate path 87B and exit the charge diverting device through the side outlet SA2, as shown. Figure 10B As further shown in .

[0082] Now refer to Figure 11 , showing Figure 1 、 2A -Alternative embodiments of the charge deflection or steering region 14 of the charge filter apparatus shown in FIG. 2D and FIG. 4A-4N. Figure 11 In the embodiment shown in , the charge deflection or steering region 14 is implemented in the form of another single inlet, multiple outlet charge steering device 14D that is configured and controllable to selectively redirect ions entering inlet A3 through one of a plurality of different ion outlets. The charge steering device 14D illustratively includes a pattern of four substantially identical and spaced-apart conductive pads C1-C4 formed on an inner major surface 90A of one substrate 90 having opposing outer major surfaces 90B, and an identical pattern of four substantially identical and spaced-apart conductive pads C1-C4 formed on an inner major surface 92A of another substrate 92 having opposing outer surface 92B. The inner major surfaces 90A, 92A of the substrates 90, 92 are spaced apart in a generally parallel relationship, and the conductive pads C1-C4 of the substrate 90 are juxtaposed above corresponding 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 define a width D therebetween. P In one embodiment, the width D of the channel 94 is P is about 5 cm, but in other embodiments, the width D P It can be larger or smaller than 5cm.

[0083] 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 opposing side outlet SA2, all of which are related to Figure 10A and 10B Edges 90C, 92C of substrates 90, 92 are illustratively aligned with one another, as are edges 90D, 92D, edges 90E, 92E, and edges 90F, 92F.

[0084] A first voltage output V1 of voltage source VS1 is electrically connected to conductive pad pairs C1, C1 and C4, C4, and a second voltage output V2 of voltage source VS1 is electrically connected to conductive pad pairs C2, C2 and C3, C3. In one embodiment, voltages V1 and V2 can be controllable, switchable DC voltages to selectively establish ion steering electric fields between respective pairs of pad pairs C1, C1, C2, C2, C3, C3 and C4, C4. In one implementation, processor 24 is illustratively operable to control V1 and V2 to the same voltage, such as ground or other potential, so that charged particles P entering inlet A3 are directed along linear axis 96 through spatial channel 94 and through ion outlet A4, as shown. Figure 11 Alternatively, assuming that the charged particles P have 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 channel 94 that is configured to cause the charged particles P entering the ion inlet A3 to be diverted along the arcuate path 98A and exit the charge diverting device through the side outlet SA1, also as shown. Figure 11 Still alternatively, again assuming that the charged particles P have 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 channel 94 that is configured to cause the charged particles P entering the ion inlet A3 to be diverted along an arcuate path and exit the charge diverting device through the side outlet SA2.

[0085] Now refer to Figure 12 , shows an embodiment of a particle measurement device 100, which includes Figure 1 An embodiment 10A of the charge filter apparatus 10 shown in and described above. Figure 12 In the embodiment shown in FIG, a charge filter instrument 10A includes a drift region 12 having an ion inlet A1, wherein a charge detector array 16 includes a plurality of charge detection cylinders 161-16 N , the plurality of charge detection cylinders 161-16 N Axially disposed within the drift tube 12A between the ion inlet A1 and its ion outlet A2, as described above, and further comprising a charge deflection or steering region 14 in the form of a charge deflector coupled to the outlet end of the drift tube 12A. The charge deflector may illustratively be implemented as either of the charge deflectors 14A, 14B shown in 8 and 9A-9B, respectively, or as Figures 10A-10Band any of the charge steering devices 14C, 14D shown in FIG11. In the latter case, the charge steering device, e.g., 14C or 14D, is illustratively controlled to operate as a charge deflector to direct ions entering the ion inlet A3 toward and through the ion outlet A4 or to prevent ions from passing through the ion outlet A4 by redirecting such ions away from the ion outlet A4, e.g., through any of the side outlets SA1, SA2. Alternatively or additionally, Figure 12 The charge deflector shown in can be implemented in the form of one or more other conventional charge deflectors, charge transferors, charge steering devices or other devices, which can be controlled as described above to selectively direct ions entering the ion inlet A3 toward and through the ion outlet A4 or to selectively prevent ions entering the ion inlet A3 from passing through the ion outlet A4 using any conventional structure and / or technology.

[0086] The particle measurement apparatus 100 further includes an ion source region 30 that is operatively coupled to the ion inlet port of the charge filter instrument 10A. The ion source region 30 is described above with reference to Figure 1 The apparatus 10A is described and illustratively includes at least one ion generator coupled to a voltage source VS2 and configured to generate ions from a sample located within or within an ion source region 30 in response to control signals generated by the processor 24, and further includes one or more conventional structures and / or devices for accelerating or otherwise propelling the generated ions through the ion inlet A1 and into the charge filter instrument 10A. In some embodiments, for example, the ion source region 30 may include at least one ion acceleration structure or region that is separate from or part of the ion generator and operatively coupled to the voltage source VS2 (see FIG. Figure 1). In this embodiment, the processor 24 can be illustratively programmed to control the voltage source VS2 to selectively establish an ion accelerating electric field having an ion accelerating structure or an ion accelerating electric field within the ion accelerating region, in any case, the ion accelerating electric field is oriented to accelerate the generated ions into the charge filter instrument 10A via the ion inlet A1. As another example in which the sample is contained within the ion source region 30, the drift region 12 can be pumped to a pressure lower than the pressure of the ion source region 30, for example, via one or more conventional pumps, and in such an embodiment, the differential pressure between the ion source region 30 and the drift region 12 can propel the generated ions into the charge filter instrument 10A via the ion inlet A1. As yet another example in which the sample is external to the ion source region 30, the ion source region and / or the drift region 12 can be pumped to a pressure lower than the ambient or atmospheric pressure, for example, via one or more conventional pumps, with the sample located therein, and in such an embodiment, the differential pressure between the ambient or atmospheric pressure outside the ion source region 30 and the lower pressure environment within the ion source region and / or the drift region 12 can propel the generated ions into the charge filter instrument 10A via the ion inlet A1. In still other embodiments, a combination of differential pressure and ion acceleration regions or structures may be used to provide the motive force used to accelerate or otherwise propel the generated ions into the charge filter instrument 10A.

[0087] In some embodiments, the ion source region 30 may include any combination of one or more ion separation instruments or stages and / or one or more ion manipulation instruments or stages. Figure 15 Some examples of various compositions of the ion source region 30 are described in detail.

[0088] The particle measurement apparatus 100 further includes (one or more) ion storage, steering and / or measurement stages 32 operatively coupled to the ion outlet port of the charge filter instrument 10A, such as Figure 1 As shown in and briefly described above. Figure 12 In the embodiment shown in FIG, the ion storage, steering and / or measurement stage(s) 32 are illustratively implemented in the form of an ion storage and measurement stage 32A that includes a conventional ion trap 102 operatively coupled to a voltage source VS3 (see FIG. Figure 1) and having an ion inlet coupled to the ion outlet A4 of the charge filter instrument 10A and an ion outlet coupled to the ion inlet of the ion measurement stage 104. In some alternative embodiments, the ion trap 102 may be omitted so that the ion outlet A4 of the charge filter instrument 10A is directly coupled to the ion inlet of the ion measurement stage 104. In any case, the ion measurement stage 104 may illustratively include one or more conventional instruments or stages for temporally separating ions according to one or more molecular properties. In some embodiments, the ion measurement stage 104 may also include one or more ion processing instruments or stages in any combination with one or more ion separation instruments or stages. Figure 1 As shown in FIG, the ion measurement stage 104 is operatively coupled to a voltage source VS3. Some examples of various components of the ion measurement stage 104 will be described below with respect to FIG. Figure 16 Provide a detailed description.

[0089] exist Figure 12In the embodiment shown in FIG, ions are provided to the charge filter instrument 10A by the ion source region 30, wherein the processor 24 is operable to determine the particle charge value and, in some embodiments, the particle velocity as the ions separate as they drift through the drift region 12 as described above, and further control the voltage source VS1, also as described above, to pass only ions having a target charge magnitude, having a charge magnitude within a selected threshold or range of target charge magnitudes, having a target charge state, or having a charge state within a selected threshold or range of target charge states (individually and collectively referred to herein as the "target charge"). In one example implementation in which the charged particle measurement apparatus 100 includes an ion trap 102, the processor 24 is illustratively programmed, for example, via instructions stored in the memory 26, to control the voltage source VS3 to collect and store ions within the ion trap 102 that have the target charge and are therefore selected by the processor 24 to pass through the charge deflectors 14A, B, C, D and 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 in time after the ion trap 102 has been operated to collect and store ions therein, the processor 24 is operable to control the voltage source VS3 to eject the collected ions into the ion inlet of the ion measurement stage 104, and the processor 24 is thereafter operable to control the voltage source VS3 in a conventional manner to control the operation of one or more ion measurement instruments comprising the ion measurement stage 104 to measure one or more molecular properties of the set of all ions having the target charge. In an alternative embodiment that does not include the ion trap 102, ions having the target charge exiting the charge filter instrument 10A are directly provided to the ion measurement stage 104, where the processor 24 is operable to control the voltage source VS3 to measure one or more molecular properties 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.

[0090] In an exemplary implementation of the particle measurement instrument 100 that should not be considered as limiting in any way, the ion measurement stage is or includes a conventional mass spectrometer or mass analyzer. In this example implementation, the processor 24 is illustratively operable to control voltage source VS1 to transfer only ions with a first target charge to the ion trap 102, then control voltage source VS3 to supply the collected ions to the mass spectrometer or mass analyzer and further control voltage source VS3 to control the mass spectrometer or mass analyzer in a conventional manner to produce the mass-to-charge ratio measurement of the collected ions. Because the charge magnitude or charge state of the collected ions are identical and known, the processor 24 is further operable to determine the mass of the collected ions as a simple ratio of mass-to-charge ratio measurement to the target charge value. In some embodiments, the ion trap 102 can be omitted, and the processor 24 can operate as just described to control voltage source VS3 to control the mass spectrometer or mass analyzer to produce the mass-to-charge ratio measurement of the charge-selected ions when the charge-selected ions leave the outlet aperture A4 of the charge filter instrument 10A. In either case, the processor 24 may further operate in a charge scan mode to repeat the above process one or more times over a selected range of target charge values. Those skilled in the art will recognize that the ion measurement stage 104 may be or include other conventional ion measurement instruments or stages configured to measure one or more molecular properties and / or may include one or more ion processing instruments or stages configured to process ions in any conventional manner, and will understand that any such implementation of the ion measurement stage 104 is intended to fall within the scope of the present disclosure. Figure 16 Several non-limiting examples of various measurement and processing instruments that may be included in the ion measurement stage 104 are described.

[0091] Now refer to Figure 13 , showing the inclusion of Figure 1 Another embodiment of a particle measurement apparatus 200 is an embodiment of the charge filter instrument 10 shown in FIG. Figure 13 In the embodiment shown in Figure 13 The charge filter instrument shown in FIG. 1 comprises a drift region 12 having an ion inlet A1 , wherein a charge detector array 16 comprises a plurality of charge detection cylinders 161 - 162 . N , the plurality of charge detection cylinders 161-16 NAxially disposed within the drift tube 12A between the ion inlet A1 and its ion outlet A2, as described above, and further comprising a charge deflection or steering region 14 coupled to the outlet end of the drift tube 12A in the form of a single-inlet, multiple-outlet charge steering device. In the illustrated embodiment, the single-inlet, multiple-outlet charge steering device is a single-inlet, three-outlet charge steering device having a single ion inlet A3, an oppositely positioned ion outlet A4, and two opposite side outlets SA1, SA2, which may illustratively be implemented as Figures 10A-10B and any of the charge steering devices 14C, 14D shown in Figures 11. Alternatively, the single-inlet, multiple-outlet charge steering device may take the form of any conventional single-inlet, multiple-outlet charged particle steering device.

[0092] The particle measurement device 200 further illustratively includes (one or more) ion storage, steering and / or measurement stages 32 in the form of three separate ion storage and measurement stages 32A1, 32A2, 32A3, each operatively coupled to a respective ion outlet A4, SA1, SA2 of the single-inlet, multiple-outlet charge steering device 14C, 14D. Figure 13 In the embodiment shown in FIG, each stage 32A1, 32A2, 32A3 is connected to Figure 12 3 and described above. For example, each stage 32A1, 32A2, 32A3 includes a respective conventional ion trap 1021, 1022, 1023 operatively coupled to a 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 other stages 32A1, 32A2, 32A3. In some alternative embodiments, one or more of the ion traps 1021, 1022, 1023 may be omitted such that the respective ion outlets of the charge steering devices 14C, D are directly coupled to the ion inlets of the respective ion measurement stages 1041, 1042, 1043. The ion measurement stages 1041, 1042, 1043 are also similar to Figure 13 The ion measurement stage 104 shown in FIG. 1 is the same as that described above.

[0093] The particle measurement apparatus 200 further includes an ion source region 30 operatively coupled to the Figure 13 The ion source region 30 is illustratively shown as above with reference to the ion inlet end of the charge filter instrument. Figure 1 and 12 described.

[0094] The operation of the particle measuring device 200 is similar to Figure 12 The operation of the particle measuring apparatus 100 shown in FIG. 1 and described above is as follows: ions are supplied from the ion source region 30 to the Figure 13 , wherein the processor 24 is operable to determine particle charge values ​​and, in some embodiments, particle velocities as ions separate as they drift through the drift region 12. However, unlike the particle measurement apparatus 100, the particle measurement apparatus 200 is not limited to a charge deflector through a single outlet of the particles, but is instead configured to direct particles through any of the three outlets of the charge steering apparatus 14C, D. Utilizing the single inlet, three outlet charge steering apparatus 14C, D, the processor 24 is illustratively programmed to control the voltage source VS1, as described above, to direct only ions having a first target charge through the outlet A4, to direct only ions having a second target charge different from the first target charge through the second outlet SA1, and to direct only ions having a third target charge different from the first and second target charges through the third outlet SA2.

[0095] In one example implementation of the charged particle measurement device 200 including the ion traps 1021, 1022, 1023, the processor 24 is illustratively programmed, e.g., via instructions stored in the memory 26, to control the voltage source VS1 to divert the charged particles P having the first target charge out of the ion outlet A4 of the charge diverting devices 14C, D and into the ion trap 1021, e.g., along Figure 13 ion travel path 2021 depicted in FIG, and controls voltage source VS3 to collect and store charged particles having a first target charge in ion trap 1021, and controls voltage source VS1 to divert charged particles P having a second target charge from ion exit SA2 of charge diverting device 14C, D and into ion trap 1022, for example, along Figure 13 ion travel path 2022 depicted in FIG, and controls voltage source VS3 to collect and store charged particles having a second target charge in ion trap 1022, and controls voltage source VS1 to divert charged particles P having a third target charge away from ion outlet SA1 of charge diverting device 14C, D and into ion trap 1023, for example, along Figure 13 , and controls the voltage source VS3 to collect and store charged particles having a third target charge within the ion trap 1023. The processor 24 is then operable to control the voltage source VS3 to selectively discharge the collected charged particles from any or all of the ion traps 1021, 1022, 1023 and into a corresponding one of the ion measurement stages 1041, 1042, 1043 for analysis. The processor 24 is also operable to collect, store, and analyze ion measurement information generated by the ion measurement stages 1041, 1042, 1043 in a conventional manner. Thus, the particle measurement apparatus 200 is similar in operation to a Figure 12The particle measurement apparatus 100 shown in and described above is configured to simultaneously collect and analyze, or subsequently analyze, ions having three different target charges using three different ion measurement stages 1041, 1042, 1043. Those skilled in the art will recognize that Figure 13 The single inlet, multiple outlet charge steering device shown in is not limited to three ion outlets and can therefore be configured to include two or more ion outlets, and in such an embodiment, therefore, the particle measurement device 200 can include two or more ion measurement stages 1041, 1042, 1043, respectively, and in an embodiment including them, two or more ion traps 1021, 1022, 1023.

[0096] Now refer to Figure 14 , showing the inclusion of Figure 1 Another embodiment of a particle measurement apparatus 300 is an embodiment 10C of the charge filter instrument 10 shown in FIG. 1 and described above. Figure 14 In the embodiment shown in FIG, the charge filter instrument 10C comprises a drift region 12 (partially shown in FIG) having an ion inlet A1. Figure 14 ), wherein the charge detector array 16 includes a plurality of charge detection cylinders 161-16 N , the plurality of charge detection cylinders 161-16 N Axially arranged in the drift tube 12A between the ion inlet A1 and the ion outlet A2, such as Figure 1 As shown in and described above, the charge filter instrument 10C further includes a charge deflection or steering region 14 coupled to the outlet end of the drift tube 12A in the form of a charge deflection or steering region 14, comprising a network of two cascaded single-inlet, multiple-outlet charge steering devices and corresponding drift tubes. In the illustrated embodiment, both the single-inlet, multiple-outlet charge steering devices are single-inlet, three-outlet charge steering devices, each having a single ion inlet A3, an oppositely positioned ion outlet A4, and two opposite side outlets SA1, SA2, which may illustratively be implemented as Figures 10A-10B and any one of the charge steering devices 14C, 14D shown in FIG11. The two single inlet, three outlet charge steering devices forming part of the charge deflection or steering region 14 are thus Figure 14 14C1, D1 and 14C2, D2, respectively. Alternatively, the single-inlet, multiple-outlet charge steering device may take the form of any conventional single-inlet, multiple-outlet charged particle steering device.

[0097] exist Figure 14In the embodiment shown in FIG, inlet A3 of a first charge steering device 14C1, D1 is coupled to ion outlet A2 of drift tube 12A, and ion outlet A4 of charge steering device 14C1, D1 is coupled to one end of a linear drift tube segment or section 302 having an opposite end coupled to ion inlet A3 of a second charge steering device 14C2, D2. Ion outlet A4 of charge steering device 14C2, D2 is coupled to one end of another linear drift tube segment or section 304 having an opposite end that defines first ion outlet 101 and a charge deflection or steering region 14. Side ion outlet SA2 of second charge steering device 14C2, D2 is coupled to one end of an arcuate drift tube segment or section 306 having an opposite end that defines second ion outlet 102 and a charge deflection or steering region 14. Side ion outlet SA1 of second charge steering device 14C2, D2 is coupled to one end of another arcuate drift tube segment or section 308 having an opposite end that defines third ion outlet 103 and a charge deflection or steering region 14. The side ion outlet SA2 of the first charge steering device 14C1, D1 is coupled to one end of yet another arcuate drift tube segment or portion 310 having an opposite end from the fourth ion outlet 104 defining the charge deflection or steering region 14, and the side ion outlet SA1 of the first charge steering device 14C1, D1 is coupled to one end of yet another arcuate drift tube segment or portion 312 having an opposite end from the fifth ion outlet 105 defining the charge deflection or steering region 14. In the illustrated embodiment, the arcuate drift tube segments or portions 306, 308, 310, and 312 are illustratively configured to steer ions along a drift path that redirects the ions' drift by approximately 90 degrees in the axial direction. Thus, ions exiting the side outlets SA1, SA2 of each of the charge steering devices 14C1, D1 and 14C2, D2 in a direction normal to the drift direction of ions entering the inlets A3 of the charge steering devices 14C1, D1 and 14C2, D2 are redirected by the arcuate drift tube segments or portions 306, 308, 310, 312 so as to exit outlets 101-105 in a direction parallel to the drift direction of ions entering the inlets A3 and exiting the outlets A4 of the charge steering devices 14C1, D1 and 14C2, D2. In alternative embodiments, one or more of the drift tube segments 306, 308, 310, and 312 may be non-arcuate or may be arcuate but configured to redirect the direction of ion drift at an acute or obtuse angle.

[0098] The particle measurement apparatus 300 further illustratively includes (one or more) ion storage, steering and / or measurement stages 32B in the form of a plurality of, e.g., five, separate ion traps 1021-1025, each having an ion inlet coupled to an outlet 101-105 of a different respective one of the drift tube segments or portions 304, 306, 308, 310, 312 and each having an outlet coupled to an inlet of a single ion measurement stage 104 via a charged particle steering network 32C. The charged particle steering network 32C illustratively includes a plurality of, e.g., five, charge steering devices operable together as an ion steering device controllable to selectively redirect charged particles from each ion trap 1021-1025 into an inlet of the ion measurement stage 104. In the illustrated embodiment, each of the plurality of ion steering devices is separately implemented as Figures 10A-10B and any one of the charge steering devices 14C, 14D shown in Figures 1 and 11, wherein some of the plurality of ion steering devices are controlled to operate as single-inlet, single-outlet ion steering devices, other steering devices in the plurality of ion steering devices are controlled to operate as dual-inlet, single-outlet ion steering devices, and one of the plurality of ion steering devices is controlled to operate as a triple-inlet, single-outlet ion steering device. For example, the ion inlet A31 of the ion steering device 14C3, D3 is coupled to the ion outlet of the ion trap 1021, the ion outlet A4 opposite to 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 corresponding ends of the two drift tube segments or portions 314 and 316, respectively. Ion inlet A31 of another ion steering device 14C4, D4 is coupled to the ion outlet of ion trap 1022, another ion inlet A32 adjacent to inlet A31 is coupled to one end of another drift tube segment or portion 318, and ion outlet SA1 opposite ion inlet A32 and adjacent to inlet A31 is coupled to the opposite end of drift tube segment or portion 314. Ion inlet A31 of yet another ion steering device 14C5, D5 is coupled to the ion outlet of ion trap 1023, another ion inlet A32 adjacent to inlet A31 is coupled to one end of yet another drift tube segment or portion 320, and ion outlet SA2 opposite ion inlet A32 and adjacent to ion inlet A31 is coupled to the opposite end of drift tube segment or portion 316. Ion inlet A3 of yet another ion steering device 14C6, D6 is coupled to the ion outlet of ion trap 1024, and ion outlet SA1 adjacent to inlet A3 is coupled to the opposite end of drift tube segment or portion 318. The ion inlet A3 of the further ion steering 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 segment or portion 320 .

[0099] The particle measurement device 300 is similar in operation to Figure 13 1 and described above, but is configured to simultaneously collect ions having five different target charges and subsequently analyze each of the five collections with a single ion measurement stage 104. For example, ions are provided to the charge filter instrument 10C by the ion source region 30, wherein the processor 24 is operable to determine particle charge values ​​and, in some embodiments, particle velocities as the ions separate as they drift through the drift region 12, as described above. The processor 24 is illustratively programmed to control the voltage source VS1, as described above, to divert ions having each of the five different target charges through the charge diverting devices 14C1, D1 and 14C2, D2. For example, ions transferred from the drift tube 12A to the ion inlet A3 of the charge steering device 14C1, D1 and having a first target charge are guided by the processor 24 via the control of the voltage source VS1 through the outlet A4 of the charge steering device 14C1, D1 and into the ion inlet A3 of the charge steering device 14C2, D2, and are further guided by the processor 24 via the control of the voltage source VS1 through the outlet A4 of the charge steering device 14C2, D2 and into the first ion trap 1021, and the processor 24 can also be operated to control the ion trap 1021 via the control voltage source VS3 to collect and store such ions in the ion trap 1021. Ions transferred from the drift tube 12A to the ion inlet A3 of the charge steering device 14C1, D1 and having the second target charge are guided by the processor 24 via the control of the voltage source VS1 through the outlet A4 of the charge steering device 14C1, D1 and into the ion inlet A3 of the charge steering device 14C2, D2, and are further guided by the processor 24 via the control of the voltage source VS1 through the outlet SA2 of the charge steering device 14C2, D2 and into the second ion trap 1022, and the processor 24 is further operable to control the ion trap 1022 via the control of the voltage source VS3 to collect and store such ions within the ion trap 1022. The processor 24 is similarly operable with respect to ions transferred from the drift tube 12A into the ion inlet A3 of the charge steering device 14C1, D1 and having the third, fourth and fifth target charges to control the voltage source VS1 to divert such ions into the third, fourth and fifth ion traps 1023-1025, respectively, and then control the voltage source VS3 to collect and store such ions in the ion traps 1023-1025.

[0100] The processor 24 is then operable to control the voltage source VS3 to selectively and, in some embodiments, sequentially eject the collected charged particles from the ion traps 1021-1025 and to control the charged particle steering network 32C to selectively direct the charged particles into the entrance of the ion measurement stage for analysis. For example, to eject the charged particles collected in the ion trap 1021 and to deflect or direct the collected ions into the ion measurement stage 104, the processor 24 is operable to control the voltage source VS3 to cause the ion trap 1021 to eject the stored ions therefrom and into the ion inlet A31 of the ion steering device 14C3, D3, and further control the voltage source VS3 to cause the ion steering device 14C3, D3 to pass the ions entering the ion inlet A31 to pass to and through its ion outlet A4 and into 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. In order to expel the charged particles collected in the ion trap 1022 and to deflect or guide the collected ions into the ion measurement stage 104, the processor 24 is operable to control the voltage source VS3 to cause the ion trap 1022 to eject the stored ions therefrom and into the ion inlet A31 of the ion steering device 14C4, D4, and further control the voltage source VS3 to cause the ion steering device 14C4, D4 to pass the ions entering the ion inlet A31 to pass to and through its ion outlet SA1 and into one end of the drift tube segment or portion 314. The processor 24 is then further operable to control the voltage source VS3 to cause the charged particles passing through the drift tube segment or portion 314 to enter the inlet A32 of the ion steering device 14C3, D3, and further control the voltage source VS3 to cause the ion steering device 14C3, D3 to pass the ions entering the ion inlet A32 to pass to and through its ion outlet A4 and into 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 introduced into the ion inlet of the ion measurement stage 104. The processor 24 is operable to control the voltage source VS3 in a similar manner to eject charged particles from the remaining ion traps 1023-1025 and selectively direct the ejected ions into the ion inlet of the ion measurement stage 104 for analysis thereof. It will be understood that when the processor 24 controls the voltage source VS3 to eject ions from various ion traps 1021-1025, the processor 24 is further operable to control the voltage source VS1 to fill one or more empty ion traps 1021-1025 with ions having a specified corresponding target charge. In any case, the processor 24 is also operable to collect, store, and analyze all ion measurement information generated by the ion measurement stage 104 in a conventional manner.

[0101] Those skilled in the art will recognize that although Figure 14The example particle measurement apparatus 300 shown in FIG is configured to simultaneously collect ions having five different target charges and then analyze each of the five collections with a single ion measurement stage 104, but Figure 14 The concepts shown in can be readily extended to devices configured to simultaneously collect more or fewer than five sets of target charges. It will be understood that the present disclosure contemplates any such alternative embodiments. It will further be understood that while Figure 14 The example particle measurement device 300 shown in includes five ion traps to collect ions having five respectively different charges, but alternative embodiments are envisioned in which one or more or all of the ion traps are omitted so that ions having (one or more) corresponding target charges can be diverted directly into the ion measurement stage 104 by the ion steering network 32C.

[0102] Now refer to Figure 15 , showing Figure 1 and 12 An example embodiment of an ion source or source region is shown in FIG. 14 and briefly described above. In the illustrated embodiment, the ion source or source region illustratively includes at least one ion generator 36 coupled to a voltage source VS2 and configured to generate ions from a sample S in response to control signals generated by processor 24. In some embodiments, the sample S is located within the ion source region 30, and in other embodiments, the ion source S is located outside the ion source region 30, such as Figure 15 . In one embodiment, ion generator 36 is a conventional electrospray ionization (ESI) source configured to generate ions from a sample in the form of a fine mist of charged droplets. In an alternative embodiment, ion generator 36 can be or include a conventional matrix-assisted laser desorption ionization (MALDI) source. It will be understood that ESI and MALDI represent only two examples of countless conventional ion generators, and ion generator 36 can be or include any such conventional device or apparatus for generating ions from a sample.

[0103] The ion source or source region further illustratively includes a number R of ion processing stages IPS1-IPS R , where R can be any positive integer. (One or more) such ion processing stages IPS1-IPS R Examples may include, but are not limited to, one or more devices and / or instruments, in any order and / or combination, for separating, collecting, and / or filtering charged particles based on one or more molecular characteristics, and / or one or more devices and / or instruments for decomposing, e.g., fragmenting, charged particles. In some embodiments, the ion generator 36 and / or ion processing stages IPS1-IPS RAt least one of the ion source region 30 includes one or more conventional structures and / or devices for accelerating or otherwise propelling the generated ions through the ion inlet A1 and into the charge filter instrument 10. Examples of one or more devices and / or instruments for separating charged particles based on one or more molecular properties include, but are not limited to, one or more mass spectrometers or mass analyzers, one or more ion mobility spectrometers, one or more instruments for separating charged particles based on magnetic moment, one or more instruments for separating charged particles based on dipole moment, and the like. In embodiments of the ion source region 30 that include one or more mass spectrometers or mass analyzers, examples of mass spectrometers or mass analyzers include, but are not limited to, time-of-flight (TOF) mass spectrometers, reflectron mass spectrometers, Fourier transform ion cyclotron resonance (FTICR) mass spectrometers, quadrupole mass spectrometers, triple quadrupole mass spectrometers, magnetic sector mass spectrometers, orbital traps, or the like. In an embodiment of the ion source region 30 including one or more ion mobility spectrometers, examples of ion mobility spectrometers include, but are not limited to, 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 one or more devices and / or instruments for collecting charged particles include, but are not limited to, a quadrupole ion trap, a hexapole ion trap, or the like. Examples of one or more devices and / or instruments for filtering charged particles include, but are not limited to, one or more devices or instruments for filtering charged particles according to mass-to-charge ratio, one or more devices or instruments for filtering charged particles according to particle mobility, and the like. Examples of one or more devices and / or instruments for decomposing charged particles include, but are not limited to, one or more devices or instruments for decomposing charged particles by collision-induced decomposition (CID), surface-induced decomposition (SID), electron capture decomposition (ECD), and / or photo-induced decomposition (PID), multiphoton decomposition (MPD), or the like.

[0104] It will be understood that the ion processing stage(s) IPS1-IPS R Any one or any combination of any such conventional ion separation instruments and / or ion manipulation instruments may be included in any order, and some embodiments may include a plurality of adjacent or spaced apart instruments of any such conventional ion separation instruments and / or ion manipulation instruments. As a non-limiting example, the ion manipulation stage(s) IPS1-IPS RThe invention also includes a charged particle filtering device or instrument after the ion generator, and a decomposition 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 so that the charged particle filtering device or instrument only passes ions above or below a threshold mass-to-charge ratio or within a specified range of mass-to-charge ratios, and further controls the voltage source VS2 to cause the decomposition device, instrument or stage to decompose, for example, to fragment the charged particles leaving the charged particle filtering device or instrument so that the decomposed charged particles leaving the decomposition 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 can be disposed between the decomposition device, instrument or stage and the inlet A1 of the charge filter instrument 10, and in such embodiments the processor 24 can be operable to control the voltage source VS2 so that the second charged particle filtering device or instrument only passes ions above or below a threshold mass-to-charge ratio or within a specified range of mass-to-charge ratios to the inlet A1 of the charge filter instrument 10. One skilled in the art will recognize one or more ion processing stages IPS1-IPS1 within the ion source or source region. R other implementations, and it will be understood that all such other implementations are intended to fall within the scope of the present disclosure.

[0105] Now refer to Figure 16 , showing Figure 1 and 12 An example embodiment of the ion measurement stage 104 is shown in FIG. 14 and briefly described above. In the illustrated embodiment, the ion measurement stage 104 illustratively includes one or more ion measurement instruments IMI1-IMI2. S , where S can be any positive integer. In some embodiments, the processor 24 is illustratively programmed to control one or more ion measurement instruments IMI1-IMI2 in a conventional manner, for example, via control of a voltage source VS3. S to cause the ion measuring instrument(s) to measure one or more molecular properties of charged particles contained therein and / or passing therethrough, and / or to measure one or more molecular properties of charged particles contained therein and / or passing therethrough and to generate information therefrom. S The generated ion measurement information is illustratively processed by processor 24 to generate, store, and in some embodiments display processed molecular characteristic information. In other embodiments, the charge-selected ions can be deposited on a suitable surface or in a matrix for collection and analysis by other methods.

[0106] This ion measurement instrument IMI1-IMI SExamples of may include, but are not limited to, one or more devices and / or instruments for temporally separating charged particles according to one or more molecular properties, one or more devices and / or instruments for filtering charged particles according to one or more molecular properties, one or more instruments for separating charged particles based on magnetic moment, one or more instruments for separating charged particles based on dipole moment, and the like, in any order and / or combination. Examples of one or more devices and / or instruments for temporally separating charged particles according to one or more molecular properties include, but are not limited to, one or more mass spectrometers, one or more ion mobility spectrometers, and the like. Examples of one or more mass spectrometers in an embodiment of the ion measurement stage 104 that includes one or more mass spectrometers include, but are not limited to, a time-of-flight (TOF) mass spectrometer, a reflectometer mass spectrometer, a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer, a quadrupole mass spectrometer, a triple quadrupole mass spectrometer, a magnetic sector mass spectrometer, an orbital trap, or the like. In an embodiment of the ion measurement stage 104 comprising one or more ion mobility spectrometers, examples of the one or more ion mobility spectrometers include, but are not limited to, 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 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 based on mass-to-charge ratio, one or more devices or instruments for filtering charged particles based on particle mobility, magnetic moment, dipole moment, and the like. In an embodiment of the ion measurement stage 104 comprising one or more devices or instruments for filtering charged particles based on mass-to-charge ratio, examples of the one or more devices or instruments for filtering charged particles based on mass-to-charge ratio include, but are not limited to, a quadrupole mass analyzer or quadrupole mass filter, a quadrupole ion trap mass analyzer or mass filter, a magnetic sector mass analyzer, a time-of-flight mass analyzer, a reflectometer mass analyzer, a Fourier transform ion cyclotron resonance (FTICR) mass analyzer, an orbital trap, or the like. In embodiments of the ion measurement stage 104 that include one or more devices or instruments for filtering charged particles based on particle mobility, examples of the one or more devices or instruments for filtering charged particles based on particle mobility include, but are not limited to, a single-tube linear ion mobility spectrometer, a multi-tube linear ion mobility spectrometer, a circular tube ion mobility spectrometer, or the like. It will be understood that the ion measurement stage 104 may include one or any combination of any such instruments for temporally separating charged particles based on one or more molecular properties and / or one or more devices and / or instruments for filtering charged particles based on one or more molecular properties, and the like in any order, and some embodiments may include multiple adjacent or spaced-apart pieces of any such instruments or devices.

[0107] Now refer to Figure 17, shows an embodiment of yet another particle measurement apparatus 400 comprising two spaced-apart charge filter instruments 101, 102 separated by an ion processing region 402. In the illustrated embodiment, the ion source region 30, as described above, is coupled to the inlet end of the first charge filter instrument 101, and the ion outlet end of the charge deflection or steering region 14 of the first charge filter instrument 101 is coupled to the inlet of the ion processing region 402, the ion outlet of the ion processing region 402 is coupled to the inlet end of the second charge filter instrument 102, and the ion outlet end of the charge deflection or steering region 14 of the second charge filter instrument 102 is coupled to the inlet of (one or more) ion storage, steering and / or measurement stages 32, also as described above. Each of the charge filter instruments 101, 102 comprises a drift region 12 having an ion inlet A1, wherein the charge detector array 16 comprises a plurality of charge detection cylinders 161-162. N , the plurality of charge detection cylinders 161-16 N Axially arranged in the drift tube 12A between the ion inlet A1 and the ion outlet A2 thereof, as in Figure 1 and described above, and further including any form of charge deflection or steering region 14 shown and / or described herein, coupled to the outlet end of drift tube 12A.

[0108] The ion processing region 402 of the particle measurement apparatus 400 illustratively includes one or more ion processing stages IS1-IS2. T , where T can be any positive integer. Ion treatment stage IS1-IS TOne or more of can illustratively include, for example, but not limited to, one or more conventional instruments for separating ions according to one or more molecular properties (e.g., according to ion mass-to-charge ratio, ion mobility, magnetic moment, dipole moment, or the like) and / or one or more conventional ion processing instruments (e.g., one or more quadrupoles, hexapole, and / or other ion traps) for collecting and / or storing ions, one or more conventional instruments or devices for filtering ions (e.g., according to one or more molecular properties, such as ion mass-to-charge ratio, ion mobility, magnetic moment, dipole moment, and the like), one or more instruments, devices, or stages for fragmenting or otherwise decomposing ions, and the like. It will be understood that an ion processing stage can include any one or any combination of any such instruments, devices, or stages in any order, and some embodiments can include multiple adjacent or spaced-apart instruments, devices, or stages of any such instruments, devices, or stages. It will be further understood that any example combination of the above-described instruments, devices, or stages can be implemented as an ion processing stage or as part of an ion processing stage. Those skilled in the art will recognize other instruments, devices, and / or stages that may be included in an ion processing stage, whether or not shown and / or described herein, and other combinations of instruments, devices, or stages that may be implemented as an ion processing stage or as part of an ion processing stage, and will understand that all such other instruments, devices, and / or stages, and any combination of any instruments, devices, and / or stages, are intended to fall within the scope of the present disclosure.

[0109] Will be understood that because the charge magnitude and / or charge state of any individual charged particle or any collection, set or group of charged particles delivered to the ion measurement stage 104 of any particle measurement device 100,200,300,400 described herein will be known, that is, as a result of the control and operation of the charge filter instrument 10 as described above, it is now possible to easily determine molecular characteristic information that has not been available from conventional ion measurement instruments to date. As a non-limiting example, the particle mass-to-charge ratio values ​​available from conventional mass spectrometers and mass analyzers can be easily converted into particle mass values ​​using known charge magnitude or charge state information. As another non-limiting example, the particle mobility values ​​available from conventional ion mobility spectrometers can be easily converted into particle collision cross-sectional area values ​​using known charge magnitude or charge state information. As a further non-limiting example, in the case of the charge magnitude or charge state of the collection, group or group of charged particles, a conventional mass-to-charge ratio filter can be operated as a true mass filter to target particles by selecting a range of particles with a specified mass or mass. Other examples will occur to those skilled in the art, and any such other examples are intended to fall within the scope of this disclosure.

[0110] Although the present disclosure is shown and described in detail in the foregoing drawings and description, it is to be considered illustrative and accordingly not restrictive, and it will be understood that only illustrative embodiments thereof are shown and described and that all changes and modifications that come within the spirit of the present disclosure are desired to be protected. For example, although several structures are shown in the drawings and described herein as controllable and / or configurable to establish one or more electric fields therein, which are configured and oriented to accelerate and / or deflect and / or otherwise manipulate charged particles, those skilled in the art will recognize that the acceleration and / or deflection of charged particles and / or other manipulations of charged particles may, in some cases, be accomplished alternatively or additionally via one or more magnetic fields. It will therefore be understood that any conventional structure and / or mechanism for replacing or enhancing the one or more electric fields described herein with one or more suitable magnetic fields is intended to fall within the scope of the present disclosure.

Claims

1. A charge filter apparatus comprising: a field-free drift region having an inlet end and an outlet end opposite the inlet end, the inlet end being configured to be coupled to an ion source to receive a plurality of ions to drift axially through the drift region from the inlet end to the outlet end, a plurality of spaced-apart charge detection cylinders disposed in the drift region and through which a plurality of ions drifting axially through the drift region pass, a plurality of charge sensitive 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 a charge of one or more of the plurality of ions passing through a corresponding at least one of the plurality of charge detection cylinders, a charge deflector having a single inlet and a single outlet and one of a charge steering device having a single inlet and a plurality of outlets, coupled to an outlet end of the drift region, means for determining a charge magnitude or charge state of each of a plurality of ions drifting axially through a drift region based on charge detection signals generated by at least some of the plurality of charge sensitive amplifiers, and Apparatus for controlling one of a charge deflector and a charge steering device to pass only ions having a determined charge magnitude or charge state equal to or within a specified range of the specified charge magnitude or charge state through a corresponding one of the single outlet and a specified one of the plurality of outlets.

2. The charge filter apparatus according to claim 1, wherein: One of a charge deflector and a charge steering device includes a charge deflector.

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

4. The charge filter apparatus of claim 3 , further comprising: an ion trap disposed between the single outlet of the charge deflector and an inlet of at least one ion measurement instrument, the ion trap being configured to capture therein ions exiting the single outlet of the charge deflector, and Means for controlling the ion trap to selectively release ions trapped therein into an ion inlet of at least one ion measurement instrument.

5. The charge filter instrument according to any one of claims 1 to 4 further comprises the ion source, the ion source comprising an ion generator, the ion generator being configured to generate a plurality of ions from a sample and supplying the generated plurality of ions to the entrance of the drift region, so that the generated plurality of ions drift axially through the drift region toward the ion outlet end of the drift region.

6. The charge filter apparatus according to claim 5, wherein: The ion source also includes at least one instrument for separating the generated ions according to at least one molecular characteristic.

7. The charge filter apparatus according to claim 5, wherein: The ion source also includes at least one dissociation stage configured to dissociate ions passing therethrough.

8. The charge filter apparatus according to claim 5, wherein: The ion source also includes at least one ion trap configured to trap ions therein and selectively release the trapped ions therefrom.

9. The charge filter apparatus according to claim 1, wherein: One of the charge deflector and the charge steering device includes a charge steering device, And wherein the means for controlling the charge steering device includes means for controlling the charge steering device to allow only ions having a first specified charge value or charge state to pass through a first of a plurality of outlets and to allow only ions having a second specified charge value or charge state different from the first specified charge value or charge state to pass through a second of a plurality of outlets.

10. The charge filter apparatus of claim 9, further comprising: at least a first ion measurement instrument having an inlet coupled to a first of the plurality of outlets of the charge steering device, the at least first ion measurement instrument being configured to measure at least one molecular characteristic of ions exiting the first of the plurality of outlets of the charge steering device, and At least a second ion measurement instrument has an inlet coupled to a second one of the plurality of outlets of the charge steering device, the at least second ion measurement instrument being configured to measure at least one molecular characteristic of ions exiting the second one of the plurality of outlets of the charge steering device.

11. The charge filter apparatus of claim 10 , further comprising: A first ion trap is arranged between the first of the multiple outlets of the charge steering device and the entrance of the first ion measurement instrument, the first ion trap is configured to capture ions leaving the first of the multiple outlets of the charge steering device therein, and a device is used to control the first ion trap to selectively release the ions captured therein into the ion entrance of the first ion measurement instrument.

12. The charge filter apparatus according to any one of claims 10 or 11, further comprising: a second ion trap disposed between a second one of the plurality of outlets of the charge steering device and an inlet of the second ion measurement instrument, the second ion trap being configured to capture ions exiting the second one of the plurality of outlets of the charge steering device therein, and means for controlling the second ion trap to selectively release the ions captured therein into the ion inlet of the second ion measurement instrument.

13. The charge filter instrument according to claim 9 further includes the ion source, which includes an ion generator, and the ion generator is configured to generate multiple ions from the sample and supply the generated multiple ions to the entrance of the drift region, so that the generated multiple ions drift axially through the drift region toward the ion outlet end of the drift region.

14. The charge filter apparatus of claim 13, wherein: The ion source also includes at least one instrument for separating the generated ions according to at least one molecular characteristic.

15. A charge filter apparatus according to claim 13 or claim 14, wherein: The ion source also includes at least one dissociation stage configured to dissociate ions passing therethrough.

16. A charge filter apparatus according to claim 13 or claim 14, wherein: The ion source also includes at least one ion trap configured to trap ions therein and selectively release the trapped ions therefrom.

17. The charge filter apparatus of claim 9, further comprising: a first ion trap having an entrance coupled to a first of the plurality of exits of the charge steering device and an exit, the first ion trap being configured to capture ions therein that exit the first of the plurality of exits of the charge steering device, a second ion trap having an entrance coupled to a second one of the plurality of exits of the charge steering device and an exit, the second ion trap being configured to capture therein ions exiting the second one of the plurality of exits of the charge steering device, at least one ion measurement instrument having an inlet and configured to measure at least one molecular characteristic of ions entering its inlet, an ion steering network having a first inlet coupled to an outlet of the first ion trap, a second inlet coupled to an outlet of the second ion trap, and an outlet coupled to an inlet of at least one ion measurement instrument, and Apparatus for controlling (i) a first ion trap to selectively release ions trapped therein into a first ion inlet of an ion steering network and the ion steering network to selectively allow ions exiting the outlet of the first ion trap to pass into the inlet of at least one ion measurement instrument, and (ii) a second ion trap to selectively release ions trapped therein into a second ion inlet of the ion steering network and the ion steering network to selectively allow ions exiting the outlet of the second ion trap to pass into the inlet of at least one ion measurement instrument.

18. The charge filter instrument according to claim 17 further includes the ion source, which includes an ion generator, and the ion generator is configured to generate multiple ions from the sample and supply the generated multiple ions to the entrance of the drift region, so that the generated multiple ions drift axially through the drift region toward the ion outlet end of the drift region.

19. The charge filter apparatus of claim 18, wherein: The ion source also includes at least one instrument for separating the generated ions according to at least one molecular characteristic.

20. A charge filter apparatus according to claim 18 or claim 19, wherein The ion source also includes at least one dissociation stage configured to dissociate ions passing therethrough.

21. A charge filter apparatus according to claim 18 or claim 19, wherein: The ion source also includes at least one ion trap configured to trap ions therein and selectively release the trapped ions therefrom.

22. The charge filter apparatus of claim 1, wherein: the electric field free drift region is a first electric field free drift region, the plurality of charge detection cylinders is a first plurality of charge detection cylinders, the plurality of charge sensitive amplifiers is a first plurality of charge sensitive amplifiers, one of the charge deflector and the charge steering device is a first charge deflector and one of the first charge steering device, the means for determining a charge magnitude or a charge state is a first means for determining a charge magnitude or a charge state, and the means for controlling is a first means for controlling, and wherein the charge filter apparatus comprising the first electric field free drift region, the first plurality of charge detection cylinders, the first plurality of charge sensitive amplifiers, one of the first charge deflector and the first charge steering device, the first means for determining a charge magnitude or a charge state, and the first means for controlling is a first charge filter apparatus, And also includes: a second charge filter apparatus identical to the first charge filter apparatus, the second charge filter apparatus comprising a second field-free drift region having a second inlet end and a second outlet end opposite the second inlet end, and a second plurality of charge detection cylinders disposed in the second field-free drift region, and At least one ion processing stage is disposed between one of the single outlet and the designated one of the plurality of outlets of the corresponding one of the first charge deflector and the first charge steering device and the second entrance end of the second electric field-free drift region of the second charge filter instrument.

23. The charge filter apparatus of claim 22, wherein: The at least one ion processing stage includes at least one of: (i) at least one instrument for temporally separating ions according to at least one molecular characteristic, (ii) at least one ion filter configured to allow only ions having a specified molecular characteristic or having a molecular characteristic within a specified range of molecular characteristics to pass therethrough, (iii) at least one ion trap configured to selectively capture ions therein and selectively release ions therefrom, and (iv) at least one decomposition stage configured to decompose ions passing therethrough.

24. The charge filter instrument according to claim 22 or claim 23 further includes the ion source, which includes an ion generator, and the ion generator is configured to generate multiple ions from the sample and supply the generated multiple ions to the entrance of the drift region, so that the generated multiple ions drift axially through the drift region toward the ion outlet end of the drift region.

25. The charge filter apparatus of claim 24, wherein: The ion source also includes at least one instrument for separating the generated ions according to at least one molecular characteristic.

26. The charge filter apparatus of claim 24, wherein: The ion source also includes at least one dissociation stage configured to dissociate ions passing therethrough.

27. The charge filter apparatus of claim 24, wherein: The ion source also includes at least one ion trap configured to trap ions therein and selectively release the trapped ions therefrom.

28. A charge filter apparatus comprising: a field-free drift region having an inlet end and an outlet end opposite the inlet end, the inlet end being configured to be coupled to an ion source to receive a plurality of ions to drift axially through the drift region from the inlet end to the outlet end, a plurality of spaced-apart charge detection cylinders disposed in the drift region and through which a plurality of ions drifting axially through the drift region pass, a plurality of charge sensitive 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 a charge of one or more of the plurality of ions passing through a corresponding at least one of the plurality of charge detection cylinders, one of a charge deflector having a single inlet and a single outlet and a charge steering device having a single inlet and multiple outlets, coupled to the outlet end of the drift region, at least one voltage source having at least one voltage output operatively coupled to one of the charge deflector and the charge steering device, at least one processor, and at least one memory having instructions stored therein, the instructions being executable by the at least one processor to cause the at least one processor to (a) monitoring charge detection signals generated by at least some of the plurality of charge sensitive amplifiers as the plurality of ions drift axially through the field-free drift region toward an exit end of the field-free drift region, (b) determining a charge magnitude or charge state of each of the plurality of ions drifting axially through the field-free drift region based on the monitored charge detection signal, and (c) controlling at least one voltage output of at least one voltage source to cause one of the charge deflector and the charge steering device to allow only ions having a determined charge magnitude or charge state equal to or within a specified range of the specified charge magnitude or charge state to pass through a corresponding one of the single outlet and the specified one of the multiple outlets.

29. The charge filter apparatus of claim 28, wherein the instructions stored in the at least one memory further comprise instructions executable by the at least one processor to cause the at least one processor to: monitoring charge detection signals generated by the plurality of charge sensitive amplifiers by monitoring edge events of the monitored charge detection signal defined by rising and falling edges of the monitored charge detection signal and by monitoring signal magnitudes between adjacent edge events of the monitored charge detection signal, and The charge magnitude or charge state of each of at least some of the plurality of ions drifting axially through the field-free drift region is determined by (i) processing edge events of the charge detection signal generated by each successive one of the plurality of charge sensitive amplifiers to identify ions entering and ions leaving each corresponding one of the charge detection cylinders, (ii) between each successive entry and exit of the ion into and out of the corresponding one of the charge detection cylinders, processing the signal magnitude of the charge detection signal produced by the corresponding one of the charge sensitive amplifiers to determine the charge magnitude or charge state of the ion, and (iii) updating the determination of the charge magnitude or charge state of the ion based on each successive determination of the charge magnitude or charge state of the ion using the corresponding one of the charge detection signals.

Images