Radial segmented ion guides and example applications thereof

Abstract

A charged particle guide includes a plurality of electrically conductive sections radially spaced apart from each other about an opening defined axially through the sections, where the opening defines a central axis centrally and axially through the opening, such that charged particles are received at one end of the opening and pass through an opposite end of the opening; at least one voltage source configured to generate and supply a separate voltage to each of the segments; and at least one control circuit configured to control the supply of a selected voltage to the section to create an electric field within the opening, the electric field is configured to cause charged particles entering the one end of the opening along a first axial path relative to the central axis to exit the opposite end of the opening along a second axial path relative to the central axis, where the first and second axial paths are non-collinear.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of and priority to U.S. Provisional Patent Application Serial No. 63 / 405,007, filed on September 9, 2022, the disclosure of which is incorporated herein by reference in its entirety. Government Rights

[0002] This invention was made with government support under Grant GM131100 awarded by the National Institutes of Health. The U.S. Government has certain rights in this invention. Technical Field

[0003] The present disclosure generally relates to the transmission of charged particles to, within, or away from a charged particle analysis instrument, and more specifically to an apparatus for focusing charged particles within, transmitting to, or away from a charged particle analysis instrument. Background Art

[0004] In charged particle analysis instruments, charged particles are typically transported into, through and / or out of various instrument stages or components axially, i.e., along and about a central axis defined therethrough. In some such instruments, axial misalignment between instrument stages and / or between two or more components of an instrument stage may result in deviations in the transport of charged particles relative to that along the central axis. In other such instruments, charged particles may not leave an instrument stage along the central axis, but may instead leave an instrument stage with a radial deviation from the central axis and in some cases also with an angular deviation from the central axis. In some such instruments, it may therefore be desirable to control the transport of charged particles into, through and / or out of one or more stages or components of a charged particle analysis instrument or system in a manner that focuses the charged particles toward the central axis within a stage or subsequent stage of the instrument or system. Summary of the invention

[0005] The present disclosure may include one or more of the features set forth in the accompanying claims, and / or one or more of the following features and combinations thereof. In a first aspect, a charged particle guide may include: a plurality of conductive segments separated from each other and radially spaced apart around an opening defined axially through the plurality of conductive segments, the opening defined in the center and axially through a central axis of the opening, the plurality of conductive segments configured to receive charged particles at one end of the opening and pass the received charged particles through an opposite end of the opening; at least one voltage source configured to generate and supply a voltage that can be individually controlled to each of the plurality of conductive segments; and at least one control circuit configured to control at least one voltage source to supply a selected voltage to each of the plurality of conductive segments to create an electric field within the opening defined by the plurality of conductive segments, the electric field configured to cause charged particles entering one end of the opening along a first axial path relative to the central axis to leave the opposite end of the opening along a second axial path relative to the central axis that is different from the first axial path.

[0006] The second aspect includes the features of the first aspect, and wherein the first axial path is co-linear with the central axis, and wherein the second axial path is radially offset from the central axis.

[0007] The third aspect includes the features of the first aspect, and wherein the second axial path is co-linear with the central axis, and wherein the first axial path is radially offset parallel to the central axis.

[0008] The fourth aspect includes the features of the first aspect, and wherein the first axial path is radially offset from the central axis, and wherein the second axial path is radially offset from the first axial path and radially offset from the central axis.

[0009] The fifth aspect includes the features of the first to fourth aspects, and wherein the opening is defined by and between the inner surfaces of each of the plurality of conductive segments.

[0010] The sixth aspect includes the features of the fifth aspect, and wherein an inner surface of at least one of the plurality of conductive segments is arcuate in shape.

[0011] A seventh aspect includes the features of the sixth aspect, and wherein the inner surface of each of the plurality of conductive segments is arcuate in shape such that the opening is circular in cross-section.

[0012] An eighth aspect includes the features of the fifth aspect, and wherein an inner surface of each of the plurality of conductive segments is non-curvilinear.

[0013] In a ninth aspect, a charged particle analysis system may include a charged particle guide as described in any one of aspects one to eight, and a charged particle analysis stage having a charged particle inlet axially spaced apart from opposite ends of an opening, the charged particle inlet being defined by a central axis centrally disposed and axially passing through the charged particle inlet, wherein the charged particle guide is configured to guide charged particles leaving its opening into the charged particle inlet of the charged particle analysis stage, wherein the central axis of the charged particle inlet of the charged particle analysis stage is radially offset from the central axis of the opening of the charged particle guide, and wherein the second axial path is colinear with the central axis of the charged particle inlet of the charged particle analysis stage, so that an electric field created by at least one control circuit within the opening is configured to guide charged particles leaving the opening of the charged particle guide toward the central axis of the charged particle inlet of the charged particle analysis stage.

[0014] The tenth aspect may include the features of the ninth aspect, and may also include a charged particle position detector configured to generate at least one detection signal corresponding to a radial position relative to a central axis of a charged particle inlet of a charged particle analysis stage or relative to a central axis of an opening of a charged particle guide, and wherein at least one control circuit is configured to select a voltage to create an electric field within the opening of the charged particle guide based on the at least one detection signal.

[0015] In an eleventh aspect, a charged particle analysis system may include a charged particle guide as described in any one of aspects one to eight, and a charged particle analysis stage having a charged particle inlet axially spaced apart from opposite ends of an opening, the charged particle inlet being defined by a central axis centrally disposed and axially passing through the charged particle inlet, wherein the central axis of the charged particle inlet of the charged particle analysis stage is radially offset from the central axis of the opening of the charged particle guide, and wherein an electric field created within the opening by at least one control circuit is configured to maximize the percentage of charged particles leaving the opening of the charged particle guide that enter the charged particle inlet of the charged particle analysis stage.

[0016] In the twelfth aspect, a charged particle analysis system may include: first and second spaced-apart ion mirrors, and a charge detection cylinder positioned between the first ion mirror and the second ion mirror, the first ion mirror, the second ion mirror and the charge detection cylinder together defining an electrostatic linear ion trap (ELIT), the electrostatic linear ion trap being configured to capture therein charged particles supplied by a charged particle source so that the trapped charged particles oscillate back and forth between the first ion mirror and the second ion mirror each time they pass through the charge detection cylinder, the ELIT defining a central axis centrally and axially passing through each of the first ion mirror and the second ion mirror and the charge detection cylinder, wherein each of the first ion mirror and the second ion mirror includes a plurality of axially spaced-apart ion mirror electrodes, each of the plurality of axially spaced-apart ion mirror electrodes defining an electrode opening through which the central axis of the ELIT passes, wherein at least one of the mirror electrodes may include a charged particle guide according to any one of aspects 1 to 8, and wherein the central axis of the opening of the charged particle guide is radially offset from the central axis of the ELIT.

[0017] A thirteenth aspect may include the features of the twelfth aspect, and wherein the electric field created within the opening by the at least one control circuit is configured to direct charged particles exiting the opening of the charged particle guide toward and along a central axis of the ELIT.

[0018] The fourteenth aspect may include the features of the twelfth aspect, and wherein, each time a charged particle passes through the charge detection cylinder, a charge is induced on the charge detection cylinder, and wherein the charged particle analysis system also includes a charge sensitive preamplifier having an input end connected to the charge detection cylinder and an output end connected to at least one control circuit, the charge sensitive preamplifier responding to each charge induced on the charge detection cylinder to produce a corresponding charge detection signal, and wherein at least one control circuit is configured to respond to the charge detection signal to determine the capture efficiency of the ELIT as the ratio of capture events in which the charged particle oscillates between the two ion mirrors within at least a predefined amount of the total capture event time period to capture events in which the charged particle does not oscillate between the two ion mirrors within at least a predefined amount of the total capture event time period, and wherein at least one control circuit is configured to select a voltage to create an electric field configured to guide the charged particles leaving the opening of the charged particle guide in a manner that maximizes the capture efficiency.

[0019] In the fifteenth aspect, a charged particle analysis system may include: a charged particle source having a charged particle outlet, through which charged particles leave the charged particle source, the charged particle outlet being defined at the center and axially passing through a central axis of the charged particle outlet; and a charged particle guide as described in any one of aspects one to eight, wherein one end of an opening of the charged particle guide is axially spaced from the charged particle outlet of the charged particle source, wherein the central axis of the charged particle outlet of the charged particle source is radially deviated from the central axis of the opening of the charged particle guide, and wherein an electric field created in the opening by at least one control circuit is configured to cause charged particles leaving the charged particle outlet of the charged particle source to leave the opening of the charged particle guide along an axial path that is colinear with or radially deviated from the central axis of the charged particle guide.

[0020] In the sixteenth aspect, a charged particle analysis system may include: a charged particle source having a charged particle outlet through which charged particles leave the charged particle source, the charged particle outlet being defined at the center and axially passing through a central axis of the charged particle outlet; and a charged particle guide described in any one of aspects one to eight, wherein one end of an opening of the charged particle guide is axially spaced apart from the charged particle outlet of the charged particle source; and a charged particle analysis stage having a charged particle inlet axially spaced apart from an opposite end of the opening of the charged particle guide, the charged particle inlet being defined at the center and axially passing through a central axis of the charged particle inlet, wherein the central axis of the opening of the charged particle guide is radially offset from at least one of the central axis of the charged particle outlet of the charged particle source and the central axis of the charged particle inlet of the charged particle analysis stage, and wherein an electric field created in the opening by at least one control circuit is configured to guide charged particles leaving the charged particle outlet of the charged particle source into the charged particle inlet of the charged particle analysis stage.

[0021] The seventeenth aspect may include the features of the sixteenth aspect, and may also include a charged particle position detector configured to generate at least one detection signal corresponding to a radial position relative to the central axis of the opening of the charged particle guide or relative to the central axis of the charged particle entrance of the charged particle analysis stage, and wherein at least one control circuit is configured to select a voltage based on the at least one detection signal to create an electric field, the electric field being configured to guide charged particles leaving the opening of the charged particle guide along a predetermined path relative to the central axis of the opening of the charged particle guide or the central axis of the charged particle entrance of the charged particle analysis stage.

[0022] An eighteenth aspect may include the features of the seventeenth aspect, and wherein the charged particle position detector is positioned between the charged particle guide and the charged particle analysis stage, and is mounted to one of the charged particle guide and the charged particle analysis stage.

[0023] The nineteenth aspect may include the features of the sixteenth aspect, and may also include a device for determining the percentage of charged particles leaving the charged particle outlet of the charged particle source that enter the charged particle inlet of the charged particle analysis stage, and wherein at least one control circuit is configured to select a voltage to create an electric field, the electric field being configured to guide the charged particles leaving the charged particle guide in a manner that maximizes the percentage of charged particles leaving the charged particle outlet of the charged particle source that enter the charged particle inlet of the charged particle analysis stage.

[0024] The twentieth aspect may include the features of the sixteenth aspect, and wherein the charged particle source comprises a multipole transmission device and an AC voltage source, the multipole transmission device being configured to receive charged particles at its charged particle inlet and to transmit the received charged particles through its charged particle outlet, the AC voltage source being operatively connected to the multipole transmission device and configured to apply an AC voltage to the multipole transmission device to guide the received charged particles through the charged particle outlet of the multipole transmission device, and wherein at least one control circuit is configured to: (i) control at least one voltage source to sequentially supply each of a number of different groups of voltages to each of a plurality of conductive segments, the number of different groups of voltages being selected to create corresponding electric fields within an opening of the charged particle guide; The invention relates to a method for controlling the charged particle guide to: (i) control the at least one charged particle analysis stage to measure the mass-to-charge ratio of the charged particles leaving the charged particle guide for each of the number of different groups of voltages supplied by at least one voltage source to produce a corresponding number of different groups of charged particle measurement results, and (iii) average the measured mass-to-charge ratios of the charged particles in the number of different groups of charged particle measurement results to produce a composite group of mass-to-charge ratios of the received charged particles.

[0025] In a twenty-first aspect, a charged particle analysis system may include: a charged particle source having a charged particle outlet; a charged particle analysis stage having a charged particle inlet; a radially segmented charged particle guide positioned between the charged particle source and the charged particle analysis stage and comprising a plurality of conductive segments separated from each other and radially spaced apart around an opening defined by a plurality of radially arranged conductive segments; at least one voltage source configured to generate an individually controllable voltage and supply it to each of the plurality of conductive segments; and a control circuit configured to control the at least one voltage source to supply a voltage to each of the plurality of conductive segments, the voltage being selected to create an electric field within the opening and configured to guide charged particles leaving the charged particle outlet of the charged particle source into the charged particle inlet of the charged particle analysis stage.

[0026] The twenty-second aspect includes the features of the twenty-first aspect, and wherein the charged particle analysis stage is defined by a first longitudinal axis extending centrally through a charged particle inlet, and wherein an opening of a radially segmented charged particle guide is defined by a second longitudinal axis extending centrally through the opening, and wherein the first longitudinal axis is radially offset from the second longitudinal axis, and wherein the created electric field is configured to guide charged particles leaving a charged particle outlet of a charged particle source along the first longitudinal axis into a charged particle inlet of the charged particle analysis stage.

[0027] A twenty-third aspect includes the features of aspect twenty-second, and wherein the charged particle source defines a third longitudinal axis extending centrally through the charged particle outlet, and wherein the charged particles exit the charged particle source along the third longitudinal axis.

[0028] The twenty-fourth aspect includes the features of the twenty-third aspect, and wherein the second longitudinal axis is co-linear with the third longitudinal axis.

[0029] The twenty-fifth aspect includes the features of the twenty-third aspect, and wherein the third longitudinal axis is radially offset from the second longitudinal axis and from the first longitudinal axis.

[0030] A twenty-sixth aspect includes the features of aspect twenty-second, and wherein the charged particle source defines a third longitudinal axis extending centrally through the charged particle outlet, and wherein the charged particles exit the charged particle source along a path radially diverging from the third longitudinal axis.

[0031] The twenty-seventh aspect includes the features of the twenty-sixth aspect, and wherein the second longitudinal axis is co-linear with the third longitudinal axis.

[0032] The twenty-eighth aspect includes the features of the twenty-sixth aspect, and wherein the third longitudinal axis is radially offset from the second longitudinal axis and from the first longitudinal axis.

[0033] The twenty-ninth aspect includes the features of the twenty-first aspect, and wherein the charged particle analysis stage is defined by a first longitudinal axis extending centrally through the charged particle inlet, and wherein the opening of the radially segmented charged particle guide is defined by a second longitudinal axis extending centrally through the opening, and wherein the first longitudinal axis is colinear with the second longitudinal axis, and wherein the created electric field is configured to guide charged particles leaving the charged particle outlet of the charged particle source along the first longitudinal axis into the charged particle inlet of the charged particle analysis stage.

[0034] The thirtieth aspect includes the features of the twenty-ninth aspect, and wherein the charged particle source defines a third longitudinal axis extending centrally through the charged particle outlet, and wherein the charged particles exit the charged particle source along the third longitudinal axis, and wherein the third longitudinal axis is radially offset from the second longitudinal axis.

[0035] The thirty-first aspect includes the features of the twenty-ninth aspect, and wherein the charged particle source defines a third longitudinal axis extending centrally through the charged particle outlet, and wherein the charged particles exit the charged particle source along a path radially diverging from the third longitudinal axis.

[0036] The thirty-second aspect includes the features of the thirty-first aspect, and wherein the third longitudinal axis is radially offset from the second longitudinal axis.

[0037] The thirty-third aspect includes the features of the thirty-first aspect, and wherein the third longitudinal axis is co-linear with the second longitudinal axis.

[0038] The thirty-fourth aspect includes the features of the thirty-first aspect, and wherein the charged particle analysis stage is defined by a first longitudinal axis extending centrally through the charged particle inlet, and wherein an opening of a radially segmented charged particle guide is defined by a second longitudinal axis extending centrally through the opening, and wherein the first longitudinal axis is colinear with the second longitudinal axis, and wherein the created electric field is configured to guide charged particles leaving a charged particle outlet of a charged particle source along a path radially deviating from the first longitudinal axis into a charged particle inlet of the charged particle analysis stage.

[0039] The thirty-fifth aspect includes the features of the thirty-fourth aspect, and wherein the charged particle source defines a third longitudinal axis extending centrally through the charged particle outlet, and wherein the charged particles exit the charged particle source along the third longitudinal axis.

[0040] The thirty-sixth aspect includes the features of the thirty-fifth aspect, and wherein the second longitudinal axis is co-linear with the third longitudinal axis.

[0041] The thirty-seventh aspect includes the features of the thirty-fifth aspect, and wherein the third longitudinal axis is radially offset from the second longitudinal axis and from the first longitudinal axis.

[0042] The thirty-eighth aspect includes the features of the thirty-fourth aspect, and wherein the charged particle source defines a third longitudinal axis extending centrally through the charged particle outlet, and wherein the charged particles exit the charged particle source along a path that deviates radially from the third longitudinal axis.

[0043] The thirty-ninth aspect includes the features of the thirty-eighth aspect, and wherein the second longitudinal axis is co-linear with the third longitudinal axis.

[0044] The fortieth aspect includes the features of the thirty-eighth aspect, wherein the third longitudinal axis is radially offset from the second longitudinal axis and from the first longitudinal axis.

[0045] The forty-first aspect includes the features of the twenty-first aspect, and wherein the charged particle analysis stage is defined by a first longitudinal axis extending centrally through the charged particle inlet, and wherein an opening of the radially segmented charged particle guide is defined by a second longitudinal axis extending centrally through the opening, and wherein the second longitudinal axis is radially offset from the first longitudinal axis, and wherein the created electric field is configured to guide charged particles leaving a charged particle outlet of a charged particle source into a charged particle inlet of the charged particle analysis stage along a path radially offset from the first longitudinal axis.

[0046] The forty-second aspect includes the features of the forty-first aspect, and wherein the charged particle source defines a third longitudinal axis extending centrally through the charged particle outlet, and wherein the charged particles exit the charged particle source along the third longitudinal axis, and wherein the third longitudinal axis is radially offset from the second longitudinal axis.

[0047] The forty-third aspect includes the features of the forty-first aspect, and wherein the charged particle source defines a third longitudinal axis extending centrally through the charged particle outlet, and wherein the charged particles exit the charged particle source along a path that deviates radially from the third longitudinal axis.

[0048] The forty-fourth aspect includes the features of the forty-third aspect, and wherein the third longitudinal axis is radially offset from the second longitudinal axis.

[0049] The forty-fifth aspect includes the features of the forty-third aspect, and wherein the third longitudinal axis is co-linear with the second longitudinal axis.

[0050] Aspect 46 includes the features of any one of aspects 21 to 43, and may also include a charged particle position detector configured to generate at least one detection signal corresponding to a radial position relative to a first longitudinal axis extending centrally through the charged particle analysis stage or relative to a second longitudinal axis extending centrally through the radially segmented charged particle guide, and wherein the control circuit is configured to select a voltage based on the at least one detection signal to create an electric field configured to guide charged particles leaving the radially segmented charged particle guide along a predetermined path relative to at least one of the first longitudinal axis or the second longitudinal axis.

[0051] The forty-seventh aspect may include the features of the forty-sixth aspect, and wherein the charged particle position detector is positioned between the radially segmented charged particle guide and the charged particle analysis stage, but is not mounted to either the radially segmented charged particle guide and the charged particle analysis stage.

[0052] The forty-eighth aspect includes the features of the forty-sixth aspect, and wherein the charged particle position detector is positioned between the radially segmented charged particle guide and the charged particle analysis stage, and is mounted to the radially segmented charged particle guide.

[0053] The forty-ninth aspect includes the features of the forty-sixth aspect, and wherein the charged particle position detector is positioned between the radially segmented charged particle guide and the charged particle analysis stage, and mounted to the charged particle analysis stage.

[0054] The fiftieth aspect includes the features of any one of aspects twenty-first to twenty-sixth, and may also include a device for determining the percentage of charged particles leaving the charged particle outlet of the charged particle source that enter the charged particle inlet of the charged particle analysis stage, and wherein the control circuit is configured to select a voltage to create an electric field configured to guide the charged particles leaving the radially segmented charged particle guide in a manner that maximizes the percentage of charged particles leaving the charged particle outlet of the charged particle source that enter the charged particle inlet of the charged particle analysis stage.

[0055] In the fifty-first aspect, a charged particle analysis system may include: a charged particle source configured to generate charged particles; an electrostatic linear ion trap (ELIT) configured to receive and capture charged particles generated by the charged particle source, the ELIT including two spaced-apart ion mirrors and a charge detection cylinder positioned between the two ion mirrors, the two ion mirrors and the charge detection cylinder together defining a first axis passing through the center thereof, each of the two ion mirrors including a plurality of axially spaced-apart ion mirror electrodes, the plurality of axially spaced-apart ion mirror electrodes each defining an electrode opening passing therethrough, at least one of the ion mirror electrodes of at least one of the two ion mirrors including a plurality of conductive segments separated from each other and radially spaced apart and arranged around corresponding electrode openings defined by a plurality of radially arranged conductive segments, the corresponding electrode openings being defined by at least one radially segmented ion mirror electrode, the at least one radially segmented ion mirror electrode The sub-mirror electrode defines a second axis passing through the center and radially deviating from the first axis; at least one voltage source, the at least one voltage source configured to generate a voltage that can be controlled individually and supply it to each of the multiple ion mirror electrodes of each of the two ion mirrors and each of the multiple conductive segments of the at least one ion mirror electrode in the ion mirror electrode; and a control circuit, the control circuit configured to: control the at least one voltage source to supply a selected voltage to the electrode of each of the two ion mirrors to create a first electric field in each of the two ion mirrors to cause the charged particles trapped in the ELIT to travel along the first axis, and supply a selected voltage to each of the multiple conductive segments to create a second electric field in the corresponding electrode opening of the at least one radially segmented ion mirror electrode, the second electric field being configured to cause the charged particles to pass through the corresponding electrode opening along the first axis deviating from the second axis, the second axis being defined centrally through the opening of the at least one radially segmented ion mirror electrode.

[0056] The fifty-second aspect may include the features of the fifty-first aspect, and wherein the first electric field and the second electric field are configured to cause a charged particle trapped in the ELIT during a capture event to oscillate back and forth between the two ion mirrors each time it passes through the charge detection cylinder to induce a corresponding charge on the charge detection cylinder, and wherein the charged particle analysis system further includes a charge sensitive preamplifier having an input end connected to the charge detection cylinder and an output end connected to the control circuit, the charge sensitive preamplifier responding to each corresponding charge induced on the charge detection cylinder The device is configured to generate a corresponding charge detection signal, and wherein the control circuit is configured to determine the capture efficiency of the ELIT in response to the charge detection signal as the ratio of capture events in which the charged particles oscillate between the two ion mirrors within at least a predefined amount of the total capture event time period to capture events in which the charged particles do not oscillate between the two ion mirrors within at least the predefined amount of the total capture event time period, and wherein the control circuit is configured to select a voltage to create an electric field configured to guide the charged particles leaving the radially segmented charged particle guide in a manner that maximizes the capture efficiency.

[0057] In the fifty-third aspect, a charged particle analysis system may include: a charged particle source configured to generate charged particles from a sample, the charged particle source including a multipole charged particle transmission device having a charged particle inlet for receiving the generated charged particles and configured to transmit the generated charged particles through a charged particle outlet of the multipole charged particle transmission device; an AC voltage source operatively connected to the multipole charged particle transmission device and configured to apply an AC voltage to the multipole charged particle transmission device to guide the generated charged particles through the charged particle outlet; at least one charged particle analysis stage having a charged particle inlet; a radially segmented charged particle guide positioned between the charged particle source and the at least one charged particle analysis stage and including a plurality of conductive segments separated from each other and radially spaced apart around an opening defined by a plurality of radially arranged conductive segments, the opening defined by a first longitudinal axis passing through the center of the opening; at least one voltage source configured The invention relates to a device for generating and supplying individually controllable voltages to each of a plurality of conductive segments; and a control circuit configured to: (i) control at least one voltage source to sequentially supply each of a certain number of different groups of voltages to each of the plurality of conductive segments, the number of different groups of voltages being selected to create a corresponding electric field within the opening, the corresponding electric field being configured to guide charged particles entering the opening from a charged particle outlet of a multipole charged particle transmission device toward the first longitudinal axis around the periphery of the first longitudinal axis so as to focus the charged particles leaving the opening of the radially segmented charged particle guide around the first longitudinal axis, (ii) control at least one charged particle analyzer to measure the mass-to-charge ratio of the charged particles leaving the radially segmented charged particle guide for each of the number of different groups of voltages supplied by the at least one voltage source to generate a corresponding number of different groups of charged particle measurement results, and (iii) average the measured mass-to-charge ratios of the charged particles in the number of different groups of charged particle measurement results to generate a mass-to-charge ratio of a composite group of generated charged particles. BRIEF DESCRIPTION OF THE DRAWINGS

[0058] Figure 1A is a simplified side view illustration of a portion of a charged particle analysis system including a radially segmented charged particle guide positioned between two axially non-aligned stages of the system for focusing charged particles exiting an upstream stage along a central axis of a downstream stage to an inlet of the downstream stage.

[0059] Figure 1Bis a simplified side view illustration of a portion of another charged particle analysis system including a radially segmented charged particle guide positioned between two stages of the system for focusing charged particles exiting an upstream stage along an axis radially offset from a central axis of the upstream stage to an entrance of the downstream stage along a central axis of the downstream stage.

[0060] Figure 2 yes Figure 1A and Figure 1B A simplified end view of an embodiment of a radially segmented charged particle guide in the form of a four-segment device in which each segment is operably coupled to a different amplitude controllable voltage output of a DC voltage source.

[0061] Figure 3A is a simplified side view illustration of an embodiment of a charged particle analysis system comprising Figure 2 A radially segmented charged particle guide as illustrated in the example in, and also includes an embodiment of a charged particle position detector positioned between a charged particle outlet of the charged particle guide and a charged particle analysis stage, the charged particle guide being used to focus charged particles leaving an upstream charged particle source to a selected position or region of a charged particle inlet of a downstream charged particle analysis stage.

[0062] Figure 3B yes Figure 3A Simplified end view of a charged particle position detector.

[0063] Figure 3C yes Figure 3A Simplified end view of a radially segmented charged particle guide illustrating example focusing of charged particles entering off-axis into a charged particle inlet to a central longitudinal axis of a charged particle outlet.

[0064] Figure 4A is a simplified side view illustration of another embodiment of a charged particle analysis system comprising Figure 2 The radially segmented charged particle guide illustrated in the example is used to focus charged particles leaving an upstream charged particle source to a selected position or area of ​​a charged particle inlet of a downstream charged particle analysis stage, wherein the charged particle analysis stage includes a virtual charged particle position detector integrated therein for estimating the position of charged particles entering the charged particle inlet of the charged particle analysis stage relative to the central longitudinal axis of the charged particle analysis stage.

[0065] Figure 4B yes Figure 3AA simplified end view of a radially segmented charged particle guide illustrating example focusing of charged particles entering off-axis from a charged particle source into a charged particle inlet to another off-axis position of a charged particle outlet so as to enter the charged particle inlet of a charged particle analysis stage along a central longitudinal axis of the charged particle analysis stage.

[0066] Figure 5 is a simplified side view illustration of a charged detection mass spectrometer (CDMS) including an embodiment of an electrostatic linear ion trap (ELIT) having control and measurement components coupled thereto.

[0067] Fig. 6A yes Figure 5 An enlarged side view of an ion mirror M1 of an ELIT is shown in FIG. 5 , wherein the mirror electrodes of M1 are controlled to generate an ion-transmitting electric field therein.

[0068] Figure 6B yes Figure 5 An enlarged side view of the ion mirror M2 of the ELIT illustrated in FIG. 1 , in which the mirror electrodes of M2 are controlled to generate an ion reflecting electric field therein.

[0069] Figure 7 is a simplified diagram of an embodiment of the processor illustrated in FIG. 1 .

[0070] FIG. 8A to FIG. 8C yes Figure 5 A simplified side view illustration of an ELIT showing sequential control and operation of the ion mirrors and charge generators to capture at least one ion within the ELIT and cause the ion(s) to oscillate back and forth between the ion mirrors and through the charge detection cylinder to measure and record multiple charge detection events.

[0071] Fig. 9 is similar to Figure 6B A simplified side view of Figure 5 Another example of an ion mirror M2 of an ELIT, where the position of the innermost mirror electrode is offset relative to the remaining mirror electrodes.

[0072] Fig.10 yes Figure 5 The capture efficiency of ELIT is determined by Fig. 9 A graph showing the relationship between the deviation distance of the innermost mirror electrode relative to the remaining mirror electrodes as shown in the example in FIG.

[0073] Fig.11 For two different offset distances Figure 5 The capture efficiency of the ELIT is related to the Fig. 9 The relationship between the potential deviation of the innermost mirror electrode and the potential deviation of the innermost mirror electrode is shown in FIG. Figure 2The radially segmented charged particle guide illustrated in the example in is implemented as an innermost mirror electrode, so that the radially segmented charged particle guide and the virtual charged particle position detector are integrated into the ELIT together.

[0074] Fig.12 is a graphic representation used to determine the Figure 5 Logic flow chart of an example embodiment of a process for adjusting the voltages of mirror electrodes of ion mirrors M1 and M2 of an ELIT, wherein the mirror electrodes are implemented as radially segmented electrodes each having eight equally sized and radially spaced segments.

[0075] Fig.13 is a graph of the capture efficiency versus the number of iterations, showing Fig.12 The convergence of the process is illustrated in FIG, where the capture efficiency is greater than 95%.

[0076] Fig.14 is a simplified illustration of yet another embodiment of a charged particle analysis system having an ELIT implemented using a radially segmented ion mirror positioned between a charged particle source and a downstream charged particle analysis stage, wherein the ELIT is as described with respect to Figures 11 to 13 The device is described as operating to act as a charged particle guide for focusing charged particles leaving an upstream charged particle source to an inlet of a downstream charged particle analysis stage.

[0077] Fig.15A is a simplified illustration of yet another embodiment of a charged particle analysis system including a radially segmented charged particle guide for focusing charged particles leaving a charged particle source into a charged particle inlet of a charged particle analysis stage.

[0078] Fig. 15B It is in the form of a four-segment device Fig.15A A simplified end view of an embodiment of a radially segmented charged particle guide of the type shown in FIG. 1 , wherein each segment is operably coupled to a different amplitude controllable voltage output of a DC voltage source, and illustrating the Fig.15A The operation of the system is to focus the charged particles passing through it. DETAILED DESCRIPTION

[0079] 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.

[0080] The present disclosure relates to various embodiments and applications of a radially segmented charged particle guide that can be controlled by selectively determining and applying DC voltages to individual segments so that charged particles entering the guide along one axis exit the guide along another axis for the purpose of focusing the charged particles along a selected axis within or between stages of a charged particle analysis system. For purposes of the present disclosure, the phrase "charged particle detection event" is defined as the detection of charge induced on a charge detector of an electrostatic linear ion trap (ELIT) by a single passage of a charged particle through the charge detector, and the phrase "charged particle measurement event" is defined as a collection of charged particle detection events resulting from oscillating a charged particle back and forth through the charge detector a selected number of times or for a selected time period. Since the oscillation of the charged particles back and forth through the charge detector is caused by the controlled capture of the charged particles within the ELIT, as will be described in detail below, the phrase "charged particle measurement event" may alternatively be referred to herein as a "charged particle capture event" or simply as a "capture event", and the phrases "charged particle measurement event", "charged particle capture event", "capture event" and their variations should be understood to be synonymous with each other. For the purposes of this disclosure, the terms "ion" and "charged particle" and their variations will be understood to be synonymous. Therefore, in any of the above definitions, the term "ion" may replace the term "charged particle".

[0081] Reference now Figure 1A , a charged particle analysis system 10 is shown and includes a charged particle source 12 separated by a distance D from a charged particle analysis stage 16. A central longitudinal axis 14 is defined through the charged particle source 12, and a central longitudinal axis 18 is defined through the charged particle analysis stage 16, wherein the axes 14, 18 are axially misaligned with each other and with respect to each other, i.e., wherein the axes 14, 18 are not co-linear. A radially segmented charged particle guide 20 is positioned between the axially misaligned charged particle source 12 and the charged particle analysis stage 16, and is Figure 1AIn the embodiment illustrated in , the longitudinal axis 14 passes centrally through the radially segmented charged particle guide 20, such that the axis 14 represents a central longitudinal axis defined by passing through the charged particle source 12 and each of the radially segmented charged particle guides 20. The charged particle analysis system 10 also illustratively includes a voltage source (VS) 22 operatively coupled between at least one control circuit 24 and the radially segmented charged particle guides 20, wherein the voltage source 22 is configured to apply an arbitrary number N of different voltages to the radially segmented charged particle guides 20, wherein N may be any positive integer. It will be understood that the additional voltage source will typically be operatively coupled between (one or more) control circuits 24 and each of the charged particle source 12 and the charged particle analysis stage 16, and may be controlled in a conventional manner to generate one or more suitable voltages for controlling the operation of the charged particle source 12, and in some embodiments, for controlling the operation of the charged particle analysis stage 16.

[0082] The at least one control circuit 24 may be conventional and include a single control circuit or a plurality of control circuits, wherein, for the purposes of this document, the term "control circuit" means a decision circuit configured to be programmed and / or manually controlled to control the operation of the voltage source 22. In some embodiments, the decision circuit may be or include at least one conventional microprocessor or microcontroller and a memory unit 25 having instructions stored therein that can be executed by the microprocessor(s) or microcontroller(s) to control the operation of the voltage source VS. In alternative embodiments, the decision circuit may be or include a dedicated digital and / or analog circuit system designed or otherwise configured to control the operation of the voltage source 22.

[0083] The charged particle source 12 may illustratively include any conventional equipment or device for generating charged particles (i.e., ions) from a sample. As an illustrative example that should not be considered to be limiting in any way, the charged particle source 12 may be or include a conventional electrospray ionization source, a matrix-assisted laser desorption ionization (MALDI) source, or other conventional instruments or devices configured to generate charged particles from a sample in the form of a solution, gas, or solid. The sample from which ions are generated may be or include any biological or other material in the form of a solution or solid, depending on the source 12. In certain embodiments, the charged particle source 12 may also include one or more devices and / or instruments for separating, collecting, filtering, guiding, controlling / setting energy, splitting, and / or normalizing or transferring the charge state of the charged particles according to one or more molecular characteristics. As a non-limiting example of such additional equipment or instruments that may be included in the charged particle source 12 or as a part of the charged particle source 12, a mass spectrometer may be implemented as a charged particle generated before the generated charged particles leave from the charged particle outlet 14 of the charged particle source 12 according to the mass-to-charge ratio separation. Such a mass spectrometer may be of any conventional design including, for example but not limited to, a time-of-flight (TOF) mass spectrometer, a reflectron mass spectrometer, a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer, a quadrupole mass spectrometer, a triple quadrupole mass spectrometer, a magnetic sector mass spectrometer, an orbital trap, and the like.

[0084] The charged particle analysis stage 16 may illustratively be or include any conventional device or a sequential combination of conventional devices, which is configured to separate, collect, filter, control / set energy, split and / or normalize or transfer the charge state of charged particles and / or measure one or more molecular characteristics and / or charge characteristics of charged particles according to one or more molecular characteristics. In an exemplary embodiment, the charged particle analysis stage 16 may be or include at least one conventional mass spectrometer or mass analyzer, which is configured to separate and detect charged particles according to mass-to-charge ratio. Alternatively or additionally, the charged particle analysis stage 16 may be or include at least one mobility device, which is configured to separate and detect charged particles according to ion mobility. Alternatively or additionally, the charged particle analysis stage 16 may be or include at least one electrostatic linear ion trap (ELIT) and / or orbital trap, which is configured to simultaneously measure the mass-to-charge ratio and charge magnitude of charged particles (the charged particle mass can then be directly determined from it). In some embodiments, the charged particle analysis stage 16 may be or include a charged particle collection structure, for example, in the form of a conventional charged particle collection target (such as a plate, pad, etc.), which is configured to collect charged particles leaving the radially segmented charged particle guide 20 thereon. In some such embodiments, the charged particle collection target may include a charged particle medium disposed thereon, and which is configured to facilitate and / or maintain the collection of charged particles on the target. Those skilled in the art will recognize other examples of conventional equipment or instruments that may be or be included in the charged particle analysis stage 16, and will understand that such other examples are intended to fall within the scope of the present disclosure. It will also be understood that none of the foregoing examples should be considered limiting in any way.

[0085] Reference now Figure 2 , shows an end view of an embodiment of a radially segmented charged particle guide 20 and a corresponding configuration of a voltage source 22 operatively coupled thereto. In the illustrated embodiment, the radially segmented charged particle guide 20 includes four arcuate segments 281-284 that are radially separated from one another and define a central opening 30 therethrough. In the illustrated embodiment, the spaces separating adjacent ones of the arcuate segments 281-284 are identical, such that the radial distances between adjacent arcuate segments 281-284 are equal to one another. In some embodiments, the inner and outer surfaces of the segments 281-284 are arcuate in shape, as indicated by Figure 2281-284, although in alternative embodiments only the inner surfaces (i.e., the inwardly facing surfaces) of the segments 281-284 may be arcuate in shape. In the illustrated embodiment, the arcuate shapes of at least the inner surfaces of the segments 281-284 together define a generally circular opening 30, i.e., such that the opening 30 has a circular cross-sectional shape, although in alternative embodiments the arcuate shapes of at least the inner surfaces of the segments 281-284 may be configured to define a non-circular opening 30 having at least one curved surface portion. In yet other embodiments, the inner surface of one or more of the segments 281-284 may have a non-arc shape, such as a planar or (one or more) other shape, such that at least a portion of the cross-sectional shape of the resulting opening 30 is not curved. In such embodiments, example cross-sectional shapes of the opening 30 may include, but are not limited to, square, rectangular, triangular, etc. In any case, the central longitudinal axis 14 extends centrally through the opening 30.

[0086] Figure 2 The voltage source 22 depicted in illustratively is configured to generate four separate DC voltages V1, V2, V3, and V4, wherein the V1 output is electrically connected to radial segment 281, the V2 output is electrically connected to radial segment 282, the V3 output is electrically connected to radial segment 283, and the V4 output is electrically connected to radial segment 284. In alternative embodiments, the radially segmented charged particle guide 20 may include any number of segments radially spaced apart from one another to define a central opening therethrough, and the voltage source 22 may be configured to correspondingly generate any number of separate DC voltages.

[0087] In by Figure 1AIn the embodiment illustrated by the example in , the charged particles 26 generated by the charged particle source 12 leave the charged particle source 12 along the central longitudinal axis 14, that is, the charged particles 26 leaving the charged particle source 12 travel along a path that is co-linear with the central longitudinal axis 14. Because the central longitudinal axis 18 defined through the charged particle analysis stage 16 is not co-linear with the axis 14, the charged particles 26 will enter the charged particle stage 16 (if any) off-axis in the absence of a radially segmented charged particle guide 20 (and controlled as described below). In fact, if the distance D is large enough and the charged particles 26 leave the charged particle source 12 along the axis 14 but at a sufficiently large angle relative to the axis 14, the charged particles 26 may be sufficiently divergent from the axis 18 and not enter the charged particle entrance (e.g., orifice) of the charged particle analysis stage 16. However, by controlling the voltage source 22 to apply a corresponding potential offset to each radial segment 281-284, the charged particles 26 entering the radially segmented charged particle guide 20 along the central longitudinal axis 14 can be redirected, i.e., guided or focused, by the resulting electric field established in the opening 30 by the potential offset to leave the radially segmented charged particle guide 20 at a point or position relative to the central longitudinal axis 14, which point or position is aligned with the central longitudinal axis 18 of the charged particle analysis stage 16, i.e., so that the charged particles 26 leave the radially segmented charged particle guide 20 along a path that is colinear with the central longitudinal axis 18 of the charged particle analysis stage 16.

[0088] If Figure 2As depicted in the example of , the charged particle source 12 and the charged particle analysis stage 16 are misaligned relative to each other such that a central longitudinal axis 18 defined through the charged particle analysis stage 16 is displaced in an upward direction relative to a central longitudinal axis 14 defined through the charged particle source 12 and through the radially segmented charged particle guide 20. In order to guide the charged particles 26 to exit the radially segmented charged particle guide 20 along a path co-linear with the central longitudinal axis 18 of the charged particle analysis stage 16, V2 and V3 should have the same amplitude, V1 and V4 should have the same amplitude, and the amplitudes of V2 and V3 should be greater than the amplitudes of V1 and V4 by an amount that will create an electric field within the opening 30 that drives the charged particles 26 from a path of travel co-linear with the axis 14 to a path of travel co-linear with the axis 18. In other words, relative to the typical equal voltages of V1-V4 at which the voltage source 22 will operate to create an electric field within the opening 30 (the electric field being configured to cause charged particles to pass through the radially segmented charged particle guide 20 centrally (i.e., along axis 14)), a negative ΔV will be applied by both voltages V1 and V4 to radial segments 281 and 284, respectively, and a positive ΔV will be applied by both voltages V2 and V3 to radial segments 282 and 283, respectively, wherein the amplitudes of the negative ΔV and positive ΔV will be selected so as to establish a changed electric field within the opening 30 that causes the charged particles 26 to leave the radially segmented charged particle guide 20 along a path colinear with the axis 18.

[0089] Now go to Figure 1B , the opposite condition is depicted with respect to the charged particle source 12 and charged particle analysis stage 16 in the system 10', wherein the axis 14 centrally passing through the charged particle source 12 and the radially segmented charged particle guide 20 also centrally passes through the charged particle analysis stage 16, but wherein the charged particles leave the charged particle source 12 along a path 18 that is parallel to the axis 14 but displaced in an upward direction relative to the axis 14, as also indicated by Figure 2In this example, in order to guide the charged particles 26 to leave the radially segmented charged particle guide 20 along a path that is co-linear with the axis 14, V2 and V3 should have the same amplitude, V1 and V4 should have the same amplitude, and the amplitudes of V1 and V4 should be greater than the amplitudes of V2 and V3 by an amount that will create an electric field within the opening 30 that will drive the charged particles 26 from a path of travel 18 that is parallel to the axis 14 but deviates from the axis 14 to a path of travel 18 that is co-linear with the axis 14. In other words, relative to the typical equal voltages V1-V4 at which the voltage source 22 would operate to cause charged particles to pass through the radially segmented charged particle guide 20 centrally (i.e., along axis 14), a positive ΔV would be applied by both voltages V1 and V4 to radial segments 281 and 284, respectively, and a negative ΔV would be applied by both voltages V2 and V3 to radial segments 282 and 283, respectively, wherein the amplitudes of the negative ΔV and positive ΔV would be selected so as to establish a changed electric field within the opening 30 that causes the charged particles 26 to leave the radially segmented charged particle guide 20 along the central longitudinal axis 14.

[0090] will understand, Figure 1A and Figure 1B The embodiments illustrated in the drawings are provided by way of example only and should not be considered to be limiting in any way, and in alternative embodiments, the radially segmented charged particle guide 20 may include more or fewer radial segments, and the voltage source 22 may be configured to generate correspondingly more or fewer DC voltages. It will also be understood that in alternative embodiments, the voltages V1-V4 may be controlled to cause charged particles entering the radially segmented charged particle guide 20 in the axial direction along any path to leave the radially segmented charged particle guide 20 in the axial direction along different paths. It will also be understood that in some embodiments, the radial segments themselves may deviate from each other in a non-uniform manner. For example, any one or more of the segments may deviate vertically, horizontally, to the right, and / or to the left relative to one or more of the remaining segments and / or relative to the longitudinal axis extending through the guide 20, and in such embodiments, the potential offset, i.e., ΔV, that causes the charged particles to leave the guide 20 along any desired path may be determined.

[0091] It is worth noting that the voltages V1-V4 determined and selected to direct the charged particles 26 to and along a particular axis or path of travel remain valid only when the charged particles 26 enter the radially segmented charged particle guide 20 along the same path as the path used to determine the voltages V1-V4. If the charged particle source 12, sample and / or system 10, 10' is changed or otherwise operable so that the charged particles 26 enter the radially segmented charged particle guide 20 along a different path, new voltages V1-V4 must be determined to direct the charged particles 26 to and along the same exit path. In any case, although not in Figure 1A or Figure 1B Although not specifically illustrated in the drawings, many but not all actual systems in which the radially segmented charged particle guide 20 is implemented will require a "sensor" to provide feedback regarding the point or position of the charged particles exiting the radially segmented charged particle guide 20 relative to an axis or other position indicator. In some embodiments, such a "sensor" may be implemented in the form of a physical sensor or sensing system coupled to the charged particle outlet or exit end of the radially segmented charged particle guide 20, coupled to the charged particle inlet end of a downstream charged particle analysis stage 16, or otherwise positioned between the charged particle outlet of the radially segmented charged particle guide 20 and the charged particle inlet of the charged particle analysis stage 16. An example system implementing an embodiment of such a physical sensing system is described in FIG. 3A to FIG. 3C , and will be described in detail below. Alternatively or additionally, the "sensor" may be implemented in the form of a virtual sensor embedded in one or more components of the downstream charged particle analysis stage 16. An example system illustrating an embodiment of such a virtual sensor is shown in FIG. 4A to FIG. 4B , and will be described in detail below. Alternatively or also in addition, the "sensor" may be implemented in the form of a virtual sensor embedded in a charged particle analysis instrument in which one or more of the radially segmented charged particle guides are also embedded. An example system illustrating an embodiment of such a virtual sensor is shown in Figures 5 to 14 , and will be described in detail below. In any such embodiment of the "sensor", the (one or more) control circuits 24 will be illustratively configured to control the operation of the voltage source 22 based on feedback provided by the "sensor", for example in the form of corresponding instructions stored in the memory 25 and executable by the (one or more) control circuits 24, to produce various DC output voltages, wherein the amplitude of the output voltage is selected to guide charged particles entering the (one or more) radially segmented charged particle guides 20 in the axial direction along one path to leave the radially segmented charged particle guides 20 in the axial direction along different paths.

[0092] Finally, an example system is illustrated in FIG. 15 and will be described in detail below in which the path along which the charged particles 26 enter the radially segmented charged particle guide 20 need not be known or repeatable, and no "sensors" are required to provide feedback regarding the point or location at which the charged particles exit the radially segmented charged particle guide 20. In any such embodiments of the radially segmented charged particle guide 20, the (one or more) control circuits 24 will illustratively be configured to control the operation of the voltage source 22, for example in the form of instructions stored in a memory 25 and executable by the (one or more) control circuits 24 to sequentially and, in some embodiments, repeatedly generate different sets of DC output voltages, wherein the amplitudes of the DC output voltages are selected to direct charged particles that enter the radially segmented charged particle guide 20 in an axial direction along various different paths to exit the radially segmented charged particle guide 20 in an axial direction along different paths that are more focused toward a central longitudinal axis defined through the radially segmented charged particle guide 20.

[0093] Reference now FIG. 3A to FIG. 3C , shows an embodiment of a charged particle analysis system 50 that includes a radially segmented charged particle guide 20 and an embodiment of a physical sensing system in the form of a charged particle position detector 54 that is configured to generate a feedback signal that can be used by (one or more) control circuits 24 to control the operation of a voltage source 22 to generate various DC output voltages, wherein the magnitude of the DC output voltage is selected to guide charged particles 26 through the radially segmented charged particle guide 20 as described above. In the illustrated embodiment, the charged particle analysis system 50 includes Figure 1A and Figure 1B, and a charged particle source 12 and a charged particle analysis stage 52 as illustrated in and described above, with a radially segmented charged particle guide 20 positioned therebetween. In one embodiment, the charged particle analysis stage 52 may be a conventional target on which charged particles leaving the charged particle source 12 are desired to be collected. In such embodiments, the radially segmented charged particle guide 20 and the charged particle position detector 54 may be used to guide or focus the charged particles to or toward a specific site or region 53 of the target 52, for example, to or toward a point or region 53 through which an axis 60 defined as being centered through the target 52 or some other point, region, or position of the target 52 extends. In other embodiments, the charged particle analysis stage 52 may be or include any number of charged particle analyzers as described above, wherein axis 60 represents a longitudinal axis extending centrally through a charged particle inlet (e.g., an inlet orifice) of the charged particle analysis stage 52, and region 53 corresponds to the charged particle inlet of the charged particle analysis stage 52.

[0094] exist FIG. 3A to FIG. 3C In the illustrated embodiment, axis 60 represents a central longitudinal axis defined through each of the charged particle source 12, the radially segmented charged particle guide 20, and the charged particle analysis stage 52, although in alternative embodiments one or more of the charged particle source 12, the radially segmented charged particle guide 20, and the charged particle analysis stage 52 may be axially misaligned with one or more of the others. Also in the illustrated embodiment, the charged particles 26 exit the charged particle source 12 off-axis (i.e., along a path that is not co-linear with the central longitudinal axis 60), although in alternative embodiments the charged particles 26 may exit the charged particle source 12 axially along any path.

[0095] If Figure 3A As depicted in the example in , the charged particle position detector 54 may be positioned between the charged particle outlet of the radially segmented charged particle guide 20 and the charged particle inlet of the charged particle analysis stage 52, i.e., such that the detector 54 is neither physically attached to the guide 20 nor to the stage 52. In some alternative embodiments, the charged particle position detector 54 may be mounted, attached, or otherwise secured to the radially segmented charged particle guide 20. In other alternative embodiments, the charged particle position detector 54 may be mounted, attached, or otherwise secured to the charged particle analysis stage 52.

[0096] Reference now Figure 3A and Figure 3B, the charged particle position detector 54 illustratively includes a plurality of radiation detectors, such as photodetectors, radially arranged around an axis 60, such that the axis 60 extends centrally through a radial space defined between the radiation detectors. In the illustrated embodiment, four such radiation detectors 561-564 are radially spaced equidistantly from each other around the axis 60, although more or fewer such radiation detectors may be included in alternative embodiments. The radiation sensing inputs of the detectors 561-564 each face the axis 60, and the signal outputs of the detectors 561-564 are electrically connected to the corresponding radiation signal detection inputs D1-D4 of the control circuit 24. The radiation source 58 (e.g., a laser or other conventional radiation source) has a radiation output aimed at the axis 60 and a control input electrically connected to the radiation source control output L of the control circuit 24. In some embodiments, the radiation source 58 is configured to generate radiation in the visible spectrum, and the detectors 561-564 are also configured to detect radiation in the visible spectrum, although in alternative embodiments the radiation source 58 and the detectors 561-564 are configured to generate and detect radiation outside the visible spectrum, respectively. In any case, the radiation source 58 is positioned to generate and focus radiation, for example in the form of a collimated beam, or to generate radiation that is subsequently focused by conventional optics and / or other conventional equipment along a narrow path 59 that intersects the portion of the axis 60 about which the radiation sensing inputs of the detectors 561-564 are aimed. Charged particles traveling along the axis 60 (i.e., co-linear with the axis 60) will be irradiated by the focused radiation generated by the radiation source 58 at the point where the radiation path 59 intersects the axis 60, and charged particles traveling in any other path that is not co-linear with the axis 60 will not be irradiated by the focused radiation generated by the radiation source 58. The irradiated charged particles will absorb and then emit radiation, and the emitted radiation will be detected by the detectors 561-564, which will generate a radiation detection signal and supply it to the control circuit 24.

[0097] In order to remove the charged particles 26 from Figure 3CIn order to guide the off-axis position illustrated in the example in the example to the axis 60, the control circuit 24 is illustratively configured to control the voltage source 22 to modify the voltages V1-V4 in a manner to guide the charged particles toward the axis 60, for example according to one or more conventional or other optimization routines. As the charged particles 26 begin to become irradiated by the radiation source 58, the control circuit 24 will continue to modify the voltages V1-V4 until the radiation detection signal generated by the detectors 561-564 reaches a maximum value, at which time the charged particles 26 will travel along a path that is colinear with the axis 60 so that the charged particles. Thereafter, the amplitude of the voltages V1-V4 can be maintained and the charged particle position detector 54 can be deactivated, and the charged particles 26 passing through the radially segmented charged particle guide 20 will be focused toward and to the point, area, or charged particle entrance 53 of the charged particle analysis stage 52.

[0098] Reference now Figure 4A and Figure 4B , another embodiment of a charged particle analysis system 100 is shown, the charged particle analysis system 100 including a radially segmented charged particle guide 20 positioned between a charged particle source 12 and a charged particle analysis stage 16, wherein the charged particle source 12 and the charged particle analysis stage 16 are as described above, and wherein the charged particle analysis stage 16 also includes an embodiment of a virtual sensor embedded therein. In the illustrated embodiment, the charged particle analysis stage 16 is or includes a charged particle detector having at least one signal operatively coupled to at least one signal detection circuit 102, for example in the form of one or more amplifiers, charge sensitive preamplifiers or other charge signal detection devices, the at least one signal detection circuit 102 being configured to generate a charged particle detection signal at its output (or multiple outputs) and supply such charged particle detection signal to a control circuit 24.

[0099] In the illustrated embodiment, the charged particle source 12 defines a longitudinal axis 108 centrally therethrough, the radially segmented charged particle guide 20 defines a longitudinal axis 110 centrally therethrough, and the charged particle analysis stage 16 defines a longitudinal axis 112 centrally therethrough. Figure 4A As illustrated in the example in FIG. 1 , the charged particles 26 leave the charged particle source 12 along the axis 108, i.e., the charged particles move along a path colinear with the central longitudinal axis 108 of the charged particle source 12 toward the charged particle inlet of the radially segmented charged particle guide 20. Figure 4BAs illustrated in the example in , none of the axes 108, 110, 112 are aligned with each other, i.e., none of the axes 108, 110, 112 are co-linear with any of the other axes. In alternative embodiments, the charged particles 26 may leave the charged particle source 12 off-axis (i.e., along a path that is not co-linear with the axis 108), and / or one or more of the axes 108, 110, 112 may be co-linear with any or both of the other axes.

[0100] In any case, the control circuit 24 is illustratively configured to process the charged particle detection signals provided thereto by the (one or more) signal detection circuits 102 to determine spectral information of the charged particles detected in a conventional manner by the charged particle analysis stage 16, e.g., particle mass-to-charge ratio, particle charge, particle mass, etc. As part of such detection of the charged particles by the charged particle analysis stage 16, the control circuit 24 is illustratively operable to determine whether the charged particles exiting the radially segmented charged particle guide 20 have entered the charged particle analysis stage 16 in a manner that produces valid charged particle measurement information; that is, the control circuit 24 is operable to determine whether the charged particles captured by the charged particle analysis stage 16 produce complete or incomplete charge detection information. In embodiments of the charged particle analysis stage 16 (e.g., one or more ELITs and / or one or more orbital traps) that operate to capture charged particles therein, such a measure of complete or incomplete charge detection is illustratively determined by the control circuit 24 in the form of a percentage of capture events. For any particular run of charged particle analysis, perfect charge detection corresponds to 100% trapping events, and zero charge detection corresponds to 0% trapping events. Figure 4A and Figure 4B In the embodiment illustrated in , the percentage of capture events is used as a virtual sensor, and the control circuit 24 is operable to monitor the percentage of capture events and control the voltage source 22 to modify the voltages V1-V4, for example, according to one or more conventional or other optimization routines, so as to maximize the percentage of capture events. In a practical sense, such modification of the voltages V1-V4 will cause the radially segmented charged particle guide 20 to cause charged particles entering the charged particle inlet of the guide 20 along path 118 to leave the charged particle outlet of the guide 20 along path 112, which is the central longitudinal axis of the charged particle analysis stage 16. Those skilled in the art will recognize other characteristics of the charged particle analysis stage 16 that can be used as virtual sensor output feedback to the control circuit 24 in place of the percentage of capture events to guide the appropriate selection of the amplitudes of the voltages V1-V4. Examples may illustratively include, but are not limited to, the capture efficiency of the charged particle analysis stage 16.

[0101] refer to Figure 5, shows another embodiment of a charged particle analysis system 200, in which the charged particle analysis system 200 can be implemented by Figure 2 At least one of the radially segmented charged particle guides 20 shown in the example in FIG. Figure 5 The charged particle analysis system 200 illustrated in the example of is a charge detection mass spectrometer (CDMS) 200, which illustratively includes a charged particle source 210 of an embodiment operatively coupled to an electrostatic linear ion trap (ELIT) 212, shown as having control and measurement components coupled to the ELIT 212. The charged particle source 210 illustratively includes any conventional device or apparatus for generating charged particles from a sample, and may also include one or more devices and / or instruments for separating, collecting, filtering, controlling / setting energy, splitting and / or normalizing or transferring the charge state of the charged particles according to one or more molecular properties. As an illustrative example that should not be considered limiting in any way, the charged particle source 210 may include a conventional electrospray ionization source, a matrix-assisted laser desorption ionization (MALDI) source, etc., coupled to the inlet of a conventional mass spectrometer. The mass spectrometer may be of any conventional design, including, for example, but not limited to, a time-of-flight (TOF) mass spectrometer, a reflectron mass spectrometer, a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer, a quadrupole mass spectrometer, a triple quadrupole mass spectrometer, a magnetic sector mass spectrometer, an orbital trap, etc. In any case, the charged particle outlet of the mass spectrometer is operatively coupled to the charged particle inlet of the ELIT 212, such as by Figure 5 The sample from which charged particles are generated may be or include any biological material or other material.

[0102] In the illustrated embodiment, the ELIT 212 illustratively includes a charge detector CD, which is surrounded by a grounded chamber or cylinder GC and is operatively connected to relative ion mirrors M1, M2 respectively positioned at opposite ends of the charged detector CD. The ion mirrors M1, M2 may alternatively be referred to herein as "end covers" or "end caps", it being understood that for the purposes of this disclosure, the terms ion mirror and end cover (or end cap) are synonymous. The ion mirror M1 is operatively positioned between the charged particle outlet of the charged particle source 210 and one end of the charge detector CD, and the ion mirror M2 is operatively positioned at the opposite end of the charge detector CD. Each ion mirror M1, M2 defines a corresponding ion mirror region R1, R2 therein. Regions R1, R2 of the ion mirrors M1, M2, the charge detector CD, and the space between the charge detector CD and the ion mirrors M1, M2 are axially aligned so that they together define a longitudinal axis 218 passing through the center thereof, which longitudinal axis illustratively represents an ideal ion travel path through the ELIT 210 and between the ion mirrors M1, M2, as will be described in more detail below. The region axially defined between the relative inner surfaces of the ion mirrors M1, M2 (i.e., in which the charge detector CD is positioned) illustratively defines a field-free region FFR, i.e., in which no electric field is established during operation of the ELIT 210, as described below.

[0103] In the illustrated embodiment, voltage sources V1, V2 are electrically coupled to ion mirrors M1, M2, respectively. Each voltage source V1, V2 illustratively comprises one or more switchable DC voltage sources that can be controlled or programmed to selectively generate a number N of programmable or controllable voltages, where N can be any positive integer. Fig. 6A and Figure 6B Illustrative examples of such voltages are described to establish each of two different operating modes for each of the ion mirrors M1, M2, as will be described in detail below. In any case, the ELIT 210 is designed so that charged particles move within the ELIT 210 near a longitudinal axis 218, which ideally extends centrally through the charge detector CD and the ion mirrors M1, M2, under the influence of the electric field selectively established in the ion mirrors M1, M2 by the voltage sources V1, V2.

[0104] The voltage sources V1, V2 are illustratively shown as being electrically connected via a number P of signal paths to a conventional processor 214 including a memory 216 having instructions stored therein which, when executed by the processor 214, cause the processor 214 to control the voltage sources V1, V2 to produce desired DC output voltages for selectively establishing an ion transmission electric field TEF and an ion reflection electric field REF in regions R1, R2 of the corresponding ion mirrors M1, M2, respectively (see, e.g. Fig. 6Aand Figure 6B ). P may be any positive integer. In some alternative embodiments, either or both of the voltage sources V1, V2 may alternatively or additionally be programmable to selectively generate one or more constant output voltages. In other alternative embodiments, either or both of the voltage sources V1, V2 may be configured to generate one or more time-varying output voltages of any desired shape. It will be appreciated that in alternative embodiments, more or fewer voltage sources may be electrically connected to the mirrors M1, M2.

[0105] The charge detector CD is illustratively provided in the form of a conductive cylinder, illustratively referred to herein as a charge detection cylinder, which is electrically connected to a signal input of a charge sensitive preamplifier CP, and a signal output of the charge sensitive preamplifier CP is electrically coupled to the processor 214. The voltage sources V1, V2 are illustratively controlled in a manner as described in detail below that selectively traps at least one charged particle entering a charged particle inlet of the ELIT 212 in the ELIT 212 and causes the at least one charged particle to oscillate back and forth between the ion mirrors M1, M2 with the ELIT 212 each time it passes axially through the charge detection cylinder CD. In the case where at least one charged particle is thus trapped within the ELIT 212 and oscillates back and forth between the ion mirrors M1, M2, the charge sensitive preamplifier CP may illustratively operate in a conventional manner to detect the charge (CH) induced on the charge detection cylinder CD when the at least one charged particle repeatedly passes through the charge detection cylinder CD between the ion mirrors M1, M2, respectively, and generate a charge detection signal (CHD) corresponding to the charge. The charge detection signal CHD is illustratively periodic and recorded in the form of amplitude and period values, and in this regard, each amplitude and period pair represents ion measurement information of a single corresponding charge detection event in which the charged particle travels through the charge detection cylinder CD. The amplitude is the amplitude of the charge induced on the charge detection cylinder by the charged particle when the charged particle passes through the charge detection cylinder, and the period value is the duration of the charged particle passing through the charge detection cylinder. A plurality of such amplitude and period values ​​are measured and recorded during a corresponding charged particle measurement event (i.e., during a charged particle capture event), and for the charged particle measurement event, the resulting plurality of recorded values ​​(i.e., a collection of recorded charged particle measurement information) are processed to determine the charged particle mass-to-charge ratio, charge magnitude, and in some cases, mass value, as will be described below. A plurality of charged particle measurement events can be processed in this manner, and a mass-to-charge ratio and / or mass and / or charge spectrum of a sample can be illustratively constructed therefrom.

[0106] Reference now Fig. 6A and Figure 6B, example embodiments of the ion mirrors M1, M2 of the ELIT 212 depicted in FIG. 1 are shown, respectively. Illustratively, the ion mirrors M1, M2 are identical to one another in that each comprises a cascade arrangement of four spaced-apart conductive mirror electrodes. For each of the ion mirrors M1, M2, a first mirror electrode 2201 has a thickness W1 and defines a passage through the center of the mirror of diameter P1, such as an end cap inner diameter. An end plate 222 is attached or otherwise coupled to an outer surface of the first mirror electrode 2201 and defines an orifice A1 through the center thereof, which orifice A1 serves as an ion inlet and / or outlet for regions R1, R2 of the respective ion mirrors M1, M2. In the case of the ion mirror M1, the end plate 222 is coupled to Figure 5 2. The charged particle outlet of the ion source 210 shown in FIG. 2 is or is a portion thereof. The aperture A1 of each end plate 222 illustratively has a diameter P2.

[0107] The second mirror electrode 2202 of each ion mirror M1, M2 is spaced apart from the first mirror electrode 2201 by a space having a width W2. Like the mirror electrode 2201, the second mirror electrode 2202 has a thickness W1 and defines a passage through its center of diameter P1. The third mirror electrode 2203 of each ion mirror M1, M2 is likewise spaced apart from the second mirror electrode 2202 by a space of width W2. The third mirror electrode 2203 has a thickness W1 and defines a passage through its center of width P1. Illustratively, the cross-section of the passage is circular, so that the corresponding regions R1, R2 formed by the mirror electrodes 2201, 2202, 2203 are substantially cylindrical, although in alternative embodiments one or more of the mirror electrodes 2201, 2202, 2203 may define a passage through it that is non-circular in cross-section. Ideally, the longitudinal axis 218 of the ELIT 212 passes centrally through each mirror electrode 2201, 2202, 2203 so that the inwardly facing terminal surfaces 225 defining passages through the mirror electrodes 2201, 2202, 2203 are aligned with each other to form uniform ion mirror regions R1, R2, respectively.

[0108] The fourth mirror electrode 2204 is spaced apart from the third mirror electrode 2203 by a space of width W2. The fourth mirror electrode 2204 illustratively has a thickness of W1 and is formed by respective ends of a grounded cylinder GC disposed around the charge detector CD. The fourth mirror electrode 2204 defines an aperture A2 passing through it at the center, the aperture A2 being illustratively conical in shape and increasing linearly between the inner and outer faces of the grounded cylinder GC from a diameter P3 defined at the inner face of the grounded cylinder GC to a diameter P1 at the outer face of the grounded cylinder GC (which is also the inner face of the respective ion mirrors M1, M2). In some alternative embodiments, the fourth mirror electrode 2204 may be identical to the mirror electrodes 2201-2203 such that the fourth mirror electrode 2204 defines an inner diameter P1 therethrough, and in such embodiments, an end plate, for example similar to the end plate 222, may be attached or otherwise connected to an outer surface of the fourth mirror electrode 2204 (i.e., the surface facing the charge detector CD), wherein the end plate defines an orifice A2 passing through it at the center.

[0109] The space defined between the mirror electrodes 2201-2204 may be a void, i.e., a vacuum gap, in some embodiments, and in other embodiments, such space may be filled with one or more non-conductive (e.g., dielectric) materials. The mirror electrodes 2201-2204 and the end plate 222 are ideally axially aligned with each other, i.e., co-linear, so that the longitudinal axis 218 passes centrally through each aligned passage of the mirror electrodes 2201-2204 of each ion mirror M1, M2 and also centrally through the orifices A1, A2. In embodiments in which the space between the mirror electrodes 2201-2204 includes one or more non-conductive materials, such materials will also define corresponding passages therethrough, which are axially aligned, i.e., co-linear, with passages defined through the mirror electrodes 2201-2204 and illustratively having a diameter of P2 or greater. Illustratively, P1>P3>P2, although other relative diameter arrangements are possible in other embodiments. In some embodiments, the thickness of the mirror electrodes 2201-2204 is the same, for example, all W1, although in alternative embodiments one or more of the mirror electrodes 2201-2204 may have a different thickness than one or more of the remaining mirror electrodes 2201-2204. In some embodiments, A1=A2, although in alternative embodiments A1 may be greater or less than A2. Although the ion mirrors M1, M2 are each shown as having four mirror electrodes 2201-2204, it will be understood that in alternative embodiments, the ion mirrors M1, M2 may include more or fewer such mirror electrodes.

[0110] Ion mirror region R1 is defined between apertures A1 , A2 of ion mirror M1 , and ion mirror region R2 is likewise defined between apertures A1 , A2 of ion mirror M2.Ion mirror regions R1 , R2 are ideally identical in shape and volume to each other.

[0111] As described above, the charge detector CD is illustratively provided in the form of an elongated conductive cylinder positioned between corresponding ones of the ion mirrors M1, M2 and spaced apart by a space of width W3. In one embodiment, W1>W3>W2, and P1>P3>P2, although other relative width arrangements are possible in alternative embodiments. In any case, the longitudinal axis 218 illustratively extends centrally through a passage defined through the charge detection cylinder CD, such that the longitudinal axis 218 ideally extends centrally through the combination of the ion mirrors M1, M2 and the charge detection cylinder CD. The axial length ML of each ion mirror M1 is therefore ML=4W1+3W2, and the axial length FFL of the field-free drift region FFR is therefore FFL=2W3+CDL, where CDL is the axial length of the charge detection cylinder CD.

[0112] In operation, the ground cylinder GC is illustratively controlled to ground potential so that the fourth mirror electrode 2204 of each ion mirror M1, M2 is always at ground potential. In some alternative embodiments, the fourth mirror electrode 2204 of either or both of the ion mirrors M1, M2 may be set to any desired DC reference potential, or to a switchable DC or other time-varying voltage source.

[0113] exist Fig. 6A and Figure 6B In the embodiment illustrated in , the voltage sources V1, V2 are each configured to generate a corresponding one of the four DC voltages D1-D4, and supply the voltage D1-D4 to a corresponding one of the mirror electrodes 2201-2204 of the corresponding ion mirrors M1, M2. In some embodiments in which one or more of the mirror electrodes 2201-2204 are to be maintained at ground potential at all times, one or more of such mirror electrodes 2201-2204 may alternatively be electrically connected to the ground reference of the corresponding voltage sources V1, V2, and the corresponding one or more voltage output terminals D1-D4 may be omitted. Alternatively or additionally, in embodiments in which any two or more of the mirror electrodes 2201-2204 are to be controlled to the same non-zero DC value, any such two or more mirror electrodes 2201-2204 may be electrically connected to a single voltage output terminal of the voltage output terminals D1-D4, and redundant output voltages of the output voltages D1-D4 may be omitted.

[0114] Each ion mirror M1, M2 is illustratively in ion transmission mode (as indicated by the selective application of voltages D1-D4). Fig. 6A ) and ion reflectance mode (as shown by Figure 6BIn the ion transmission mode, the voltages D1-D4 generated by the corresponding voltage sources V1 and V2 establish an ion transmission electric field (TEF) in their respective regions R1 and R2, and in the ion reflection mode, the voltages D1-D4 generated by the corresponding voltage sources V1 and V2 establish an ion reflection electric field (REF) in their respective regions R1 and R2. The region FFR defined between the ion mirrors M1 and M2 (in which the charge detection cylinder CD resides) is illustratively always kept free of electric field, as described above. As shown by Fig. 6A As illustrated in the example in, once the charged particles from the charged particle source 210 are transmitted into the region R1 of the ion mirror M1 through the entrance orifice A1 of the ion mirror M1, the charged particles are focused toward the longitudinal axis 218 of the ELIT 212 by the ion transmission electric field TEF established in the region R1 of the ion mirror M1 via the selective control of the voltages D1-D4 of V1. As a result of the focusing effect of the transmission electric field TEF in the region R1 of the ion mirror M1, the charged particles leaving the region R1 of the ion mirror M1 through the orifice A2 of the grounded chamber GC obtain a narrow trajectory into and through the charge detector CD, i.e., a path for the ions to travel through the charge detector CD in a manner that is close to or co-linear with the longitudinal axis 218. Sometimes, the same ion transmission electric field TEF may be selectively established in the region R2 of the ion mirror M2 via similar control of the voltages D1-D4 of the voltage source V2. In ion transmission mode, charged particles entering region R2 from charge detection cylinder CD via aperture A2 of M2 are focused toward longitudinal axis 218 by the ion transmission electric field TEF within region R2, causing the charged particles to exit aperture A1 of ion mirror M2.

[0115] If Figure 6B As illustrated in the example in , the ion reflection electric field REF established in region R2 of ion mirror M2 by selective control of voltages D1-D4 of V2 is used to decelerate and stop charged particles entering ion region R2 from charge detection cylinder CD through ion entrance orifice A2 of M2, and then accelerate the stopped charged particles in the opposite direction back through orifice A2 of M2 and into the end of charge detection cylinder CD adjacent to M2, as depicted by ion trajectory 232, and focus the charged particles toward the central longitudinal axis 218 within region R2 of ion mirror M2 so as to maintain a narrow trajectory of the charged particles returning toward ion mirror M1 through charge detector CD. The charged particles are in a state relative to the surface of mirror electrode 2204 facing charge detection cylinder CD as shown in FIG. Figure 6B The distance a charged particle penetrates through the ion mirror M2 before reversing direction as shown in FIG.

[0116] Sometimes, for example during a trapping event, the same ion reflection electric field REF may be selectively established within region R1 of the ion mirror M1 via similar control of the voltages D1-D4 of the voltage source V1. In the ion reflection mode, a charged particle entering region R1 from the charge detection cylinder CD via the orifice A2 of M1 is decelerated and stopped by the ion reflection electric field REF established within region R1, then accelerated in the opposite direction back through the orifice A2 of M1 and into the end of the charge detection cylinder CD adjacent to M1, and focused toward the central longitudinal axis 20 within region R1 of the ion mirror M1 so as to maintain a narrow trajectory of the charged particle returning toward the ion mirror M1 through the charge detector CD. As just described, a charged particle that traverses the length of the ELIT 14 and is reflected by the ion reflection electric field REF in the ion regions R1, R2 to continue traveling back and forth through the charge detection cylinder CD between the ion mirrors M1, M2 is considered to be trapped within the ELIT 212.

[0117] An example set of output voltages D1-D4 to be generated by voltage sources V1, V2, respectively, to control the respective ion mirrors M1, M2 to the ion transmission and reflection modes described above are shown below in Table I. It will be understood that the following values ​​of D1-D4 are provided as examples only, and other values ​​of one or more of D1-D4 may alternatively be used. Table I

[0118] Reference now Figure 7 , showing Figure 5 . In the illustrated embodiment, the processor 214 includes a conventional amplifier circuit 240 having an input terminal receiving a charge detection signal CHD generated by a charge sensitive preamplifier CP and an output terminal electrically connected to an input terminal of a conventional analog-to-digital (A / D) converter 242. The output terminal of the A / D converter 242 is electrically connected to the processor 250 (P1). The amplifier 240 is operable in a conventional manner to amplify the charge detection signal CHD generated by the charge sensitive preamplifier CP, and the A / D converter 242 is in turn operable in a conventional manner to convert the amplified charge detection signal CHD into a digital charge detection signal CDS.

[0119] Figure 5The processor 214 illustrated in FIG. 2 also includes a conventional comparator 244 having a first input terminal receiving a charge detection signal CHD generated by a charge sensitive preamplifier CP, a second input terminal receiving a threshold voltage CTH generated by a threshold voltage generator (TG) 246, and an output terminal electrically connected to the processor 250. The comparator 244 is operable in a conventional manner to generate a trigger signal TR at its output terminal, which trigger signal TR depends on the amplitude of the charge detection signal CDH relative to the amplitude of the threshold voltage CTH. In one embodiment, for example, as long as CHD is less than CTH, the comparator 244 is operable to generate an "inactive" trigger signal TR at or near a reference voltage (e.g., ground potential), and is operable to generate an "active" TR signal at or near a supply voltage of the circuit system 240, 242, 244, 246, 250 or otherwise distinguishable from an inactive TR signal when CHD equals or exceeds CTH. In an alternative embodiment, the comparator 244 is operable to generate an "inactive" trigger signal TR at or near the supply voltage as long as CHD is less than CTH, and the comparator 244 is operable to generate an "active" trigger signal TR at or near the reference potential when CHD equals or exceeds CTH. Those skilled in the art will recognize other different trigger signal amplitudes and / or different trigger signal polarities that can be used to establish the "inactive" and "active" states of the trigger signal TR, so long as such different trigger signal amplitudes and / or different trigger signal polarities can be distinguished by the processor 250, and it will be understood that any such other different trigger signal amplitudes and / or different trigger signal polarities are intended to fall within the scope of the present disclosure. In any case, the comparator 244 can additionally be designed in a conventional manner to include a desired amount of hysteresis to prevent rapid switching of the output between the reference voltage and the supply voltage.

[0120] The processor 250 is illustratively operable to generate a threshold voltage control signal THC and supply THC to the threshold generator 246 to control its operation. In some embodiments, the processor 250 is programmed or programmable to control the generation of the threshold voltage control signal THC in a manner that controls the threshold voltage generator 246 to generate a CTH having a desired amplitude and / or polarity. In other embodiments, a user may provide instructions to the processor 250 in real time, for example, through a downstream processor (e.g., via a virtual control and visualization unit) to control the generation of the threshold voltage control signal THC in a manner that controls the threshold voltage generator 246 to generate a CTH having a desired amplitude and / or polarity. In either case, in some embodiments, the threshold voltage generator 246 is illustratively implemented in the form of a conventional controllable DC voltage source that is configured to respond to a digital form of the threshold control signal THC (e.g., in the form of a single serial digital signal or a plurality of parallel digital signals) to generate an analog threshold voltage CTH having a polarity and amplitude defined by the digital threshold control signal THC. In some alternative embodiments, the threshold voltage generator 246 may be provided in the form of a conventional digital-to-analog (D / A) converter that responds to a serial or parallel digital threshold voltage TCH to generate an analog threshold voltage CTH having an amplitude and, in some embodiments, a polarity defined by a digital threshold control signal THC. In some such embodiments, the D / A converter may form part of the processor 250. Those skilled in the art will recognize other conventional circuits and techniques for selectively generating a threshold voltage CTH of a desired amplitude and / or polarity in response to one or more digital and / or analog forms of the control signal THC, and will understand that any such other conventional circuits and / or techniques are intended to fall within the scope of the present disclosure.

[0121] In addition to the aforementioned functions performed by the processor 250, the processor 250 is also operable to control the voltage sources V1, V2, as described above with respect to Fig. 6A , Figure 6BAs described, to selectively establish ion transmission fields and reflection fields in regions R1 and R2 of ion mirrors M1 and M2, respectively. In some embodiments, processor 250 is programmed or capable of being programmed to control voltage sources V1 and V2. In other embodiments, (one or more) voltage sources V1 and / or V2 may be programmed or otherwise controlled by a user, for example, in real time through a downstream processor 252 (e.g., via a virtual control and visualization unit). In either case, in one embodiment, processor 250 is illustratively provided in the form of a field programmable gate array (FPGA) that is programmed or otherwise instructed by a user to collect and store charge detection signals CDS for charge detection events and for ion measurement events, to generate (one or more) threshold control signals TCH from which the amplitude and / or polarity of a threshold voltage CTH is determined or derived, and to control voltage sources V1 and V2. In this embodiment, with respect to Figure 5 The memory 216 described is integrated into and forms part of the programming of the FPGA. In alternative embodiments, the processor 250 may be provided in the form of one or more conventional microprocessors or controllers and one or more associated memory units having instructions stored therein which, when executed by the one or more microprocessors or controllers, cause the one or more microprocessors or controllers to operate as just described. In other alternative embodiments, the processing circuitry 250 may be implemented purely in the form of one or more conventional hardware circuits designed to operate as described above, or as a combination of one or more such hardware circuits and at least one microprocessor or controller operable to execute instructions stored in the memory to operate as described above.

[0122] Figure 7 The embodiment of the processor 214 depicted in also illustratively includes a second processor 252 coupled to the first processor 250 and also coupled to at least one memory unit 254. In some embodiments, the processor 252 may include one or more peripheral devices, such as a display monitor, one or more input and / or output devices, etc., although in other embodiments the processor 252 may not include any such peripheral devices. In any case, the processor 252 is illustratively configured (i.e., programmed) to perform at least one process for analyzing ion measurement events. Data in the form of charge magnitude and charge timing data (i.e., detection of the timing of charges induced by ions on the charge detection cylinder relative to each other) received by the processor 250 via the charge detection signal CDS is illustratively transmitted directly from the processor 250 to the processor 252 upon completion of each ion measurement event for processing and analysis.

[0123] In some embodiments, processor 252 is illustratively provided in the form of a high-speed server that is operable to perform both the collection / storage and analysis of such data. In such embodiments, one or more high-speed memory units 254 may be coupled to processor 252 and operable to store data received and analyzed by processor 252. In one embodiment, one or more memory units 254 illustratively include at least one local memory unit for storing data that is being used or to be used by processor 252, and at least one permanent storage memory unit for long-term storage of data. In one such embodiment ... Xeon TM Processor (e.g., E5-465Lv2, 12 cores, 2.4GHz) Server (e.g., OpenSuse Leap 42.1). In this embodiment, the PC (e.g., i5-2500K, 4 cores, 3.3GHz), an increase of more than 100 times the average analysis time of a single ion measurement event file is achieved. Similarly, the processor 252 of this embodiment, together with (one or more) high-speed / high-performance memory units 254, illustratively provides an increase of more than 100 times the data storage speed. Those skilled in the art will recognize that one or more other high-speed data processing and analysis systems that can be implemented as processor 252, and will understand that any such one or more other high-speed data processing and analysis systems are intended to fall within the scope of the present disclosure. In an alternative embodiment, the processor 252 can be provided in the form of one or more conventional microprocessors or controllers and one or more supporting memory units, the memory unit having instructions stored therein, when executed by one or more microprocessors or controllers, the instructions cause one or more microprocessors or controllers to operate as described herein.

[0124] In the illustrated embodiment, memory unit 254 illustratively has instructions stored therein that are executable by processor 252 to analyze ion measurement event data generated by ELIT 212 to determine ion mass spectral information for the sample under analysis. In one embodiment, processor 252 is operable to receive ion measurement event data in the form of charge magnitude and charge detection timing information measured during each of a plurality of "charge detection events" (as such term is defined above) constituting an "ion measurement event" (as such term is defined above) from processor 250, and process such charge detection events constituting such ion measurement events to determine ion charge and mass-to-charge ratio data, and then determine ion mass data therefrom. Multiple ion measurement events can be processed in a similar manner to create mass spectral information for the sample under analysis.

[0125] As mentioned above about Fig. 6A and Figure 6B As briefly described, voltage sources V1, V2 are illustratively controlled by processor 250 (e.g., via processor 252) in such a manner that ion transmission electric fields and ion reflection electric fields are selectively established in region R1 of ion mirror M1 and in region R2 of ion mirror M2 to guide ions introduced into ELIT 212 from charged particle source 210 through ELIT 212 and then cause at least one charged particle to be selectively captured and confined within ELIT 212 such that the (one or more) captured charged particles repeatedly pass through charge detector CD as they oscillate back and forth between M1 and M2. Reference FIG. 8A to FIG. 8C , showing Figure 5 2 is a simplified diagram of an ELIT 212 depicting an example of such sequential control and operation of ion mirrors M1, M2 of the ELIT 212. In the following examples, the processor 252 will be described as controlling the operation of the voltage sources V1, V2 in accordance with its programming, although it will be understood that the operation of the voltage source V1 and / or the operation of the voltage source V2 may be at least partially controlled by the processor 250 virtually.

[0126] like Fig. 8A As shown in FIG. 1 , the ELIT control sequence begins with the processor 252 controlling the voltage source V1 to control the ion mirror M1 to the ion transmission mode of operation (T) by establishing an ion transmission field in the region R1 of the ion mirror M1, and also controlling the voltage source V2 to control the ion mirror M2 to the ion transmission mode of operation (T) by similarly establishing an ion transmission field in the region R2 of the ion mirror M2. As a result, the charged particles generated by the charged particle source 210 enter the ion mirror M1, and when they enter the charge detection cylinder CD, they are directed by the ion transmission field established in the region R1 toward the central longitudinal axis 218 (see FIG. 2 ). Figure 5 ) is focused. The charged particles then pass through the charge detection cylinder CD and enter the ion mirror M2, where the ion transmission field established in the region R2 of M2 focuses the charged particles toward the longitudinal axis 218, causing the charged particles to pass through the exit orifice A1 of M2, as indicated by Fig. 8A As illustrated by the ion trajectory 260 depicted in .

[0127] Reference now Figure 8B, after both ion mirrors M1, M2 have been operated in the ion transmission mode of operation for a selected period of time and / or until successful ion transmission therethrough has been achieved (e.g., by monitoring the charge detection signal CDS to determine the presence of charged particles passing through the charge detection cylinder CD), the processor 252 may illustratively operate to control the voltage source V2 to control the ion mirror M2 to the ion reflection mode of operation (R) by establishing an ion reflection field within a region R2 of the ion mirror M2, while maintaining the ion mirror M1 in the ion transmission mode of operation (T), as shown. As a result, at least one charged particle generated by the charged particle source 210 enters the ion mirror M1 and is focused toward the central longitudinal axis 218 by the ion transmission field T established in the region R1, so that the at least one charged particle passes through the ion mirror M1 and enters the charge detection cylinder CD, as just described. Fig. 8A The charged particle(s) then passes through the charge detection cylinder CD and enters the ion mirror M2, where the ion reflection field R established within the region R2 of M2 reflects the charged particle(s) to cause them to travel in the opposite direction and return to the charge detection cylinder CD, as indicated by Figure 8B As shown in FIG. 262 , the ion trajectory in FIG.

[0128] Reference now Figure 8C After the ion reflection electric field has been established in the region R2 of the ion mirror M2, the processor 252 is operable to control the voltage source V1 to control the ion mirror M1 to the ion reflection operation mode (R) by establishing the ion reflection field in the region R1 of the ion mirror M1, while maintaining the ion mirror M2 in the ion reflection operation mode (R) so as to trap (one or more) charged particles in the ELIT 212, so that (one or more) charged particles oscillate back and forth between the ion mirrors M1 and M2 each time they pass through the charge detection cylinder CD. As shown by Figure 6B As illustrated in the example in , the ions penetrate to a distance IPD (ion penetration depth) in the ion mirror M2 before reversing direction, and since the ion mirrors M1 and M2 are controlled identically in reflection mode, the ions also penetrate to a distance IPD in the ion mirror M1 before reversing direction.

[0129] In some embodiments, processor 252 is illustratively operable (ie, programmed) to control ELIT 212 in a "random capture mode" or a "continuous capture mode" in which the ELIT 212 is captured after the ELIT 212 has been captured. Figure 8B After operating in the state illustrated in FIG. 2 (i.e., M1 is in ion transmission mode and M2 is in ion reflection mode) for a selected period of time, the processor 252 is operable to control the ion mirror M1 to the reflection operation mode (R). Until the selected period of time has passed, the ELIT 212 is controlled to operate in the state illustrated in FIG. Figure 8B. In other embodiments, the processor 252 is operable (i.e., programmed) to control the ELIT 212 in a "triggered capture mode", which illustratively has a significantly greater probability of capturing one or more charged particles therein compared to the random capture mode. In the "triggered capture mode", the processor 252 is operable to control the ion mirror M1 to a reflective operating mode (R) after at least one charged particle has been detected as passing through the charge detection cylinder CD.

[0130] In any case, when both ion mirrors M1, M2 are controlled to the ion reflection mode of operation (R) to trap ions within the ELIT 212, the opposing ion reflection fields established in regions R1 and R2 of the ion mirrors M1 and M2, respectively, cause at least one charged particle to oscillate back and forth between the ion mirrors M1 and M2 each time it passes through the charge detection cylinder CD, as indicated by Figure 8C In one embodiment, the processor 250 is operable to maintain Figure 8C until at least one charged particle passes through the charge detection cylinder CD a selected number of times. In an alternative embodiment, the processor 250 is operable to control M1 (and in some embodiments M2) to the ion reflection operation mode (R) after Figure 8C The operating state illustrated in is maintained for a selected period of time. Figure 8C The number of cycles or time spent in the state illustrated in may illustratively be programmed, for example, via instructions stored in the memory 254, or controlled via a user interface, and in any case the ion detection event information generated by each passage of the ions through the charge detection cylinder CD is temporarily stored in the processor 250, for example, in the form of an ion measurement file, which may illustratively have a predefined data or sample length. When (one or more) charged particles have passed through the charge detection cylinder CD a selected number of times or have oscillated back and forth between the ion mirrors M1, M2 for a selected time period, the total number of charged particle detection events stored in the processor 250 defines a charged particle measurement event for each of the (one or more) charged particles, and when the charged particle measurement event is completed, the stored charged particle detection events (e.g., charged particle measurement event files) defining the charged particle measurement events are passed to or retrieved by the processor 252. Then, FIG. 8A to FIG. 8C The sequence shown in the figure returns to Fig. 8A , wherein the voltage sources V1, V2 are controlled as described above to control the ion mirrors M1, M2 to the ion transmission mode of operation (T) by establishing ion transmission fields in the regions R1, R2 of the ion mirrors M1, M2, respectively. The illustrated sequence is then repeated a desired number of times.

[0131] In some embodiments, the charged particle measurement event file is analyzed in the frequency domain using a fast Fourier transform (FFT) algorithm. In such embodiments, the mass-to-charge ratio (m / z) of the charged particles moving through the ELIT 212 is determined from the oscillation frequency (f0) of the charged particle measurement event data using a calibration constant (C) (Equation 1), the charge of the charged particle is determined by the amplitude of the fundamental frequency peak in the FFT, and the mass of the charged particle is then determined as the product of m / z and ion charge. Equation 1:

[0132] In an alternative embodiment, the signal measurements contained in the charged particle measurement event file may be analyzed in the time domain in conjunction with the FFT by incorporating information contained in higher order harmonics by fitting the signal measurements to an analog waveform to more accurately measure the ion charge. Details regarding an example process for performing such a time domain analysis may be found in co-pending International Application No. PCT / US2021 / 016435, filed on February 3, 2021 and published as WO 2021 / 158676A1, the disclosure of which is expressly incorporated herein by reference in its entirety.

[0133] A prior ELIT design configured to optimize the accuracy of charge measurements and simultaneously reduce the contribution of ion energy distribution to m / z resolution, an example of which is disclosed in co-pending U.S. Patent Application Publication No. US2020 / 0357626, the disclosure of which is expressly incorporated herein in its entirety by reference. A method has also been developed for optimizing the geometric and electrostatic parameters of the cylindrical ELIT 212 so that the oscillation frequency of the trapped charged particles, and therefore the measured m / z, is highly resistant to changes with changes in the energy and trajectory of the trapped charged particles, while also retaining features of the design that produce high charge resolution, as disclosed in co-pending International Application No. PCT / US2022 / 073503 filed on July 7, 2022, the disclosure of which is expressly incorporated herein in its entirety by reference.

[0134] As described above, the ELIT 212 is illustratively designed so that charged particles move within the ELIT 212 near a longitudinal axis 218 under the influence of an electric field selectively established in the ion mirrors M1, M2 by voltage sources V1, V2, the longitudinal axis 218 ideally extending centrally through the charge detector CD and the ion mirrors M1, M2. However, in a physical implementation of the ELIT in which the ion mirrors M1, M2 are comprised of a plurality of ion mirror electrodes, such as by Fig. 6A and Figure 6BAs illustrated in the example of , one or more of the ion mirror electrodes may not be perfectly aligned with the other ion mirror electrodes. Fig. 9 , for example, shows Figure 6B An embodiment of the ion mirror M2 in which the innermost ion mirror electrode 2203 is displaced upward relative to the remaining ion mirror electrodes 2201, 2202 and relative to the charge detection cylinder CD. As a result, the central longitudinal axis 218' defined through the ion mirror electrode 2203 deviates radially from the central longitudinal axis 218 of the ELIT 212. As described above, applying a voltage D3 to the ion mirror electrode 2203 in the ion reflection operating mode R will therefore focus the charged particles traveling through the ion mirror M2 toward and along the central longitudinal axis 218', which deviates from the central longitudinal axis 218 defined through the remaining ion mirror electrodes 2201, 2202 and through the charge detection cylinder CD. When a charged particle travels through the ion mirror electrode 2203 toward the charge detection cylinder CD, focusing the charged particle from the central longitudinal axis 218 defined by passing through the ion mirror electrode 2202 to and along the central longitudinal axis 218' of the ion mirror electrode 2203 may in some cases force the charged particle to come into contact with the ion mirror electrode 2204 or with the charge detection cylinder CD, thereby resulting in the loss of the charged particle and the corresponding loss of the charged particle measurement data.

[0135] As just described, such physical misalignment(s) between one or more of the ion mirror electrodes 2201, 2202, 2203 leading to potential loss of charged particle data may therefore adversely affect the capture efficiency of the ELIT 212, where, for purposes of this disclosure, "capture efficiency" is defined as the percentage of "complete" capture events relative to a set number of capture events. A "complete" capture event is illustratively defined as one in which a charged particle is trapped within the ELIT 212 for at least a set amount of the total capture time of the capture event, for example, at least 90% of the total capture time of the capture event.

[0136] The trapping efficiency of ELIT 212 is determined by processor 214 by monitoring the charge detection event data for each of a set number of consecutive trapping events and calculating the trapping efficiency as the ratio of complete trapping events (i.e., where the charge detection event data is consistent with a complete trapping event) to incomplete trapping events (i.e., where the charge detection event data is inconsistent with a complete trapping event). Fig.10, for example, shows a graph 300 of the capture efficiency of the ELIT 212 as a function of the deviation of the central longitudinal axis 218' of the ion mirror electrode 2203 relative to the central longitudinal axis 218 of the ELIT 212. In the illustrated example, a deviation of five ten-thousandths of an inch causes the capture efficiency to drop from nearly 100% with perfect alignment of the axes 218, 218' to approximately 30%.

[0137] By implementing in the form of radially segmented electrode rings Fig. 9 The deviated ion mirror electrode 2203 (e.g., as provided by Figure 2 212 and described above), the resulting radially segmented ion mirror electrode can be controlled via applying corresponding DC voltages to the corresponding radial segments to create a modified electric field within the opening 225 defined by the radially segmented ion mirror electrode 2203, the electric field being configured to cause the travel path of the charged particles therethrough to move toward and ideally co-linearly with the central longitudinal axis 218 defined through the ELIT 212. By applying a potential offset to each electrode segment, the capture efficiency can be restored while maintaining the resolution capability of the ELIT 212. In this embodiment, the capture efficiency is thus used as a virtual sensor to provide feedback to the control circuit 214 to guide the control circuit 214 to appropriately select the amplitude of the corresponding DC voltage to be applied to the corresponding radial segment.

[0138] refer to Fig.11 , for example, shows that Fig. 9 302 of an example of capture efficiency versus potential offset in which the position of an ion mirror electrode 2203 implemented as a radially segmented electrode ring having four radial segments is shifted in an upward direction by 5 ten-thousandths of an inch, i.e., such that a central longitudinal axis 218' defined through the radially segmented ion mirror is offset in an upward direction by 5 ten-thousandths of an inch from a central longitudinal axis 218 of the ELITE 212. Under such mechanical misalignment conditions, a potential offset of approximately 2.3 volts applied to the radial segments restores the capture efficiency to nearly 100%. Because the physical offset of the radially segmented ion mirror electrode 2203 is in the upward direction, a potential offset of 2.3 volts is illustratively applied in the form of a negative ΔV to the bottom two radial segments (i.e., at Figure 2 282 and 283 in the example depicted in FIG. 1 ) and applied in the form of a positive ΔV to the top two radial segments (i.e., at Figure 2 281 and 284 in the example depicted in FIG. 1 ). Fig.11 Graph 304 of similarly depicts the restoration of nearly 100% capture efficiency for a four radial segment ion mirror electrode 2203 displaced one thousandth of an inch in the upward direction by a potential shift of approximately 4.2 volts applied to the radial segments as just described.

[0139] In by Figures 5 to 6B In the ELIT 212 illustrated in the example of FIG. 1 , any single, any combination, or all of the ion mirror electrodes 2201-2204 of either or both of the ion mirrors M1, M2 may be implemented in the form of radially segmented ion mirror electrodes, i.e., in the form of radially segmented ion mirror electrodes. Figure 2 The example of the embodiment of the invention can be implemented in the form of a radially segmented charged particle guide 20, each charged particle guide 20 having an arbitrary number of radial segments, and the voltage sources V1, V2 can be correspondingly configured to apply a separate DC voltage to each radial segment of each radially segmented annular electrode, all of which are as described above with respect to Figures 1A to 2 Described. In one embodiment, each radially segmented ion mirror electrode includes eight radial segments, which are each isolated from each other by, for example, air gaps or dielectrics as described above, although in alternative embodiments one or more radially segmented ion mirror electrodes may include more or fewer radial segments. In an example embodiment, which should not be considered to be limiting in any way, each of the internal ion mirror electrodes 2203 is radially segmented, and in another example embodiment, each ion mirror electrode 2201-2203 of each ion mirror M1 and M2 is radially segmented. In other embodiments, any one or a combination of the ion mirror electrodes 2201-2203 of the ion mirror M1 and / or ion mirror M2 may be radially segmented.

[0140] In this embodiment, the memory 216 illustratively has instructions stored therein that are executable by the processor(s) 214 to control the voltage sources V1, V2 to determine in real time the magnitudes of the various voltages to be applied to the respective radial segments that maximize the capture efficiency of the ELIT 212. Mechanical misalignment between two or more of the ion mirror electrodes of the ion mirror M1 and / or the ion mirror M2 will be compensated for by appropriate selection of the various voltages so as to cause the charged particles to be focused to and along the central longitudinal axis 218 of the ELIT 212. In this embodiment, Figure 2One or more radially segmented charged particle guides of the type illustrated in and described above are thus directly integrated into the ELIT 212. The charged particle position sensor for providing an indicator of the desired position of a charged particle relative to the central longitudinal axis of the one or more radially segmented charged particle guides is a virtual sensor in the form of a capture efficiency determination made by the processor(s) 214, and is thus also directly integrated into the ELIT 212. In this embodiment, the exact position of a charged particle entering the(s) radially segmented charged particle guides (i.e., the(s) radially segmented ion mirror electrodes) need not be known; instead, determining and applying various voltages to segments of the one or more radially segmented ion mirror electrodes in a manner that drives the capture efficiency of the ELIT 212 to its maximum achievable value will automatically guide charged particles entering the(s) radially segmented charged particle guides to and along the central longitudinal axis 218 of the ELIT 212.

[0141] Instructions are stored in the memory 216 and are executable by the processor(s) 214 to control the voltage sources V1, V2 to determine the magnitudes of various voltages to be applied to corresponding radial segments of one or more radially segmented ion mirror electrodes of M1 and / or M2 in order to maximize the capture efficiency of the ELIT 212, which instructions may be combined with any conventional optimization strategy. In one embodiment, which should not be considered to be limited in any way, the ELIT 212 may be used. Fig.12 The optimization strategy illustrated in the logic flow chart 306 of . The basic premise of the optimization strategy 306 starts with an evolution-based approach, in which several previously determined potential combinations of each ion mirror electrode are tested. These potentials correspond to the average value between 0.5-ten-thousandths of an inch deviation and 0.1-thousandths of an inch deviation in each direction in increments of 45 degrees, one of which is the case when the radially segmented ion mirrors are fully aligned. This corresponds to a total of 9 total potential (voltage) combinations for each 8-segment ion mirror electrode. In an embodiment in which all ion mirror electrodes of each of M1 and M2 are radially segmented, there are a total of 81 potential combinations for all ion mirror electrodes of each of the combined M1 and M2. Whenever the word "run" is used in the optimization process 306, the ion capture efficiency and resolution are determined for each potential combination.

[0142] Once each potential combination is run, the optimization strategy 306 will check the combination of potentials that has the highest capture efficiency. If all capture efficiencies are zero, the optimization strategy 306 illustratively begins to perform a random walk (randomly adjusting the potential) on each radially segmented ion mirror electrode until it finds a non-zero capture efficiency. Once a non-zero capture efficiency value is found, the optimization strategy 306 will begin to shift the ion mirror electrodes one at a time in the positive and negative directions in half-volt increments. From there, each new iteration is compared to the current best iteration, and the better of the two is retained. Depending on their relationship, the optimization strategy will choose which step to perform next, such as Fig.12 As shown in the flowchart depicted in . Fig.13 A graph 308 of an example convergence of the optimization process 306 is illustrated in , where the capture efficiency is plotted against the number of iterations. It can be seen that the capture efficiency remains at zero for several iterations, and then a combination with an efficiency greater than zero is found as a starting point for further optimization, eventually reaching a capture potential of more than 95% at or after about 50 iterations. Thus, once a close capture potential combination is found, a large increase in capture efficiency occurs, and the jagged upper portion of the graph 308 represents the logic brain slowly pushing one ion mirror electrode at a time toward the maximum achievable capture efficiency.

[0143] Reference now Fig.14, shows yet another embodiment of a charged particle analysis system 400, the system including an ELIT 402 as a charged particle guide, the ELIT 402 having one or more ion mirror electrodes implemented in the form of radially segmented ion mirror electrodes, as described above with respect to the ELIT 212. In this embodiment, the ELIT 402 is positioned between the charged particle source 12 and the downstream charged particle analysis stage 16, wherein the charged particle source 12 and the charged particle analysis stage 16 may be as described above. As an example, which should not be considered limiting in any way, the charged particle analysis stage 16 may be or include another ELIT (with or without (one or more) radially segmented ion mirror electrodes), an orbital trap, a target, or another charged particle analyzer. In the illustrated embodiment, the charged particle source 12 is defined at a longitudinal axis 408 passing through its center, the ELIT 402 is defined at a longitudinal axis 410 passing through its center, and the charged particle analysis stage 16 is defined at a longitudinal axis 412 passing through its center. The charged particles 26 may exit the charged particle source 12 along the axis 408, i.e., such that the charged particles move along a path that is collinear with the central longitudinal axis 408 of the charged particle source 12 toward the charged particle inlet of the ELIT 402, or may alternatively exit the charged particle source 12 along any axial path. Illustratively, the axes 410 and 412 are aligned with each other, i.e., collinear with each other, although in alternative embodiments the axes 410, 412 may not be aligned with each other. The axis 408 may or may not be aligned with the axis 410 and / or with the axis 412. Although not in Fig.14 402, but it will be understood that the system 400 includes at least components electrically coupled to the ELIT 402, such as by Figures 5 to 7 As illustrated in the examples and described above.

[0144] The control circuit 214 is illustratively configured to control voltage sources connected to segments of the various radially segmented ion mirror electrodes, as described above with respect to Figures 5 to 13 However, in Fig.14In the illustrated embodiment, the ELIT 402 is not operated in this manner for the purpose of collecting charged particle mass or charge data as described above, but rather to cause charged particles to move through the ELIT 402 along the axis 410. Once the ELIT 402 is set to achieve this purpose, the control circuit 214 can thereafter be operated to control the ELIT 402 to capture one or more charged particles leaving the charged particle source 12, and cause one or more captured charged particles to oscillate back and forth between the ion mirrors M1, M2, as described above. After some time period or after some number of passes, the (one or more) charged particles should travel along the axis 410, i.e., co-linear with the axis 410, and the control circuit 214 can then be operated to control the ion mirror M2 to the transmission mode, as described above, so that the (one or more) captured charged particles pass out of the ELIT 402 and enter the charged particle inlet of the downstream charged particle analysis stage 16. Thus, in the system 400 , the ELIT acts as a charged particle guide to maximize the entry of charged particles leaving the charged particle source 12 into the charged particle analysis stage 16 .

[0145] Reference now Fig.15A and Fig. 15B , shows yet another embodiment of a charged particle analysis system 500, the system including a radially segmented charged particle guide 20 positioned between a charged particle source 12 and a charged particle analysis stage 16, wherein the charged particle source 12 and the charged particle analysis stage 16 are generally as described above. In the illustrated embodiment, the charged particle source 12 is defined at a center through the longitudinal axis 14, the radially segmented charged particle guide 20 is defined at a center through the longitudinal axis 21, and the charged particle analysis stage 16 is defined at a center through the longitudinal axis 18. As shown by Fig.15A As illustrated in the example of , the axes 14, 21, 18 are aligned with each other, that is, the axes 14, 21, 18 are collinear with each other, although in alternative embodiments, one or more of the axes 14, 21, 18 may not be collinear with one or two of the other axes. In any case, the charged particle source 12 defines a charged particle outlet 15 through which the charged particles leave the charged particle source 12, and the charged particle analysis stage 16 defines a charged particle inlet 19 through which the charged particles enter the charged particle analysis stage 16. Although in Fig.15A Not shown in the drawings, but it will be understood that the system 500 includes at least a voltage source 22 electrically connected to each segment of the radially segmented charged particle guide 20 and a control circuit 24, all of which are as shown in FIG. Figures 1A to 2 As shown in the figure and described above.

[0146] In some embodiments of the charged particle source 12, the charged particles may leave the charged particle outlet 15 with different trajectories and / or at different axial positions relative to a central longitudinal axis 14 defined through the charged particle source 12. As an example, which should not be considered limiting in any way, the last stage of the charged particle source 12 may be or include a multipole device configured to operate as a charged particle guide or mass-to-charge ratio filter. Such a multipole device may be illustratively implemented in the form of a conventional quadrupole device, but may alternatively be implemented in the form of a hexapolar, octopole or other multipole configuration. When configured to operate as a charged particle guide or mass-to-charge ratio filter, an AC voltage signal, such as an RF sine wave, is applied between paired poles or electrodes of the multipole device, and such a device in the form of a quadrupole with an applied RF voltage is typically referred to as an "RF-only quadrupole" charged particle guide. When configured to operate as a charged particle mass-to-charge ratio filter, a DC voltage is additionally applied between pairs of the multipole device, and the amplitude of the DC voltage defines the mass-to-charge ratio range of the charged particles that will leave the multipole device.

[0147] As a result of the time-varying nature of the AC voltage applied to the electrode pairs of the multipole device, the charged particles traverse the multipole device axially while also oscillating in the radial direction around the central longitudinal axis 14. In embodiments where the AC voltage applied is, for example, a sinusoidal RF voltage, when the charged particles travel axially along the multipole device and pass through the charged particle outlet 15, the charged particles move in a sinusoidal pattern in the radial direction around the central longitudinal axis 14. As a result of such RF confinement, the charged particles may leave the charged particle outlet 15 at a so-called "node" (defined at and by the central longitudinal axis 14), at a so-called "anti-node" (defined as the farthest radial distance from the central longitudinal axis 14), and at any point between the node and the anti-node. This phenomenon is referred to as "noding", and results in an angular deviation of at least some of the charged particles leaving the charged particle source 12 relative to the central longitudinal axis 14. As the charged particles travel toward the charged particle inlet 19 of the charged particle analysis stage 16, the charged particles exiting the charged particle outlet 15 at the antinode are dispersed at an angle away from the central axis 14. Fig.15A As illustrated by the dashed line 502 in FIG. 5 , the angular deviation of the charged particles at the charged particle outlet 15 of the charged particle source 12 is aggravated by the distance D between the charged particle outlet 15 of the charged particle source 12 and the charged particle inlet 19 of the charged particle analysis stage 16. As a result, some of the charged particles reaching the charged particle analysis stage 16 may be too widely dispersed to enter the charged particle inlet 19 of the charged particle analysis stage 16, as also shown by Fig.15AThus, while most or all of the charged particles focused about the central longitudinal axis 14 will travel a distance D and enter the charged particle inlet 19 of the charged particle analysis stage 16, some of the charged particles that exit the charged particle outlet 15 of the charged particle source 12 at or near the antinode will not do so.

[0148] A novel technique for eliminating or at least reducing the effects of node offsets as described above is to sweep the frequency of the RF voltage over a frequency range and then average the charged particle measurement data obtained over multiple sweeps by the charged particle analysis stage 16. Additional details related to this technique are disclosed in co-pending U.S. patent application serial number 63 / 405,004, filed on September 9, 2022, entitled “METHODOF CONTROLLING A MULTI-POLE DEVICE TO REDUCE OMISSION OF EXITING CHARGEDPARTICLES FROM DOWNSTREAM ANALYSIS,” the disclosure of which is incorporated herein by reference in its entirety.

[0149] Another method for eliminating or at least reducing the effects of the node offset described above is also achieved by Fig.15A , in which a radially segmented charged particle guide 20 is positioned between the charged particle source 12 and the charged particle analysis system 16. Illustratively, the radially segmented charged particle guide 20 is positioned sufficiently close to the charged particle outlet 15 of the charged particle source 12 so that most or all of the charged particles leaving the charged particle outlet 15 of the charged particle source 12 will pass through the radially segmented charged particle guide 20.

[0150] refer to Fig. 15B , the control circuit 24 is illustratively configured to eliminate or at least reduce the effects of the node offset described above by controlling the voltage source 22 by sequentially modifying the amplitudes of the voltages V1-V4 so as to force charged particles entering the radially segmented charged particle guide 20 around the periphery of the central longitudinal axis 14 to axially exit the radially segmented charged particle guide 20 along a path at least closer to the central longitudinal axis 14. This approach has the effect of focusing the charged particles entering the radially segmented charged particle guide 20 radially toward the central longitudinal axis 14 in the radial space defined between the central longitudinal axis 14 and the inner edges of the defined openings 30 of the radial segments 281-284, thereby ensuring that such charged particles exit the guide 20 along a path that is aligned with the charged particle inlet 19 of the charged particle analysis stage 16.

[0151] exist Fig. 15BIn the example illustrated in , a perimeter or radial path 510 radially spaced from and surrounding the central longitudinal axis 14 is selected, and a certain number of discrete positions 512 are defined around the radial path 510. In the illustrated example, eight such discrete positions 512 are defined as being equally spaced from one another around the radial path 510, although in alternative embodiments, more or fewer such discrete positions may be defined around the radial path 510. For each discrete position 512, the magnitude of the voltages V1-V4 is then determined, such as via simulation or other conventional techniques, which will force charged particles entering the radially segmented charged particle guide 20 at that position to exit the radially segmented charged particle guide 20 along the central longitudinal axis 14, thereby generating eight different sets of modified voltages V1-V4. In operation, the control circuit 24 is configured to control V1-V4 at equal amplitudes for some time periods so that charged particles focused about the axis 14 pass through the guide 20 and enter the charged particle analysis stage 16, and then sequentially control V1-V4 to each of eight different sets of modified voltages V1-V4 for the same time periods so that charged particles entering the guide 20 in the region of each corresponding discrete position 512 are forced to exit the guide 20 closer to the central axis 14 so as to be captured by the charged particle analysis stage 16. Thereafter, the charged particle measurement data for each of the nine sets of voltages V1-V4 are averaged to provide a composite set of charged particle measurement data that in many cases will contain charged particle measurement data that would otherwise be lost due to the effects of the node offset. In some severe cases of nodal offset, another number of discrete positions 516 may alternatively or additionally be defined around another radial path 514 that is spaced apart from the radial path 510 such that the radial path 514 is positioned between the radial path 510 and the inner periphery of the defined opening 30 of the radial segments 281-284. In such a case, alternative or additional modified sets of voltage amplitudes V1-V4 may be determined, each of which will force charged particles entering the radially segmented charged particle guide 20 at a corresponding position 516 to exit the radially segmented charged particle guide 20 along the central longitudinal axis 14, and the control circuit 24 may be operable as described above to collect and average the charged particle measurement data obtained for each set of voltages.

[0152] In what has just been described Fig.15A and Fig. 15BIn the example system 500 illustrated in , the path(s) along which the charged particles enter the radially segmented charged particle guide 20 need not be known or repeatable. In addition, the system 500 does not require a "sensor" to provide feedback about the point or position of the charged particles leaving the radially segmented charged particle guide 20, because the goal of the control of the guide 20 is to force the charged particles that enter the guide 20 off-axis toward the axis 14, but not necessarily to reach the axis 14 exactly. In any such embodiment of the radially segmented charged particle guide 20, the control circuit(s) 24 will illustratively be configured to control the operation of the voltage source 22, for example in the form of instructions stored in a memory 25 and executable by the control circuit(s) 24, to sequentially and, in some embodiments, repeatedly generate different sets of DC output voltages having amplitudes selected to direct charged particles entering the radially segmented charged particle guide 20 along various different paths to exit the radially segmented charged particle guide 20 in an axial direction along paths that are more focused toward a central longitudinal axis 14 defined through the radially segmented charged particle guide 20.

[0153] Although the present disclosure has been illustrated and described in detail in the foregoing drawings and descriptions, the drawings and descriptions should be considered illustrative rather than restrictive, and it should be understood that only illustrative embodiments thereof are shown and described, and it is desired to protect all changes and modifications that fall within the spirit of the present disclosure. For example, it will be understood that the ELIT 212 illustrated in the drawings and described herein is provided only as an example, and the concepts, structures, and techniques described above may be directly implemented in ELITs of various alternative designs. Any such alternative ELIT design may, for example, include any one or combination of two or more ELIT regions, more, fewer, and / or differently shaped ion mirror electrodes, more or fewer voltage sources, more or fewer voltage signals generated by one or more of the voltage sources, one or more ion mirrors that define additional electric field regions, and the like.

Claims

1. A charged particle guide, comprising: a plurality of conductive segments separated from one another and radially spaced apart about an opening defined axially through the plurality of conductive segments, the opening defining a central axis centrally disposed and axially passing through the opening, the plurality of conductive segments being configured to receive charged particles at one end of the opening and pass the received charged particles through an opposite end of the opening, at least one voltage source configured to generate and supply an individually controllable voltage to each of the plurality of conductive segments, and at least one control circuit configured to control the at least one voltage source to supply a selected voltage to each of the plurality of conductive segments to create an electric field within an opening defined through the plurality of conductive segments, the electric field configured to cause charged particles entering the one end of the opening along a first axial path relative to the central axis to exit the opposite end of the opening along a second axial path relative to the central axis that is different from the first axial path, Wherein, the first axial path and the second axial path are not collinear.

2. The charged particle guide according to claim 1, wherein: The first axial path is collinear with the central axis, And wherein the second axial path is radially offset from the central axis.

3. The charged particle guide according to claim 1, wherein: the second axial path is co-linear with the central axis, And wherein the first axial path is radially offset from the central axis in parallel.

4. The charged particle guide according to claim 1, wherein: the first axial path radially diverges from the central axis, And wherein the second axial path is radially offset from the first axial path and radially offset from the central axis.

5. The charged particle guide according to any one of claims 1 to 4, wherein: The opening is defined by and between the inner surface of each of the plurality of conductive segments.

6. The charged particle guide according to claim 5, wherein: The inner surface of at least one of the plurality of conductive segments is arcuate in shape.

7. The charged particle guide according to claim 6, wherein: The inner surface of each of the plurality of conductive segments is arcuate in shape such that a cross-section of the opening is circular.

8. The charged particle guide according to claim 5, wherein: The inner surface of each of the plurality of conductive segments is non-curvilinear.

9. A charged particle analysis system comprising: The charged particle guide according to any one of claims 1 to 8, and a charged particle analysis stage having a charged particle inlet axially spaced from the opposite ends of the opening, the charged particle inlet defining a central axis centrally disposed and axially extending through the charged particle inlet, wherein the charged particle guide is configured to guide the charged particles leaving the opening thereof into the charged particle inlet of the charged particle analysis stage, wherein the central axis of the charged particle inlet of the charged particle analysis stage is radially offset from the central axis of the opening of the charged particle guide, And wherein, the second axial path is colinear with the central axis of the charged particle inlet of the charged particle analysis stage, so that the electric field created by the at least one control circuit within the opening is configured to guide the charged particles leaving the opening of the charged particle guide toward the central axis of the charged particle inlet of the charged particle analysis stage.

10. The charged particle analysis system according to claim 9, further comprising a charged particle position detector, the charged particle position detector being configured to generate at least one detection signal corresponding to a radial position relative to the central axis of the charged particle inlet of the charged particle analysis stage or relative to the central axis of the opening of the charged particle guide, And among them, The at least one control circuit is configured to select a voltage to create the electric field within the opening of the charged particle guide based on the at least one detection signal.

11. A charged particle analysis system, comprising: The charged particle guide according to any one of claims 1 to 8, and a charged particle analysis stage having a charged particle inlet axially spaced from the opposite ends of the opening, the charged particle inlet defining a central axis centrally disposed and axially extending through the charged particle inlet, wherein the central axis of the charged particle inlet of the charged particle analysis stage is radially offset from the central axis of the opening of the charged particle guide, And wherein the electric field created by the at least one control circuit within the opening is configured to maximize the percentage of charged particles exiting the opening of the charged particle guide that enter the charged particle entrance of the charged particle analysis stage.

12. A charged particle analysis system comprising: first and second spaced-apart ion mirrors, and a charge detection cylinder positioned between the first ion mirror and the second ion mirror, the first ion mirror and the second ion mirror and the charge detection cylinder together defining an electrostatic linear ion trap (ELIT), the electrostatic linear ion trap being configured to capture therein charged particles supplied by a charged particle source such that the trapped charged particles oscillate back and forth between the first ion mirror and the second ion mirror each time they pass through the charge detection cylinder, the ELIT defining a central axis centrally and axially passing through each of the first ion mirror and the second ion mirror and the charge detection cylinder, wherein each of the first ion mirror and the second ion mirror comprises a plurality of axially spaced ion mirror electrodes, each of the plurality of axially spaced ion mirror electrodes defining an electrode opening through which the central axis of the ELIT passes, wherein at least one of the mirror electrodes comprises a charged particle guide according to any one of claims 1 to 8, and wherein the central axis of the opening of the charged particle guide is radially offset from the central axis of the ELIT.

13. The charged particle analysis system according to claim 12, wherein: The electric field created by the at least one control circuit within the opening is configured to direct charged particles exiting the opening of the charged particle guide toward and along the central axis of the ELIT.

14. The charged particle analysis system according to claim 12, wherein: Each time a charged particle passes through the charge detection cylinder, a charge is induced on the charge detection cylinder. And wherein the charged particle analysis system further comprises a charge sensitive preamplifier having an input end coupled to the charge detection cylinder and an output end coupled to the at least one control circuit, the charge sensitive preamplifier responding to each charge induced on the charge detection cylinder to generate a corresponding charge detection signal, and wherein the at least one control circuit is configured to determine, in response to the charge detection signal, a trapping efficiency of the ELIT as a ratio of trapping events in which the charged particle oscillates between the two ion mirrors within at least a predefined amount of a total trapping event time period to trapping events in which the charged particle does not oscillate between the two ion mirrors within at least the predefined amount of the total trapping event time period, And wherein the at least one control circuit is configured to select the voltage to create the electric field configured to guide charged particles exiting the opening of the charged particle guide in a manner that maximizes the capture efficiency.

15. A charged particle analysis system, comprising: a charged particle source having a charged particle outlet through which charged particles exit the charged particle source, the charged particle outlet defining a central axis centrally disposed and axially passing through the charged particle outlet, and The charged particle guide according to any one of claims 1 to 8, wherein the one end of the opening of the charged particle guide is axially spaced from the charged particle outlet of the charged particle source, wherein the central axis of the charged particle outlet of the charged particle source is radially offset from the central axis of the opening of the charged particle guide, And wherein, the electric field created by the at least one control circuit within the opening is configured to cause charged particles leaving the charged particle outlet of the charged particle source to leave the opening of the charged particle guide along an axial path that is co-linear with the central axis of the charged particle guide or radially deviated from the central axis of the charged particle guide.

16. A charged particle analysis system comprising: a charged particle source having a charged particle outlet through which charged particles exit the charged particle source, the charged particle outlet being defined by a central axis centrally disposed and axially passing through the charged particle outlet, A charged particle guide according to any one of claims 1 to 8, wherein the one end of the opening of the charged particle guide is axially spaced from the charged particle outlet of the charged particle source, and a charged particle analysis stage having a charged particle inlet axially spaced from the opposite end of the opening of the charged particle guide, the charged particle inlet being defined by a central axis centrally disposed and axially passing through the charged particle inlet, wherein the central axis of the opening of the charged particle guide is radially offset from at least one of the central axis of the charged particle outlet of the charged particle source and the central axis of the charged particle inlet of the charged particle analysis stage, And wherein the electric field created by the at least one control circuit within the opening is configured to direct charged particles exiting the charged particle outlet of the charged particle source into the charged particle inlet of the charged particle analysis stage.

17. The charged particle analysis system according to claim 16, further comprising a charged particle position detector configured to generate at least one detection signal corresponding to a radial position relative to the central axis of the opening of the charged particle guide or relative to the central axis of the charged particle inlet of the charged particle analysis stage, And among them, The at least one control circuit is configured to select the voltage to create the electric field based on the at least one detection signal, and the electric field is configured to guide charged particles leaving the opening of the charged particle guide along a predetermined path relative to the central axis of the opening of the charged particle guide or the central axis of the charged particle entrance of the charged particle analysis stage.

18. The charged particle analysis system according to claim 17, wherein: The charged particle position detector is positioned between the charged particle guide and the charged particle analysis stage and is mounted to one of the charged particle guide and the charged particle analysis stage.

19. The charged particle analysis system of claim 16, further comprising means for determining a percentage of charged particles exiting the charged particle outlet of the charged particle source that enter the charged particle inlet of the charged particle analysis stage, And among them, The at least one control circuit is configured to select the voltage to create the electric field, which is configured to guide the charged particles leaving the charged particle guide in a manner that maximizes the percentage of the charged particles leaving the charged particle outlet of the charged particle source that enter the charged particle inlet of the charged particle analysis stage.

20. The charged particle analysis system according to claim 16, wherein: The charged particle source comprises a multipole transmission device configured to receive charged particles at its charged particle inlet and transmit the received charged particles through its charged particle outlet, and an AC voltage source operatively coupled to the multipole transmission device and configured to apply an AC voltage to the multipole transmission device to guide the received charged particles through the charged particle outlet of the multipole transmission device, And wherein, the at least one control circuit is configured to: (i) control the at least one voltage source to sequentially supply each of a certain number of different groups of voltages to each of the plurality of conductive segments, the number of different groups of voltages being selected to create a corresponding electric field within the opening of the charged particle guide, the corresponding electric field being configured to guide the charged particles entering the opening from the charged particle outlet of the multipole transmission device toward the central axis of the opening around the periphery of the central axis of the opening of the charged particle guide so as to focus the charged particles leaving the opening of the charged particle guide around the central axis of the charged particle guide, (ii) control the at least one charged particle analysis stage to measure the mass-to-charge ratio of the charged particles leaving the charged particle guide for each of the number of different groups of voltages supplied by the at least one voltage source to produce a corresponding number of different groups of charged particle measurement results, and (iii) average the measured mass-to-charge ratios of the charged particles in the number of different groups of charged particle measurement results to produce a composite group of mass-to-charge ratios of the received charged particles.

21. A charged particle analysis system, comprising: a charged particle source having a charged particle outlet, a charged particle analysis stage having a charged particle inlet, a radially segmented charged particle guide positioned between the charged particle source and the charged particle analysis stage and comprising a plurality of conductive segments separated from one another and radially spaced apart around an opening defined through the plurality of radially arranged conductive segments, at least one voltage source configured to generate and supply an individually controllable voltage to each of the plurality of conductive segments, and A control circuit configured to control the at least one voltage source to supply a voltage to each of the plurality of conductive segments, the voltage being selected to create an electric field within the opening and configured to direct charged particles leaving the charged particle outlet of the charged particle source into the charged particle inlet of the charged particle analysis stage.

22. The charged particle analysis system according to claim 21, wherein: The charged particle analysis stage defines a first longitudinal axis extending centrally through the charged particle inlet, and wherein the opening of the radially segmented charged particle guide defines a second longitudinal axis extending centrally through the opening, and wherein the first longitudinal axis is radially offset from the second longitudinal axis, And wherein the created electric field is configured to guide charged particles exiting the charged particle outlet of the charged particle source along the first longitudinal axis into the charged particle inlet of the charged particle analysis stage.

23. The charged particle analysis system according to claim 22, wherein: the charged particle source defines a third longitudinal axis extending centrally through the charged particle outlet, And wherein the charged particles exit the charged particle source along the third longitudinal axis.

24. The charged particle analysis system according to claim 23, wherein: The second longitudinal axis is collinear with the third longitudinal axis.

25. The charged particle analysis system according to claim 23, wherein: The third longitudinal axis is radially offset from the second longitudinal axis and from the first longitudinal axis.

26. The charged particle analysis system according to claim 22, wherein: the charged particle source defines a third longitudinal axis extending centrally through the charged particle outlet, And wherein the charged particles exit the charged particle source along a path that deviates radially from the third longitudinal axis.

27. The charged particle analysis system according to claim 26, wherein: The second longitudinal axis is collinear with the third longitudinal axis.

28. The charged particle analysis system according to claim 26, wherein: The third longitudinal axis is radially offset from the second longitudinal axis and from the first longitudinal axis.

29. The charged particle analysis system according to claim 21, wherein: The charged particle analysis stage defines a first longitudinal axis extending centrally through the charged particle inlet, and wherein the opening of the radially segmented charged particle guide defines a second longitudinal axis extending centrally through the opening, and wherein the first longitudinal axis is collinear with the second longitudinal axis, And wherein the created electric field is configured to guide charged particles exiting the charged particle outlet of the charged particle source along the first longitudinal axis into the charged particle inlet of the charged particle analysis stage.

30. The charged particle analysis system according to claim 29, wherein: the charged particle source defines a third longitudinal axis extending centrally through the charged particle outlet, and wherein the charged particles exit the charged particle source along the third longitudinal axis, And wherein the third longitudinal axis is radially offset from the second longitudinal axis.

31. The charged particle analysis system according to claim 29, wherein: the charged particle source defines a third longitudinal axis extending centrally through the charged particle outlet, And wherein the charged particles exit the charged particle source along a path that deviates radially from the third longitudinal axis.

32. The charged particle analysis system according to claim 31, wherein: The third longitudinal axis is radially offset from the second longitudinal axis.

33. The charged particle analysis system according to claim 31, wherein: The third longitudinal axis is collinear with the second longitudinal axis.

34. The charged particle analysis system according to claim 21, wherein: The charged particle analysis stage defines a first longitudinal axis extending centrally through the charged particle inlet, and wherein the opening of the radially segmented charged particle guide defines a second longitudinal axis extending centrally through the opening, and wherein the first longitudinal axis is collinear with the second longitudinal axis, And wherein the created electric field is configured to direct charged particles exiting the charged particle outlet of the charged particle source along a path radially deviating from the first longitudinal axis into the charged particle inlet of the charged particle analysis stage.

35. The charged particle analysis system according to claim 34, wherein: the charged particle source defines a third longitudinal axis extending centrally through the charged particle outlet, And wherein the charged particles exit the charged particle source along the third longitudinal axis.

36. The charged particle analysis system according to claim 35, wherein: The second longitudinal axis is collinear with the third longitudinal axis.

37. The charged particle analysis system according to claim 35, wherein: The third longitudinal axis is radially offset from the second longitudinal axis and from the first longitudinal axis.

38. The charged particle analysis system according to claim 34, wherein: the charged particle source defines a third longitudinal axis extending centrally through the charged particle outlet, And wherein the charged particles exit the charged particle source along a path that deviates radially from the third longitudinal axis.

39. The charged particle analysis system according to claim 38, wherein: The second longitudinal axis is collinear with the third longitudinal axis.

40. The charged particle analysis system according to claim 38, wherein: The third longitudinal axis is radially offset from the second longitudinal axis and from the first longitudinal axis.

41. The charged particle analysis system according to claim 21, wherein: The charged particle analysis stage defines a first longitudinal axis extending centrally through the charged particle inlet, and wherein the opening of the radially segmented charged particle guide defines a second longitudinal axis extending centrally through the opening, and wherein the second longitudinal axis is radially offset from the first longitudinal axis, And wherein the created electric field is configured to direct charged particles exiting the charged particle outlet of the charged particle source along a path radially deviating from the first longitudinal axis into the charged particle inlet of the charged particle analysis stage.

42. The charged particle analysis system according to claim 41, wherein: the charged particle source defines a third longitudinal axis extending centrally through the charged particle outlet, and wherein the charged particles exit the charged particle source along the third longitudinal axis, And wherein the third longitudinal axis is radially offset from the second longitudinal axis.

43. The charged particle analysis system according to claim 41, wherein: the charged particle source defines a third longitudinal axis extending centrally through the charged particle outlet, And wherein the charged particles exit the charged particle source along a path that deviates radially from the third longitudinal axis.

44. The charged particle analysis system according to claim 43, wherein: The third longitudinal axis is radially offset from the second longitudinal axis.

45. The charged particle analysis system according to claim 43, wherein: The third longitudinal axis is collinear with the second longitudinal axis.

46. ​​The charged particle analysis system according to any one of claims 21 to 43, further comprising a charged particle position detector configured to generate at least one detection signal corresponding to a radial position relative to a first longitudinal axis extending centrally through the charged particle analysis stage or relative to a second longitudinal axis extending centrally through the radially segmented charged particle guide, And among them, The control circuit is configured to select the voltage based on the at least one detection signal to create the electric field, which is configured to guide charged particles leaving the radially segmented charged particle guide along a predetermined path relative to at least one of the first longitudinal axis or the second longitudinal axis.

47. The charged particle analysis system according to claim 46, wherein: The charged particle position detector is positioned between the radially segmented charged particle guide and the charged particle analysis stage but is not mounted to either of the radially segmented charged particle guide and the charged particle analysis stage.

48. The charged particle analysis system according to claim 46, wherein: The charged particle position detector is positioned between the radially segmented charged particle guide and the charged particle analysis stage and is mounted to the radially segmented charged particle guide.

49. The charged particle analysis system according to claim 46, wherein: The charged particle position detector is positioned between the radially segmented charged particle guide and the charged particle analysis stage and is mounted to the charged particle analysis stage.

50. A charged particle analysis system according to any one of claims 21 to 46, further comprising means for determining a percentage of charged particles leaving the charged particle outlet of the charged particle source that enter the charged particle inlet of the charged particle analysis stage, And among them, The control circuit is configured to select the voltage to create the electric field, which is configured to guide the charged particles leaving the radially segmented charged particle guide in a manner to maximize the percentage of the charged particles leaving the charged particle outlet of the charged particle source that enter the charged particle inlet of the charged particle analysis stage.

51. A charged particle analysis system comprising: a charged particle source configured to generate charged particles, An electrostatic linear ion trap (ELIT) configured to receive and capture therein charged particles generated by the charged particle source, the ELIT comprising two spaced-apart ion mirrors and a charge detection cylinder positioned between the two ion mirrors, the two ion mirrors and the charge detection cylinder together defining a first axis passing centrally therethrough, each of the two ion mirrors comprising a plurality of axially spaced-apart ion mirror electrodes, the plurality of axially spaced-apart ion mirror electrodes each defining an electrode opening therethrough, at least one of the ion mirror electrodes of at least one of the two ion mirrors comprising a plurality of conductive segments, the plurality of conductive segments being separated from each other and radially spaced apart around corresponding electrode openings defined by the plurality of radially arranged conductive segments, the corresponding electrode openings being defined by the at least one radially segmented ion mirror electrode, the at least one radially segmented ion mirror electrode defining a second axis passing centrally therethrough and radially offset from the first axis, at least one voltage source configured to generate and supply an individually controllable voltage to each of the plurality of ion mirror electrodes of each of the two ion mirrors and to each of the plurality of conductive segments of the at least one of the ion mirror electrodes, and A control circuit configured to: control the at least one voltage source to supply a selected voltage to the electrode of each of the two ion mirrors to create a first electric field within each of the two ion mirrors to cause charged particles trapped in the ELIT to travel along the first axis, and supply a selected voltage to each of the multiple conductive segments to create a second electric field within the corresponding electrode opening of the at least one radially segmented ion mirror electrode, the second electric field being configured to cause charged particles to pass through the corresponding electrode opening along the first axis deviating from the second axis, the second axis being defined at a center passing through the opening of the at least one radially segmented ion mirror electrode.

52. The charged particle analysis system according to claim 51, wherein: the first electric field and the second electric field being configured to cause a charged particle trapped in the ELIT to oscillate back and forth between the two ion mirrors each time it passes through the charge detection cylinder during a trapping event to induce a corresponding charge on the charge detection cylinder, and wherein the charged particle analysis system further comprises a charge sensitive preamplifier having an input coupled to the charge detection cylinder and an output coupled to the control circuit, the charge sensitive preamplifier being responsive to each corresponding charge induced on the charge detection cylinder to produce a corresponding charge detection signal, and wherein the control circuit is configured to respond to the charge detection signal to determine a capture efficiency of the ELIT as a ratio of capture events in which the charged particle oscillates between the two ion mirrors within at least a predefined amount of a total capture event time period to capture events in which the charged particle does not oscillate between the two ion mirrors within at least the predefined amount of the total capture event time period, And wherein the control circuit is configured to select the voltage to create the electric field configured to guide charged particles exiting the radially segmented charged particle guide in a manner that maximizes the capture efficiency.

53. A charged particle analysis system comprising: a charged particle source configured to generate charged particles from a sample, the charged particle source comprising a multipole charged particle transmission device having a charged particle inlet for receiving the generated charged particles and configured to transmit the generated charged particles through a charged particle outlet of the multipole charged particle transmission device, an AC voltage source operatively connected to the multipole charged particle transmission device and configured to apply an AC voltage to the multipole charged particle transmission device to guide the generated charged particles through the charged particle outlet, at least one charged particle analysis stage having a charged particle inlet, a radially segmented charged particle guide positioned between the charged particle source and the at least one charged particle analysis stage and comprising a plurality of conductive segments separated from one another and radially spaced apart about an opening defined through the plurality of radially arranged conductive segments, the opening being defined by a first longitudinal axis centrally passing through the opening, at least one voltage source configured to generate and supply an individually controllable voltage to each of the plurality of conductive segments, and A control circuit configured to: (i) control the at least one voltage source to sequentially supply each of a certain number of different groups of voltages to each of the plurality of conductive segments, the number of different groups of voltages being selected to create a corresponding electric field within the opening, the corresponding electric field being configured to guide charged particles entering the opening from the charged particle outlet of the multipolar charged particle transmission device toward the first longitudinal axis around the periphery of the first longitudinal axis so as to focus the charged particles leaving the opening of the radially segmented charged particle guide around the first longitudinal axis, (ii) control the at least one charged particle analyzer to measure the mass-to-charge ratio of the charged particles leaving the radially segmented charged particle guide for each of the number of different groups of voltages supplied by the at least one voltage source to produce a corresponding number of different groups of charged particle measurement results, and (iii) average the measured mass-to-charge ratios of the charged particles in the number of different groups of charged particle measurement results to produce a mass-to-charge ratio of a composite group of generated charged particles.

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