Patent Publication Number: US-9905410-B2

Title: Time-of-flight mass spectrometry using multi-channel detectors

Description:
RELATED APPLICATIONS 
     This application claims the benefit of U.S. Provisional Patent Application Ser. No. 62/110,508, filed Jan. 31, 2015, titled “TIME-OF-FLIGHT MASS SPECTROMETRY USING MULTI-CHANNEL DETECTORS,” the content of which is incorporated by reference herein in its entirety. 
    
    
     TECHNICAL FIELD 
     The present invention relates generally to time-of-flight mass spectrometry (TOF-MS), and particularly to processing multiple ion beams in TOF-MS instruments. 
     BACKGROUND 
     A mass spectrometry (MS) system in general includes an ion source for ionizing molecules of a sample of interest, followed by one or more ion processing devices providing various functions, followed by a mass analyzer for separating ions based on their differing mass-to-charge ratios (or m/z ratios, or more simply “masses”), followed by an ion detector at which the mass-sorted ions arrive. An MS analysis produces a mass spectrum, which is a series of peaks indicative of the relative abundances of detected ions as a function of their m/z ratios. Mass spectrometers are commonly used to determine the chemical composition of mixtures by precise measurement of the mass-to-charge ratio of the constituent molecular ions. 
     One particular type of mass spectrometer is a time-of-flight mass spectrometer (TOF-MS), which is utilized for molecular and elemental identification within a variety of disciplines ranging from medicine, biological research, environmental monitoring, chemical manufacturing, energy, and forensics. Time-of-flight mass spectrometry (TOF-MS) offers a powerful combination of mass resolution, accuracy, speed, and mass range which together make the technique well-suited for the analytical challenges presented by these fields. TOF-MS utilizes a high-resolution mass analyzer (TOF analyzer) in the form of a flight tube, which encloses a space that is electric field-free except for localized fields imparted by devices in the flight tube such as an ion mirror. An ion accelerator (or pulser) injects ions in pulses (or packets) into the flight tube. Ions of differing masses travel at different velocities through the flight tube and thus separate (spread out) according to their differing masses before arriving at the ion detector, enabling mass resolution based on time-of-flight. In a typical TOF-MS, ions travel along a drift direction through one or more gas-filled ion guides, and one or more beam-limiting apertures operating in a collision-free environment, and into the pulsed ion accelerator. In an orthogonal acceleration TOF-MS (oaTOF-MS), the ion accelerator receives the ions along the drift direction and injects the ions along an acceleration direction orthogonal to the drift direction. The flight tube may include one or more ion mirrors (or “reflectrons”) that increase the length of the ion flight path and provide certain advantages. 
     In TOF-MS, chemical composition is determined by accurately measuring the masses of individual ions drawn from the sample. The critical mass measurement stage is realized by measuring the time elapsed as ions travel from an ion accelerator through a known path length. Ions end their flight on a fast ion detector at which a single ion is transformed into a nanosecond-scale electronic signal, which is digitized with a high speed data acquisition system. The inherent simplicity and speed of this process translates into multiple analytical advantages for the end user. Because TOF-MS is able to gather a complete mass spectrum for each firing of the ion accelerator, it is particularly well-suited for tandem mass spectrometry (MS/MS) in which the fragmentation spectrum associated with a particular parent ion mass is measured. 
     Orthogonal-acceleration TOF-MS instruments have a primary ion beam that travels at low energy (10-50 eV) in a direction known as the drift direction, and an ion accelerator that accelerates the ions in an acceleration direction orthogonal to the drift direction. A well-known problem attending a TOF-MS instrument is that its duty cycle is inherently inefficient. The origin of the duty-cycle inefficiency lies in the fact that the ion accelerator is inherently pulsed while most mass spectrometer ion sources are continuous. The mass analysis time, and hence the firing period of the ion accelerator, is equal to the time-of-flight for the largest mass measured (i.e., the longest flight time associated with any ion packet injected into the flight tube) and is generally much longer than the time it takes to fill the ion accelerator. Consequently, ions that enter the ion accelerator more than one fill-time before the next firing of the ion accelerator are lost. The duty cycle is the portion of ions of the primary ion beam that is accelerated and transmitted through the ion accelerator into the TOF mass analyzer. Duty cycle is equal to the ratio of the ion accelerator fill-time to the firing period and depends on ion mass. 
     Known methods for improving duty cycle loss can be divided into two classes. The first class of methods involves trapping the ions before the ion accelerator to create a pulsed beam from the original continuous beam. The trapping methods suffer from difficulties associated with ejecting the ions from the trap with appropriate timing, particularly when ion-ion repulsion is considered, as well as the ion loss associated with the mass separation between the ion trap and the ion accelerator. The second class of methods employ what is known as “multi-pulsing” or “multiplexing” wherein the ion accelerator is fired to inject a new ion packet before the previous ion packet has completed its flight path in the mass analyzer. Multi-pulsing results in more than one ion packet being present in the flight tube at the same time, which can lead to overlapping between successive ion packets, with the slower ions of one ion packet being overtaken by the faster ions of a subsequently fired ion packet. Multi-pulsing thus often necessitates reconstruction of a meaningful mass spectrum from the convoluted raw detector data, which requires some means of determining from which accelerator firing each detected ion originates. Known multi-pulsing methods use slight variations in pulse firing time (dithering) to encode the firing number. Signal processing algorithms are then used to reconstruct the actual mass spectrum based on the knowledge of the encoding scheme. The algorithms rely on statistical inference and are subject to error due to imperfect reconstruction, and often require a large amount of computer processing. 
     Therefore, there is a need for improving the duty cycle in TOF-MS while avoiding the problems associated with the known, conventional approaches. 
     SUMMARY 
     To address the foregoing problems, in whole or in part, and/or other problems that may have been observed by persons skilled in the art, the present disclosure provides methods, processes, systems, apparatus, instruments, and/or devices, as described by way of example in implementations set forth below. 
     According to one embodiment, a time-of-flight mass spectrometry (TOF-MS) system includes: an ion source; a TOF analyzer comprising an ion accelerator, a flight tube, and an ion detector comprising a plurality of channels; and an ion dispersion device configured for dispersing ions from the ion source into a plurality of spatially separated flight paths in the flight tube, wherein respective channels are aligned with the flight paths. 
     According to another embodiment, a method for performing time-of-flight mass spectrometry (TOF-MS) includes: transmitting ions along a drift axis into an ion accelerator; injecting the ions as a plurality of sequential ion packets from the ion accelerator into a flight tube; modulating a drift energy of the ions according to a repeating modulation sequence comprising a plurality of iterations, wherein the drift energy at each iteration is different from the drift energies of the other iterations, and wherein the ions travel in the flight tube in a plurality of flight paths spatially separated along the drift axis; and detecting arrival times of the ions at a plurality of channels of an ion detector aligned with the respective flight paths. 
     According to another embodiment, a method for performing time-of-flight mass spectrometry (TOF-MS) includes: transmitting ions along a drift axis into an ion accelerator; injecting the ions as a plurality of sequential ion packets from the ion accelerator into a flight tube; modulating a transverse position the ions such that the ions travel in the flight tube in a plurality of flight paths spatially separated along a transverse axis orthogonal to the drift axis; and detecting arrival times of the ions at a plurality of channels of an ion detector aligned with the respective flight paths. 
     According to another embodiment, a method for performing time-of-flight mass spectrometry (TOF-MS) includes: transmitting ions along a drift axis into an ion accelerator; injecting the ions into a flight tube in a plurality of sequential accelerator firing events; detecting arrival times of the ions at a multi-channel ion detector; measuring masses of the ions of each of the ion packets; and based on the detected arrival times and measured masses, determining from which accelerator firing event each ion was injected. 
     According to another embodiment, a method for performing time-of-flight mass spectrometry (TOF-MS) includes: transmitting ions into a sector instrument, and outputting the ions from the sector instrument in a plurality of mass-discriminated ion beams that are spatially separated along a transverse axis; transmitting the ion beams simultaneously into an ion accelerator along a drift axis orthogonal to the transverse axis; injecting ion packets from each of the ion beams into a flight tube, wherein the ion packets travel through the flight tube simultaneously in a plurality of flight paths spatially separated along the transverse axis, the flight paths corresponding to the respective ion beams; and detecting arrival times of the ions at a plurality of channels of an ion detector aligned with the respective flight paths. 
     Other devices, apparatus, systems, methods, features and advantages of the invention will be or will become apparent to one with skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, methods, features and advantages be included within this description, be within the scope of the invention, and be protected by the accompanying claims. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The invention can be better understood by referring to the following figures. The components in the figures are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. In the figures, like reference numerals designate corresponding parts throughout the different views. 
         FIG. 1  is a schematic view of an example of a time-of-flight mass spectrometer (TOF-MS) or time-of-flight mass spectrometry (TOF-MS) system according to some embodiments, which may be utilized in the implementation of the subject matter described herein. 
         FIG. 2  is a schematic view in the y-z plane of an example of a TOF analyzer according to some embodiments. 
         FIG. 3  illustrates an example of a simulation of a TOF analyzer operating with five ion channels in a 1-meter long TOF flight tube, according to some embodiments. 
         FIG. 4  illustrates an example of a simulation of a multi-reflecting TOF instrument with four ion channels in a 13-meter flight path, according to some embodiments. 
         FIG. 5  is a schematic view of an example of an ion accelerator and upstream optics, illustrating examples of DC potentials that may be applied during the loading and acceleration phases. 
         FIG. 6  is a zoomed-in view of the entrance region of the ion accelerator illustrated in  FIG. 5 . 
         FIG. 7  is a schematic view of an example of an ion accelerator and an ion deflector according to some embodiments. 
         FIG. 8  is a schematic view in the x-z plane of an example of a TOF-MS system according to other embodiments. 
         FIG. 9  is a schematic view in the y-z plane of an example of a TOF analyzer according to other embodiments. 
         FIG. 10  is a schematic view in the x-z plane of an example of a TOF-MS system according to other embodiments. 
         FIG. 11  is a schematic view in the x-z plane of an example of an RF ion guide configured as a multi-channel ion fragmentation device, according to some embodiments. 
         FIG. 12A  is a side (length-wise) view in the y-z plane of another example of an RF ion guide configured as a multi-channel ion fragmentation device, according to some embodiments. 
         FIG. 12B  is a cross-sectional view in the x-y plane of the RF ion guide illustrated in  FIG. 12A . 
         FIG. 13  is a perspective view of another example of an RF ion guide configured as a multi-channel ion fragmentation device, according to some embodiments. 
     
    
    
     DETAILED DESCRIPTION 
       FIG. 1  is a schematic view of an example of a time-of-flight mass spectrometer (TOF-MS) or time-of-flight mass spectrometry (TOF-MS) system  100  according to some embodiments, which may be utilized in the implementation of the subject matter disclosed herein. The operation and design of various components of TOF-MS systems are generally known to persons skilled in the art and thus need not be described in detail herein. Instead, certain components are briefly described to facilitate an understanding of the subject matter presently disclosed. 
     For illustrative purposes,  FIG. 1  (and other figures) includes a Cartesian coordinate frame of reference comprising a drift axis (z-axis), an acceleration axis (y-axis) orthogonal to the drift axis, and a transverse axis (x-axis) (into and out of the drawing sheet, in  FIG. 1 ) orthogonal to the acceleration axis and to the drift axis. The acceleration axis and the transverse axis, which may both be referred to herein as “transverse” axes, lie in a transverse (x-y) plane orthogonal to the drift (z) axis. The coordinate frame is primarily intended to show the relative orientations of the three axes; the origin (0,0,0) of the coordinate frame relative to the TOF-MS system  100  has been arbitrarily located. In the present disclosure, the term “direction” may be used interchangeably with the term “axis.” The primary direction of ion travel through the TOF-MS system  100  is along the drift axis, left to right from the perspective of  FIG. 1 . 
     The TOF-MS system  100  may generally include, in series of ion process flow along the drift axis, an ion source  104 , one or more ion guides  108 , ion optics  112 , a time-of-flight (TOF) mass analyzer (TOF analyzer)  116 , an ion detector  120 , and a computing device  140 . In general operation, sample molecules are introduced into the ion source  104 , and the ion source  104  produces ions from sample molecules and transmits the ions to the ion guide(s)  108 . The ion guide(s)  108  focus the ions as an ion beam and transmit the ions to the ion optics  112 . The ion guide(s)  108  may perform additional ion processing functions such as compressing the ion beam, thermalizing (cooling) the ions, and other functions described below. The ion optics  112  transmit the ions to the TOF analyzer  116 . The ion optics  112  may provide a collision-free environment and include beam-limiting apertures that shape the ion beam. The TOF analyzer  116  allows the ions to disperse based on differing flight times (due to their differing mass-to-charge (m/z) ratios) and travel to the ion detector  120 . The ion detector  120  produces an ion signal that is then utilized to calculate actual times-of-flight from which m/z ratios are correlated, and construct a mass spectrum descriptive of the sample molecules as appreciated by persons skilled in the art. 
     The ion source  104  may be any type of continuous-beam or pulsed ion source suitable for producing analyte ions for spectrometry. Examples of ion sources  104  include, but are not limited to, electron ionization (EI) sources, chemical ionization (CI) sources, photo-ionization (PI) sources, electrospray ionization (ESI) sources, atmospheric pressure chemical ionization (APCI) sources, atmospheric pressure photo-ionization (APPI) sources, field ionization (FI) sources, plasma or corona discharge sources, laser desorption ionization (LDI) sources, and matrix-assisted laser desorption ionization (MALDI) sources. In some embodiments, the ion source  104  may include two or more ionization devices, which may be of the same type or different type. Depending on the type of ionization implemented, the ion source  104  may reside in a vacuum chamber or may operate at or near atmospheric pressure. Sample material to be analyzed may be introduced to the ion source  104  by any suitable means, including hyphenated techniques in which the sample material is an output  124  of an analytical separation instrument such as, for example, a gas chromatography (GC) or liquid chromatography (LC) instrument (not shown). 
     One or more ion guides  108  may include an arrangement of electrodes configured for confining ions along an axis while enabling the ions to be transmitted along the axis. For this purpose, depending on the type of ion guide radio frequency (RF) and/or direct current (DC) voltages may be applied to the ion guide electrodes. One or more of the ion guides  108  may have a converging geometry that compresses the ion beam so as to improve transmission into the next device. One or more of the ion guides  108  may be configured as a multipole structure with electrodes elongated generally along the direction of ion travel. One or more of the ion guides  108  may alternatively be configured as a straight cylindrical stacked-ring structure or an ion funnel, with ring-shaped electrodes or aperture-containing plate electrodes oriented orthogonal to the direction of ion travel. As a further alternative, one or more of the ion guides  108  may have a planar geometry as described below. 
     The ion optics  112  may occupy an evacuated volume of a desired axial length between the ion guide(s)  108  and the entrance to the TOF analyzer  116 . The evacuated volume may be essentially collision-free, i.e., substantially devoid of neutral gas-phase molecules. The ion optics  112  may include one or more ion lenses arranged about an axis. An ion lens may be, as examples, a cylindrical electrode coaxial with the axis, a plate with an aperture on-axis, or pair of plates or half-cylinders separated by a gap on-axis. DC potentials may be applied to one or more of the ion lenses. One or more of the ion lenses may be configured as an ion slicer that ensures that the geometry of the ion beam matches the acceptance area of the entrance to the TOF analyzer  116 , and that the ion energy distribution in at least one direction transverse to the direction of ion travel is a desired low value. 
     The TOF analyzer  116  includes an ion accelerator  162  leading into an evacuated TOF flight tube  164  that defines an electric field-free flight region. In the illustrated embodiment, the ion accelerator  162  is an orthogonal ion accelerator that receives ions along the drift (z) axis and accelerates ion packets into the flight tube  164  along the acceleration (y) axis. For this purpose the electrodes of the ion accelerator  162  may include a repeller plate  166  (bottom electrode), acceleration grids  168  above the repeller plate  166 , and a top grid or exit grid  170  above the acceleration grids  168 . Ions enter the ion accelerator  162  in a loading region between the repeller plate  166  and the acceleration grids  168 , and are accelerated into the flight tube  164  through application of appropriate potentials to the repeller plate  166  and acceleration grids  168 . In the orthogonal configuration, the flight tube  164  is elongated along the acceleration (y) axis. 
     The illustrated embodiment further has a reflectron configuration in which the ion detector  120  is positioned generally at the same axial end (relative to the acceleration axis) of the flight tube  164  as the ion accelerator  162 , and spaced at a distance along the drift axis from the ion accelerator  162 . An ion mirror (or reflector)  174  is positioned at the opposite axial end (relative to the acceleration axis) of the flight tube  164 , whereby the ion mirror  174  is spaced from both the ion accelerator  162  and the ion detector  120  along the acceleration (y) axis. 
     The ion mirror  174  may be a single-stage, dual-stage, or gridless reflectron. The ion mirror  174  generates a potential gradient that decelerates ions down to zero velocity along the y direction and then accelerates the ions in the opposite direction, whereby ions exit the ion mirror  174  at the same kinetic energy they had when they entered the ion mirror  174 . However, for ions of the same mass (m/z ratio), faster ions entering the ion mirror  174  sooner at higher kinetic energies penetrate deeper into the ion mirror  174  before stopping and turning around to exit, in comparison to slower ions of the same mass as the faster ions. These slower ions enter the ion mirror  174  later at lower kinetic energies and do not penetrate as far into the ion mirror  174  as the faster ions before stopping and turning around to exit. Hence, the slower ions do not spend as much time in the ion mirror  174  as the faster ions of the same mass, and thus are able to catch up with the faster ions such that all slower ions and faster ions of the same mass arrive at the ion detector  120  ideally at the same time. The ion mirror  174  thus creates a reflected focal point at the location of the ion detector  120 , and reduces the variation in flight time spread due to the kinetic energy spread of ions of the same mass. The ion mirror  174  also increases the focal length of the TOF analyzer  116  and thus the overall flight times of the ions, which improves peak separation.  FIG. 1  schematically depicts a representative ion flight path  178  through the flight tube  164 , including the turning point imposed by the ion mirror  174 . 
     In operation, the ion accelerator  162  accelerates (injects) ions into the flight tube  164  at a predetermined pulsing rate (or firing rate). Hence, the ion accelerator  162  injects discrete ion packets (or ion pulses) into the flight tube  164 . Each ion packet may include a range of ion masses. In each ion packet, ions of different masses travel through the flight tube  164  at different velocities and thus have different overall times-of-flight, i.e., ions of smaller masses travel faster than ions of larger masses. Each ion packet spreads out (is dispersed) in space in accordance with the time-of-flight distribution. The ion detector  120  detects and records the time that each ion arrives at (impacts) the ion detector  120 . A data acquisition process implemented by the computing device  140  correlates the recorded times-of-flight with m/z ratios. 
     In some embodiments, the ion accelerator  162  is operated at a multi-pulsing (or multiplexing) rate. In the multi-pulsing or multiplexing mode, the ion accelerator  162  fires at a rate fast enough that more than one ion packet occupies the flight tube  164  at the same time. That is, before all ions of a previous ion packet have completed their flight paths in the flight tube  164  and reached the ion detector  120 , the next ion packet is injected into the flight tube  164 . 
     In typical embodiments of the present disclosure, the ion detector  120  is a multi-channel ion detector. As appreciated by persons skilled in the art, a multi-channel ion detector is configured for collecting and measuring the flux (or current) of mass-discriminated ions over a plurality of channels. Each channel, or pixel, corresponds to a discrete detection area or spot on the detector face, and is capable of detecting the impact of an ion at that detection spot and convert the detection event into an electrical signal independently from the other channels. Thus, a multi-channel ion detector is capable of making multiple measurements at multiple positions on the detector, and thereby generate multiple measurement signal outputs. Moreover, multiple channels can operate in this manner simultaneously provided they are spatially (optically) aligned with multiple ion flight paths. Each channel, for example, may be configured or operate as an individual electron multiplier, with each detection spot being a slot or tube. The size of the detection spots, and the spacing between adjacent detection spots, may be on the order of micrometers (e.g., less than 20 μm). The multiple channels may be arranged in a one-dimensional (linear) array along a desired direction (e.g., the drift axis or transverse axis), or in a two-dimensional (2D) array. One non-limiting example of a multi-channel detector is a micro-channel plate (MCP) detector. 
     In some embodiments, the TOF-MS system  100  may be configured for implementing tandem MS (MS/MS). For example, the TOF-MS system  100  may be configured as a qTOF, or QqTOF instrument. Thus, the TOF-MS system  100  may include a first mass analyzer  132  upstream of the other mass analyzer  116  (the second, or final mass analyzer, in such embodiments), and an ion fragmentation device  136  between the first mass analyzer  132  and the second mass analyzer  116 . The first mass analyzer  132  is configured for selecting ions of a specific m/z ratio (mass) or m/z ratio range and is typically, but not necessarily, configured as a quadrupole mass filter. The ion fragmentation device  136  is often a collision cell, which typically includes a non-mass-resolving, RF-only ion guide enclosed in a cell. The collision cell is pressurized by an inert gas to a level sufficient for producing fragment ions by collision-induced dissociation (CID) as appreciated by persons skilled in the art. However, a fragmentation device other than a CID-based device may be utilized such as, for example, a device configured for implementing electron capture dissociation (ECD), electron transfer dissociation (ETD), or infrared multiphoton dissociation (IRMPD). The second mass analyzer  116  resolves the fragment ions outputted by the ion fragmentation device  136  on the basis of m/z ratio (mass,) and transmits the mass-resolved fragment ions to the ion detector  120 , which outputs measurement signals from which fragment mass spectra are then produced. 
     The TOF-MS system  100  also includes a vacuum system for maintaining various interior regions of the TOF-MS system  100  at controlled, sub-atmospheric pressure levels. As appreciated by persons skilled in the art, the vacuum system may include vacuum lines communicating with the various interior regions via vacuum ports or exhaust ports, one or more vacuum-generating pumps, and associated components. The vacuum lines may also remove residual non-analytical neutral molecules from the ion path of the TOF-MS system  100 . 
     The TOF-MS system  100  may also include a computing device (or system controller)  140 . The computing device  140  is schematically depicted as representing one or more modules (or units, or components) configured for controlling, monitoring and/or timing various functional aspects of the TOF-MS system  100  described above. One or more modules of the computing device  140  may be, or be embodied in, for example, a desktop computer, laptop computer, portable computer, tablet computer, handheld computer, mobile computing device, personal digital assistant (PDA), smartphone, etc. The computing device  140  may also schematically represent all voltage sources not specifically shown, as well as timing controllers, clocks, frequency/waveform generators and the like as needed for applying voltages to various components of the TOF-MS system  100 , including voltages applied to an ion dispersion device such as an ion deflector, sector instrument, or ion lenses as described below. The computing device  140  may also be configured for receiving the ion detection signals from the ion detector  120  and performing tasks relating to data acquisition and signal analysis as necessary to generate chromatograms, drift spectra, and mass (m/z ratio) spectra characterizing the sample under analysis. The computing device  140  may also be configured for providing and controlling a user interface that provides screen displays of spectrometric data and other data with which a user may interact. The computing device  140  may include one or more reading devices on or in which a tangible computer-readable (machine-readable) medium may be loaded that includes instructions for performing all or part of any of the methods disclosed herein. For all such purposes, the computing device  140  may be in signal communication with various components of the TOF-MS system  100  via wired or wireless communication links (as partially represented, for example, by a dashed line between the computing device  140  and the TOF analyzer  116 ). Also for these purposes, the computing device  140  may include one or more types of hardware, firmware and/or software, as well as one or more memories and databases. 
     In the conventional operation of a TOF-MS system, the average drift-energy of the primary ion beam transmitted into the ion accelerator  162  is typically 10-50 eV and fixed to ensure the ions hit a single-channel detector. The drift energy, together with the flight path length and energy, determine where the ion detector  120  should optimally be located to capture the ions. In the conventional TOF-MS system, the drift energy is fixed for optimum detection efficiency. In such a system, the duty cycle is inherently low as described above. The duty cycle can be improved by operating in a multi-pulsing mode, but conventionally this has required demultiplexing algorithms that are problematic, as also described above. 
     According to some embodiments of the present disclosure, a technique referred to herein as “drift energy labeling” or “drift energy modulation” is provided to improve the duty cycle of a TOF-MS system. In this technique, the drift energy of the ions is modulated between successive firings of the ion accelerator to send ion packets from successive acceleration pulses to different channels of the ion detector. One embodiment of the drift energy labeling technique is illustrated in  FIG. 2 .  FIG. 2  is a schematic view in the y-z plane of an example of a TOF analyzer  216 , showing an ion accelerator  262  and a multi-channel ion detector  220 . A repeating pulse sequence of N ion pulses (N firing events of the ion accelerator  262 ) is defined. In the illustrated example N=3 but in other examples may be less than or more than 3. The drift energy of the ions in each iteration (firing of the ion accelerator  262 ) of the pulse sequence is set to a value different from the respective drift energies of the ions in the other iterations of the sequence. Thus in the illustrated example (N=3), the ions of a first ion packet injected during “firing number  1 ” of the ion accelerator  262  have a first drift energy, the ions of a second (next) ion packet injected during “firing number  2 ” have a second drift energy different from the first drift energy, and the ions of a third (next) ion packet injected during “firing number  3 ” have a third drift energy different from the first drift energy and from the second drift energy. This sequence may be repeated any number of times during the normal course of analyzing the sample under investigation by way of TOF-MS. Each different value of drift energy is uniquely associated with one of the iterations (firing numbers) of the sequence. Hence, the ion pulses of the sequence are encoded by the drift energy values respectively assigned to the ion pulses. 
     As illustrated in  FIG. 2 , the drift energy of a given ion determines the flight path that the ion ultimately takes to arrive at the ion detector  220 . That is, ions having different drift energies will travel through the flight tube along different flight paths. Different channels of the ion detector  220  are aligned with the different flight paths. In the illustrated example, a primary ion beam  242  is transmitted into the ion accelerator  262  during a loading phase. The drift energy is modulated such that in the first pulse of the sequence the ion packet travels along a first flight path  278 A, and in the second pulse of the sequence the ion packet travels along a second flight path  278 B, and in the third pulse of the sequence the ion packet travels along a third flight path  278 C. As schematically illustrated in  FIG. 2 , because the drift energy is different during each iteration of the pulsing sequence, the flight paths  278 A,  278 B, and  278 C are spatially separated from each other along the drift axis. The ion detector  220  includes a plurality of different detector channels. In the present embodiment, the ion detector  220  at the least includes a plurality of different ion detector channels  222 A,  222 B, and  222 C spaced along the drift axis. The ion detector channels  222 A,  222 B, and  222 C are spatially (or optically) aligned with the respective flight paths  278 A,  278 B, and  278 C. Thus, signals outputted by the ion detector channels  222 A,  222 B, and  222 C can be correlated with the respective flight paths  278 A,  278 B, and  278 C, and thus with the respective ion packets injected by the respective accelerator firing numbers of the repeating sequence. 
     A small range of drift energies may map onto each particular detector channel  222 A,  222 B, and  222 C. If the drift energy spread is small enough, the drift energy of a particular accelerator pulse and its corresponding detector channel  222 A,  222 B, and  222 C can encode the accelerator firing number (firing event). By cycling through a series of predetermined drift energies, the ion accelerator  262  can be fired faster than normal and hence duty cycle is improved. It can be seen that this drift energy modulation technique makes multi-pulsing feasible and desirable, as any deconvolution process needed to construct a single TOF mass spectrum from the raw spectral information obtained from the signals outputted from the ion detector channels  222 A,  222 B, and  222 C may be quite simple and accurate. 
     Denoting the number of detector channels as N det , it is seen that the duty cycle is improved by a factor of N det , up to the point at which it reaches 100%. The maximum number of detector channels may be determined by the available space and the ability of the ion optics to focus the primary beam into resolvable spots on the ion detector  220 . The resolvable spot size, and hence N det , may be determined by the drift energy spread and the tolerable resolution loss associated with the ion focusing.  FIG. 3  illustrates an example of a simulation of a TOF analyzer operating with five ion channels in a 1-meter long TOF flight tube, where the duty cycle is improved by 5× when the drift energy spread is 0.4 eV. 
     For longer TOF instruments, including multi-reflecting TOF instruments, the relative energy modulation may be less than 0.4 eV.  FIG. 4  illustrates an example of a simulation of a multi-reflecting TOF instrument with a 13-meter flight path and four resolvable channels for a 0.2 eV energy spread. The drift energy modulation technique disclosed herein may be particularly well-suited for multi-reflecting planar TOF systems with gridless mirrors, as the planar symmetry of these mirrors allows for large acceptance along the drift direction. To further increase the number of detector channels, it may be advantageous to reduce the drift energy spread with buffer gas cooling in the ion beam source (i.e., at a location upstream of the TOF analyzer) and to optimize the optics that focus the ions into spots dispersed along the drift direction. 
     If it is not possible to reduce the drift energy, it may be advantageous to filter the ions by drift energy before they enter the ion accelerator  262 . This might also be necessary for situations in which it is not possible to reduce the drift energy spread to an acceptable level (e.g., &lt;0.5 eV) with buffer gas cooling. Such a filter could be one or more electrostatic mirrors, sectors, or lenses that separate ions in space based on their drift energy, in conjunction with an aperture that selects for ions of the required drift energy. 
     In some embodiments, drift energy modulation is performed on the ions in the primary ion beam  242  transmitted into the ion accelerator  262 . For example, the drift energy modulation may be realized by varying the voltages that accelerate the primary ion beam  242  into the ion accelerator  262 . The primary beam energy is determined by the difference in DC voltages applied to the ion beam source (e.g., ion optics upstream of the ion accelerator  262 , such as a buffer gas filled RF ion guide) and the ion accelerator  262  prior to the application of the high-voltage pulse that injects the ions into the flight tube, i.e., during the loading phase. The drift energy modulation may be realized by varying either the ion beam source DC voltage or the accelerator DC voltage, or both. It may be particularly advantageous to vary the ion accelerator voltage applied during loading, since this method avoids complications associated with the inter-mixing of ions of different masses and different energies in the region between the ion beam source and the ion accelerator  262 . 
       FIG. 5  is a schematic view of an example of an ion accelerator and upstream optics, illustrating examples of DC potentials that may be applied during the loading and acceleration phases. In this example, the same loading voltage is applied to both the bottommost “pusher” electrode and the gridded electrode above it, so there is no deflecting electric field in the acceleration direction during the loading phase. The variation in the loading voltage magnitude between subsequent firings is typically 1 to 20 V depending on the flight path length.  FIG. 6  is a zoomed-in view of the entrance region of the ion accelerator illustrated in  FIG. 5 .  FIG. 6  shows that the expansion and focusing associated with a 2 V deceleration potential is minimal. 
     In other embodiments, drift energy modulation may be performed on the ions while they are in the accelerator or after they have been accelerated into the flight tube. For example, the effective drift energy may be modulated by operating an ion deflector that is integrated into the ion accelerator or positioned just after it in the flight tube.  FIG. 7  is a schematic view of an example of an ion accelerator  762  and an ion deflector  744 . In this example, the ion deflector  744  includes two parallel electrodes. However, the ion deflector  744  generally may be realized by various configurations entailing the use of various types of electrodes (e.g., plate electrodes, grid electrodes, etc.), as appreciated by persons skilled in the art. Generally, DC potentials are applied to the electrodes of the ion deflector  744  at magnitudes and polarities effective for producing N different flight paths (e.g., flight paths  778 A,  778 B, and  778 C) spatially separated along the drift axis, containing ion packets extracted from a primary ion beam  742  transmitted into the ion accelerator  762 , and associated with respective N firings of the ion accelerator  762  according to a predetermined repeatable sequence. It will be noted that the use of an ion deflector in the flight tube may cause TOF aberration, potentially degrading mass resolution, and thus may be less preferred than performing drift energy modulation on the ions prior to acceleration into the flight tube. 
     According to other embodiments of the present disclosure, a technique referred to herein as “transverse position labeling” or “transverse position modulation” is provided to improve the duty cycle of a TOF-MS system. In this technique, the transverse position of the ions is modulated to send ion packets to different channels of the ion detector arranged along the transverse axis. One embodiment of the transverse position labeling technique is illustrated in  FIG. 8 .  FIG. 8  is a schematic view in the x-z plane of an example of a TOF-MS system  800 . The TOF-MS system  800  includes an ion dispersion device (or ion beam modulator)  844  followed by a TOF analyzer  816 , which includes an ion accelerator  862  and a multi-channel ion detector  820 . The ion detector  820  includes a plurality of detection channels, for example detection channels  822 A,  822 B,  822 C, and  822 D, spatially separated along the transverse axis. In the illustrated embodiment, the transverse position of the ions is modulated upstream of the ion accelerator  862 . Accordingly, the ion dispersion device  844  is positioned upstream of the ion accelerator  862 . The ion dispersion device  844  may be an ion deflector, such as described above. By varying DC potentials applied to appropriately positioned electrodes of the ion dispersion device  844 , the ion dispersion device  844  converts a primary ion beam  842  into N different ion beams, for example ion beams  846 A,  846 B,  846 C, and  846 D. In the illustrated example N=4 but in other examples may be less than or more than 4. 
     The ion beams  846 A,  846 B,  846 C, and  846 D may then be transmitted into the ion accelerator  862 , either simultaneously or at different firing rates. The ion accelerator  862  may then inject successive ion packets from each ion beam  846 A,  846 B,  846 C, and  846 D simultaneously. Consequently, the ion packets travel through the flight tube simultaneously (i.e., occupy the flight tube at the same time) in N different flight paths  878 A,  878 B,  878 C, and  878 D that are spatially separated along the transverse axis. The ions in the N different flight paths  878 A,  878 B,  878 C, and  878 D thus arrive at respective detection channels  822 A,  822 B,  822 C, and  822 D, which are spatially (or optically) aligned with the respective flight paths  878 A,  878 B,  878 C, and  878 D. The impact of an ion on a particular detection channel  822 A,  822 B,  822 C, and  822 D thus determines the ion packet (associated with one of the flight paths  878 A,  878 B,  878 C, and  878 D) and the ion beam  846 A,  846 B,  846 C, and  846 D from which that particular ion originated. 
     It will be noted that in  FIG. 8 , the bends in the flight paths  878 A,  878 B,  878 C, and  878 D are to be considered as being located at elevations on the acceleration axis. Thus, the flight paths  878 A,  878 B,  878 C, and  878 D are to be considered as projecting out of the drawing sheet. 
     Alternatively, the ion dispersion device  844  may be sector instrument. The sector instrument converts a primary ion beam  842  into N different ion beams, for example ion beams  846 A,  846 B,  846 C, and  846 D, by applying a static magnetic field and/or electrostatic field to the primary ion beam  842 . In response to the magnetic field, ions of different masses will physically separate into the different ion beams  846 A,  846 B,  846 C, and  846 D. Use of a sector instrument in this case results in the ion beams  846 A,  846 B,  846 C, and  846 D, and thus the ion packets in the respective flight paths  878 A,  878 B,  878 C, and  878 D, spanning narrower mass ranges. The sector instrument may include one or more magnetic sectors, or one or more electric (electrostatic) sectors, or a combination of both, as appreciated by persons skilled in the art. 
     As schematically shown in  FIG. 8 , the ion accelerator  862  is configured so as to be wide enough along the transverse axis to simultaneously receive multiple, transversely spaced ion beams. The ion accelerator  862  thus may be considered as including multiple loading/injection sites. In some embodiments, the ion accelerator  862  may include a plurality of transversely spaced, individually controllable ion accelerators. The separate ion accelerators may be operated to accelerate ion packets from respective ion beams  846 A,  846 B,  846 C, and  846 D simultaneously and at the same firing rate, or at different rates. Similarly, the TOF analyzer  816  may include one wide ion mirror or multiple ion mirrors in the flight tube. 
     The transverse position labeling technique implements multi-pulsing at least by way of simultaneously transmitting respective ion packets in parallel flight paths in the flight tube, and simultaneously detecting ion arrival times at the same number of detector channels. In some embodiments, the ion packets are accelerated at a normal (non-multiplexed) firing rate. In this case, with N det  detector channels, again it is seen that the duty cycle is improved by a factor of N det , up to the point at which it reaches 100%. Moreover, the raw data produced by the N det  detector channels are easily processed to construct a single mass spectrum. In other embodiments, the ion packets may be accelerated at a multiplexed firing rate, resulting in more than one ion packet traveling in each parallel flight path in the flight tube at the same time. In this case, some form of deconvolution/demodulation/decoding algorithm would likely be required to produce an easily interpretable mass spectrum. 
     In still other embodiments, a combination of the drift energy labeling technique described above and the transverse position labeling technique may be implemented. This combined technique enables ion packets to be accelerated at a multiplexed firing rate simultaneously into multiple parallel, transversely spaced flight paths. The combined technique, which may be characterized as entailing “two-dimensional” multi-pulsing or multiplexing, may result in a significantly improved duty cycle. The combined technique further enables a simplified demodulation algorithm to be implemented. The combined technique may utilize an ion accelerator having a two-dimensional array of detector channels, arranged along the drift axis and along the transverse axis. 
     In other embodiments of the transverse position labeling technique, the transverse position of the ions may modulated at or downstream from the ion accelerator  862 . In such embodiments, the ion dispersion device  844  may be integrated with or positioned downstream from the ion accelerator  862 . The ion dispersion device  844  may be an ion deflector, such as described above. Alternatively, the ion dispersion device  844  may be a sector instrument as described above, located in the flight tube. These other embodiments may be less preferable if they result in TOF aberrations. 
     Transverse position labeling may be more advantageous when a gridded ion mirror is utilized, in comparison to a grid-less ion mirror. The curved fields in a grid-less mirror restrict the size of the transverse acceptance. On the other hand, a gridded mirror has an approximately uniform electric field within each stage, and consequently its acceptance in the transverse direction is typically larger than a grid-less mirror of the same size. 
     According to other embodiments of the present disclosure, the duty cycle of a TOF-MS system is improved by measuring ion mass directly in addition to the ion time of flight. The ion accelerator may again be multi-pulsed, meaning the TOF mass analyzer is multiplexed and has multiple different accelerator launches in it at any given time. A second ion detection channel that is sensitive to ion mass is used in conjunction with the TOF measurement to determine from which accelerator firing each ion originates. Together the TOF channel and the mass-sensitive channel are utilized to determine the actual ion time of flight. The mass-sensitive detector may be embodied in channels of a multi-channel detector. Alternatively, an in-flight mass-dispersive sector may be provided upstream of the multi-channel detector, either upstream of the ion accelerator or in the flight tube. 
     Several different mass-sensitive detector channels are possible. For example, the average single ion pulse height outputted by many electron multiplier ion detectors scales as 1/√m where m is the ion mass, although other scalings are possible. Average single-ion pulse height encodes ion mass provided a single ion at a time is observed on each detector channel, the scaling is monotonic, and the pulse height distribution is sufficiently narrow. By using multiple detector channels or pixels, the single ion regime can be extended to higher total ion fluxes. The resolution of the direct ion mass measurement will be limited by the pulse height distribution. 
     In another embodiment, a mass-dispersive sector located in the TOF flight path. The ions are dispersed in space according to mass, and the position on the multi-channel detector encodes ion mass. The position on the multi-channel detector and time of ion arrival may be utilized together to constrain the possible accelerator firings and hence determine TOF.  FIG. 9  is a schematic view in the y-z plane of an example of a TOF analyzer  916 , showing an ion accelerator  962  and a multi-channel ion detector  920 . The ion detector  920  includes a plurality of detection channels, for example detection channels  922 A,  922 B, and  922 C, spatially separated along the drift axis. In the illustrated embodiment, the mass of the ions is analyzed (measured) in the flight tube, downstream of the ion accelerator  962 . Accordingly a mass-sensitive ion dispersion device  944 , such as a sector instrument as described above, is positioned in the flight tube. In operation, a primary ion beam  942  is transmitted into the ion accelerator  962 , which injects ion packets into the flight tube along a main flight path  978 , at pulse rate that may be a multiplexed pulse rate. The ion dispersion device  944  is positioned to receive the ion packets and output the ions into N different mass-resolved flight paths, for example flight paths  946 A,  946 B, and  946 C, which are spatially separated along the drift axis. In the illustrated example N=3 but in other examples may be less than or more than 3. The ions in the flight paths  946 A,  946 B, and  946 C arrive at respective detection channels  922 A,  922 B, and  922 C that are spatially (optically) aligned with the flight paths  946 A,  946 B, and  946 C. 
     Alternatively, the mass-sensitive ion dispersion device  944  may be positioned (oriented) to cause ion deflection in the flight tube along the transverse axis instead of along the drift axis. In this case, the detection channels  922 A,  922 B,  922 C, and  922 D would be spatially separated along the transverse axis. In a further embodiment, the mass-sensitive ion dispersion device  944  may be positioned to output ion beams spaced in parallel along the transverse axis as just described, and is operated in combination with the drift energy labeling technique described above. In this case, the ion accelerator  962  may include a two-dimensional array of detector channels arranged along the drift axis and along the transverse axis. 
     In another embodiment, the mass-sensitive ion dispersion device  944  may be located upstream of the ion accelerator  962 , as described above and illustrated in  FIG. 8 . In this case, the ion beam modulator  944  outputs multiple parallel, transversely spaced, mass-resolved ion beams that are simultaneously transmitted into the ion accelerator  962 . This embodiment is similar to the transverse position labeling technique discussed above in which an ion deflector is utilized, except that in this embodiment the mass range each detector channel sees is restricted and the aberrations caused by the magnetic or electric deflection do not degrade mass resolution because the deflection occurs outside the flight tube. As also described above, in such embodiment the ion accelerator  962  may include an array of ion accelerators arranged along the transverse axis. The ion accelerators may be operated at different rates, each optimized for their respective mass range. 
       FIG. 10  is a schematic view in the x-z plane of an example of a TOF-MS system  1000  according to other embodiments. In particular,  FIG. 10  illustrates an example of implementing a tandem MS technique on parallel ion beams spaced along the transverse axis. The TOF-MS system  1000  includes a mass-sensitive ion dispersion device  1044 , followed by a multi-channel (or multi-beam) ion fragmentation device  1036 , followed by a TOF analyzer  1016 . 
     The mass-sensitive ion dispersion device  1044  operates as described above, receiving a primary ion beam  1042  (a beam of “precursor,” or “parent,” ions in this embodiment) and outputting a plurality of parallel ion beams  1046 A,  1046 B,  1046 C, and  1046 D spatially dispersed along the transverse axis according to ion mass. In the illustrated example, the number N of parallel ion beams is four but in other examples may be less than or more than four. The TOF analyzer  1016  includes an ion accelerator  1062  and a multi-channel ion detector  1020 . The ion detector  1020  includes a plurality of detection channels, for example detection channels  1022 A,  1022 B,  1022 C, and  1022 D, spatially separated along the transverse axis. The ion beams  1046 A,  1046 B,  1046 C, and  1046 D are processed in the ion fragmentation device  1036  as described below, and then transmitted into the ion accelerator  1062  simultaneously. The ion accelerator  1062  then injects successive ion packets from each ion beam  1046 A,  1046 B,  1046 C, and  1046 D either simultaneously or at different firing rates. Consequently, the ion packets travel through the flight tube simultaneously in N different flight paths  1078 A,  1078 B,  1078 C, and  1078 D that are spatially separated along the transverse axis. The ions in the N different flight paths  1078 A,  1078 B,  1078 C, and  1078 D thus arrive at respective detection channels  1022 A,  1022 B,  1022 C, and  1022 D, which are spatially (or optically) aligned with the respective flight paths  1078 A,  1078 B,  1078 C, and  1078 D. The impact of an ion on a particular detection channel  1022 A,  1022 B,  1022 C, and  1022 D thus determines the ion packet (associated with one of the flight paths  1078 A,  1078 B,  1078 C, and  1078 D) and the ion beam  1046 A,  1046 B,  1046 C, and  1046 D from which that particular ion originated. 
     It will be noted that in  FIG. 10 , the bends in the flight paths  1078 A,  1078 B,  1078 C, and  1078 D are to be considered as being located at elevations on the acceleration axis. Thus, the flight paths  1078 A,  1078 B,  1078 C, and  1078 D are to be considered as projecting out of the drawing sheet. 
     As schematically shown in  FIG. 10 , the ion accelerator  1062  is configured so as to be wide enough along the transverse axis to simultaneously receive multiple, transversely spaced ion beams. The ion accelerator  1062  thus may be considered as including multiple loading/injection sites or as including a plurality of transversely spaced, individually controllable ion accelerators, as described above in conjunction with  FIG. 8 . Thus, the separate ion accelerators may be operated to accelerate ion packets from respective ion beams  1046 A,  1046 B,  1046 C, and  1046 D simultaneously and at the same firing rate, or at different rates. Similarly, the TOF analyzer  1016  may include one wide ion mirror or multiple ion mirrors in the flight tube. 
     The ion fragmentation device  1036  may generally have any configuration effective for fragmenting ions in each ion beam  1046 A,  1046 B,  1046 C, and  1046 D, i.e., performing fragmentation simultaneously on N different ion beams (or channels). In some implementations, the ion fragmentation device  1036  is a buffer gas-filled collisional cell that implements CID, although alternatively may be another type of ion fragmentation device as described above. The ion fragmentation device  1036  may include a plurality of discrete devices arranged in parallel to separately receive the respective ion beams  1046 A,  1046 B,  1046 C, and  1046 D and output respective beams of fragment ions (“product” or “daughter” ions). Alternatively, the ion fragmentation device  1036  may be a single or integrated device configured for maintaining localized ion beams while performing fragmentation on the ion beams simultaneously. For example, in some embodiments the ion fragmentation device  1036  may be an RF ion guide. 
       FIG. 11  is a schematic view of an example of an RF ion guide  1136  configured for maintaining localized ion beams while performing fragmentation on the ion beams simultaneously. The RF ion guide  1136  is configured to generate an RF field in its interior that has pseudo-potential barriers extending along the axial length of the RF ion guide. In the transverse direction, the RF field alternates between pseudo-potential barriers and local minima, thereby forming parallel ion channels along the axial length of the RF ion guide  1136 .  FIG. 11  includes a simulation of parallel ion beams traveling through the respective channels. The pseudo-potential barriers may be configured to reduce or prevent cross-talk between adjacent channels. 
     Referring again to  FIG. 10 , in operation the mass-sensitive ion dispersion device  1044  operates as the first-stage mass analyzer of the TOF-MS system  1000 . The parallel ion beams  1046 A,  1046 B,  1046 C, and  1046 D are transmitted into the ion fragmentation device  1036  simultaneously. In the ion fragmentation device  1036 , the ions travel in localized channels, i.e., the distinct parallel ion beams  1046 A,  1046 B,  1046 C, and  1046 D are maintained, which correspond to different ranges of parent ion m/z values due to the spatial separation induced by the mass-sensitive ion dispersion device  1044 . In each channel, fragment ions are produced from the parent ions by CID or other fragmentation mechanism. The ion beams  1046 A,  1046 B,  1046 C, and  1046 D are outputted from the ion fragmentation device  1036  and then transmitted into the ion accelerator  1062  simultaneously. The TOF analyzer  1016  operates as described above to produce fragmentation spectra from the outputs of the detection channels  1022 A,  1022 B,  1022 C, and  1022 D. It is thus evident that the combination of the mass-sensitive ion beam modulator  1044 , multi-channel (or multi-beam) ion fragmentation device  1036 , and multi-channel (or multi-beam) TOF analyzer  1016  enable the fragmentation spectra of multiple different parent ions to be analyzed simultaneously in the TOF mass analyzer  1016 , which improves the net ion transmission efficiency. 
     The TOF-MS system  1000  implements multi-pulsing at least by way of simultaneously transmitting respective ion packets in parallel flight paths in the flight tube, and simultaneously detecting ion arrival times at the same number of detector channels. In some embodiments, the ion packets are accelerated at a normal (non-multiplexed) firing rate. In this case, with N det  detector channels, again it is seen that the duty cycle is improved by a factor of N det , up to the point at which it reaches 100%. Moreover, the raw data produced by the N det  detector channels are easily processed to construct a single mass spectrum. In other embodiments, the ion packets may be accelerated at a multiplexed firing rate, resulting in more than one ion packet traveling in each parallel flight path in the flight tube at the same time. In this case, some form of deconvolution/demodulation/decoding algorithm would likely be required to produce an easily interpretable mass spectrum. 
     In other embodiments, the TOF-MS system  1000  may be configured to perform a combination of the transverse parent ion mass separation technique just described and the drift energy labeling technique described earlier in this disclosure. As described earlier in this disclosure, this “two-dimensional” multi-pulsing or multiplexing technique enables ion packets to be accelerated at a multiplexed firing rate simultaneously into multiple parallel, transversely spaced flight paths, which may result in a significantly improved duty cycle while enabling a simplified demodulation algorithm to be employed due to the use of drift energy encoding. The ion accelerator  1062  in such embodiments may provide a two-dimensional array of detector channels, arranged along the drift axis and along the transverse axis. 
       FIG. 12A  is a side (length-wise) view in the y-z plane of an example of an RF ion guide  1236  configured as a multi-channel ion fragmentation device, which may be utilized in the TOF-MS system  1000  or other TOF-MS system.  FIG. 12B  is a cross-sectional view in the x-y plane of the RF ion guide  1236 . The RF ion guide  1236  is a multipole ion guide that includes a plurality of ion guide electrodes (or rods) elongated along a central axis  1204  of the RF ion guide  1236  (z-axis in  FIG. 12A ). The ion guide electrodes extend from an ion entrance end  1208  to an ion exit end  1212  of the RF ion guide  1236 . The ion guide electrodes may be considered as including upper ion guide electrodes  1216  located at a transverse distance from the central axis  1204  in the positive y-direction, lower ion guide electrodes  1220  located at a transverse distance from the central axis  1204  in the negative y-direction (axially opposite the upper ion guide electrodes  1216 ), and lateral ion guide electrodes  1224  located axially opposite each other relative to the x-axis and between the upper ion guide electrodes  1216  and lower ion guide electrodes  1220  relative to the y-axis. In the present context, the terms “upper” and “lower” are used merely in a relative sense, and not as a limitation of the spatial orientation of the RF ion guide  1236 . The ion guide electrodes  1216 ,  1220 , and  1224  are spaced from each other around the central axis  1204  in the transverse (x-y) plane orthogonal to the axis, such that the ion guide electrodes  1216 ,  1220 , and  1224  surround an ion guide volume that is elongated along the central axis  1204 . 
     As shown in  FIG. 12B , the ion guide electrodes  1216 ,  1220 , and  1224  are positioned such that the cross-section of the ion guide volume is relatively wide along the x-axis and relatively narrow or “flattened” along the y-axis. The cross-section of the ion guide volume as being shaped as a flattened circle, flattened oval, or racetrack. The distance between opposing upper ion guide electrodes  1216  and lower ion guide electrodes  1220  is indicated as d 1 . The distance between adjacent upper ion guide electrodes  1216  and between adjacent lower ion guide electrodes  1220  is indicated as d 2 . RF potentials are applied to the ion guide electrodes  1216 ,  1220 , and  1224  such that the phase on each ion guide electrode is shifted 180 degrees (π rads) from the phase on the two adjacent ion guide electrodes. In other words, the polarity of the RF potential alternates from one ion guide electrode to the next, as depicted by positive “+” and negative “−” signs in  FIG. 12B . Also in the present embodiment with the flattened geometry, the polarity is the same on opposing upper ion guide electrodes  1216  and lower ion guide electrodes  1220 . If the distance d 1  is small enough, the pseudo-potential exhibited by the RF field will provide alternating pseudo-potential barriers and local minima as described above, enabling confinement of multiple parallel ion beams  1246 A,  1246 B,  1246 C,  1246 C,  1246 D,  1246 E, and  1246 F. The isolation between the ion beams may improve as the distance d 1  approaches the distance d 2 . 
     In the non-limiting example of  FIG. 12B , the RF ion guide  1236  is a 14-pole ion guide that includes six upper ion guide electrodes  1216 , six lower ion guide electrodes  1220 , and two lateral ion guide electrodes  1224 . This geometry results in the formation of six ion beam channels, whereby six ion beams  1246 A,  1246 B,  1246 C,  1246 C,  1246 D,  1246 E, and  1246 F may be confined. However, less or more than fourteen poles may be realized. In one non-limiting example of a class of geometries that may be realized for the RF ion guide  1236 , the total number n of ion guide electrodes  1216 ,  1220 , and  1224  may be described by n=2m+2, where m is the number of ion beam channels formed by the RF field. 
     In some embodiments and as illustrated in  FIG. 12A , the ion guide electrodes  1216 ,  1220 , and  1224  may have a converging geometry along at least the y-axis, and over the entire axial length of the RF ion guide  1236  or at least a portion thereof. That is, the distance d 1  ( FIG. 12B ) tapers down as one moves in the positive direction along the central axis  1204  toward the ion exit end  1212 . In other embodiments, however, the ion guide electrodes  1216 ,  1220 , and  1224  may have a straight geometry in which they are all parallel with the central axis  1204  along the entire axial length of the RF ion guide  1236 . The converging geometry may be implemented for the purpose of, for example, compressing the ion beams  1246 A,  1246 B,  1246 C,  1246 C,  1246 D,  1246 E, and  1246 F. On the other hand, it may be desirable to reduce taper angle, possibly down to zero degrees (straight geometry) to reduce cross-talk between the ion beam channels at the ion entrance end  1208 . 
       FIG. 13  is a perspective view of another example of an RF ion guide  1336  configured as a multi-channel ion fragmentation device, which may be utilized in the TOF-MS system  1000  or other TOF-MS system. The RF ion guide  1336  includes a plurality of planar ion guide electrodes (or strips) elongated along a central axis of the RF ion guide  1336  (z-axis in  FIG. 13 ). The ion guide electrodes extend from an ion entrance end  1308  to an ion exit end  1312  of the RF ion guide  1236 . The ion guide electrodes may be considered as including upper ion guide electrodes  1316  located at a transverse distance from the central axis in the positive y-direction, and lower ion guide electrodes  1320  located at a transverse distance from the central axis in the negative y-direction (axially opposite the upper ion guide electrodes  1316 . In the present context, the terms “upper” and “lower” are used merely in a relative sense, and not as a limitation of the spatial orientation of the RF ion guide  1336 . The upper ion guide electrodes  1316  are spaced from each other along x-axis  1204 , and the lower ion guide electrodes  1320  are likewise spaced from each other along x-axis  1204 . An ion guide volume is defined between the upper ion guide electrodes  1316  and the lower ion guide electrodes  1320 , and is likewise elongated along the central axis. 
     The upper ion guide electrodes  1316  may be supported on a planar upper substrate  1332 , and the lower ion guide electrodes  1320  may be likewise supported on a planar lower substrate  1334 . For illustrative purposes, the upper ion guide electrodes  1316  and lower ion guide electrodes  1320  are shown detached from the upper substrate  1332  and lower substrate  1334 . In some embodiments, the upper ion guide electrodes  1316  and lower ion guide electrodes  1320  have features (e.g., thickness or height from the substrates  1332  and  1334 , width along x-axis) on the order of micrometers, and may be fabricated on the substrates  1332  and  1334  by techniques utilized in the fabrication of micro-electronics, micro-electromechanical systems (MEMS), etc. 
     As in the case of the RF ion guide  1236  described above and illustrated in  FIG. 12A  and  FIG. 12B , the upper ion guide electrodes  1316  and lower ion guide electrodes  1320  are positioned such that the cross-section of the ion guide volume is relatively wide along the x-axis and relatively narrow or “flattened” along the y-axis. RF potentials are applied to the upper ion guide electrodes  1316  and lower ion guide electrodes  1320  such that the phase on each upper ion guide electrode  1316  is shifted 180 degrees from the phase on any upper ion guide electrode  1316  adjacent thereto, and the phase on each lower ion guide electrode  1320  is shifted 180 degrees from the phase on any lower ion guide electrode  1320  adjacent thereto. Also, the polarity is the same on opposing upper ion guide electrodes  1316  and lower ion guide electrodes  1320 . As in the case of the RF ion guide  1236  of  FIG. 12A  and  FIG. 12B , the upper ion guide electrodes  1316  and lower ion guide electrodes  1320  are configured such that the pseudo-potential exhibited by the RF field will provide alternating pseudo-potential barriers and local minima, enabling confinement of multiple parallel ion beams. In the non-limiting example of  FIG. 13 , the RF ion guide  1336  includes five upper ion guide electrodes  1316  and five lower ion guide electrodes  1320 . This geometry results in the formation of five ion beam channels, whereby six may be confined. However, less or more than five pairs of upper ion guide electrodes  1316  and lower ion guide electrodes  1320  may be realized. Sidewalls opposing each other along the x-axis, and positioned in the y-z plane between the upper substrate  1332  and lower substrate  1334 , may be or include electrodes to which repelling DC potentials are applied to provide lateral ion barriers. 
     As described above with regard to the RF ion guide  1236  of  FIG. 12A  and  FIG. 12B , the upper ion guide electrodes  1316  and lower ion guide electrodes  1320  may have a converging geometry along at least the y-axis as illustrated, or alternatively may have a straight geometry in which the upper ion guide electrodes  1316  and lower ion guide electrodes  1320  are all parallel with the central axis. 
     Embodiments of TOF analyzers herein have been described primarily in the context of orthogonal acceleration (oa-TOF). However, the present disclosure also encompasses coaxial TOF analyzers, i.e., TOF analyzers that accelerate ion packets into the flight tube along the same drift axis as the primary ion beam supplying the ions to the ion accelerator. For example, embodiments disclosed herein entailing modulation or dispersion of the ion beam along the transverse axis may be implemented with coaxial TOF analyzers. In addition, the present disclosure encompasses TOF analyzers that do not include ion mirrors in the flight tube. 
     From the foregoing, it is seen that embodiments disclosed herein may improve some of the major sources of poor ion transmission efficiency in TOF-MS. One or more embodiments utilize multi-channel ion detectors to significantly improve the average ion transmission and thereby improve sensitivity, dynamic range, mass accuracy, resolution, and speed. One or more embodiments address the so-called duty-cycle loss. One or more embodiments address the losses associated with mass isolation in tandem MS by utilizing multi-channel ion detectors and associated ion optics to parallelize the measurement. One or more embodiments utilize multi-pulsing of the ion-accelerator, and utilize the ion signals from multiple detector channels to reconstruct the mass spectrum. Unlike past approaches to multipulsing, one or more embodiments disclosed herein utilize reduced statistical inference, or no statistical inference, to reconstruct the spectrum. 
     EXEMPLARY EMBODIMENTS 
     Exemplary embodiments provided in accordance with the presently disclosed subject matter include, but are not limited to, the following: 
     1. A time-of-flight mass spectrometry (TOF-MS) system, comprising: an ion source; a TOF analyzer comprising an ion accelerator, a flight tube, and an ion detector comprising a plurality of channels; and an ion dispersion device configured for dispersing ions from the ion source into a plurality of spatially separated flight paths in the flight tube, wherein respective channels are aligned with the flight paths. 
     2. The TOF-MS system of embodiment 1, wherein the ion dispersion device is positioned upstream of the ion accelerator, at the ion accelerator, or in the flight tube. 
     3. The TOF-MS system of embodiment 1, wherein the ion dispersion device comprises a voltage source communicating with the ion accelerator, with ion optics upstream of the ion accelerator, or with both of the foregoing. 
     4. The TOF-MS system of embodiment 1 or 2, wherein the ion dispersion device comprises an ion deflector or a sector instrument. 
     5. The TOF-MS system of any of the preceding embodiments, wherein the ion dispersion device comprises a first dispersion device configured for dispersing ions along a drift axis, and a second dispersion device configured for dispersing ions along a transverse axis orthogonal to the drift axis, and wherein the flight paths are spatially separated according to positions defined by both the transverse axis and the drift axis. 
     6. The TOF-MS system of any of embodiments 1, 2, 4 or 5, wherein the ion dispersion device is configured for dispersing ions into a plurality of spatially separated ion beams, and the ion accelerator comprises a plurality of ion accelerators positioned to receive the respective ion beams. 
     7. The TOF-MS system of any of the preceding embodiments, wherein the ion detector is configured for both detecting arrival times of ions and measuring masses of the ions. 
     8. The TOF-MS system of embodiment 1, 2, 4, 6, or 7, wherein the ion dispersion device is configured for dispersing ions into a plurality of spatially separated ion beams, and further comprising an ion guide between the ion dispersion device and the ion accelerator, the ion guide configured for receiving the spatially separated ion beams simultaneously from the ion dispersion device, and wherein the ion accelerator is configured for receiving the spatially separated ion beams. 
     9. The TOF-MS system of embodiment 8 wherein the ion guide is configured for generating a radio frequency (RF) electric field in the ion guide, wherein the RF electric field comprises pseudo-potential barriers that isolate adjacent ion beams. 
     10. The TOF-MS system of embodiment 8 or 9, wherein the ion guide is configured for fragmenting the ions in each ion beam. 
     11. The TOF-MS system of any of embodiments 8 to 10, wherein the ion guide comprises a plurality of electrodes elongated along a drift axis and defining an ion guide volume having a cross-section defined by a transverse axis orthogonal to the drift axis and an acceleration axis orthogonal to the drift axis and to the transverse axis, and wherein the cross-section is larger along the transverse axis than along the acceleration axis, and the ion beams a spatially separated along the transverse axis. 
     12. A method for performing time-of-flight mass spectrometry (TOF-MS), the method comprising: transmitting ions along a drift axis into an ion accelerator; injecting the ions as a plurality of sequential ion packets from the ion accelerator into a flight tube; modulating a drift energy of the ions according to a repeating modulation sequence comprising a plurality of iterations, wherein the drift energy at each iteration is different from the drift energies of the other iterations, and wherein the ions travel in the flight tube in a plurality of flight paths spatially separated along the drift axis; and detecting arrival times of the ions at a plurality of channels of an ion detector aligned with the respective flight paths. 
     13. The method of embodiment 12, comprising injecting the ions as a plurality of sequential ion packets at a multiplexed pulse rate. 
     14. The method of embodiment 12 or 13, comprising producing a plurality of raw mass spectra from the respective channels, and deconvoluting the modulation sequence from the raw mass spectra to produce a single mass spectrum. 
     15. The method of any of embodiments 12 to 14, comprising modulating the drift energy of the ions according to a modulation selected from the group consisting of: modulating the drift energy of the ions before the ions are transmitted into the ion accelerator; modulating the drift energy of the ions after the ions are transmitted into the ion accelerator and before the ions are injected as ion packets into the flight tube; modulating the drift energy of the ions after the ions are injected as ion packets into the flight tube; and a combination of two or more of the foregoing. 
     16. The method of any of embodiments 12 to 15, comprising modulating the drift energy by varying a voltage at which the ions in the ion beam are transmitted into the ion accelerator. 
     17. The method of embodiment 16, wherein varying the voltage comprises varying a direct current (DC) potential applied to the ion accelerator, varying a DC potential applied to an ion optics element upstream of the ion accelerator, or both of the foregoing. 
     18. The method of any of embodiments 12 to 15, comprising modulating the drift energy by operating an ion dispersion device at the ion accelerator or in the flight tube. 
     19. The method of embodiment 18, wherein the ion dispersion device comprises an ion deflector or a sector instrument. 
     20. A method for performing time-of-flight mass spectrometry (TOF-MS), the method comprising: transmitting ions along a drift axis into an ion accelerator; injecting the ions as a plurality of sequential ion packets from the ion accelerator into a flight tube; modulating a transverse position the ions such that the ions travel in the flight tube in a plurality of flight paths spatially separated along a transverse axis orthogonal to the drift axis; and detecting arrival times of the ions at a plurality of channels of an ion detector aligned with the respective flight paths. 
     21. The method of embodiment 20, comprising modulating the transverse position according to a repeating modulation sequence comprising a plurality of iterations, wherein at each iteration the ions are dispersed to a transverse position different from the transverse positions of the other iterations. 
     22. The method of embodiment 21, wherein the ions are injected as a plurality of sequential ion packets in a plurality of corresponding accelerator firing events, and further comprising: associating the iterations of the modulation sequence with respective firing events such that different transverse positions of the modulation sequence are correlated with different accelerator firing events; producing a plurality of raw mass spectra from the respective channels; and deconvoluting the modulation sequence from the raw mass spectra to produce a single mass spectrum. 
     23. The method of embodiment 22, comprising injecting the ions as a plurality of sequential ion packets at a multiplexed pulse rate. 
     24. The method of any of embodiments 20 to 23, comprising modulating the transverse position of the ions according to a modulation selected from the group consisting of: dispersing the ions into a plurality of ion beams upstream of the ion accelerator, wherein the ion beams are spatially separated along the transverse axis, and the ion beams are transmitted along the drift axis into the ion accelerator; after transmitting the ions into the ion accelerator, dispersing the ions in the ion accelerator such that the ion packets are injected into the flight tube along the respective flight paths; after injecting the ion packets into the flight tube, dispersing ions from the ion packets into the respective flight paths; and a combination of two or more of the foregoing. 
     25. The method of any of embodiments 20 to 24, comprising modulating the transverse position by operating an ion dispersion device upstream of the ion accelerator, at the ion accelerator, or in the flight tube. 
     26. The method of embodiment 25, wherein ion dispersion device comprises an ion deflector or a sector instrument. 
     27. The method of any of embodiments 20 to 26, comprising modulating a drift energy of the ions according to a repeating modulation sequence comprising a plurality of iterations, wherein the drift energy at each iteration is different from the drift energies of the other iterations, and wherein the ions travel in the flight tube in a plurality of different flight paths that are spatially separated along the drift axis in addition to being spatially separated along the transverse axis, and the arrival times of the ions are detected at respective channels of the ion detector that are arranged in a two-dimensional array along the transverse axis and the drift axis. 
     28. The method of any of embodiments 20 to 27, comprising producing a plurality of raw mass spectra from the respective channels, and deconvoluting the modulation from the raw mass spectra to produce a single mass spectrum. 
     29. The method of any of embodiments 20 to 28, wherein: modulating the transverse position of the ions comprises dispersing the ions into a plurality of ion beams upstream of the ion accelerator, wherein the ion beams are spatially separated along the transverse axis, and the ion beams are transmitted along the drift axis into the ion accelerator; the ion accelerator comprises a plurality of ion accelerators respectively aligned with the ion beams; and further comprising operating the ion accelerators at different pulse rates. 
     30. A method for performing time-of-flight mass spectrometry (TOF-MS), the method comprising: transmitting ions along a drift axis into an ion accelerator; injecting the ions into a flight tube in a plurality of sequential accelerator firing events; detecting arrival times of the ions at a multi-channel ion detector; measuring masses of the ions of each of the ion packets; and based on the detected arrival times and measured masses, determining from which accelerator firing event each ion was injected. 
     31. The method of embodiment 30, wherein measuring masses is done at one or more mass-sensitive channels of the ion detector. 
     32. The method of embodiment 31, wherein measuring masses comprises measuring average pulse heights outputted by the ion detector for each ion detected. 
     33. The method of embodiment 30, wherein measuring masses comprises transmitting the ions into a sector instrument in the flight tube, and outputting the ions from the sector instrument in a plurality of mass-discriminated, spatially separated flight paths, such that the arrival times of the ions are detected at a plurality of channels of the ion detector respectively aligned with the flight paths. 
     34. The method of embodiment 33, wherein the mass-discriminated flight paths are spaced from each other along the drift axis, or along a transverse axis orthogonal to the drift axis. 
     35. The method of embodiment 30, wherein: measuring masses comprises transmitting the ions into a sector instrument upstream of the ion accelerator, and outputting the ions from the sector instrument in a plurality of mass-discriminated, spatially separated ion beams; transmitting ions along the drift axis into the ion accelerator comprises transmitting the ions in the respective ion beams into the ion accelerator; injecting the ions into the flight tube comprises transmitting the ions in a plurality of mass-discriminated, spatially separated flight paths corresponding to the respective ion beams; and the arrival times of the ions are detected at a plurality of channels of the ion detector respectively aligned with the flight paths. 
     36. The method of embodiment 35, wherein the ion accelerator comprises a plurality of ion accelerators respectively aligned with the ion beams, and further comprising operating the ion accelerators at different pulse rates. 
     37. The method of any of embodiments 30 to 36, comprising producing a plurality of raw mass spectra from respective channels of the ion detector, and based on a correlation between each ion and the accelerator firing event from which the ion was injected, deconvoluting the raw mass spectra to produce a single mass spectrum. 
     38. The method of any of embodiments 30 to 37, comprising injecting the ions into the flight tube at a multiplexed pulse rate. 
     39. A method for performing time-of-flight mass spectrometry (TOF-MS), the method comprising: transmitting ions into a sector instrument, and outputting the ions from the sector instrument in a plurality of mass-discriminated ion beams that are spatially separated along a transverse axis; transmitting the ion beams simultaneously into an ion accelerator along a drift axis orthogonal to the transverse axis; injecting ion packets from each of the ion beams into a flight tube, wherein the ion packets travel through the flight tube simultaneously in a plurality of flight paths spatially separated along the transverse axis, the flight paths corresponding to the respective ion beams; and detecting arrival times of the ions at a plurality of channels of an ion detector aligned with the respective flight paths. 
     40. The method of embodiment 39, comprising transmitting the ion beams simultaneously through an ion guide between the sector instrument and the ion accelerator, wherein the ion guide is configured for maintaining a separation of the ion beams along the transverse axis. 
     41. The method of embodiment 40, comprising generating a radio frequency (RF) electric field in the ion guide, wherein the RF electric field comprises pseudo-potential barriers along the drift axis that isolate adjacent ion beams. 
     42. The method of embodiment 40 or 41, comprising fragmenting the ions in each ion beam while transmitting the ion beams through the ion guide. 
     43. The method of any of embodiments 40 to 42, wherein the ion guide comprises a plurality of electrodes elongated along the drift axis and defining an ion guide volume that is larger along the transverse axis than along an acceleration axis orthogonal to the drift axis and to the transverse axis. 
     44. The method of any of embodiments 39 to 43, wherein the ion accelerator comprises a plurality of ion accelerators respectively aligned with the ion beams, and further comprising operating the ion accelerators at different pulse rates. 
     45. The method of any of embodiments 39 to 44, comprising producing a plurality of raw mass spectra from the respective channels, and producing a single mass spectrum from the raw mass spectra. 
     46. The method of any of embodiments 39 to 45, comprising modulating a drift energy of the ions according to a repeating modulation sequence comprising a plurality of iterations, wherein the drift energy at each iteration is different from the drift energies of the other iterations, and wherein the ions travel in the flight tube in a plurality of different flight paths that are spatially separated along the drift axis in addition to being spatially separated along the transverse axis, and the arrival times of the ions are detected at respective channels of the ion detector that are arranged in a two-dimensional array along the transverse axis and the drift axis. 
     47. A time-of-flight mass spectrometry (TOF-MS) system configured for performing all or part of the method of any of the preceding embodiments. 
     48. A time-of-flight mass spectrometry (TOF-MS) system comprising: an ion source; a TOF analyzer; an ion detector; and a computing device configured for performing all or part of the method of any of the preceding embodiments. 
     49. A system for acquiring spectral data from a sample, the system comprising: a processor and a memory configured for performing all or part of the method of any of the preceding embodiments. 
     50. The system of embodiment 49, comprising a computing device and an ion detector, wherein the computing device comprises the processor and the memory, and the ion detector is configured for transmitting ion measurement signals to the computing device. 
     51. A computer-readable storage medium comprising instructions for performing all or part of the method of any of the preceding embodiments. 
     52. A system comprising the computer-readable storage medium of embodiment 51. 
     It will be understood that one or more of the processes, sub-processes, and process steps described herein may be performed by hardware, firmware, software, or a combination of two or more of the foregoing, on one or more electronic or digitally-controlled devices. The software may reside in a software memory (not shown) in a suitable electronic processing component or system such as, for example, the computing device  140  schematically depicted in  FIG. 1 . The software memory may include an ordered listing of executable instructions for implementing logical functions (that is, “logic” that may be implemented in digital form such as digital circuitry or source code, or in analog form such as an analog source such as an analog electrical, sound, or video signal). The instructions may be executed within a processing module, which includes, for example, one or more microprocessors, general purpose processors, combinations of processors, digital signal processors (DSPs), or application specific integrated circuits (ASICs). Further, the schematic diagrams describe a logical division of functions having physical (hardware and/or software) implementations that are not limited by architecture or the physical layout of the functions. The examples of systems described herein may be implemented in a variety of configurations and operate as hardware/software components in a single hardware/software unit, or in separate hardware/software units. 
     The executable instructions may be implemented as a computer program product having instructions stored therein which, when executed by a processing module of an electronic system (e.g., the computing device  140  in  FIG. 1 ), direct the electronic system to carry out the instructions. The computer program product may be selectively embodied in any non-transitory computer-readable storage medium for use by or in connection with an instruction execution system, apparatus, or device, such as an electronic computer-based system, processor-containing system, or other system that may selectively fetch the instructions from the instruction execution system, apparatus, or device and execute the instructions. In the context of this disclosure, a computer-readable storage medium is any non-transitory means that may store the program for use by or in connection with the instruction execution system, apparatus, or device. The non-transitory computer-readable storage medium may selectively be, for example, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device. A non-exhaustive list of more specific examples of non-transitory computer readable media include: an electrical connection having one or more wires (electronic); a portable computer diskette (magnetic); a random access memory (electronic); a read-only memory (electronic); an erasable programmable read only memory such as, for example, flash memory (electronic); a compact disc memory such as, for example, CD-ROM, CD-R, CD-RW (optical); and digital versatile disc memory, i.e., DVD (optical). Note that the non-transitory computer-readable storage medium may even be paper or another suitable medium upon which the program is printed, as the program may be electronically captured via, for instance, optical scanning of the paper or other medium, then compiled, interpreted, or otherwise processed in a suitable manner if necessary, and then stored in a computer memory or machine memory. 
     It will also be understood that the term “in signal communication” as used herein means that two or more systems, devices, components, modules, or sub-modules are capable of communicating with each other via signals that travel over some type of signal path. The signals may be communication, power, data, or energy signals, which may communicate information, power, or energy from a first system, device, component, module, or sub-module to a second system, device, component, module, or sub-module along a signal path between the first and second system, device, component, module, or sub-module. The signal paths may include physical, electrical, magnetic, electromagnetic, electrochemical, optical, wired, or wireless connections. The signal paths may also include additional systems, devices, components, modules, or sub-modules between the first and second system, device, component, module, or sub-module. 
     More generally, terms such as “communicate” and “in . . . communication with” (for example, a first component “communicates with” or “is in communication with” a second component) are used herein to indicate a structural, functional, mechanical, electrical, signal, optical, magnetic, electromagnetic, ionic or fluidic relationship between two or more components or elements. As such, the fact that one component is said to communicate with a second component is not intended to exclude the possibility that additional components may be present between, and/or operatively associated or engaged with, the first and second components. 
     It will be understood that various aspects or details of the invention may be changed without departing from the scope of the invention. Furthermore, the foregoing description is for the purpose of illustration only, and not for the purpose of limitation—the invention being defined by the claims.