CHARGE FILTER ARRANGEMENT AND APPLICATIONS THEREOF

A charge filter instrument includes a field-free drift region, a plurality of charge detection cylinders in the drift region through which ions drifting axially therethrough pass, a plurality of charge sensitive amplifiers each coupled to at least one charge detection cylinder and configured to produce a charge detection signal corresponding to a charge of one or more of ions passing therethrough, a single inlet, single outlet charge deflector or a single inlet, multiple outlet charge steering device coupled to the outlet end of the drift region, means for determining charge magnitudes or charge states of ions drifting axially through the drift region based on the charge detection signals, and means for controlling the charge deflector or the charge steering device to pass through the single outlet or through a specified one of the multiple outlets only ions having a specified charge magnitude or charge state.

TECHNICAL FIELD

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

BACKGROUND

Spectrometry instruments provide for the identification of chemical components of a substance by measuring one or more molecular characteristics of the substance. Some such instruments are configured to analyze the substance in solution and others are configured to analyze charged particles of the substance in a gas phase. Molecular information produced by many such charged particle measuring instruments is limited because such instruments lack the ability to measure particle charge or to process particles based on their charge.

SUMMARY

The present disclosure may comprise one or more of the features recited in the attached claims, and/or one or more of the following features and combinations thereof. In one aspect, a charge filter instrument may comprise an electric field-free drift region having an inlet end and an outlet end opposite the inlet end, the inlet end configured to be coupled to an ion source to receive ions to drift axially through the drift region from the inlet end toward the outlet end, a plurality of spaced-apart charge detection cylinders disposed in the drift region and through which ions drifting axially through the drift region pass, a plurality of charge sensitive amplifiers each coupled to a at least one of the plurality of charge detection cylinders and each configured to produce a charge detection signal corresponding to a magnitude of charge of one or more of ions passing through a respective at least one of the plurality of charge detection cylinders, one of a charge deflector, having a single inlet and a single outlet, and a charge steering device, having a single inlet and multiple outlets, coupled to the outlet end of the drift region, means for determining charge magnitudes or charge states of ions drifting axially through the drift region based on the charge detection signals produced by at least some of the plurality of charge sensitive amplifiers, and means for controlling the one of the charge deflector and the charge steering device to pass through a corresponding one of the single outlet and a specified one of the multiple outlets only ions having a specified charge magnitude or charge state.

In another aspect, an ion filter instrument may comprise an electric field-free drift region having an inlet end and an outlet end opposite the inlet end, the inlet end configured to be coupled to an ion source to receive ions to drift axially through the drift region from the inlet end toward the outlet end, a plurality of spaced-apart charge detection cylinders disposed in the drift region and through which ions drifting axially through the drift region pass, a plurality of charge sensitive amplifiers each coupled to at least one of the plurality of charge detection cylinders and each configured to produce a charge detection signal corresponding to a magnitude of charge of one or more of ions passing through a respective at least one of the plurality of charge detection cylinders, one of a charge deflector, having a single inlet and a single outlet, and a charge steering device, having a single inlet and multiple outlets, coupled to the outlet end of the drift region, at least one voltage source having at least one voltage output operatively coupled to the one of the charge deflector and the charge steering device, at least one processor, and at least one memory having instructions stored therein executable by the at least one processor to cause the at least one processor to (a) monitor the charge detection signals produced by at least some of the plurality of charge sensitive amplifiers as ions drift axially through the field-free drift region toward the outlet end thereof, (b) determine charge magnitudes or charge states of ions drifting axially through the field-free drift region based on the monitored charge detection signals, and (c) control the at least one voltage output of the at least one voltage source to cause the one of the charge deflector and the charge steering device to pass through a corresponding one of the single outlet and a specified one of the multiple outlets only ions having a specified charge magnitude or charge state.

DESCRIPTION OF THE ILLUSTRATIVE EMBODIMENTS

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

This disclosure relates to apparatuses and techniques for determining charges or charge states of charged particles moving through a drift region, and for filtering the charged particles as a function of charge value or charge state by selectively passing those of the charged particles having a specified charge value or charge state, or by selectively steering charged particles having different specified charge values or charge states along different respective travel paths. For purposes of this document, the terms “charged particle” and “ion” may be used interchangeably, and both terms are intended to refer to any particle having a net positive or negative charge.

Referring now toFIG.1, a diagram is shown of a charge filter instrument10configured to filter ions as a function of ion charge by selectively passing ions having a specified charge or by selectively steering ions having different specified charges along different respective ion travel paths. In the illustrated embodiment, the charge filter instrument10includes a drift region12having an ion inlet A1at one end thereof and an ion outlet A2at an opposite end thereof. In the embodiment depicted inFIG.1, the drift region12is a linear drift region defined within an elongated drift tube12A. The drift region12has a length DRL between the inlet A1and the outlet A2, and a longitudinal axis20extends centrally through the drift region12and centrally through each of the inlet and outlet Al, A2respectively. It will be understood that whereas the drift region12is illustrated inFIG.1in the form of a linear drift region, the drift region12may, in alternate embodiments, be non-linear in whole or in part. As one non-limiting example, the drift region12may be provided in the form of a circular drift region including conventional ion inlet (i.e., entrance) and ion outlet (i.e., exit) structures. Other examples of at least partially non-linear drift regions will occur to those skilled in the art, and it will be understood that any such alternate configurations are intended to fall within the scope of this disclosure.

A charge deflection or steering region14is coupled to or otherwise positioned at the outlet end of the drift region12. In the illustrated embodiment, the charge deflection or steering region14has an ion inlet A3defined by or positioned adjacent to the ion outlet A2of the drift region12, and an ion outlet A4. In some embodiments, the charge deflection or steering region14may be implemented in the form of a charge deflector controllable to selectively pass or prevent passage ions therethrough, some non-limiting example embodiments of which are illustrated inFIGS.8-9Band will be described in detail below. In other embodiments, the charge deflection or steering region14may be implemented in the form of one or more single inlet, multiple outlet charge steering instruments or structures each controllable to selectively steer ions entering the single inlet through one or more of the multiple outlets, some non-limiting example embodiments of which are illustrated inFIGS.10A-11and will be described in detail below.

A voltage source VS1is electrically connected to the charge deflection or steering region14via a number, K, of signal paths, where K may be any positive integer. In some embodiments, the voltage source VS1may be implemented in the form of a single voltage source, and in other embodiments the voltage source VS1may include any number of separate voltage sources. In some embodiments, the voltage source VS1may be configured or controlled to produce and supply one or more time-invariant (i.e., DC) voltages of selectable magnitude. Alternatively or additionally, the voltage source VS1may be configured or controlled to produce and supply one or more switchable time-invariant voltages, i.e., one or more switchable DC voltages. Alternatively or additionally, the voltage source VS1may be configured or controllable to produce and supply one or more time-varying signals of selectable shape, duty cycle, peak magnitude and/or frequency. As one specific example of the latter embodiment, which should not be considered to be limiting in any way, the voltage source VS1may be configured or controllable to produce and supply one or more time-varying voltages in the form of one or more sinusoidal (or other shaped) voltages.

The voltage source VS1is illustratively shown electrically connected by a number, J, of signal paths to a conventional processor24, where J may be any positive integer. The processor24is illustratively conventional and may include a single processing circuit or multiple processing circuits. The processor24illustratively includes or is coupled to a memory26having instructions stored therein which, when executed by the processor24, cause the processor24to control the voltage source VS1to produce one or more output voltages for selectively controlling operation of the charge deflection or steering region14. In some embodiments, the processor24may be implemented in the form of one or more conventional microprocessors or controllers, and in such embodiments the memory26may be implemented in the form of one or more conventional memory units having stored therein the instructions in a form of one or more microprocessor-executable instructions or instruction sets. In other embodiments, the processor24may be alternatively or additionally implemented in the form of a field programmable gate array (FPGA) or similar circuitry, and in such embodiments the memory26may be implemented in the form of programmable logic blocks contained in and/or outside of the FPGA within which the instructions may be programmed and stored. In still other embodiments, the processor24and/or memory26may be implemented in the form of one or more application specific integrated circuits (ASICs). Those skilled in the art will recognize other forms in which the processor24and/or the memory26may be implemented, and it will be understood that any such other forms of implementation are contemplated by, and are intended to fall within, this disclosure. In some alternative embodiments, the voltage source VS1may itself be programmable to selectively produce one or more constant and/or time-varying output voltages.

A charge detector array16is illustratively disposed within, or integral with, the drift region12. In the embodiment illustrated inFIG.1, the charge detector array16illustratively includes a plurality, N, of spaced-apart, cascaded charge detection cylinders161-16N, where N may be any positive integer greater than 2. In one example embodiment, which should not be considered limiting in any way, N may be approximately100, although in other embodiments N may be less than100or greater than100. In any case, the charge detection cylinders161-16Neach define a bore therethrough so as to allow ions to pass through the respective cylinder, and in the illustrated embodiment the charge detection cylinders161-16Nare arranged end-to-end so that the central, longitudinal axis20of the drift region12passes centrally through each. In the illustrated embodiment, each charge detection cylinder161-16Ndefines a length CDL between ion inlet and ion outlet ends thereof, although in alternate embodiments one or more of the charge detection cylinders161-16Nmay have a length that is greater or less than the length CDL. The minimum CDL is illustratively that which is physically realizable and which will produce an electrically detectable signal response to one or more ions passing therethrough. Although no upper limit on CDL exists in theory, practical considerations, such as available space and instrument operating conditions, will typically limit the maximum useful CDL in any particular application.

In the illustrated embodiment, each of a plurality of ground rings182-18N-1is positioned within the space defined between each adjacent pair of charge detection cylinders161-16N, another ground ring181is positioned adjacent to the ion inlet of the first charge detection cylinder161and yet another ground ring18Nis positioned adjacent to the ion outlet of the last charge detection cylinder16N. Each ground ring181-18Nillustratively defines a ring aperture RA therethrough and through which the longitudinal axis20centrally passes, where RA is illustratively less than or equal to the inner diameters of the charge detection cylinders161-16N. In the illustrated embodiment, the charge detection cylinders161-16Nare axially spaced apart from one another by a space length SL. In the illustrated embodiment, each of the ground rings181-18Nis positioned such that the distances between the ion inlets of the charge detection cylinders161-16Nand respective ones of the ground rings181-18N-1are substantially equal to one another, the distances between the ion outlets of the charge detection cylinders161-16Nand respective ones of the ground rings182-18Nare substantially equal to one another, and the distances between the ion inlets of the charge detection cylinders161-16Nand respective ones of the ground rings181-18N-1are substantially equal to the distances between the ion outlets of the charge detection cylinders161-16Nand respective ones of the ground rings182-18N. In some embodiments, one or more of the ground rings181-18Nmay be omitted.

In one example embodiment, the drift tube12A is provided in the form of an electrically conductive cylinder which is illustratively coupled to ground potential (as depicted inFIG.1) or to another reference potential, and within which the plurality of charge detection cylinders161-16Nare suitably mounted. In such embodiments which include one or more ground rings181-18N, such one or more ground rings may be electrically and mechanically coupled to an inner surface of the electrically conductive cylinder, or may be formed integral with the electrically conductive cylinder such that the electrically conductive cylinder and the one or more ground rings181-18Nare of unitary construction. In another example embodiment, the drift tube12A may be formed of an interconnected series of alternating electrically conductive or electrically insulating spacers and respective ones of the plurality of ground rings181-18N, within which the plurality of charge detection cylinders161-16Nmay be suitably mounted. In still another example embodiment, the drift tube12A may be provided in the form of a sheet of flexible or semi-flexible, electrically insulating material, e.g., a flexible circuit board, to which a plurality of spaced-apart, parallel, electrically conductive strips are attached or upon which a plurality of spaced-apart, parallel, electrically conductive strips are formed in a conventional manner, e.g., using conventional metallic pattern deposition techniques. In this embodiment, the electrically conductive strips are illustratively oriented so when opposite ends of the flexible or semi-flexible sheet are brought together to form an elongated cylinder the plurality of spaced-apart, parallel, electrically conductive strips form the plurality of charge detection cylinders and the one or more ground rings181-18N. Those skilled in the art will recognize other forms in which the drift tube12A and/or the charge detection cylinders161-16Nand/or the one or more ground rings181-18N(in embodiments which include them) may be provided, and it will be understood the any such other forms are intended to fall within the scope of this disclosure.

In the illustrated embodiment, each charge detection cylinder161-16Nis electrically connected to a signal input of a corresponding one of N charge sensitive amplifiers CA1-CAN, and the signal outputs of each charge sensitive amplifier CA1-CAN is electrically connected to the processor24. In alternate embodiments, any, some or all of the charge sensitive amplifiers may be electrically connected to more than one charge detection cylinder, and in such embodiments the number of charge sensitive amplifiers will accordingly be less than the number of charge detection cylinders. As charged particles entering the ion inlet A1move axially through the drift region12toward and through the ion outlet A2, each such charged particle passes sequentially through the plurality of charge detection cylinders161-16N. As each such charged particle passes through a charge detection cylinder161-16N, a charge induced thereby on the charge detection cylinder161-16Nhas a magnitude that is proportional to the magnitude of the charge of that particle. The charge sensitive amplifiers CA1-CAN are each illustratively conventional and responsive to charges induced by charged particles on a respective one of the charge detectors161-16Nto produce corresponding charge detection signals at the output thereof, and to supply the charge detection signals to the processor24. The magnitudes of the charge detection signals produced by the charge sensitive amplifiers CA1-CAN are, at any point in time, proportional to: (i) in the case of a single charged particle passing through a respective one of the charge detection cylinders161-16N, the magnitude of the charge of that single charged particle, or (ii) in the case of multiple charged particles simultaneously passing through a respective one of the charge detection cylinders161-16N, the combined magnitudes of the charges of those multiple charged particles. The processor24is, in turn, illustratively operable to receive and digitize the charge detection signals produced by each of the charge sensitive amplifiers CA1-CAN, and to store the digitized charge detection signals in the memory26or in one or more other memory units coupled to or otherwise accessible by the processor24.

The processor24is further illustratively coupled via a number, P, of signal paths to one or more peripheral devices28(PD), where P may be any positive integer. The one or more peripheral devices28may include one or more devices for providing signal input(s) to the processor24and/or one or more devices to which the processor24provides signal output(s). In some embodiments, the peripheral devices28include at least one of a conventional display monitor, a printer and/or other output device, and in such embodiments the memory26has instructions stored therein which, when executed by the processor24, cause the processor24to control one or more such output peripheral devices28to display and/or record analyses of the stored, digitized charge detection signals.

The ion inlet end of the drift tube12A, i.e., the end at which the ion inlet A1is located, is illustratively configured to be coupled to an ion outlet end of an ion source30, i.e., an end of the ion source30at which an ion outlet A5is located, as illustrated by example inFIG.1. In embodiments in which the ion source30is coupled to the charge filter instrument10, a second voltage source VS2is illustratively connected to the ion source30via a number, H, of signal paths, where H may be any positive integer, and is further connected to the processor24via a number, G, of signal paths, where G may be any positive integer. VS2may illustratively take any of the forms described above with respect to VS1, such that VS2may be configured or controlled to produce any number of time invariant, e.g., constant, and/or time-varying output voltages to selectively control one or more aspects of the ion source30.

As will be described in greater detail below with respect toFIG.15, the ion source30illustratively includes any conventional device or apparatus for generating ions from a sample and may further include one or more devices and/or instruments for separating, collecting and/or filtering ions according to one or more molecular characteristics and/or for dissociating, e.g., fragmenting, ions. As one illustrative example, which should not be considered to be limiting in any way, the ion source30may include a conventional electrospray ionization source, a matrix-assisted laser desorption ionization (MALDI) source or other conventional ion generator configured to generate ions from a sample. The sample from which the ions are generated may be any biological or other material.

The drift region12of the charge filter instrument10is a field-free drift region (i.e., no electric field) such that ions entering the inlet A1of the drift tube12A from the ion source30with initial velocities drift toward and through the ion outlet A2with substantially constant velocities. In this regard, the ion source30will typically provide a motive force for passing ions into the drift tube12A with initial velocities. The motive force may illustratively be provided in any one or combination of several different forms, examples of which may include, but are not limited to, one or more ion-accelerating electric fields, one or more magnetic fields, a pressure differential between the external environment and the ion source30and/or a pressure differential between the ion source30and the drift tube12A, or the like. In any case, as the charged particles drift through the field-free drift region12, they will separate in time according to mass-to-charge ratio with the charged particles having lower mass-to-charge ratios reaching the ion outlet A2more quickly than the charged particles having higher mass-to-charge ratios.

As will be described in detail below with respect to the examples illustrated inFIGS.4A-7, the memory26illustratively has instructions stored therein which are executable by the processor24to cause the processor24to process the charge detection signals produced by at least some of the charge sensitive amplifiers CA1-CAN to determine the charge magnitudes and/or charge states of the charged particles as they separate along the length of the drift region12, so that the charge magnitude and/or charge state of each charged particle is known prior to passing through the ion outlet A2of the drift tube12A. In some embodiments, the memory26further illustratively has instructions stored therein which are executable by the processor24to cause the processor24to control the voltage source VS1to cause the charge deflection or steering region14to selectively pass only charged particles having a selected charge magnitude or only charged particles having charge magnitudes within a selected range of charge magnitudes, or to pass only charged particles having a selected charge state. In other embodiments, the memory26further illustratively has instructions stored therein which are executable by the processor24to cause the processor24to control the voltage source VS1to cause the charge deflection or steering region14to selectively steer charged particles having different charge magnitudes, or having charges within different ranges of charge magnitudes, along different ion travel paths, or to selectively steer charged particles having different charge states along different ion travel paths. In some embodiments, it may be desirable to determine the velocities of the charged particles traveling through the drift region12so that the future positions of the charged particles within the charge deflection or steering region14can be accurately estimated when controlling the voltage source VS1to selectively pass or steer charged particles through charge deflection or steering region14.

The ion outlet end of the ion deflection or steering region14, i.e., the end at which the ion outlet A4is located, is illustratively configured to be coupled to an ion inlet end of an ion storage, steering and/or measurement stage(s)32, i.e., an end of the ion inlet end of an ion storage, steering and/or measurement stage(s)32at which an ion inlet A6is located, as illustrated by example inFIG.1. In embodiments in which the ion storage, steering and/or measurement stage(s)32is coupled to the charge filter instrument10, a third voltage source VS3is illustratively connected to the ion storage, steering and/or measurement stage(s)32via a number, M, of signal paths, where M may be any positive integer, and is further connected to the processor24via a number, L, of signal paths, where L may be any positive integer. VS3may illustratively take any of the forms described above with respect to VS1, such that VS3may be configured or controlled to produce any number of time invariant, e.g., constant, and/or time-varying output voltages to selectively control one or more aspects of the ion storage, steering and/or measurement stage(s)32.

As will be described in greater detail below with respect to the application examples illustrated inFIGS.12-14and16, the ion storage, steering and/or measurement stage(s)32may include any conventional device or apparatus for storing ions, for measuring ions, for processing ions following or prior to measurement thereof, and/or for steering ions between one or more devices. The one or more ion measurement instruments, devices, apparatuses or stages are illustratively connected to the processor24via a number, Q, of signal paths, where Q may be any positive integer.

As briefly described above, the memory26illustratively includes instructions executable by the processor24to cause the processor24to determine the charge magnitudes and/or charge states of each of the charged particles moving through the drift region12, and to then control the voltage source VS1to selectively pass or steer the charged particles through the charge deflection or steering region14based on their charge magnitudes or charge states. In some embodiments, such as when the ion source30is configured to generate and supply a plurality of ions simultaneously to the ion inlet A1of the drift tube12A, for example, it may be desirable to configure the drift tube12A to include a pre-array space12B of length PRL between the ion inlet A1of the drift tube12A and the first ground ring181(or the ion inlet end of the first charge detection cylinder161in embodiments in which the first ground ring181is omitted), as illustrated by example inFIG.1. This will allow the charged particles moving axially through the drift region12to undergo some amount of axial separation in time (as a function of mass-to-charge ratio in the field-free region12) prior to conducting charge measurements with the charge detector array16, and may thereby increase the quality and usefulness of the charge detection signals produced by the first one or more of the charge sensitive amplifiers CA1-CAN. The length PRL of the pre-array space12B may illustratively be chosen based on the application, and in some embodiments the pre-array space12B may be omitted in its entirety. Alternatively or additionally, it may be desirable in some embodiments to configure the drift tube12A to include a post-array space12C of length POL between the last ground ring18N(or the ion outlet end of the last charge detection cylinder16Nin embodiments in which the last ground ring18Nis omitted), as further illustrated by example inFIG.1. In some such embodiments, some or all of the length POL of the post-array space12C may be provided in the front end, i.e., adjacent to the ion inlet A3, of the charge deflection or steering array14. In any case, the post-array space12C, in embodiments which include it, will provide some amount of time between charge particles passing through the final charge detection cylinder16Nand thereafter exiting the ion outlet A2of the drift tube12A, and may thereby relax the decision and control timing and/or switching speed requirements of the charge deflection or steering region14. The length POL of the post-array space12C may illustratively be chosen based on the application, and in some embodiments the post-array space12C may be omitted in its entirety.

Referring now toFIGS.2A-2D, a simplified example of the charge filter instrument10ofFIG.1is shown which includes three charge detection cylinders161-163axially arranged between the ion inlet A1of the drift tube12A and the charge deflection or steering region14. With this simplified instrument10,FIGS.2A-2Ddepict a single charge particle P drifting successively through each of the three charge detection cylinders161-163as a function of time, andFIG.3depicts example charge detection signals produced by the three respective charge sensitive amplifiers CA1-CA3as the charged particle passes therethrough. As illustrated inFIGS.2A and3, the charged particle P enters the first charge detection cylinder161at a time T1and exits the charge detection cylinder161at a subsequent time T2, and while within the charge detection cylinder161the charged particle induces a charge on the charge detection cylinder161of magnitude C1. In some embodiments, the time T1may be a time relative to an ion generation or acceleration event which is controlled at the ion source30at a prior time T0. In alternate embodiments, the output signal produced by CA1may be monitored after an ion generation or acceleration event, and T1may simply be the time at which the first (and only in this example) particle P is detected, e.g., via the rising edge of the charge detection signal output produced by CA1, as entering the first charge detection cylinder161following the ion generation or acceleration event. In any case, at a time T3>T2, the charged particle P having exited the first charge detection cylinder161now enters the second charge detection cylinder162, and the charged particle P thereafter exits the charge detection cylinder162at a subsequent time T4, as depicted inFIG.2B. While within the charge detection cylinder162the charged particle induces a charge on the charge detection cylinder162of magnitude C2as depicted inFIG.3. At a time T5>T4, the charged particle P having exited the second charge detection cylinder162now enters the third and final charge detection cylinder163, and the charged particle P thereafter exits the charge detection cylinder163at a subsequent time T6, as depicted inFIG.2C. While within the charge detection cylinder163the charged particle induces a charge on the charge detection cylinder163of magnitude C1as depicted inFIG.3.

As the charged particle P moves successively through the charge detection cylinders161-163, as illustrated by example inFIGS.2A-2C, the processor24is illustratively operable, pursuant to execution of corresponding instructions stored in the memory26, to determine the magnitude and/or the charge state of the charged particle P based on the charge detection signals produced by the charge sensitive amplifiers CA1-CA3. In one embodiment, the processor24is operable to make such a determination based on the charge detection signal produced by the first charge sensitive amplifier CA1, and to then successively update the charge determination based on the charge detection signals produced by the remaining charge sensitive amplifiers CA2and CA3after the charged particle passes through the respective charge detection cylinders161and162. In some embodiments, the processor24is further operable, pursuant to execution of corresponding instructions stored in the memory26, to likewise determine the velocity of the charge particle P based on the charge detection signal produced by the first charge sensitive amplifier CA1, and to then update the velocity determination based on the charge detection signals produced by the remaining charge sensitive amplifiers CA2and CA3after the charged particle passes through the respective charge detection cylinders161and162.

Using this example model, the processor24is illustratively operable to determine an initial magnitude of the charge CH of the particle P after the particle P exits the first charge detection cylinder161, e.g., as indicated by the falling edge of CA1, as the magnitude CH=C1produced by the charge sensitive amplifier CA1between the rising edge of CA1at time T1and the falling edge of CA1at time T2. In some embodiments, the processor24is further operable to determine an initial velocity of the charged particle as VelP=CDL/(T2−T1). After detection of the falling edge of CA2at time T4, the processor24is operable to determine an updated magnitude of the charge of the particle P based on the magnitude C2produced by the charge sensitive amplifier CA2between the rising edge of CA2at time T3and the falling edge of CA2at time T4as CH=(CH+C2). In some embodiments, the processor24is further operable to determine an updated velocity of the charged particle as VelP=VelP+CDL/(T4−T3). After detection of the falling edge of CA3at time T6, the processor24is operable to determine a final updated magnitude of the charge of the particle P based on the magnitude C1produced by the charge sensitive amplifier CA3between the rising edge of CA3at time T5and the falling edge of CA3at time T6as CH=CH+C3. In some embodiments, the processor24is further operable to determine an updated velocity of the charged particle as VelP=VelP+(CDL/(T6−T5)). After the ion has traveled through all of the charge detectors, the average charge is calculated from CH=CH/N, where N is the number of measurements (in this case3) and the average velocity is calculated from VelP=VelP/N.

At the point in time just after T6, the processor24has determined the charge magnitude CH, and in some embodiments the velocity Velp, of the particle P based on the averages of the charge detection signals produced by the charge sensitive amplifiers CA1-CA3. In some embodiments, the processor24may be operable to convert the charge magnitude to a charge state, e.g., by dividing CH by the elementary charge constant e (e.g., 1.602716634×10−19Coulombs), or may be operable to compute the initial and updated charge values as charge state values rather than charge magnitudes. In any case, if the determined charge magnitude or charge state CH is equal to, or within a specified range of, a specified or target charge magnitude or charge state value, the processor24is operable to control the voltage source VS1to apply one or more voltage values to the charge deflection or steering region14which causes the charge deflection or steering region14to pass the charged particle P therethrough. Otherwise, the processor24is operable to control the voltage source VS2to apply one or more voltage values to the charge deflection or steering region14which causes the charge deflection or steering region14to prevent passage of the charged particle P therethrough or to steer the charged particle P away from the region14. In some embodiments of the charge deflection or steering region14, such control of the voltage source VS1should occur before the charged particle P enters the region14at a time T7>T6, and in other embodiments such control of the voltage source VS1may occur after the charged particle P has entered the region14but before the charged particle P exits the region14. In either case, the determined velocity Velp, in embodiments in which the processor24determines Velp, may be used along with the dimensional information of the drift region12and/or the charge deflection or steering region14to estimate the future position of the charged particle P entering, within and/or traveling through the region14for purposes of determining the timing of control of the voltage source VS1to pass, prevent passage or steer the charged particle P through the region14. In alternate embodiments, the processor24may base the timing of control of the voltage source VS1solely on the determined speed VelPof the charged particle approaching the region14.

Those skilled in the art will recognize other techniques for determining the magnitude and/or charge state and/or velocity of the charged particle P based on one or more of the charge detection signals produced by the charge sensitive amplifiers CA1-CAN and/or for determining the timing of control of the voltage source VS1to pass/ prevent passage or steer the charge particle P through the region14. It will be understood that any such other techniques are intended to fall within the scope of this disclosure.

Referring now toFIGS.4A-4N, another simplified example of the charge filter instrument10ofFIG.1is shown which includes three charge detection cylinders161-163axially arranged between the ion inlet A1of the drift tube12A and the charge deflection or steering region14. With this simplified instrument10,FIGS.4A-4Ndepict two charged particles P1, P2drifting successively through each of the three charge detection cylinders161-163as a function of time, wherein P1has a slightly lower mass-to-charge ratio than that of P2.FIG.5depicts an example charge detection signal produced by the first charge sensitive amplifier CA1as the charged particles pass therethrough, andFIGS.6and7depict the same for the second and third charge sensitive amplifiers CA2and CA3respectively. As illustrated inFIGS.4A-4E, the charged particles P1and P2enter the first charge detection cylinder161at times T1and T2respectively, where T2>T1.At time T3>T2, the charged particle P1exits the charge detection cylinder161, and at time T5>T3the charged particle P2exits the charge detection cylinder161. With the particle P1alone moving within the charge detection cylinder161between T1and T2, the charged particle P1induces a charge on the charge detection cylinder161of magnitude C1as depicted inFIG.5. Between T2and T3in which both of the charged particles P1and P2are moving through the charge detection cylinder161, the charged particles P1and P2together induce a charge on the charge detection cylinder161of magnitude C2>C1, and between T3and T5in which only the charged particle P2is moving through the charge detection cylinder161, the charged particle P2induces a charge on the charge detection cylinder161of C3<C1.

In the case of multiple charged particles drifting axially through the drift region12and thus axially through each successive charge detection cylinder161-16N, a process similar to that described above with respect toFIGS.2A-3may be used to track ion charge and velocity based on detection by the processor24of rising and falling edges of the charge detection signal produced by successive ones of the charge sensitive amplifiers CA1-CAN. In particular, the instructions stored in the memory26may illustratively include instructions executable by the processor24to monitor the charge detection signals produced by the charge sensitive amplifiers CA1-CAN and count each rising edge of a charge detection signal as a single charged particle entering a respective one of the charge detection cylinders161-16N, to count each falling edge the charge detection signal as a single charged particle exiting the respective charge detection cylinder161-16N, to record the various magnitudes of the charge detection signal as the magnitudes of single ones and combinations of the charged particles and to record the velocities of each of the multiple charged particles based on the rising and falling edges of the charge detection signal.

Using the charge detection signal produced by CA1, for example, the first rising edge is counted as a first charged particle having a charge magnitude equal to the magnitude of the charge detection signal between the first rising edge and the next rising or falling edge. If the next edge event is a falling edge, then the velocity of the first charged particle is equal to the ratio of the length CDL of the charge detection cylinder161and the difference in time between the rising and falling edges. If instead the next edge event is another rising edge, the second rising edge is counted as a second charged particle having a combined charge magnitude equal to the magnitude of the charge detection signal between the second rising edge and the next rising or falling edge. This process continues with each rising edge. Upon detection of the first falling edge, this is counted as the first charged particle exiting the charge detection cylinder161, the velocity of the first charged particle is equal to the ratio of the length CDL of the charge detection cylinder161and the difference in time between the first rising edge and the first falling edge, and the magnitude of the charge detection signal produced by CA1after the first falling edge is the combined charge magnitude of the charged particles remaining in the charge detection cylinder161. This process continues until the last falling edge of the charge detection signal produced by CA1, and the same process is executed with respect to the charge detection signals produced by each of the remaining charge sensitive amplifiers CA1-CAN.

Referring again toFIG.5, the processor24executing the above-described process is operable to determine that the charge CHP1of the first charged particle P1between T1and T2is C1, the combined charge CHP1P2of the charged particles P1and P2between T2and T3is C2and the charge CHP2of the second charged particle P2between T3and T5is C3. In embodiments in which the velocities of the charged particles passing through the charge detection cylinder161are determined by the processor24as part of the above-described process, the processor24is operable to determine the velocity of the first charged particle P1as VelP1=CDL/(T3−T1), and to determine the velocity of the second charged particle P2as VelP2=CDL/(T5−T2). In some embodiments, the processor24may be operable to modify CHP1and CHP2such that CHP1and CHP2further satisfy the measured relationship CHP1+CHP2=C2. In alternate embodiments, such modification of CHP1and CHP2may be factored into the charge magnitude values CHP1and CHP2following processing of charge detection signals produced by one or more, or all, of the downstream charge sensitive amplifiers CA2-CAN.

As illustrated inFIGS.4D-41, the charged particles P1and P2enter the second charge detection cylinder162at times T4and T6respectively, where T6>T4>T3. At time T7>T6, the charged particle P1exits the charge detection cylinder162, and at time T9>T7the charged particle P2exits the charge detection cylinder162. With the particle P1alone moving within the charge detection cylinder162between T4and T6, the charged particle P1induces a charge on the charge detection cylinder162of magnitude C4as depicted inFIG.6. Between T6and T7in which both of the charged particles P1and P2are moving through the charge detection cylinder162, the charged particles P1and P2together induce a charge on the charge detection cylinder162of magnitude C5>C4, and between T7and T9in which only the charged particle P2is moving through the charge detection cylinder162, the charged particle P2induces a charge on the charge detection cylinder162of C6<C4. Again using the above-described process, the processor24is operable to update the charge CHP1of the first charged particle P1as CHP1=CHP1+C4, to update the charge CHP2of the second charged particle P2as CHP2=CHP2+C6, and to determine the combined charge CHP1P2of the charged particles P1and P2between T6and T7is C5. In embodiments in which the velocities of the charged particles passing through the charge detection cylinder162are determined by the processor24as part of the above-described process, the processor24is operable to update the velocity of the first charged particle P1as VelP1=VelP1+CDL/(T7−T4), and to update the velocity of the second charged particle P2as VelP2=VelP2+CDL/(T9−T6). In some embodiments, the processor24may be operable to modify CHP1and CHP2such that CHP1and CHP2further satisfy the measured relationship CHP1+CHP2=C5. In alternate embodiments, such modification of CHP1and CHP2may be factored into the charge magnitude values CHP1and CHP2following processing of charge detection signals produced by one or more, or all, of the downstream charge sensitive amplifiers CA3-CAN.

As illustrated inFIGS.4H-4M, the charged particles P1and P2enter the third charge detection cylinder163at times T8and T10respectively, where T10>T8>T7. At time T11>T10, the charged particle P1exits the charge detection cylinder163, and at time T13>T11the charged particle P2exits the charge detection cylinder163. At the time T12, where T11<T12<T13such that the second charged particle P2is still within the third charge detection cylinder163, the first charged particle P1enters the charge deflection or steering region14as depicted inFIG.4L, and at the time T14>T13, the second charged particle P2enters the charge deflection or steering region14. With the particle P1alone moving within the charge detection cylinder163between T8and T10, the charged particle P1induces a charge on the charge detection cylinder163of magnitude C7as depicted inFIG.7. Between T10and T11in which both of the charged particles P1and P2are moving through the charge detection cylinder163, the charged particles P1and P2together induce a charge on the charge detection cylinder163of magnitude C8>C7, and between T11and T13in which only the charged particle P2is moving through the charge detection cylinder163, the charged particle P2induces a charge on the charge detection cylinder163of C9<C7.

Again using the above-described process, the processor24is operable to update the charge CHP1of the first charged particle P1between T11and T12as CHP1=CHP1+C7. In embodiments in which the velocities of the charged particles passing through the charge detection cylinder163are determined by the processor24as part of the above-described process, the processor24is further operable between T11and T12to update the velocity of the first charged particle P1as VelP1=VelP1+CDL/(T11−T8). As the charge detection cylinder163is the final charge detection cylinder in the example illustrated inFIGS.4A-4N, the value of CHP1at a time between T11and T12is the final measured value of the charge magnitude of the first charged particle P1and, in embodiments which include it, the value VelP1at the time between T11and T12is the final measured value of the velocity of the first charged particle P1. The average charge is calculated from CHP1=CHP1/N, where N is the number of measurements (in this case3) and the average velocity is calculated from VelP1=VelP1/N. Prior to the first charged particle P1entering the charge deflection or steering region14, the processor24is operable to compare CHP1to one or more target charge magnitude values, or to compute the charge state CSP1of the first charged particle P1(CSP1=CHP1/e) and compare CSP1to one or more target charge states, and to then control the voltage source VS1at or after T12, but before T14, to pass/block the first charged particle P1or to steer the first charged particle P1along one of multiple different paths of the region14based on the outcome of the comparison of CHP1or CSP1with the one or more target charge magnitudes or target charge states. In embodiments in which the particle velocities are computed, the timing of such control by the processor24of the voltage source VS1may be based on, or at least take into account, the velocity VelP1of the charged particle P1and/or an estimated future position of the charged particle P1, based on VelP1and dimensional information of the charge filter instrument10, relative to and/or within the charge deflection or steering region14.

The processor24is subsequently operable between T13and T14to update the charge CHP2of the second charged particle P2as CHP2=CHP2+C9. In some embodiments, the processor24may be further operable between T13and T14to modify CHP2in order to satisfy the measurement CHP1+CHP2=C8produced by the charge sensitive amplifier CA3. In embodiments in which the velocities of the charged particles passing through the charge detection cylinder163are determined by the processor24as part of the above-described process, the processor24is further operable between T13and T14to update the velocity of the second charged particle P2as VelP2=VelP2+CDU(T13−T10). Again, as the charge detection cylinder163is the final charge detection cylinder in the example illustrated inFIGS.4A-4N, the value of CHP2at a time between T13and T14is the final measured value of the charge magnitude of the second charged particle P2and, in embodiments which include it, the value VelP2at the time between T13and T14is the final measured value of the velocity of the second charged particle P2. The average charge is calculated from CHP2=CHP2/N, where N is the number of measurements (in this case3) and the average velocity is calculated from VelP2=VelP2/N. Following entrance of the first charged particle P1into the charge deflection or steering region14at T12and, in some embodiments, control by the processor24of the voltage source VS1to cause the charge deflection or steering region14to pass/block or steer the first charged particle P1, and in any case prior to the second charged particle P2entering the charge deflection or steering region14, the processor24is operable to compare CHP2to one or more target charge magnitude values, or to compute the charge state CSP2of the second charged particle P2(CSP2=CHP2/e) and compare CSP2to one or more target charge states, and to then control the voltage source VS1at or after T14to pass/block the second charged particle P2or to steer the second charged particle P2along one of multiple different paths of the region14based on the outcome of the comparison of CHP2or CSP2with the one or more target charge magnitudes or target charge states. In embodiments in which the particle velocities are computed, the timing of such control by the processor24of the voltage source VS1may be based on, or at least take into account, the velocity VelP2of the charged particle P2and/or an estimated future position of the charged particle P2, based on VelP2and dimensional information of the charge filter instrument10, relative to and/or within the charge deflection or steering region14.

It will be understood that the examples illustrated inFIGS.2A-7are provided only for the purpose of describing operation of the charge filter instrument10, and are not intended to be limiting in any way. Those skilled in the art will appreciate that the above-described process, or variant thereof, may be applied directly to the determination of charge magnitudes, charge states and/or velocities and of passing/blocking and/or steering of many charged particles, e.g., hundreds, thousands or more. Alternatively, those skilled in the art will recognize other techniques for determining the magnitude and/or charge state and/or velocity of the multiple charged particles based on one or more of the charge detection signals produced by the charge sensitive amplifiers CA1-CAN and/or for determining the timing of control of the voltage source VS1to pass/ prevent passage or steer the charge particle P through the region14, and it will be understood that any such other techniques are intended to fall within the scope of this disclosure. For example, in some embodiments the charge detection signals produced by the charge sensitive amplifiers CA1-CAN may be differentiated. A positive-going pulse will result each time an ion enters a charge detection cylinder, and a negative-going ion will result each time an ion exits a charge detection cylinder. If the rise and fall times of the output signals of the charge sensitive amplifiers CA1-CAN (e.g., seeFIGS.3,5,6and7) are much shorter than the time constant for differentiation, then the charge is given by the peak height. If, on the other hand, the rise and fall times are much longer than the time constant for differentiation, then the charge is given by the peak area. The amplitudes of the positive-going and negative-going pulses associated with any particular ion should be the same, and this provides an identifier to pair up positive-going and negative-going pulses so that the velocities and average charges can be determined. This alternative data analysis technique may be advantageous when, for example, the number of ions drifting through the drift tube16A is large.

It will be further understood that in the charge filter instrument10illustrated inFIG.1, not all of the charge detection signals may be used to determine particle charge values and/or particle velocities. In some embodiments in which charged particles may be bunched together exiting the ion source30, for example, the charge detection signals produced by the first one or several charge sensitive amplifiers may be ignored by the processor24. Alternatively or additionally, the drift tube12A may be configured to include the pre-array space12B of any desired length to allow such bunched particles to at least begin to separate in the axial direction of the drift region12prior to passing through the first of multiple charge detection cylinders161-16N. As another example, the processor24may be configured or programmed to conclude charge value and/or particle velocity determinations before the charged particles reach the last charge detection cylinder16Nor before the charged particles reach the last several charge detection cylinders16N-Y-16N, where Y may be any positive integer less than N. Alternatively or additionally, the drift tube12A may be configured to include the post-array space12C of any desired length in order to relax the timing requirements for the control of the voltage source VS1following determination of particle charge values and/or velocities. As yet another example, the processor24may be configured or programmed in some embodiments to determine only the charge values, i.e., not determine particle velocity values, and to base control of the voltage source VS1solely on the charge value determinations and, in some embodiments, dimensional information of the charge filter instrument10.

As briefly described above, the charge deflection and steering region14is controllable, i.e., by controlling the voltage source VS1, to pass, block or steer ions based on their charge magnitudes or charge states. In this regard, ions of a particular charge magnitude, of a particular charge state, having charges within a specified range of charge magnitudes or having computed charge states within a specified range or ranges of one or more particular integer charge states, may be analyzed and/or collected for analysis of one or more molecular characteristics. Because all such ions will have a common charge magnitude or charge state that is known as a result of the charge measurement information produced by the charge sensitive amplifiers CA1-CAN, the known ion charge magnitudes and/or charge states of such ions may be used in any such downstream analysis to determine molecular characteristic information not previously determinable by conventional instruments. For example, in one non-limiting example application in which the charge filter instrument10is controlled, e.g., as described above, to pass only ions having a +1charge state, then such charge information can be used to directly determine particle mass values using a conventional mass spectrometer or mass analyzer which measures ion mass-to-charge ratio. As another non-limiting example application in which the charge filter instrument10is controlled, e.g., as described above, to pass only ions having a +1 charge state, such charge information can be used to directly determine particle mobility values using a conventional ion mobility spectrometer which measures ion mobility as a function of particle charge. As yet another non-limiting example, the charge filter instrument10may be configured and controlled, e.g., as described above, to steer and analyze, or collect for analysis, different sets of ions each having different charge magnitudes or different states, e.g., +1, +2, +3, etc. The known charge magnitude or charge state of each such set may then be used with one or more molecular analysis stages to determine one or more molecular characteristics of the set, e.g., particle mass, particle mobility, etc.

Referring now toFIG.8, an embodiment is shown of the charge deflection or steering region14of the charge filter instrument illustrated inFIGS.1,2A-2D and4A-4N. In the illustrated embodiment, the charge deflection or steering region14is implemented in the form of a single inlet, single outlet charge deflector14A configured and controllable to selectively pass or block passage of ions therethrough. The charge deflector14A includes a pair of electrically conductive members60,62each of length DL, illustratively in the form plates, grids or other electrically conductive material(s), spaced apart from one another to define a channel64therethrough between the single ion inlet A3and the single ion outlet A4. In the illustrated embodiment, the members60,62are depicted as planar components such that the channel64is a square or rectangular channel. In alternate embodiments, the electrically conductive members60,62may be implemented in other shapes without limitation. In any case, a first voltage output V1of the voltage source VS1is electrically connected to the electrically conductive member62, and a second voltage output V2of the voltage source VS1is electrically connected to the electrically conductive member60. In one embodiment, the voltages V1and V2may be switchable DC voltages, or one of the voltages V1, V2may be set to a reference potential, e.g., ground or other reference potential, and the other voltage V1, V2may be a switchable DC voltage. In alternate embodiments, the voltage V1and/or the voltage V2may be a time-varying voltage.

In any case, the charge deflector14A is illustratively operable to deflect a charged particle P entering the inlet A3into one or the other of the members60,62by controlling the voltage(s) V1and/or V2to create an electric field E of sufficient magnitude to divert and accelerate the charged particle P into the member60,62as illustrated by example inFIG.8. Conversely, the charge deflector14A is illustratively operable to pass the charged particle P entering the inlet A3to, and through, the outlet A4, as depicted in dashed-line representation inFIG.8, so long as an electric field E is not established between the members60,62or an electric field E is established between the members60,62but is not of sufficient magnitude to deflect the charged particle P into one or the other of the members60,62. In one illustrative example, which should not be considered limiting in any way, in which the charged particle P has a positive charge, V1=V2=0 volts (ground potential) to pass the charged particle P through the channel64, and V1=0 volts, V2=+Z volts to deflect the charged particle P toward and into the electrically conductive member62, wherein Z is selected to establish an electric field E between the members60,62with sufficient magnitude to guide and accelerate the charged particle P onto the surface of the member62before the charged particle P reaches the outlet A4to thereby block passage the charged particle P through the charge deflector14A. It will be understood that in alternate embodiments, the roles of V1and V2may be reversed. In other alternate embodiments, the electric field E may be a time-varying electric field established by one or more time-varying voltages V1, V2.

Referring now toFIGS.9A and9B, another embodiment is shown of the charge deflection or steering region14of the charge filter instrument illustrated inFIGS.1,2A-2D and4A-4N. In the embodiment illustrated inFIGS.9A and9B, the charge deflection or steering region14is implemented in the form of another single inlet, single outlet charge deflector14B configured and controllable to selectively pass or block passage of ions therethrough. The charge deflector14B is illustratively provided in the form of a quadrupole filter including four elongated electrically conductive rods70,72,74,76each of length RL and radially spaced apart from one another to define a channel78therethrough between the single ion inlet A3and the single ion outlet A4. In the illustrated embodiment, the rods70-76are depicted as cylindrical rods having generally circular cross-sectional shapes, although in alternate embodiments the rods70-76may have non-circular cross-sectional shapes. In any case, a first voltage output V1of the voltage source VS1is electrically connected to the electrically conductive rods70and72, and a second voltage output V2of the voltage source VS1is electrically connected to the electrically conductive rods74,76, wherein the rod70is positioned radially opposite the rod72and the rod74is positioned radially opposite the rod76. In one embodiment, the voltages V1and V2may include time-varying voltages, e.g., RF voltages,180degrees out of phase with one another and may further include a DC voltage between the rod pairs70,72and74,76. In some alternate embodiments, V1and V2may include only time-varying, e.g., RF, voltages, and in other alternate embodiments V1and V2may include only DC voltages.

In any case, the charge deflector14B is illustratively operable to deflect a charged particle P entering the inlet A3into one of the rods70-76by controlling the voltage(s) V1and/or V2in a conventional manner to create a non-resonant electric field E between the rods70-76of sufficient magnitude to divert the charged particle P into one of the rods70-76to thereby block passage of the charged particle P through the charge deflector14B. Conversely, the charge deflector14B is illustratively operable to pass the charged particle P entering the inlet A3to, and through, the outlet A4by controlling the voltage(s) V1and/or V2in a conventional manner to create a resonant electric field E between the rods70-76which confines the charged particle P within the channel78and thus allows the charged particle P entering the inlet A3to pass axially through the channel78and exit through ion outlet A4. In some alternate embodiments, the charge deflector14B may be used in combination with one or more other charge deflection or steering components to pass only ions having mass-to-charge ratios above a threshold mass-to-charge ratio, e.g., by controlling V1and V2to supply only time-varying voltages (i.e., no DC voltages).

Referring now toFIGS.10A and10B, yet another embodiment is shown of the charge deflection or steering region14of the charge filter instrument illustrated inFIGS.1,2A-2D and4A-4N. In the embodiment illustrated inFIGS.10A and10B, the charge deflection or steering region14is implemented in the form of a single inlet, multiple-outlet charge steering device14C configured and controllable to selectively steer ions entering the inlet A3through one of multiple different ion outlets. The charge steering device14C is illustratively provided in the form of a single-inlet, three-outlet quadrupole charge steering device having four elongated electrically conductive arcuate members80,82,84,86spaced apart from one another to define an ion steering space88therebetween. Each of the electrically conductive arcuate members80,82,84,86has a convex surface facing the steering space88with the members80,82positioned opposite one another on either side of the space88and with the members84,86also positioned opposite one another on either side of the space88. Each adjacent pair of arcuate members defines an ion inlet or outlet therebetween. For example, the arcuate members80and84are radially spaced apart from one another to define the ion inlet A3of the steering device14B therebetween, and the arcuate members82and86are likewise radially spaced apart from one another to define one ion outlet A4therebetween which is axially opposite the ion inlet A3. The arcuate members80and86are axially spaced apart from one another to define one side outlet SA1therebetween, and the arcuate members82,84are likewise axially spaced apart from one another to define another side outlet SA2therebetween which is radially opposite the side outlet SA1.

In the embodiment illustrated inFIG.10B, a first voltage output V1of the voltage source VS1is electrically connected to the electrically conductive members80and82, and a second voltage output V2of the voltage source VS1is electrically connected to the electrically conductive members84and86. In one embodiment, the voltages V1and V2may include time-varying voltages, e.g., RF voltages, 180 degrees out of phase with one another and may further include a DC voltage between the rod pairs80,82and84,86. In some alternate embodiments, V1and V2may include only time-varying, e.g., RF, voltages, and in other alternate embodiments V1and V2may include only DC voltages. In one illustrative implementation, the voltages V1and V2are switchable DC voltages, and the processor24is illustratively operable to control V1and V2to the same voltage, e.g., ground or other potential, to cause the charged particle P entering the inlet A3to pass directly through the space88along a linear axis85and through the ion outlet A4as illustrated by dashed lines inFIG.10B. Alternatively, assuming the charged particle P has a positive charge, the processor24may be operable to control V1to a negative potential and to control V2to an opposite positive potential to create an electric field within the space88configured to steer the charged particle P entering the ion inlet A3along an arcuate path87A and exit the charge steering device14B through the side exit SA1as also illustrated inFIG.10B. Alternatively still, again assuming the charged particle P has a positive charge, the processor24may be operable to control V1to a positive potential and to control V2to an opposite negative potential to create an electric field within the space88configured to steer the charged particle P entering the ion inlet A3along an arcuate path87B and exit the charge steering device14B through the side exit SA2as further illustrated inFIG.10B.

Referring now toFIG.11, a further embodiment is shown of the charge deflection or steering region14of the charge filter instrument illustrated inFIGS.1,2A-2D and4A-4N. In the embodiment illustrated inFIG.11, the charge deflection or steering region14is implemented in the form of another single inlet, multiple-outlet charge steering device14D configured and controllable to selectively steer ions entering the inlet A3through one of multiple different ion outlets. The charge steering device14D is illustratively includes a pattern of4substantially identical and spaced apart electrically conductive pads C1-C4formed on an inner major surface90A of one substrate90having an opposite outer major surface90B, and an identical pattern of4substantially identical and spaced apart electrically conductive pads C1-C4formed on an inner major surface92A of another substrate92having an opposite outer surface92B. The inner surfaces90A,92A of the substrates90,92are spaced apart in a generally parallel relationship, and the electrically conductive pads C1-C4of the substrate90are juxtaposed over respective ones of the electrically conductive pads C1-C4of the substrate92. The spaced-apart, inner major surfaces90A and92A of the substrates90,92illustratively define a channel or space94therebetween of width DP. In one embodiment, the width, DP, of the channel94is approximately5cm, although in other embodiments the distance DP may be greater or lesser than5cm.

The opposed pad pairs C1, C1and C3, C3define the ion inlet A3therebetween, and the opposed pad pairs C2, C2and C4, C4define the ion outlet A4therebetween. The opposed pad pairs C1, C1and C2, C2define a side outlet SA1therebetween, and the opposed pad pairs C3, C3and C4, C4define an opposite side outlet SA2, all similarly as described with respect to the embodiment illustrated inFIGS.10A and10B. Edges90C,92C of the substrates90,92are illustratively aligned with one another, as are edges90D,92D, edges90E,92E and edges90F,92F.

A first voltage output V1of the voltage source VS1is electrically connected to the electrically conductive pad pairs C1, C1and C4, C4, and a second voltage output V2of the voltage source VS1is electrically connected to the electrically conductive pad pairs C2, C2and C3, C3. In one embodiment, the voltages V1and V2may be switchable DC voltages controllable to selectively establish an ion-steering electric field between various one of the pad pairs C1, C1, C2, C2, C3, C3and C4, C4. In one implementation, the processor24is illustratively operable to control V1and V2to the same voltage, e.g., ground or other potential, to cause the charged particle P entering the inlet A3to pass directly through the space channel94along a linear axis96and through the ion outlet A4as illustrated inFIG.11. Alternatively, assuming the charged particle P has a positive charge, the processor24may be operable to control V1to a negative potential and to control V2to an opposite positive potential to create an electric field within the channel96configured to steer the charged particle P entering the ion inlet A3along an arcuate path98A and exit the charge steering device14B through the side exit SA1as also illustrated inFIG.11. Alternatively still, again assuming the charged particle P has a positive charge, the processor24may be operable to control V1to a positive potential and to control V2to an opposite negative potential to create an electric field within the channel94configured to steer the charged particle P entering the ion inlet A3along an arcuate path and exit the charge steering device14B through the side exit SA2.

Referring now toFIG.12, an embodiment is shown of a particle measurement device100which includes an embodiment10A of the charge filter instrument10illustrated inFIG.1and described above. In the embodiment illustrated inFIG.12, the charge filter instrument10A includes the drift region12having an ion inlet A1with the charge detector array16including the plurality of charge detection cylinders161-16Naxially arranged within the drift tube12A between the ion inlet A1and ion outlet A2thereof as described above, and further includes the charge deflection or steering region14coupled to the outlet end of the drift tube12A in the form of a charge deflector. The charge deflector may illustratively be implemented as either of the charge deflectors14A,14B illustrated inFIGS.8and9A-9Brespectively, or as either of the charge steering devices14C,14D illustrated inFIGS.10A-10B and11respectively. In the latter case, the charge steering device, e.g.,14C or14D, is illustratively controlled to operate as a charge deflector to either pass ions entering the ion inlet A3toward and through the ion outlet A4or to block ion passage through the ion outlet A4by steering such ions away from the ion outlet A4, e.g., through either of the side outlets SA1, SA2. Alternatively or additionally, the charge deflector illustrated inFIG.12may be implemented in the form of one or more other conventional charge deflectors, charge diverters, charge steering devices or other devices which may be controlled as described above to selectively pass ions entering the ion inlet A3toward and through the ion outlet A4or to selectively block ions entering the ion inlet A3from passing through the ion outlet A4using any conventional structures and/or techniques.

The particle measurement device100further includes an ion source region30operatively coupled to the ion inlet end of the charge filter instrument10A. The ion source region30is as described above with reference toFIG.1and illustratively includes at least one ion generator coupled to the voltage source VS2and configured to be responsive to control signals produced by the processor24to generate ions from a sample positioned within or outside of the ion source region30, and further includes one or more conventional structures and/or devices for accelerating or otherwise propelling the generated ions through the ion inlet A1and into the charge filter instrument10A. In some embodiments, for example, the ion source region30may include at least one ion acceleration structure or region separate from or part of the ion generator and operatively coupled to the voltage source VS2(seeFIG.1). In this embodiment, the processor24may illustratively be programmed to control of the voltage source VS2to selectively establish an ion accelerating electric field with the ion acceleration structure or within the ion acceleration region which is, in any case, oriented to accelerate the generated ions into the charge filter instrument10A via the ion inlet Al. As another example in which the sample is contained within the ion source region30, the drift region12may be pumped, e.g., via one or more conventional pumps, to a lower pressure than that of the ion source region30, and in such embodiments the differential pressure between the ion source region30and the drift region12may propel the generated ions into the charge filter instrument10A via the ion inlet Al. As still another example in which the sample is outside of the ion source region30, the ion source region and/or the drift region12may be pumped, e.g., via one or more conventional pumps, to a pressure that is lower than ambient or atmospheric pressure in which the sample is located, and in such embodiments the differential pressure between ambient or atmospheric pressure external to the ion source region30and the lower pressure environment within the ion source region and/or drift region12may propel the generated ions into the charge filter instrument10A via the ion inlet Al. In still other embodiments, a combination of differential pressure and an ion acceleration region or structure may be used to provide the motive force for accelerating or otherwise propelling the generated ions into the charge filter instrument10A.

In some embodiments, the ion source region30may include one or more ion separation instruments or stages and/or one or more ion processing instruments or stages in any combination. Some examples of various compositions of the ion source region30will be described in detail below with respect toFIG.15.

The particle measurement device100further includes an ion storage, steering and/or measurement stage(s)32operatively coupled to the ion outlet end of the charge filter instrument10A as illustrated inFIG.1and briefly described above. In the embodiment illustrated inFIG.12, the ion storage, steering and/or measurement stage(s)32is illustratively implemented in the form of an ion storage and measurement stage32A including a conventional ion trap102operatively coupled to the voltage source VS3(seeFIG.1) and having an ion inlet coupled to the ion outlet A4of the charge filter instrument10A and an ion outlet coupled to an ion inlet of an ion measurement stage104. In some alternate embodiments, the ion trap102may be omitted such that the ion outlet A4of the charge filter instrument10A is coupled directly to the ion inlet of the ion measurement stage104. The ion measurement stage104may, in any case, illustratively include one or more conventional instruments or stages for separating ions in time according to one or more molecular characteristics. In some embodiments, the ion measurement stage104may further include one or more ion processing instruments or stages in any combination with the one or more ion separating instruments or stages. The ion measurement stage104is operatively coupled to the voltage source VS3as illustrated inFIG.1. Some examples of various compositions of the ion measurement stage104will be described in detail below with respect toFIG.16.

In the embodiment illustrated inFIG.12, ions are supplied by the ion source region30to the charge filter instrument10A where the processor24is operable to determine particle charge values, and particle velocities in some embodiments, as the ions separate while drifting through the drift region12as described above, and to further control the voltage source VS1, as also described above, to pass only ions having a target charge magnitude, having a charge magnitude that is within a selected threshold or range of the target charge magnitude, having a target charge state or having a charge state that is within a selected threshold or range of the target charge state (individually and collectively referred to herein as a “target charge”). In one example implementation in which the charged particle measurement device100includes the ion trap102, the processor24is illustratively programmed, e.g., via instructions stored in the memory26, to control the voltage source VS3to collect and store ions within the ion trap102having the target charge and therefore selected by the processor24to pass through the charge deflector14A, B, C, D and into the ion trap102. The processor24is illustratively configured to control the voltage source VS3to collect and store ions within the ion trap102for any period of time. At some point in time after the ion trap102has been operating to collect and store ions therein, the processor24is operable to control the voltage source VS3to eject the collected ions into the ion inlet of the ion measurement stage104, and the processor24is thereafter operable to control the voltage source VS3in a conventional manner to control operation of the one or more ion measurement instruments making up the ion measurement stage104to measure one or more molecular characteristics of the collection of ions all having the target charge. In alternate embodiments which do not include the ion trap102, ions with the target charge exiting the charge filter instrument10A are supplied directly to the ion measurement stage104where the processor24is operable to control the voltage source VS3to measure one or more molecular characteristics of the exiting ions. In either case, the processor24is further operable to collect, store and analyze the ion measurement information produced by the ion measurement stage104in a conventional manner.

In one example implementation of the particle measurement instrument100, which should not be considered to be limiting in any way, the ion measurement stage is or includes a conventional mass spectrometer or mass analyzer. In this example implementation, the processor24is illustratively operable to control the voltage source VS1to pass only ions having a first target charge to the ion trap102, to subsequently control the voltage source VS3to supply the collected ions into the mass spectrometer or mass analyzer and to further control the voltage source VS3to control the mass spectrometer or mass analyzer in a conventional manner to produce mass-to-charge ratio measurements of the collected ions. Because the charge magnitudes or charge states of the collected ions are the same and are known, the processor24is further operable to determine the masses of the collected ions as a simple ratio of the mass-to-charge ratio measurements and the target charge value. In some embodiments, the ion trap102may be omitted, and the processor24may be operable as just described to control the voltage source VS3to control the mass spectrometer or mass analyzer to produce mass-to-charge ratio measurements of the charge-selected ions as they exit the outlet aperture A4of the charge filter instrument10A. In either case, the processor24may be further operable in a charge scanning mode to repeat the above-described process one or more times over a selected range of target charge values. Those skilled in the art will recognize that the ion measurement stage104may be or include other conventional ion measurement instruments or stages configured to measure one or more molecular characteristics and/or may include one or more ion processing instruments or stages configured to process ions in any conventional manner, and it will be understood that any such implementation of the ion measurement stage104is intended to fall within the scope of this disclosure. Several non-limiting examples of various measurement and processing instruments that may be included in the ion measurement stage104will be described below with respect toFIG.16.

Referring now toFIG.13, an embodiment is shown of another particle measurement device200which includes an embodiment10B of the charge filter instrument10illustrated inFIG.1and described above. In the embodiment illustrated inFIG.13, the charge filter instrument10B includes the drift region12having an ion inlet A1with the charge detector array16including the plurality of charge detection cylinders161-16Naxially arranged within the drift tube12A between the ion inlet A1and ion outlet A2thereof as described above, and further includes the charge deflection or steering region14coupled to the outlet end of the drift tube12A in the form of a single-inlet, multiple-outlet charge steering device. In the illustrated embodiment, the single-inlet, multiple outlet charge steering device is a single-inlet, three-outlet charge steering device having a single ion inlet A3, an oppositely-positioned ion outlet A4and two opposing side outlets SA1, SA2, which may illustratively be implemented as either of the charge steering devices14C,14D illustrated inFIGS.10A-10B and11respectively. Alternatively, the single-inlet, multiple-outlet charge steering device may take the form of any conventional single-inlet, multiple-outlet charged particle steering device.

The particle measurement device200further illustratively includes an ion storage, steering and/or measurement stage(s)32in the form of three separate ion storage and measurement stages32A1,32A2,32A3each operatively coupled to a respective ion outlet A4, SA1, SA2of the single-inlet, multiple-outlet charge steering device14C,14D. In the embodiment illustrated inFIG.13, each stage32A1,32A2,32A3is identical to the stage32A illustrated inFIG.12and described above. For example, each stage32A1,32A2,32A3includes a respective conventional ion trap1021,1022,1023operatively coupled to a respective ion measurement stage1041,1042,1043. In some alternate embodiments, one or more of the stages32A1,32A2,32A3may be configured differently than others of the stages32A1,32A2,32A3. In some alternate embodiments, one or more of the ion traps1021,1022,1023may be omitted such that the respective ion outlet of the charge steering device14C, D is coupled directly to the ion inlet of a respective ion measurement stage1041,1042,1043. The ion measurement stages stage1041,1042,1043are likewise identical to the ion measurement stage104illustrated inFIG.13and described above.

The particle measurement device200further includes an ion source region30operatively coupled to the ion inlet end of the charge filter instrument10B. The ion source region30is illustratively as described above with reference toFIGS.1and12.

Operation of the particle measurement device200is similar to that of the particle measurement device100illustrated inFIG.12and described above in that ions are supplied by the ion source region30to the charge filter instrument10B where the processor24is operable to determine particle charge values, and particle velocities in some embodiments, as the ions separate while drifting through the drift region12. Unlike the particle measurement device100, however, the particle measurement device200is not limited to passage of particles through a single outlet of a charge deflector, but instead configured to pass particles through any of the three outlets of the charge steering device14C, D. With the single-inlet, three-outlet charge steering device14C, D, the processor24is illustratively programmed to control the voltage source VS1, as described above, to pass through the outlet A4only ions having a first target charge, to pass through the second outlet SA1only ions having a second target charge different than the first target charge and to pass through the third outlet SA2only ions having a third target charge different than the first and second target charges.

In one example implementation in which the charged particle measurement device200includes the ion traps1021,1022,1023, the processor24is illustratively programmed, e.g., via instructions stored in the memory26, to control the voltage source VS1to steer charged particles P having the first target charge out of the ion outlet A4of the charge steering device14C, D and into the ion trap1021, e.g., along the ion travel path2021depicted inFIG.13, and to control the voltage source VS3to collect and store charged particles within the ion trap1021having the first target charge, to control the voltage source VS1to steer charged particles P having the second target charge out of the ion outlet SA2of the charge steering device14C, D and into the ion trap1022, e.g., along the ion travel path2022depicted inFIG.13, and to control the voltage source VS3to collect and store charged particles within the ion trap1022having the second target charge, and to control the voltage source VS1to steer charged particles P having the third target charge out of the ion outlet SA1of the charge steering device14C, D and into the ion trap1023, e.g., along the ion travel path2023depicted inFIG.13, and to control the voltage source VS3to collect and store charged particles within the ion trap1023having the third target charge. The processor24is then operable to control the voltage source VS3to selectively expel the collected charged particles from any or all of the ion traps1021,1022,1023and into a respective one of the ion measurement stages1041,1042,1043for analysis thereof. The processor24is further operable to collect, store and analyze the ion measurement information produced by the ion measurement stages1041,1042,1043, in a conventional manner. The particle measurement device200is thus similar in operation to the device100illustrated inFIG.12and described above, but is configured to simultaneously collect and analyze, or subsequently analyze, with three different ion measurement stages1041,1042,1043ions having three different target charges. Those skilled in the art will recognize that the single-inlet, multiple-outlet charge steering device illustrated inFIG.13is not limited to three ion outlets and may thus be configured to include two or more than three ion outlets, and in such embodiments the particle measurement device200may accordingly include respectively two or more than three ion measurement stages1041,1042,1043and, in embodiments which include them, two or more than three ion traps1021,1022,1023.

Referring now toFIG.14, an embodiment is shown of yet another particle measurement device300which includes an embodiment10C of the charge filter instrument10illustrated inFIG.1and described above. In the embodiment illustrated inFIG.14, the charge filter instrument10C includes the drift region12(partially shown inFIG.14) having an ion inlet A1with the charge detector array16including the plurality of charge detection cylinders161-16Naxially arranged within the drift tube12A between the ion inlet A1and ion outlet A2thereof as depicted inFIG.1and described above. The charge filter instrument10C further includes the charge deflection or steering region14coupled to the outlet end of the drift tube12A in the form of a charge steering region14including a network of two cascaded single-inlet, multiple-outlet charge steering devices and corresponding drift tubes. In the illustrated embodiment, the single-inlet, multiple outlet charge steering devices are both single-inlet, three-outlet charge steering devices each having a single ion inlet A3, an oppositely-positioned ion outlet A4and two opposing side outlets SA1, SA2, which may illustratively be implemented as either of the charge steering devices14C,14D illustrated inFIGS.10A-10B and11respectively. The two single-inlet, three-outlet charge steering devices forming part of the charge steering region14are thus illustrated inFIG.14as14C1, D1and14C2, D2respectively. Alternatively, the single-inlet, multiple-outlet charge steering devices may take the form of any conventional single-inlet, multiple-outlet charged particle steering devices.

In the embodiment illustrated inFIG.14, the inlet A3of the first charge steering device14C1, D1is coupled to the ion outlet A2of the drift tube12A, and the ion outlet A4of the charge steering device14C1, D1is coupled to one end of a linear drift tube segment or section302having an opposite end coupled to the ion inlet A3of the second charge steering device14C2, D2. The ion outlet A4of the charge steering device14C2, D2is coupled to one end of another linear drift tube segment or section304having an opposite end defining a first ion outlet IO1of the charge steering region14. The side ion outlet SA2of the second charge steering device14C2, D2is coupled to one end of an arcuate drift tube segment or section306having an opposite end defining a second ion outlet IO2of the charge steering region14. The side ion outlet SA1of the second charge steering device14C2, D2is coupled to one end of another arcuate drift tube segment or section308having an opposite end defining a third ion outlet IO3of the charge steering region14. The side ion outlet SA2of the first charge steering device14C1, D1is coupled to one end of yet another arcuate drift tube segment or section310having an opposite end defining a fourth ion outlet IO4of the charge steering region14, and the side ion outlet SA1of the first charge steering device14C1, D1is coupled to one end of still another arcuate drift tube segment or section312having an opposite end defining a fifth ion outlet IO5of the charge steering region14. In the illustrated embodiment, the arcuate drift tube segments or sections306,308,310and312are illustratively configured to steer ions along a drift path which reorients the axial direction of ion drift approximately90degrees. Ions exiting the side outlets SA1, SA2of each of the charge steering devices14C1, D1and14C2, D2in directions normal to the drift direction of ions entering the inlets A3of the charge steering devices14C1, D1and14C2, D2are thus redirected by the arcuate drift tube segments or sections306,308,310,312such so as to exit the outlets IO1-IO5in directions parallel with the drift direction of ions entering the inlets A3and exiting the outlets A4of the charge steering devices14C1, D1and14C2, D2. In alternate embodiments, one or more of the drift tube segments306,308,310and312may be non-arcuate or may be arcuate but configured to reorient the direction of ion drift to by an acute or obtuse angle.

The particle measurement device300further illustratively includes an ion storage, steering and/or measurement stage(s)32B in the form of multiple, e.g.,5, separate ion traps1021-1025each having an ion inlet coupled to an outlet IO1-IO5of a different respective one of the drift tube segments or sections304,306,308,310,312and each having an outlet coupled via a charged particle steering network32C to an inlet of a single ion measurement stage104. The charged particle steering network32C illustratively includes multiple, e.g.,5, charge steering devices operable as ion steering devices together controllable to selectively steer charged particles from each of the ion traps1021-1025into the inlet of the ion measurement stage104. In the illustrated embodiment, the multiple ion steering devices are each implemented as either of the charge steering devices14C,14D illustrated inFIGS.10A-10B and11respectively, wherein some of the multiple ion steering devices are controlled to operate as a single inlet, single outlet ion steering device, others of the multiple ion steering devices are controlled to operate as dual-inlet, single outlet ion steering devices and one of the multiple ion steering devices is controlled to operate as a three-inlet, single outlet ion steering device. For example, an ion inlet A31of an ion steering device14C3, D3is coupled to an ion outlet of the ion trap1021, a ion outlet A4opposite the ion inlet A31is coupled to the ion inlet of the ion measurement stage104, and opposite side inlets A32and A33, adjacent to the ion inlet A31and the ion outlet A4, are coupled to respective ends of two drift tube segments or sections314and316respectively. An ion inlet A31of another ion steering device14C4, D4is coupled to an ion outlet of the ion trap1022, another ion inlet A32adjacent to the inlet A31is coupled to one end of another drift tube segment or section318, and an ion outlet SA1opposite the ion inlet A32, and adjacent to the inlet A31, is coupled to the opposite end of the drift tube segment or section314. An ion inlet A31of yet another ion steering device14C5, D5is coupled to an ion outlet of the ion trap1023, another ion inlet A32adjacent to the inlet A31is coupled to one end of yet another drift tube segment or section320, and an ion outlet SA2opposite the ion inlet A32and adjacent to the ion inlet A31, is coupled to an opposite end of the drift tube segment or section316. An ion inlet A3of still another ion steering device14C6, D6is coupled to an ion outlet of the ion trap1024, and an ion outlet SA1adjacent to the inlet A3is coupled to the opposite end of the drift tube segment or section318. An ion inlet A3of a further ion steering device14C7, D7is coupled to an ion outlet of the ion trap1025, and an ion outlet SA2adjacent to the inlet A3is coupled to the opposite end of the drift tube segment or section320.

The particle measurement device300is similar in operation to the device200illustrated inFIG.13and described above, but is configured to simultaneously collect ions having five different target charges, and to subsequently analyze each of the five collections with a single ion measurement stage104. For example, ions are supplied by the ion source region30to the charge filter instrument10C where the processor24is operable to determine particle charge values, and particle velocities in some embodiments, as the ions separate while drifting through the drift region12as described above. The processor24is illustratively programmed to control the voltage source VS1, as described above, to steer through the charge steering devices14C1, D1and14C2, D2ions having each of five different target charges. For example, ions passing from the drift tube12A into the ion inlet A3of the charge steering device14C1, D1and having a first target charge are directed by the processor24, via control of the voltage source VS1, through the outlet A4of the charge steering device14C1, D1and into the ion inlet A3of the charge steering device14C2, D2, and are further directed by the processor24, via control of the voltage source VS1, through the outlet A4of the charge steering device14C2, D2and into the first ion trap1021, and the processor24is further operable to control the ion trap1021, via control of the voltage source VS3, to collect and store such ions within the ion trap1021. Ions passing from the drift tube12A into the ion inlet A3of the charge steering device14C1, D1and having a second target charge are directed by the processor24, via control of the voltage source VS1, through the outlet A4of the charge steering device14C1, D1and into the ion inlet A3of the charge steering device14C2, D2, and are further directed by the processor24, via control of the voltage source VS1, through the outlet SA2of the charge steering device14C2, D2and into the second ion trap1022, and the processor24is further operable to control the ion trap1022, via control of the voltage source VS3, to collect and store such ions within the ion trap1022. The processor24is similarly operable with respect to ions passing from the drift tube12A into the ion inlet A3of the charge steering device14C1, D1and having third, fourth and fifth target charges to control the voltage source VS1to steer such ions into the third, fourth and fifth ion traps1023-1025respectively, and to then control the voltage source VS3to collect and store such ions within the ion traps1023-1025.

The processor24is then operable to control the voltage source VS3to selectively, and in some embodiments sequentially, expel the collected charged particles from the ion traps1021-1025and control the charged particle steering network32C to selectively guide the charged particles into the inlet of the ion measurement stage for analysis thereof. For example, to expel the charged particles collected in the ion trap1021and steer or guide the collected ions into the ion measurement stage104, the processor24is operable to control the voltage source VS3to cause the ion trap1021to eject ions stored therefrom and into the ion inlet A31of the ion steering device14C3, D3, and to further control the voltage source VS3to cause the ion steering device14C3, D3to pass the ions entering the ion inlet A31to pass to, and through, the ion outlet A4thereof and into the ion inlet of the ion measurement stage104. The processor24is then operable to control the voltage source VS3in a conventional manner to cause the ion measurement stage104to measure one or more molecular characteristics of the incoming charged particles. To expel the charged particles collected in the ion trap1022and steer or guide the collected ions into the ion measurement stage104, the processor24is operable to control the voltage source VS3to cause the ion trap1022to eject ions stored therefrom and into the ion inlet A31of the ion steering device14C4, D4, and to further control the voltage source VS3to cause the ion steering device14C4, D4to pass the ions entering the ion inlet A31to pass to, and through, the ion outlet SA1thereof and into one end of the drift tube segment or section314. The processor24is then further operable to control the voltage source VS3to cause the charged particles passing through the drift tube segment or section314into the inlet A32of the ion steering device14C3, D3, and to further control the voltage source VS3to cause the ion steering device14C3, D3to pass the ions entering the ion inlet A32to pass to, and through, the ion outlet A4thereof and into the ion inlet of the ion measurement stage104. The processor24is then operable to control the voltage source VS3in a conventional manner to cause the ion measurement stage104to measure one or more molecular characteristics of the incoming charged particles the ion inlet of the ion measurement stage104. The processor24is operable to control the voltage source VS3in like manner to eject the charged particles from the remaining ion traps1023-1025and to selectively guide the ejected ions into the ion inlet of the ion measurement stage104for analysis thereof. It will be appreciated that while the processor24is controlling the voltage source VS3to eject ions from the various ion traps1021-1025, the processor24may be further operable to control the voltage source VS1to fill one or more emptied ion traps1021-1025with ions having a specified respective target charge. In any case, the processor24is further operable to collect, store and analyze all ion measurement information produced by the ion measurement stage104in a conventional manner.

Those skilled in the art will recognize that while the example embodiment300illustrated inFIG.14is configured to simultaneously collect ions having five different target charges, and to subsequently analyze each of the five collections with a single ion measurement stage104, the concepts illustrated inFIG.14may be readily extended to devices configured to simultaneously collect more or fewer than five sets of target charges. It will be understood that any such alternate embodiments are contemplated by this disclosure. It will be further understood that while the example embodiment300illustrated inFIG.14includes five ion traps to collect ions having five respectively different charges, alternate embodiments are contemplated in which one or more, or all, of the ion traps are omitted such that ions having the respective target charge(s) may be steered by the ion steering network32C directly into the ion measurement stage104.

Referring now toFIG.15, an example embodiment is shown of the ion source or source region30illustrated inFIGS.1and12-14and briefly described above. In the illustrated embodiment, the ion source or source region30illustratively includes at least one ion generator36coupled to the voltage source VS2and configured to be responsive to control signals produced by the processor24to generate ions from a sample S. In some embodiments, the sample S is positioned within the ion source region30, and in other embodiments the ion source S is positioned outside of the ion source region30as illustrated by dashed-line representation inFIG.15. In one embodiment, the ion generator36is a conventional electrospray ionization (ESI) source configured to generate ions from the sample in the form of a fine mist of charged droplets. In alternate embodiments, the ion generator36may be or include a conventional matrix-assisted laser desorption ionization (MALDI) source. It will be understood that ESI and MALDI represent only two examples of myriad conventional ion generators, and that the ion generator36may be or include any such conventional device or apparatus for generating ions from a sample.

The ion source or source region30further illustratively includes a number R, of ion processing stage(s) IPS1-IPSR, where R may be any positive integer. Examples of such ion processing stage(s) IPS1-IPSRmay include, but are not limited to, in any order and/or combination, one or more devices and/or instruments for separating, collecting and/or filtering charged particles according to one or more molecular characteristics, and/or one or more devices and/or instruments for dissociating, e.g., fragmenting, charged particles. In some embodiments, the ion generator36and/or at least one of the ion processing stages IPS1-IPSRincludes one or more conventional structures and/or devices for accelerating or otherwise propelling the generated ions through the ion inlet A1and into the charge filter instrument10. Examples of the one or more devices and/or instruments for separating charged particles according to one or more molecular characteristics include, but are not limited to, one or more mass spectrometers or mass analyzers, one or more ion mobility spectrometers, one or more instruments for separating charged particles based on magnetic moment, one or more instruments for separating charged particles based on dipole moment, and the like. Examples of the mass spectrometer or mass analyzer, in embodiments of the ion source30which include one or more thereof, include, but are not limited to, a time-of-flight (TOF) mass spectrometer, a reflectron mass spectrometer, a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer, a quadrupole mass spectrometer, a triple quadrupole mass spectrometer, a magnetic sector mass spectrometer, an orbitrap, or the like. Examples of the ion mobility spectrometer, in embodiments of the ion source30which include one or more thereof, include, but are not limited to, a single-tube linear ion mobility spectrometer, a multiple-tube linear ion mobility spectrometer, a circular-tube ion mobility spectrometer, or the like. Examples of one or more devices and/or instruments for collecting charged particles include, but are not limited to, a quadrupole ion trap, a hexapole ion trap, or the like. Examples of one or more devices and/or instruments for filtering charged particles include, but are not limited to, one or more devices or instruments for filtering charged particles according to mass-to-charge ratio, one or more devices or instruments for filtering charged particles according to particle mobility, and the like. Examples of one or more devices and/or instruments for dissociating charged particles include, but are not limited to, one or more devices or instruments for dissociating charge particles by collision-induced dissociation (CID), surface-induced dissociation (SID), electron capture dissociation (ECD) and/or photo-induced dissociation (PID), multiphoton dissociation (MPD), or the like.

It will be understood that the ion processing stage(s) IPS1-IPSRmay include one or any combination, in any order, of any such conventional ion separation instruments and/or ion processing instruments, and that some embodiments may include multiple adjacent or spaced-apart ones of any such conventional ion separation instruments and/or ion processing instruments. As one non-limiting example, the ion processing stage(s) IPS1-IPSRinclude a charged particle filtering device or instrument following the ion generator, and a dissociation device, instrument or stage following the charged particle filtering device or instrument. In this example, the processor24is illustratively programmed to control the voltage source VS2to cause the charged particle filtering device or instrument to pass only ions above or below a threshold mass-to-charge ratio or within a specified range of mass-to-charge ratios, and to further control the voltage source VS2to cause the dissociation device, instrument or stage to dissociate, e.g., fragment, the charged particles exiting the charged particle filtering device or instrument such that the dissociated charged particles exiting the dissociation device, instrument or stage enter the inlet A1of the charge filter instrument10. In some embodiments, a second charged particle filtering device or instrument may be disposed between the dissociation device, instrument or stage and the inlet A1of the charge filter instrument10, and the processor24may be operable in such embodiments to control the voltage source VS2to cause the second charged particle filtering device or instrument to pass to the inlet A1of the charge filter instrument10only dissociated ions above or below a threshold mass-to-charge ratio or within a specified range of mass-to-charge ratios. Other implementations of the one or more ion processing stage(s) IPS1-IPSRwithin the ion source or source region30will occur to those skilled in the art, and it will be understood that all such other implementations are intended to fall within the scope of this disclosure.

Referring now toFIG.16, an example embodiment is shown of the ion measurement stage104illustrated inFIGS.1and12-14and briefly described above. In the illustrated embodiment, the ion measurement stage104illustratively includes one or more ion measurement instruments IMI1-IMIS, where S may be any positive integer. In some embodiments, the processor24is illustratively programmed to control each of the one or more ion measurement instruments IMI1-IMIS, e.g., via control of the voltage source VS3, in a conventional manner to cause the ion measurement instrument(s) to measure one or more molecular characteristics of charged particles contained therein and/or passing therethrough, and/or to measure and produce information from which one or more molecular characteristics of charged particles contained therein and/or passing therethrough. In any case, ion measurement information produced by the one or more ion measurement instruments IMI1-IMISis illustratively processed by the processor24to produce, store and, in some embodiments, display the processed molecular characteristic information. In other embodiments, charge selected ions could be deposited on a suitable surface or in a matrix for collection and analysis by other methods.

Examples of such ion measurement instruments IMI1-IMISmay include, but are not limited to, in any order and/or combination, one or more devices and/or instruments for separating charged particles in time according to one or more molecular characteristics, one or more devices and/or instruments for filtering charged particles according to one or more molecular characteristics, one or more instruments for separating charged particles based on magnetic moment, one or more instruments for separating charged particles based on dipole moment, and the like. Examples of the one or more devices and/or instruments for separating charged particles in time according to one or more molecular characteristics include, but are not limited to, one or more mass spectrometers, one or more ion mobility spectrometers, and the like. Examples of the one or more mass spectrometers, in embodiments of the ion measurement stage104which include one or more thereof, include, but are not limited to, a time-of-flight (TOF) mass spectrometer, a reflectron mass spectrometer, a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer, a quadrupole mass spectrometer, a triple quadrupole mass spectrometer, a magnetic sector mass spectrometer, an orbitrap, or the like. Examples of the one or more ion mobility spectrometers, in embodiments of the ion measurement stage104which include one or more thereof, include, but are not limited to, a single-tube linear ion mobility spectrometer, a multiple-tube linear ion mobility spectrometer, a circular-tube ion mobility spectrometer, or the like. Examples of one or more devices and/or instruments for filtering charged particles include, but are not limited to, one or more devices or instruments for filtering charged particles according to mass-to-charge ratio, one or more devices or instruments for filtering charged particles according to particle mobility, magnetic moment, dipole moment, and the like. Examples of the one or more devices or instruments for filtering charged particles according to mass-to-charge ratio, in embodiments of the ion measurement stage104which include one or more thereof, include, but are not limited to, a quadrupole mass analyzer or quadrupole mass filter, a quadrupole ion trap mass analyzer or mass filter, a magnetic sector mass analyzer, a time-of-flight mass analyzer, a reflectron mass analyzer, a Fourier transform ion cyclotron resonance (FTICR) mass analyzer, an orbitrap, or the like. Examples of the one or more devices or instruments for filtering charged particles according to particle mobility, in embodiments of the ion measurement stage104which include one or more thereof, include, but are not limited to, a single-tube linear ion mobility spectrometer, a multiple-tube linear ion mobility spectrometer, a circular-tube ion mobility spectrometer, or the like. It will be understood that the ion measurement stage104may include one or any combination, in any order, of any such instruments for separating charged particles in time according to one or more molecular characteristics and/or one or more devices or instruments for filtering charged particles according to one or more molecular characteristics, and the like, and that some embodiments may include multiple adjacent or spaced-apart ones of any such instruments or devices.

Referring now toFIG.17, an embodiment is shown of still another particle measurement device400which includes two spaced-apart charge filter instruments101,102separated by an ion processing region402. In the illustrated embodiment, an ion source region30, as described above, is coupled to an inlet end of a first charge filter instrument101, and the ion outlet end of the charge deflection or steering region14of the first charge filter instrument101is coupled to an inlet of the ion processing region402, an ion outlet of the ion processing region402is coupled to the inlet end of the second charge filter instrument102, and the ion outlet end of the charge deflection or steering region14of the second charge filter instrument102is coupled to an inlet of an ion storage, steering and/or measurement stage(s)32, also as described above. Each of the charge filter instruments101,102includes a drift region12having an ion inlet A1with the charge detector array16including the plurality of charge detection cylinders161-16Naxially arranged within the drift tube12A between the ion inlet A1and ion outlet A2thereof as depicted inFIG.1and described above, and further includes the charge deflection or steering region14, in any of the forms illustrated and/or described herein, coupled to the outlet end of the drift tube12A.

The ion processing region402of the particle measurement device400illustratively includes one or more ion processing stages IS1-IST, where T may be any positive integer. The one or more of the ion processing stages IS1-ISTmay illustratively include, for example, but is not limited to, one or more conventional instruments for separating ions according to one or more molecular characteristics (e.g., according to ion mass-to-charge ratio, ion mobility, magnetic moment, dipole moment, or the like) and/or one or more conventional ion processing instruments for collecting and/or storing ions (e.g., one or more quadrupole, hexapole and/or other ion traps), one or more conventional instruments or devices for filtering ions (e.g., according to one or more molecular characteristics such as ion mass-to-charge ratio, ion mobility, magnetic moment, dipole moment, and the like), one or more instruments, devices or stages for fragmenting or otherwise dissociating ions, and the like. It will be understood that the ion processing stage402may include one or any combination, in any order, of any such instruments, devices or stages, and that some embodiments may include multiple adjacent or spaced-apart ones of any such instruments, devices or stages. It will be further understood that any of the example combinations of instruments, devices or stages described above may be implemented as, or as part of, the ion processing stage402. Those skilled in the art will recognize other instruments, devices and/or stages that may be included in the ion processing stage402, whether or not illustrated and/or described herein, as well as other combinations of instruments, devices or stages that may be implemented as, or as part of, the ion processing stage402, and it will be understood that all such other instruments, devices and/or stages, as well as any combination of any instruments, devices and/or stages, are intended to fall within the scope of this disclosure.

It will be appreciated that because the charge magnitude and/or charge state of any individual charged particle, or of any collection, set or group of charged particles, passed to the ion measurement stage104of any of the particle measurement instruments100,200,300,400described herein will be known, i.e., as a result of the control and operation of the charge filter instrument10as described above, molecular characteristic information not heretofore obtainable from conventional ion measurement instruments may now be easily determined. As one non-limiting example, particle mass-to-charge ratio values obtainable from conventional mass spectrometers and mass analyzers may be easily converted to particle mass values using the known charge magnitude or charge state information. As another non-limiting example, particle mobility values obtainable from conventional ion mobility spectrometers may be easily converted to particle collision cross-sectional area values using the known charge magnitude or charge state information. As a further non-limiting example, with the charge magnitude or charge state of collections, groups or sets of charged particles known, conventional mass-to-charge ratio filters may be operated as true mass filters to select for passage particles having a specified mass or range of masses. Other examples will occur to those skilled in the art, and any such other examples are intended to fall within the scope of this disclosure.

While this disclosure has been illustrated and described in detail in the foregoing drawings and description, the same is to be considered as illustrative and not restrictive in character, it being understood that only illustrative embodiments thereof have been shown and described and that all changes and modifications that come within the spirit of this disclosure are desired to be protected. For example, while several structures are illustrated in the attached figures and are described herein as being controllable and/or configurable to establish one or more electric fields therein configured and oriented to accelerate and/or steer and/or otherwise operate on charged particles, those skilled in the art will recognize that acceleration and/or steering of and/or other operation on charged particles may, in some cases, be alternatively or additionally accomplished via one or more magnetic fields. It will be accordingly understood that any conventional structures and/or mechanisms for substituting or enhancing one or more of the electric fields described herein with one or more suitable magnetic fields are intended to fall within the scope of this disclosure.