Shield between ion beam steering device and mass analyzer of mass spectrometer

Abstract

A mass spectrometer includes at least one ion beam steering device, a time-of-flight (TOF) mass analyzer positioned downstream of said at least one ion beam steering device with an inlet configured to receive an ion beam exiting an outlet of said at least one ion beam steering device, said TOF mass analyzer having an ion accelerator including a pusher electrode configured to generate an electric field in response to application of one or more voltage pulses thereto for deflecting the received ion beam to an ion drift region of said TOF mass analyzer. An electrically conductive shield is positioned between the outlet of said at least one ion beam steering device and the inlet of said TOF mass analyzer. The electrically conductive shield is configured to substantially shield at least a portion of a region between said outlet and said inlet, through which the ion beam propagates, from said electric field.

Description

[0001] IDF-24974

[0002] SHIELD BETWEEN ION BEAM STEERING DEVICE AND MASS ANALYZER OF MASS SPECTROMETER

[0003] RELATED APPLICATIONS

[0004] This application claims priority to U.S. Provisional Application No. 63 / 779,716 filed on March 28, 2025, the content of which is incorporated herein by reference in its entirety.

[0005] TECHNICAL FIELD

[0006] The present disclosure relates generally to systems and methods for performing mass spectrometry, amongst other things, and in particular to time-of-flight (TOF) mass spectrometers having an electrically conductive shield positioned between an ion beam steering device and a mass analyzer of a mass spectrometer.

[0007] BACKGROUND

[0008] Mass spectrometry (MS) is an analytical technique for determining the structure of chemical substances with both qualitative and quantitative applications. MS can be useful for identifying unknown compounds, determining the composition of atomic elements in a molecule, determining the structure of a compound by observing its fragmentation, and quantifying the amount of a particular chemical compound in a mixed sample. Mass spectrometers detect chemical entities as ions, so a conversion of the analytes to charged ions must occur.

[0009] Some mass spectrometers employ a TOF mass analyzer for generating ion detection signals. Such TOF mass analyzers typically include an inlet through which an ion beam can enter an ion accelerator of the mass analyzer, where the ion accelerator includes a pusher electrode to which voltage pulses can be applied to deflect the ions in the ion beam in a direction orthogonal to their initial propagation direction so as to introduce the ions into a drift region of the mass analyzer. The ions can be separated according to their m / z ratios based on their travel times through the drift region.

[0010] SUMMARYIDF-24974 After extensive technical study and testing, a significant opportunity has been identified for improving TOF mass spectrometers. By allowing the frequency of the voltage pulses applicable to a pusher electrode to be higher than those conventionally employed, mass analysis of ions can be further expedited, a development or arrangement that may advantageously enhance efficiency and / or accuracy of mass spectrometry.

[0011] In one aspect, a mass spectrometer is disclosed, which includes at least one ion beam steering device, a time-of-flight (TOF) mass analyzer positioned downstream of said at least one ion beam steering device and having an inlet configured to receive an ion beam exiting an outlet of said at least one ion beam steering device, said TOF mass analyzer having an ion accelerator including a pusher electrode configured to generate an electric field in response to application of one or more voltage pulses thereto for deflecting the received ion beam to an ion drift region of said mass analyzer. An electrically conductive shield is positioned between the outlet of said at least one ion beam steering device and the inlet of said TOF mass analyzer to substantially shield at least a portion of a region between said outlet and said inlet, through which the ion beam propagates, from said electric field.

[0012] In accordance with a preferred embodiment, the electrically conductive shield is configured to allow operation of a TOF mass analyzer of the mass spectrometer at higher frequencies, preferably without mass peak distortions.

[0013] By way of example, in various embodiments, the shield can include a plate electrode having an opening through which the ion beam can pass. In some such embodiments, the plate electrode is disposed at a distance in a range of about 1 mm to about 5 mm from the inlet of the mass analyzer.

[0014] In various embodiments, the shield further includes an electrically conductive tubular element that extends from the outlet of the at least one ion beam steering device to the plate electrode so as to surround at least a portion of said region.

[0015] In various embodiments, the electrically conductive tubular element can include a pair of tubular electrodes that are axially separated from one another such that an electric potential can be established between them. In some such embodiments, the pair of axially separated tubularIDF-24974 electrodes is configured such that the application of a voltage differential between the electrodes can be used to shape an ion beam passing through the electrodes. By way of example, the voltage differential can be used to compress, expand or steer the ion beam.

[0016] In various embodiments, the electric shield can be maintained at the electric ground potential. In other embodiments, the electric shield can be maintained at a fixed or a floating voltage.

[0017] In various embodiments, the ion accelerator can include an electrode that is maintained at the electric ground potential and that is positioned downstream of the pusher electrode. In some such embodiments, the electric shield can include a shield electrode that is mechanically and electrically coupled at a first end thereof to the ground electrode of the ion accelerator and is mechanically coupled at a second end thereof to a portion of a housing of the ion accelerator. In some such embodiments, an electrically insulating material, e.g., a ceramic element, can be positioned between the second end of the electrode and said portion of the housing so as to ensure that the shield is maintained at the electric ground potential due to its electrical coupling with the ground electrode of the ion accelerator.

[0018] In various embodiments, the at least one ion beam steering device can include two ion beam steering devices that allow controlled deflection, compression and / or expansion of the ion beam along two orthogonal axes.

[0019] In a related aspect, a method of operating a mass spectrometer having a time-of-flight (TOF) mass analyzer is disclosed, which includes providing an ion path that is substantially free of an electric field between an outlet of an ion beam steering device positioned upstream of said TOF mass analyzer and an inlet of an ion accelerator of said TOF mass analyzer, and introducing an ion beam into said ion beam steering device such that the ion beam exits said ion beam steering device to propagate along said ion path to said inlet of the ion accelerator of the TOF mass analyzer.

[0020] In various embodiments of the above method, the ion accelerator can include a pusher electrode to which voltage pulses can be applied for directing the ion beam entering the ion accelerator toward an ion drift region of the TOF mass analyzer.IDF-24974 In various embodiments, voltage pulses are applied to the pusher electrode at a frequency such that the pulses are temporally separated to allow detection of a last ion associated with a voltage pulse by an ion detector of the TOF mass analyzer prior to the application of a subsequent voltage pulse to the pusher electrode.

[0021] By way of example, and without limitation, the frequency of the voltage pulses applied to the pusher electrode can be at least about 10 kHz, or at least about 20 kHz, or at least about 30 kHz, or at least about 40 kHz, or at least about 50 kHz, or at least about 80 kHz, or at least about 90 kHz, e.g., in a range of about 10 kHz to about 100 kHz.

[0022] In various embodiments of the above method, the step of providing the ion path includes

[0023] positioning an electrically conductive shield between the outlet of said ion beam steering device and the inlet of said ion accelerator so as to substantially shield said ion path from an electric field generated by the pusher electrode in response to the application of said voltage pulses thereto.

[0024] In a related aspect, a mass spectrometer is disclosed, which includes an ion source for receiving a sample and generating a plurality of ions, an ion guide for receiving the plurality of ions and generating an ion beam, at least one ion beam steering device for receiving the ion beam and providing a controlled deflection, compression or expansion of said ion beam, and a time-of-flight (TOF) mass analyzer positioned downstream of said at least one ion beam steering device for receiving, via an inlet thereof, the ion beam exiting said at least one ion beam steering device, said TOF mass analyzer having an ion accelerator including a pusher electrode to which voltage pulses can be applied for deflecting ions in the received ion beam toward an ion drift region of the TOF mass analyzer. The mass spectrometer further includes an electrically conductive shield that is positioned between an outlet of said at least one ion beam steering device and the inlet of said mass analyzer so as to substantially shield at least a portion of a region between said outlet and said inlet from an electric field generated by the pusher electrode in response to application of said voltage pulses thereto so as to provide a substantially electric field free path through which the ion beam exiting the at least one ion beam steering device can propagate to reach said inlet of the mass analyzer.IDF-24974 The mass spectrometer can further include a voltage source for application of the voltage pulses to the pusher electrode and a controller that is in communication with the voltage source for adjusting a frequency of the voltage pulses. By way of example, and without limitation, the frequency of the voltage pulses applied to the pusher electrode can be in a range of about 10 kHz to about 100 kHz, e.g., in a range of about 20 kHz to about 50 kHz.

[0025] In various embodiments of the mass spectrometer, the electrically conductive shield includes a plate electrode having an opening through which the ion beam can pass. In some embodiments, the electrically conductive shield can further include an electrically tubular conductive element that extends from the outlet of the ion beam steering device to the plate electrode and surrounds at least a portion of the region that is substantially free of the electric field. While in some embodiments, the tubular conductive element and the plate electrode are formed as a single unitary unit, in other embodiments they can be formed as separate units and attached to one another, e.g., via a plurality of fasteners, such that an electrically conductive path is present to each one of them.

[0026] The mass spectrum, obtained through mass spectrometry, is configured to provide information used to identify and design a chemical. While it doesn’t directly make a chemical, it provides vital information that helps chemists create or analyze compounds. Here's how the information contained in the mass spectrum may be used: (A) Molecular Composition: chemists can use a mass spectrum to detect the molecular weight of components of a test sample, and confirm composition before manufacturing or identify unknown substances; (B) Structural Information: chemists can analyze fragmentation patterns displayed in a mass spectrum that they can use to infer atomic arrangements within a molecule, which is essential for designing and manufacturing a chemical structure; (C) Purity Assessment: chemical impurities in a test sample can be detected in a mass spectrum, confirming purity before manufacturing; (D) Reaction Monitoring: during synthesis, the mass spectrum can track intermediates and confirm reactions have proceeded as planned; (E) Quantification: by comparing the intensity of signals in a mass spectrum, chemists can quantify the amount of a compound in a test sample, ensuring that correct proportions have been used during chemical synthesis.IDF-24974 Further understanding of various aspects of the present teachings can be obtained by reference to the following detailed description in conjunction with the associated drawings, which are described briefly below.

[0027] BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1A schematically depicts a conventional TOF mass analyzer, which receives ions from a collision cell via a pair of ion beam steering devices,

[0028] FIG. IB schematically depicts an ion accelerator employed in the TOF mass analyzer as shown in FIG. 1A,

[0029] FIG. 1C shows a theoretical simulation of the path of an ion beam entering the ion accelerator of the TOF mass analyzer of FIGS. 1A and IB in absence of application of voltage pulses to the pusher electrode of the mass analyzer,

[0030] FIG. ID shows a theoretical simulation of ions deflected by the pusher electrode of the TOF mass analyzer to propagate through the ion drift region of the mass analyzer and be detected by an ion detector,

[0031] FIG. IE shows a theoretical simulation of an example of the effect of an electric field generated by the pusher electrode of the ion accelerator on incoming ions in a region between the outlet of an ion beam steering device and the inlet of the ion accelerator of the TOF mass analyzer, which leads to the deflection of some of the ions away from the inlet of the ion accelerator,

[0032] FIG. 2A schematically depicts an embodiment of the present teachings in which an electrically conductive shield is positioned in a region between the outlet of an ion beam steering device and the inlet of the ion accelerator to substantially shield at least a portion of said region from the electric field generated by the pusher electrode of the ion accelerator,

[0033] FIG. 2B is a schematic side view of the electrically conductive shield employed in the embodiment of FIG.2A,

[0034] FIG. 2C shows a theoretical simulation of the passage of an ion beam exiting an ionIDF-24974 beam steering device through an electrically conductive shield according to an embodiment into an ion accelerator of a TOF mass analyzer when a voltage pulse is applied to the pusher electrode,

[0035] FIG. 3 schematically depicts an example of an electrical and mechanical coupling of an electrically conductive shield according to an embodiment to an ion accelerator of a TOF mass analyzer,

[0036] FIG. 4 is a schematic side view of an electrically conductive shield according to an embodiment, where the shield includes two electrically conductive portions that are separated axially by a gap such that a voltage difference can be maintained between the two portions for any of deflecting, compressing or expanding an ion beam propagating through the shield,

[0037] FIG. 5A schematically depicts an embodiment in which a shield in the form of a plate electrode having a central opening is disposed in a region between the outlet of an ion beam steering device and the inlet of an ion accelerator of a TOF mass analyzer with no voltage applied to the pusher electrode of the ion accelerator,

[0038] FIG. 5B schematically depicts the embodiment shown in FIG. 5A with a voltage applied to the pusher electrode of the ion accelerator,

[0039] FIG. 6 is a schematic view of a TOF mass spectrometer according to an embodiment,

[0040] FIGS. 7A, 7B, 7C, and 7D depict TOF mass signals obtained in four channels of a mass detector of a TOF mass analyzer, where the TOF mass signals were obtained at three operating frequencies of the TOF mass analyzer (i.e., at three different frequencies at which voltage pulses were applied to the pusher electrode of the TOF mass analyzer), namely, 40 kHz, 45 kHz and 50 kHz,

[0041] FIGS. 8A, 8B, 8C, and 8D show TOF mass signals for ions with different m / z ratios, which were obtained using a TOF mass analyzer that was operated at 50 kHz, i.e., the frequency of the voltage pulses applied to the pusher electrode of the TOF mass analyzer was 50 kHz,

[0042] FIGS. 9A, 9B, 9C, and 9D show the same mass signals as those depicted in FIGS. 7A, 7B, 7C, and 7D, respectively, but acquired while using a shield such as that illustrated in FIG.IDF-24974 2A between the ion beam steering device and the ion accelerator, and

[0043] FIG. 10 schematically depicts theoretical results depicting penetration of an electric field generated by a pusher electrode of a TOF mass analyzer outside of the mass analyzer with two different types of shields and in the absence of a shield.

[0044] DETAILED DESCRIPTION

[0045] It will be appreciated that for clarity, the following discussion will explicate various aspects of embodiments of the applicant’s teachings, while omitting certain specific details wherever convenient or appropriate to do so. For example, discussion of like or analogous features in alternative embodiments may be somewhat abbreviated. Well-known ideas or concepts may also be for brevity and not be discussed in any great detail. The skilled person will recognize that some embodiments of the applicant’s teachings may not require certain of the specifically described details in every implementation, which are set forth herein only to provide a thorough understanding of the embodiments. Similarly, it will be apparent that the described embodiments may be susceptible to alteration or variation according to common general knowledge without departing from the scope of the disclosure. The following detailed description of embodiments is not to be regarded as limiting the scope of the applicant’s teachings in any manner.

[0046] As used herein, the terms "about" and "substantially equal" refer to variations in a numerical quantity that can occur, for example, through measuring or handling procedures in the real world; through inadvertent error in these procedures; through differences in the manufacture, source, or purity of compositions or reagents; and the like. Typically, the terms "about" and "substantially" as used herein mean 10% greater or less than the value or range of values stated or the complete condition or state. For instance, a concentration value of about 30% or substantially equal to 30% can mean a concentration between 27% and 33%. The terms also refer to variations that would be recognized by one skilled in the art as being equivalent so long as such variations do not encompass known values practiced by the prior art.

[0047] As used herein the term "and / or" includes any and all combinations of one or more of the associated listed items and may be abbreviated asIDF-24974 TOF mass analyzers are employed in a variety of mass spectrometers, e.g., to obtain high-resolution mass data. It has been discovered that the operation of a TOF mass analyzer via application of voltage pulses to its pusher electrode at a frequency greater than about 40 kHz can adversely affect the mass peaks shapes associated with the ion detection signals generated by the mass analyzer and / or inhibit the entry of at least some of the ions into the ion accelerator of the TOF mass analyzer.

[0048] More specifically, it has been discovered that an electric field generated by the pusher electrode in response to the application of a voltage pulse thereto for extracting incoming ions and directing them to the drift region of the mass analyzer can extend beyond a region of interest in front of the pusher electrode (for ease of description, such electric field is also referred to herein as stray electric field). In particular, such an electric field can extend outside the mass analyzer through its ion beam inlet. When the frequency of voltage pulses applied to the pusher electrode is low (e.g., in a conventional range of about 1 kHz to about 20 kHz), poorly focused ions will have sufficient time to transit through the pulsing region and be lost while a well-focused ion beam can fill the accelerator prior to the next pulse. In contrast, when the pulsing frequency is greater than a certain threshold (e.g., 40 kHz), ions that are not well focused may be accelerated via voltage pulses applied to the pusher electrode and hence generate artifacts in the mass peaks associated with ion detection signals generated by the TOF mass analyzer, and / or inhibit the entry of some ions into the ion accelerator.

[0049] As discussed in more detail below, in various embodiments, an electrically conductive shield can be positioned upstream of an inlet of an ion accelerator of a time-of-flight (TOF) mass analyzer, typically between an outlet of an ion beam steering device positioned upstream of the TOF mass analyzer and the inlet of the mass analyzer’s ion accelerator, so as to provide an ion path that is substantially free of an electric field generated by the pusher electrode of the ion accelerator, in response to the application of voltage pulses thereto, for propagation of ions exiting the ion beam steering device to the TOF mass analyzer.

[0050] The electrically conductive shield can be implemented in a variety of different ways. By way of example, and without limitation, the electrically conductive shield can be in the form of an electrode, e.g., a plate-shaped electrode, that includes an opening therein to allow passage ofIDF-24974 ions therethrough and is positioned sufficiently close to the inlet of the ion accelerator to shield at least a portion of a region extending from the shield to the outlet of the ion beam steering device from an electric field generated by the pusher electrode. The ions exiting the ion beam steering device can follow an ion path that is contained within this region so that the ions are substantially unaffected by the electric field as they propagate from the ion beam steering device to the mass analyzer. In a related embodiment, the shield can include an electrically conductive tubular element that is electrically connected to the plate electrode and extends at least partially from the plate electrode to the ion beam steering device so as to enclose a region therebetween. In such an embodiment, the combination of the plate electrode and the tubular element can shield the region from the electric field. In various such embodiments, the plate electrode and the tubular element can be maintained at the ground electric potential, though in other embodiments, the plate electrode and / or the tubular element can be maintained at a fixed or a dynamic potential.

[0051] The term “tubular element” as used herein, refers to a structure that includes a hollow lumen. Although in some cases a tubular element can be in the form of a hollow cylinder, in other cases, a tubular element can have other shapes, such as a shape characterized by a polygonal cross section.

[0052] The term “substantially shielding” is intended to mean inhibiting the penetration of an electric field into a region such that the magnitude of the electric field within the region is less than about 1000 volts per meter, and preferably zero.

[0053] The term “a substantially field free region” refers to a region in which an electric field, if present, has a magnitude of less than about 1000 volts per meter, and preferably zero.

[0054] With reference to FIGS. 1A and IB, a time-of-flight (TOF) mass analyzer 100 is depicted that is positioned downstream of an ion beam steering device 102, which is in turn positioned downstream of a collision cell 104 of a mass spectrometer to receive ions therefrom. The TOF mass analyzer 100 includes an ion accelerator 106 having an inlet 106a through which ions can be introduced into the ion accelerator. The ion accelerator 106 further includes a pusher electrode 108 to which voltage pulses generated by a pulsed voltage source 110 can be applied to generate pulsed electric field within the ion accelerator so as to accelerate ions received by theIDF-24974 ion accelerator in a direction substantially orthogonal to their original propagation direction into an ion drift region 112 of the TOF mass analyzer.

[0055] More specifically, in addition to the pusher electrode 108, the ion accelerator 106 includes a plurality of additional electrodes, which are herein collectively referred to as electrodes 114 and are positioned downstream of the pusher electrode such that a difference in the electrical potential between the pusher electrode and the electrodes 114 results in the generation of an electric field Gradient in a direction substantially perpendicular to the pusher electrode to direct the ions received via the inlet of the ion accelerator to the ion drift region 112 of the TOF mass analyzer.

[0056] FIG. 1C shows the results of a theoretical simulation depicting the trajectory of an ion beam 118 as the ion beam exits the collision cell 104 and passes through the ion beam steering device to enter the ion accelerator 106 via its inlet 106a in absence of the application of an acceleration voltage to the pusher electrode.

[0057] FIG. ID, in turn, shows simulation results depicting the trajectory of the ion beam that was deflected from its initial trajectory as it entered the ion accelerator via application of a voltage pulse to the pusher electrode 108 to propagate from the ion accelerator 106 through the ion drift region 112 to an ion detector 116 of the TOF mass analyzer, where the ion detector generates ion detection signals in response to the detection of the ions incident thereon.

[0058] As noted above, the extension of a pulsed electric field generated by the pusher electrode 108, in response to the application of voltage pulses thereto, into a region between the outlet of the last ion beam steering device in the ion path upstream of the TOF mass analyzer and the inlet of the ion accelerator (such a region is schematically delineated by a dashed square in FIG. 1C, by way of illustration, though the boundary contour is generally not as precisely defined as that shown by the dashed square) can generate artifacts in the ion signals and in some cases can even deflect the ions such that they will not enter the TOF mass analyzer.

[0059] By way of illustration, FIG. IE shows the simulation results for an ion beam with an ion energy of about 40-90 eV exiting the ion beam steering device 102 via the outlet 102a thereof to enter the region between the ion beam steering device 102 and the ion accelerator 106 while aIDF-24974 voltage of about 900V is applied to the pusher electrode. The simulation shows that an electric field generated by the pusher electrode can extend into the region between the outlet of the ion beam steering device and the inlet of the ion accelerator and can cause the deflection of at least a portion of the ions in the ion beam away from the inlet of the TOF mass analyzer, thereby inhibiting their entry into the TOF mass analyzer. In practice, in some cases, when a voltage pulse is applied to the pusher electrode, it causes at least some ions in the region between the ion beam steering device and the ion accelerator to be deflected away from their propagation path, e.g., it can cause the reversal of the ion propagation direction back towards the ion source when the ion energies are lower than that needed to overcome an electric potential generated by the electric field penetrating outside of the ion accelerator.

[0060] Generally, such a perturbation of the ion beam will not cause any performance degradation when the rate at which the voltage pulses are applied to the pusher electrode is sufficiently low so as to allow the re-establishment of the ion beam as a coherent beam before the next voltage pulse is applied to the pusher electrode. However, at high voltage pulsing rates, the perturbed ion beam (or at least a portion thereof) can enter the ion accelerator and be subjected to the next voltage pulse before it can pass through the ion accelerator. The deflection of such a perturbed ion beam toward the ion detector can result in the generation of signal artifacts.

[0061] As discussed above, in various embodiments, an electric shield can be positioned in the region between the outlet of the ion beam steering device 102 and the inlet of the ion accelerator 106 to substantially shield at least a portion of this region from the electric field generated by the pusher electrode 108. By way of example, FIG.2 A schematically depicts such an electric shield 200 that is positioned in the region between the outlet 102a of the ion beam steering device 102 and the inlet 106a of the ion accelerator 106 so as to substantially shield at least a portion of this region from the electric field generated by the pusher electrode 108.

[0062] More specifically, with reference to FIG. 2B, the shield 200 includes a tubular section 201 and a substantially flat plate electrode section 203 having an opening 203a. Ions exiting the ion beam steering device 102 can enter the lumen of the shield via an inlet opening 201a and can exit the shield through the opening 203a of the flat plate electrode section 203, which providesIDF-24974 an outlet of the shield. While in this embodiment the shield 200 is formed as a single unitary electrically conductive structure, in other embodiments the tubular section and the electrode plate section can be separate units that are assembled (e.g., via fasteners) to form the shield such that there is an electrical connection between the two units, or such that a differential voltage can be maintained between the separate units.

[0063] The shield can be formed of any suitable electrically conductive material. By way of example, in various embodiments, the shield can be formed of a suitable metal. Some examples of suitable metals include, without limitation, beryllium, copper, stainless steel, and nickel-plated aluminum. The dimensions of the shield can be selected based on a particular instrument in which it will be utilized to provide a desired shielding of the electric field generated by the pusher electrode so as to generate a substantially field free path for the passage of the ions exiting the ion beam steering device 102 to the ion accelerator 106 of the downstream TOF mass analyzer. By way of example, and without limitation, the shield 200 can have a length (L) in a range of about 2 mm to about 20 mm with the diameter of its inlet and outlet openings and an internal diameter of its lumen being in a range of about 3 mm to about 10 mm.

[0064] While in this embodiment the shield 200 is electrically grounded, in other embodiments the shield 200 can be maintained at a fixed or a dynamic electric potential.

[0065] Referring again to FIG.2A, a theoretically simulated path of the ion beam 118 with ions having an energy of 70eV exiting the ion beam steering device 102 to enter the lumen of the shield 200 is shown, where the ion beam enters the ion accelerator of the TOF mass analyzer after passage through the shield 200. In this case, the voltage applied to the pusher electrode is zero.

[0066] FIG. 2C shows the ion trajectory of the same ion beam as that depicted in FIG.2A when a voltage of about 900V is applied to the pusher electrode 108 of the TOF mass analyzer. The simulation shows that the shield helps reduce the deflection of the ions away from the inlet of the ion accelerator of the TOF mass analyzer. In this simulation, after the pusher electrode applies a voltage pulse to the ions that had previously arrived at the ion accelerator, the ion beam in a region external to the ion accelerator can be slightly deflected via the electric field generated by the pusher electrode and will subsequently enter the ion accelerator to be subjected to the nextIDF-24974 pulse generated by the pusher electrode.

[0067] FIG. 3 schematically depicts an embodiment in which the shield 200 extends along the entire length of the axial separation between the outlet of the ion beam steering device 102 and the inlet of the ion accelerator of the TOF mass analyzer. More specifically, in this embodiment, the plate electrode section 203 of the shield 200 is fastened at one end 203-1 thereof, via a fastener 206, to an electrode 114a of the ion accelerator 106 so as to be in conductive electrical contact with that electrode, which is maintained at the electric ground potential. At its other end 203-2, the plate electrode section 203 is mechanically coupled to the pusher electrode 108 of the TOF mass analyzer with an electrically insulating (e.g., ceramic) spacer 109 electrically insulating the plate electrode section 203 from the pusher electrode so as to ensure that the shield is maintained at the ground electric potential.

[0068] The inlet of the shield (i.e., the inlet end of the tubular section of the shield) is in turn coupled to the outlet of the ion beam steering device 102 such that the shield spans across the entire length of the region separating the ion beam steering device from the TOF mass analyzer. In other embodiments, the shield may extend partially along the length separating the outlet of the ion beam steering device from the inlet of the ion accelerator of the TOF mass analyzer.

[0069] In various embodiments, a shield can include two or more portions that are electrically insulated from one another such that a voltage differential can be maintained across those portions. By way of illustration, FIG. 4 schematically depicts a shield 400 that includes two portions 400a and 400b that are separated (spaced-apart) from each other by a gap 401 such that a voltage differential can be maintained between them. In this implementation, the portion 400a is in the form of a hollow cylinder while the portion 400b has the same structure as the shield 200 discussed above. By way of example, in various embodiments, such a shield can be utilized to provide final steering of the ion beam, e.g., spreading the ion beam out to a desired degree, focusing the ion beam to fit inside of a narrow detector aperture, or correcting for small misalignments. A voltage source 403 can apply a voltage between the two portions 400a and 400b in a manner known in the art as informed by the present teachings, for example, to deflect, compress, or enhance an ion beam passing through the shield.

[0070] The shape of the shield utilized in various embodiments of the present teachings is notIDF-24974 limited to that described above. With reference to FIGS. 5A and 5B, in various embodiments, a shield 500 in the form of a single plate electrode having a central opening 500a is positioned between the outlet of the ion beam steering device 102 and the inlet of the ion accelerator 106 to shield at least a portion of the region between the ion beam steering device and the ion accelerator from an electric field generated by the pusher electrode 108 in response to the application of voltage pulses thereto. While in this embodiment, the shield 500 is electrically grounded, in other embodiments it can be held at a fixed or a dynamic electric potential.

[0071] More specifically, referring again to FIG. 5A, a theoretically simulated path of the ion beam 118 with ions exiting the ion beam steering device 102 to enter a region between the outlet of the ion beam steering device 102 and the inlet of the ion accelerator is illustrated. The ions pass through the opening 500a of the shield 500 to reach the ion accelerator. In this case, the voltage applied to the pusher electrode is zero.

[0072] FIG. 5B, in turn, shows the ion trajectory of the same ion beam as that depicted in FIG.

[0073] 5A when a deflecting voltage is applied to the pusher electrode 108 of the TOF mass analyzer. The simulations show that the shield helps reduce the deflection of the ions away from the inlet of the ion accelerator of the TOF mass analyzer. In this simulation, after the pusher electrode applies a voltage pulse to the ions that had previously arrived at the ion accelerator, the ion beam in a region external to the ion accelerator can be slightly deflected via the electric field generated by the pusher electrode and will subsequently enter the ion accelerator to be subjected to the next pulse generated by the pusher electrode.

[0074] In various embodiments, a combination of two or more of the shields discussed above can be utilized. For example, in some such embodiments, a combination of the shields 200 and 500 described above can be employed for providing a substantially field free ion path for the passage of ions from the ion beam steering device 102 to the ion accelerator 106.

[0075] A shield according to various embodiments can be employed in a variety of mass spectrometric systems in which a TOF mass analyzer is incorporated. By way of example, FIG.

[0076] 6 schematically depicts a mass spectrometric system 600 according to an embodiment that includes an LC column 602 that can receive a sample and separate a plurality of analytes in the sample based on their elution times from the LC column. The mass spectrometric system 600IDF-24974 further includes an ion source 604 that receives an eluate exiting the LC column and ionizes one or more analytes contained in the eluate to generate a plurality of precursor ions.

[0077] In many implementations, one or more ion guides 606 receive the precursor ions and provide focusing of the ions to generate an ion beam that is received by a mass filter 608. By way of example, the ion guide(s) can include a plurality of rods arranged in a quadrupole configuration to which RF and DC voltages generated by an RF / AC voltage source 610 and a DC voltage source 612 can be applied in a manner known in the art to provide radial confinement of the received ions. The RF / AC voltage source 610 is configured to selectively provide RF voltage and / or AC voltage as may be required to perform specific tasks and / or functions.

[0078] In other embodiments, an ion mobility spectrometer (IMS), such as a differential mobility spectrometer (DMS), can be utilized as a separation device to separate ions based on their mobility with the ions exiting the IMS being received by the one or more ion guides 606.

[0079] The mass filter 608 provides an ion transmission window that allows transmission of ions having m / z values within an m / z range through the mass filter. By way of example, the mass filter 608 can include a plurality of rods arranged in a quadrupole configuration to which RF voltages as well as a discriminating DC voltage can be applied via the RF and the DC voltage sources 610 and 612, respectively, to generate an ion transmission window. The RF and DC voltage sources are controlled by a controller 624. In this implementation, the ions passing through the mass filter 608 are received by an ion fragmentation device 614 that causes fragmentation of the precursor ions to generate a plurality of product ions. The product ions are received by a pair of ion beam steering devices (616a, 616b), where in this embodiment (A) the first ion beam steering device 616a provides controlled deflection of the ion beam along a direction in a plane that is orthogonal to the ion beam’s propagation direction (e.g., along the vertical direction), and (B) the second ion beam steering device 616b provides controlled deflection of the ion beam along a direction in a plane containing the ion beam (e.g., along a horizontal direction).

[0080] The mass spectrometric system 600 further includes an electrically conductive shield 618, such as the above shield 200, which is positioned between the outlet of the ion beam steeringIDF-24974 device 616b and an inlet of a TOF mass analyzer 620. As discussed in detail above, the shield 618 helps reduce, and preferably eliminate, the exposure of the ions to an electric field generated by the pusher electrode of the TOF mass analyzer as the ions traverse a region between the outlet of the ion beam steering device 616b and the inlet of the TOF mass analyzer. Ion detection data generated by the TOF mass analyzer 620 is received by an analysis module 622 that is configured to process the ion detection data and generate a mass spectrum of the ions.

[0081] The use of an electrically conductive shield according to the present teachings is not limited to the mass spectrometer discussed above. In fact, such a shield according to the present teachings can be utilized in any mass spectrometer that includes a TOF mass analyzer.

[0082] The following examples are provided to elucidate various aspects of the present teachings and are not presented to provide necessarily an optimal way of practicing the present teachings and / or optimal results that may be obtained.

[0083] Example

[0084] As discussed above, it has been discovered that as the pulsing frequency of a linear TOF mass analyzer is increased, the electric field generated by the pusher electrode of the TOF mass analyzer can lead to the generation of artifacts in the TOF ion detection signals and / or inhibit the entry of at least some ions into the TOF mass analyzer.

[0085] By way of illustration, FIGS. 7 A, 7B, 7C, and 7D depict TOF mass signals obtained in four channels of an ion detector of a TOF mass analyzer, where the TOF mass signals were obtained at three operating frequencies of the TOF mass analyzer (i.e., at three different frequencies at which voltage pulses were applied to the pusher electrode of the TOF mass analyzer), namely, 40 kHz, 45 kHz and 50 kHz. It was observed that as the operating frequency of the TOF mass analyzer increased, so did the intensity of the mass peaks shoulder artifacts that were observed in the mass spectra.

[0086] By way of further illustration, FIGS. 8A, 8B, 8C, and 8D show TOF mass signals for ions with different m / z ratios, which were obtained using a TOF mass analyzer that was operated at 50 kHz, i.e., the frequency of the voltage pulses applied to the pusher electrode of the TOF mass analyzer was 50 kHz. These figures show that mass peak shoulder artifacts (designated byIDF-24974 arrows) became more pronounced as the m / z ratio associated with the primary mass peak increased.

[0087] Without being limited to any particular theory, it is believed that the appearance of such artifacts is due to the electric field created by the pusher electrode of the TOF mass analyzer extending outside the ion accelerator and affecting the trajectory of the ions directed towards the ion accelerator. For example, some incoming ions that are subjected to the electric field pulse outside of the ion accelerator can be displaced such that they enter the ion accelerator farther away from the pusher electrode than the bulk of ions. Such displaced ions would follow a different trajectory to the ion detector and hence would lead, at high operating frequencies, to the generation of mass signal(s) that are offset relative to the primary mass signal associated with the bulk of the ions. Although such electric field effects may also be present at lower operating frequencies, at lower frequencies, such displaced ions can move along (transit through) the ion acceleration region prior to the arrival of a subsequent voltage pulse. Hence, the mass peak artifacts can be more pronounced at higher operating frequencies.

[0088] As noted above, it has been discovered that the use of a shield outside of the ion accelerator and in proximity of its inlet, typically between the outlet of an ion beam steering device positioned upstream of the TOF mass analyzer and the inlet of the ion accelerator of the mass analyzer, can reduce, and preferably, eliminate exposure of ions propagating into the ion accelerator to the electric field pulses generated by the pusher electrode of the ion accelerator that extend outside of the ion accelerator, thereby reducing, and preferably eliminating, the appearance of artifacts in acquired mass spectra.

[0089] By way of example, FIGS.9A, 9B, 9C, and 9D show the same mass signals as those depicted in FIGS. 7 A, 7B, 7C, and 7D, respectively, but acquired while using a shield such as that illustrated in FIG.2A between the ion beam steering device and the ion accelerator. A comparison of the data depicted in FIGS.9A-9D with the respective data presented in FIGS. 7A-7D shows that the use of the shield results in substantial removal of the mass peak artifacts.

[0090] FIG. 10 schematically depicts a theoretical simulation of the magnitude of the electric field generated via application of a voltage pulse to the pusher electrode of a TOF mass analyzer as a function of the distance from an outlet of a collision cell (e.g., the ion fragmentation deviceIDF-24974 illustrated in FIG.6) that is positioned upstream of the TOF mass analyzer in the following three states: (A) in the absence of a shield according to the present teachings, (B) with a shield in the form of a plate having a central opening, and (C) with a shield formed as a combination of a plate having a central opening and a cylindrical tube. The simulation data shows that the use of the shields significantly reduces the penetration of the electric field generated by the pusher electrode into a region outside the ion accelerator of the TOF mass analyzer. Further, the simulation results show that the shield in the form of a combination of a plate and a tube is more effective in shielding the electric field than the shield that is in the form of a only a plate having a central opening.

[0091] As used herein the term "and / or" includes any and all combinations of one or more of the associated listed items and may be abbreviated as " / ". Although some aspects have been described in the context of an apparatus, it is clear that these aspects also represent a description of the corresponding method, where a block or device corresponds to a method step or a feature of a method step. Analogously, aspects described in the context of a method step also represent description of a corresponding block or item or feature of a corresponding apparatus. Some or all of the method steps may be executed by (or using) a hardware apparatus, for example, a processor, a microprocessor, a programmable computer, or an electronic circuit. In some embodiments, some one or more of the most important method steps may be executed by such an apparatus.

[0092] Depending on certain implementation requirements, embodiments of the invention can be implemented in hardware and / or in software. The implementation can be performed using a non-transitory storage medium such as a digital storage medium, for example a floppy disc, a DVD, a Blu-Ray, a CD, a ROM, a PROM, and EPROM, an EEPROM or a FLASH memory, having electronically readable control signals stored thereon, which cooperate (or are capable of cooperating) with a programmable computer system such that the respective method is performed. Therefore, the digital storage medium may be computer readable.

[0093] While various embodiments have been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive; embodiments of the present disclosure are not limited to theIDF-24974 disclosed embodiments. Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing embodiments of the present disclosure, from a study of the drawings, the disclosure, and the appended claims.

[0094] In the claims, the word “comprising” does not exclude other elements or steps, and the indefinite article “a” or “an” does not exclude a plurality. A single processor or other processing unit may fulfill the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measured cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope.

Claims

IDF-24974 What is claimed is:

1. A mass spectrometer, comprising:at least one ion beam steering device,a time-of-flight (TOF) mass analyzer positioned downstream of said at least one ion beam steering device and having an inlet configured to receive an ion beam exiting an outlet of said at least one ion beam steering device, said TOF mass analyzer having an ion accelerator including a pusher electrode configured to generate an electric field in response to application of one or more voltage pulses thereto for deflecting the ion beam, which was received, to an ion drift region of said TOF mass analyzer,an electrically conductive shield positioned between the outlet of said at least one ion beam steering device and the inlet of said TOF mass analyzer, andsaid electrically conductive shield configured to substantially shield at least a portion of a region between said outlet and said inlet, through which the ion beam, in use, propagates from said electric field.

2. The mass spectrometer of Claim 1, wherein said electrically conductive shield comprises a plate electrode having an opening for accommodating passage of the ion beam therethrough.

3. The mass spectrometer of Claim 2, wherein said plate electrode is disposed at a distance in a range of about 1 mm to about 5 mm from said inlet of the TOF mass analyzer.

4. The mass spectrometer of any one of Claims 1-3, wherein said electrically conductive shield further comprises an electrically conductive tubular element extending from the outlet of the at least one ion beam steering device to said plate electrode so as to surround at least said portion of said region.

5. The mass spectrometer of Claim 4, wherein said electrically conductive tubular element comprises a pair of tubular electrodes axially separated from one another by a gap.

6. The mass spectrometer of Claim 5, wherein said pair of tubular electrodes are configured such that application of a voltage differential between them is used for shaping of the ionIDF-24974 beam passing therethrough, wherein optionally the shaping of the ion beam comprises at least one of focusing the ion beam, expanding the ion beam and steering the ion beam.

7. The mass spectrometer of any one of the preceding claims, wherein said electrically conductive shield is maintained at electric ground potential.

8. The mass spectrometer of Claim 1, wherein said ion accelerator comprises a ground electrode positioned downstream of said pusher electrode and maintained at electric ground potential.

9. The mass spectrometer of Claim 8, wherein said electrically conductive shield comprises a shield electrode mechanically and electrically coupled at a first end thereof to said ground electrode of the ion accelerator and mechanically coupled at a second end thereof to a portion of a housing of said ion accelerator.

10. The mass spectrometer of Claim 9, further comprising an electrically insulating material positioned between said second end of said shield electrode and said portion of the housing.

11. The mass spectrometer of Claim 1 , wherein said at least one ion beam steering device comprises two ion beam steering devices for controlled deflection of the ion beam along two orthogonal directions.

12. A method of operating a mass spectrometer having a time-of-flight (TOF) mass analyzer, the method comprising:providing an ion path that is substantially free of an electric field between an outlet of an ion beam steering device positioned upstream of said TOF mass analyzer and an inlet of an ion accelerator of said TOF mass analyzer, andintroducing an ion beam into said ion beam steering device such that the ion beam, in use, exits said ion beam steering device and propagates along said ion path to said inlet of the ion accelerator of the TOF mass analyzer.

13. The method of Claim 12, wherein said ion accelerator comprises a pusher electrode to which voltage pulses are applied for directing the ion beam entering the ion accelerator toward an ion drift region of said TOF mass analyzer.IDF-2497414. The method of Claim 13, further comprising applying said voltage pulses to said pusher electrode at a frequency such that the voltage pulses are temporally separated to allow detection of a last ion associated with one voltage pulse by an ion detector of the TOF mass analyzer prior to application of a subsequent voltage pulse to the pusher electrode.

15. The method of Claim 13, further comprising applying said voltage pulses to said pusher electrode at a frequency of in range from about 10 kHz to 100 kHz.

16. The method of any one of Claims 12- 15, wherein the step of providing the ion path comprises positioning an electrically conductive shield between the outlet of said ion beam steering device and said inlet of the ion accelerator so as to substantially shield said ion path from the electric field generated by said pusher electrode in response to application of said voltage pulses thereto.

17. A mass spectrometer, comprising:an ion source for receiving a sample and generating a plurality of ions, an ion guide for receiving said plurality of ions and generating an ion beam, at least one ion beam steering device for receiving the ion beam and providing a controlled deflection, compression or expansion of said ion beam, anda time-of-flight (TOF) mass analyzer positioned downstream of said at least one ion beam steering device for receiving, via an inlet thereof, the ion beam exiting said at least one ion beam steering device, said TOF mass analyzer having an ion accelerator including a pusher electrode, in which a voltage applied to said pusher electrode, in use, deflects ions in the ion beam, which was received by said at least one ion beam steering device, toward an ion drift region of the TOF mass analyzer,an electrically conductive shield positioned between an outlet of said at least one ion beam steering device and said inlet of said TOF mass analyzer, andsaid electrically conductive shield configured to substantially shield at least a portion of a region between said outlet and said inlet from an electric field generated by said pusher electrode in response to application of voltage pulses thereto so as to provide a substantially electric field free path through which the ion beam, in use, exits said at least one ion beam steering device and propagates to reach said inlet of the TOF massIDF-24974 analyzer.

18. The mass spectrometer of Claim 17, further comprising a voltage source for application of said voltage pulses to said pusher electrode.

19. The mass spectrometer of any one of Claims 17 and 18, further comprising a controller in communication with said voltage source for adjusting a frequency of said voltage pulses, wherein optionally the frequency of said voltage pulses is in a range of any one of (A) about 10 kHz to about 100 kHz, and (B) about 20 kHz to about 50 kHz.

20. The mass spectrometer of any one of Claims 17-20, wherein said electrically conductive shield comprises a plate electrode having an opening through which the ion beam, in use, passes therethrough, and, optionally, an electrically conductive tubular element extending from said outlet of said at least one ion beam steering device to said plate electrode and surrounding at least said portion of said region that is substantially free of the electric field.

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