Ion guide bandpass filter with LINAC electrodes

Abstract

In one aspect, a method for transporting ions in a mass spectrometer includes: using rods arranged in a multi-pole configuration and extending from near an inlet of an ion guide to near an outlet of the ion guide to generate an electromagnetic field for radially constraining ions received via the inlet into a space between the rods; using auxiliary electrodes positioned between the rods to generate an electric field in a first region of the ion guide for reducing radial confinement of a first subset of ions received in the first region to inhibit them from leading to a downstream second region of the ion guide while allowing the second subset of ions to reach the downstream second region; and axially accelerating the second subset of ions in the downstream second region to promote exit of the second subset of ions from the ion guide.

Description

[0001] Related Applications

[0002] This application claims priority to U.S. Provisional Application No. 63 / 430,141, filed on Dec. 5, 2022, the entire content of which is incorporated herein by reference. Technical Field

[0003] The present disclosure relates to mass spectrometry, and more particularly, to methods and systems for obtaining MRM mass spectra of compounds. Background Art

[0004] The present teachings generally relate to systems and methods for mass spectrometry, and more particularly, to ion guides that can be used in a mass spectrometer.

[0005] Mass spectrometry (MS) is an analytical technique for determining the structure of a test chemical substance, having both qualitative and quantitative applications. MS can be used to identify unknown compounds, thereby determining the elemental composition of atoms in a molecule, determining the structure of a compound by observing its fragments, and quantifying the amount of a specific chemical compound in a mixed sample. A mass spectrometer detects chemical entities as ions, such that conversion of the analyte into charged ions must occur.

[0006] In some mass spectrometry systems, an ion guide can receive ions from an upstream ion source and can focus the ions into an ion beam for transmission to downstream ion optics. In some mass spectrometers, such an ion guide allows all ions received by the ion guide to be continuously transmitted to the downstream ion optics. In some other mass spectrometers, the ion guide can include a set of electrodes (e.g., in the form of a T-strip), which can be used to generate a controllable high-mass cut-off within the ion guide, which can prevent unwanted high-mass ions from being transmitted to the downstream ion optics, thereby preventing contamination of these components. For example, in a mass spectrometer operating in multiple reaction monitoring (MRM) mode, ions passing through the ion guide are received by a downstream ion filter, which can select precursor ions having a target m / z ratio for fragmentation to generate product ions for MRM analysis. In such a mass spectrometer, the voltage applied to such T-strip electrodes can be set to produce a high-mass cut-off (HMCO) above the precursor mass under the current analysis, and a calibration table can be used to correlate the T-strip voltage with the precursor mass. Ions filtered during one MRM detection cycle need to be re-introduced into the ion guide for analysis in subsequent MRM cycles.

[0007] The ion transport time through the ion guide can affect the refilling of the ion guide with previously filtered ions and thus affect the duty cycle of the mass measurement. The ion transport time through the ion guide is affected by space charge as well as the m / z ratio of the ions, the ion beam intensity, and the pressure within the ion guide. Generally, for ions with a lower m / z ratio and a higher charge state, the ion transport time is shorter. The ion transport time can also vary with space charge. Additionally, an elevated pressure within the ion guide can slow down the transport of ions through the ion guide.

[0008] By way of example, in some cases, the ion transport time can be in the range of about 0.1 ms to about 30 ms, such as in the range of about 1 ms to 20 ms or in the range of about 5 ms to about 10 ms. Additionally, in rapid MRM measurements, the transport time of ions in the ion guide may need to be shorter than about 5 ms. In such cases, the ions may not have sufficient time to refill the ion guide during the pause time between consecutive MRM dwell times. For some workflows, it is desirable to maximize the total number of monitored MRM transitions by reducing the analytical measurement time (dwell time) and the optical refill time (pause time) between measurements. Summary of the Invention

[0009] In one aspect, a method for transporting ions through an ion guide in a mass spectrometer is disclosed. The method includes: using a plurality of rods arranged in a multipole configuration and each rod extending continuously from near the entrance of the ion guide to near the exit of the ion guide to generate a radially confining electromagnetic field for radially confining ions received via the entrance of the ion guide in the space between the rods; using a plurality of auxiliary electrodes positioned between the multipole rods to generate an electric field in at least one region of the ion guide for reducing the radial confinement of a first subset of ions received in the at least one region to inhibit their passage to a downstream region of the ion guide while allowing a second subset of ions to reach the downstream region of the ion guide; and axially accelerating the second subset of ions in the downstream region of the ion guide to facilitate the exit of the second subset of ions from the ion guide.

[0010] The step of using the multipole rods to generate a radially confining electromagnetic field can include applying one or more RF voltages to the multipole rods. Additionally, the step of using the plurality of auxiliary electrodes to generate an electric field can include applying a DC bias voltage to at least one of the auxiliary electrodes to generate a DC electric field. By way of example, the DC bias voltage can be in the range of about -1000 volts to about +1000 volts. In some cases, the DC bias voltage can be distributed across 2 poles rather than being applied to only one pole.

[0011] The DC electric field is generated along a direction substantially perpendicular to the longitudinal axis of the ion guide.

[0012] The step of axially accelerating a second subset of ions includes applying a DC offset voltage between an ion acceleration electrode set positioned in the downstream region of the ion guide and the multipole rods. By way of example, in some embodiments, such a DC offset voltage can be in the range of about -1000 volts to about +1000 volts, such as in the range of about -500 volts to about +500 volts, or in the range of about -100 volts to about -150 volts.

[0013] In some embodiments, the multipole configuration can be any one of a quadrupole, hexapole, and octopole configuration. In other embodiments, the multipole configuration can include any number of rods.

[0014] In a related aspect, an ion guide for use in a mass spectrometer is disclosed, which includes an inlet for receiving ions and an outlet through which ions can leave the ion guide. The ion guide can also include a plurality of rods arranged in a multipole configuration and continuously extending from near the inlet of the ion guide to near the outlet, and configured to apply an RF voltage thereto to generate a radial confinement electromagnetic field in the space between the rods. Ions entering the ion guide through its inlet pass through a first region in which the ions only experience the radial confinement electromagnetic field generated by the voltage applied to the multipole rods.

[0015] A plurality of auxiliary electrodes are positioned between the rods and configured to apply at least one DC voltage thereto for generating an electric field in a second region of the ion guide located downstream of the first region, for reducing the radial confinement of a first subset of ions in this second region to inhibit their passage to the downstream region of the ion guide (also referred to herein as the third region), while allowing a second subset of ions to reach the third region. In addition, an additional electrode set (also referred to herein as the ion acceleration electrode) is positioned in the ion guide for generating an axial acceleration electric field in the downstream third region of the ion guide for accelerating the second subset of ions, thereby facilitating their exit via the outlet of the ion guide. Since the ion guide rods are continuous, there is a radial confinement field in the third region, similar to the first region. In the second region, applying a DC voltage to the T-strip electrodes can result in a weakening of the radial confinement field for a subset of ions.

[0016] In some embodiments, these additional electrodes can be arranged in any suitable configuration capable of providing the axial electric field required for accelerating ions. An example of such a configuration is referred to herein as LINAC TM, although any suitable configuration that will provide an axial electric field for accelerating ions within the third region can be used. By way of further illustration, in a first region immediately adjacent to the entrance of the ion guide, the ions received by the ion guide only experience a radial confinement RF field generated by the (one or more) RF voltages applied to the rods. When the ions enter a second downstream region in which an auxiliary electrode is located, the ions experience both an RF field generated by the (one or more) RF voltages applied to the rods and a DC field generated by the (one or more) DC voltages applied to the auxiliary electrode, which results in a weakening of the radial confinement field for a subset of the ions, thus inhibiting those ions from reaching the third region of the ion guide in which the acceleration electrode is located. The subset of ions that reach the third region are accelerated via an axial electric field generated by the acceleration electrode to facilitate their transport through the ion guide, while also experiencing a radial confinement RF field.

[0017] In this embodiment, the auxiliary electrode can have a T-shaped configuration, characterized by a stem extending from a base towards the space between the plurality of rods.

[0018] The ion guide can also include an RF voltage source for generating an RF voltage to be applied to the plurality of multipole rods and a DC voltage source for generating a DC voltage to be applied to any auxiliary electrode and the ion acceleration electrode. In some embodiments, the DC voltage source is configured to apply a DC voltage to at least one of the ion acceleration electrodes such that a DC offset voltage in the range of about -2000 volts to about +2000 volts is generated between the ion acceleration electrode and the multipole rods. Additionally, by way of example, the (one or more) RF voltages applied to the multipole rods can have a frequency in the range of about 0.1 MHz to about 5 MHz.

[0019] An ion mass filter can be positioned downstream of the ion guide for receiving ions exiting the ion guide.

[0020] In a related aspect, a method for transporting ions through an ion guide in a mass spectrometer is disclosed, which includes a plurality of rods arranged in a multipole configuration and configured to have an RF voltage applied thereto to generate a radial confinement electromagnetic field within the space between the rods, wherein the shape and dimensions of the rods are such that the radial confinement electromagnetic field extends from near the entrance of the ion guide (through which ions can enter the ion guide) to the exit of the ion guide (through which ions can leave the ion guide). A plurality of auxiliary electrodes are positioned between the rods and configured to have at least one DC voltage applied thereto to generate an electric field within a region of the ion guide for reducing the radial confinement of a first subset of ions in that region so as to inhibit their passage to a downstream region of the ion guide, while allowing a second subset of ions to reach the second downstream region; and an ion acceleration electrode group (such as a LINAC) positioned within the ion guideTM An electrode) for generating an axially accelerating electric field in a downstream region to facilitate the exit of a second subset of ions from the ion guide via the outlet of the ion guide.

[0021] A further understanding of various aspects of the present teachings can be obtained by referring to the following detailed description and in conjunction with the drawings briefly described below. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1A An ion guide according to an embodiment of the present teachings is schematically depicted.

[0023] Figure 1B Schematically depicted Figure 1A A end view of the ion guide depicted in

[0024] Figure 1C is Figure 1A A schematic perspective view of the ion guide depicted in

[0025] Figure 1D A schematic perspective view of an ion acceleration electrode, illustrating its tapered shape.

[0026] Figure 2 Shows an example of the ion transit time of ions having an m / z of 922 through the Q0 ion guide of a prototype mass spectrometer.

[0027] Figure 3 Shows TM The offset potential of Q0 relative to the ion path as a result of the (one or more) LINAC voltages in an ion guide according to an embodiment as a function of the DC offset voltage between the LINAC electrode and the quadrupole, the ion guide having a quadrupole, a T-bar, and a LINAC Figure 1A similar to those shown in the ion guide depicted in TM electrode.

[0028] Figure 4 Shows a comparison of the transit times of ions having an m / z of 829.5 through an exemplary ion guide according to the present teachings under various LINAC TM voltages and T-bar conditions.

[0029] Figure 5 Shows data indicating that ions can be accelerated via the application of an acceleration voltage to recover ion signal loss on a TOF mass spectrometry system with a T-bar bandpass, and

[0030] Figure 6 Shows data indicating that ions can be accelerated via the application of an acceleration voltage to recover ion signal loss on a triple quadrupole mass spectrometry system with a T-bar bandpass. Detailed Embodiments

[0031] It will be understood that, for clarity, the following discussion will set forth various aspects of some embodiments taught by the applicant, while omitting certain specific details as long as doing so is convenient or appropriate. For example, the discussion of the same or similar features in alternative embodiments may be simplified. For the sake of brevity, well-known ideas or concepts may not be discussed in detail. Those skilled in the art will recognize that some embodiments taught by the applicant may not require some of the details specifically described in each implementation, and these details are set forth herein only to provide a thorough understanding of some embodiments. Similarly, it will be clear that the described embodiments can be readily changed or varied according to common general knowledge without departing from the scope of the present disclosure. The following detailed description of the embodiments should not be construed as limiting the scope of the applicant's teachings in any way.

[0032] As used herein, the terms "about" and "substantially equal to" refer to variations in numerical amounts that can occur, for example, through real-world measurement or processing procedures, through inadvertent errors in such procedures, through differences in the manufacture, source, or purity of a component or reagent, etc. Generally, as used herein, the terms "about" and "substantially" mean greater or less than the stated value or range of values or completeness condition or state by 10%. For example, a concentration value of about 30% or substantially equal to 30% can mean a concentration between 27% and 33%. These terms also refer to variations that those skilled in the art will recognize as equivalent, as long as such variations do not cover known values in the prior art practice.

[0033] As used herein, the term "and / or" includes any and all combinations of one or more of the related listed items and can be abbreviated as " / ".

[0034] As mentioned above, during multiple reaction monitoring (MRM) mass analysis in which ions are pre-filtered, the ion transfer time through the ion guide located upstream of the ion filter in a mass spectrometer can affect the refilling of the ion guide and thus affect the duty cycle of the mass measurement. The ion transfer time through the ion guide is affected by space charge as well as the m / z ratio of the ions, the ion beam intensity, and the pressure inside the ion guide. Generally, for ions with a lower m / z ratio and a higher charge state, the ion transfer time is shorter. The ion transfer time can also vary with space charge and is generally longer for lower TICs. In addition, an elevated pressure in the ion guide can slow down the transfer of ions through the ion guide.

[0035] By way of example, in some cases, the ion transfer time can be in the range of less than 0.1 ms to about 30 ms, such as in the range of about 1 ms to about 20 ms or in the range of about 5 ms to about 10 ms. When running a rapid MRM experiment, it is desirable to minimize the duty cycle of the measurement, including both the pause time for setting the potential and the dwell time for acquiring data. In such cases, when conventional techniques are used for ion filtering, the ions may not have enough time to refill the ion guide during each MRM cycle.

[0036] In a mass spectrometer that utilizes an ion guide (referred to herein as Q0 or Q0 ion guide for ease of description) for focusing ions generated by an upstream ion source for transfer to a downstream ion filter (referred to herein as Q1 or Q1 filter for ease of description), an auxiliary electrode can be utilized, for example, in the form of a T-shaped electrode (also referred to herein as a T-strip), to generate a controllable high-mass cut-off (HMCO), which can prevent unwanted high-mass ions from being transmitted to the downstream ion optics, which could otherwise result in contamination of those ion optics. In other words, while a conventional ion guide can allow all ions received from the upstream ion optics to pass through continuously, the T-strip incorporated in such an ion guide can be used to generate HMCO windows that only allow those ions with an m / z ratio less than the cut-off to pass through the ion guide. For example, the voltage applied to the T-strip can generate an HMCO in Q0 that is higher than the maximum m / z ratio selected by Q1 for multiple reaction monitoring (MRM) analysis, and a calibration table can be used to correlate the T-strip voltage with the ion mass. More specifically, in some embodiments, the combination of the HMCO provided by the T-strip electrode and the low-mass cut-off (LMCO) provided by the RF voltage amplitude applied to the multipole rod set generates a band-pass window. By way of example, the T-strip electrodes disclosed in U.S. Patent No. US10,741,378 and U.S. Published Patent Application No. US20210327700 can be used in the practice of the present teachings, each of which is incorporated herein by reference in its entirety.

[0037] When analyzing multiple compounds by MRM, it is necessary to switch conditions between the MRM analyses of each of those compounds. If the bandpass window excludes other m / z ratio(s), the ions will be eliminated from the ion guide. Therefore, it will be necessary to refill the Q0 optics again to allow ions with the next m / z ratio to pass through the mass analyzer before acquiring the next MRM transition. Thus, the ion transit time in Q0 is a parameter that can affect the duty cycle of an MRM mass spectrometer. Under normal operation, a "dwell" time or "acquisition" time can be defined during which the signal of the first compound or range of compounds is measured. Before the next dwell time, the method includes a "pause" time to allow for setting potentials and refilling the front-end ion optics. If the transit time is very short, the pause time can be minimized, resulting in an increased analysis measurement or dwell time.

[0038] The ion transit time is affected by space charge as well as the m / z of the ions, the ion beam intensity, and the Q0 pressure level. In rapid MRM analysis of compounds, the dwell time (i.e., the time required to monitor a specific MRM transition) can be shorter than 5 ms. In such a case, using conventional T-strip filtering, the ions may not have enough time to refill Q0 during each MRM. In some techniques, this problem is addressed by employing a "single" high-mass cut-off to ensure that all ions of interest for analysis pass continuously through multiple bandpass windows by adjusting the window size based on the Q1 precursor m / z. The HMCO can be determined by the highest m / z in the ion list. This method uses a relatively large window to provide sufficient time for refilling Q0, but it may limit the protection of downstream optics from contamination. By way of example, assume an MRM analysis of a set of ions where most ions have an m / z ratio in the range of 400 - 1000 and a few ions have an m / z of 1500. Then the HMCO of Q0 can be set at an m / z of, for example, 1600 or higher. In this case, for m / z 400, the HMCO offset will be 1200 Da, and for m / z 1000, it will be 600 Da. For lower m / z ratios, the T-strip voltage will be close to zero to produce a large window size. Additionally, the optimized RF voltage applied to the ion guide for the highest m / z ions can be sufficient to filter out low m / z ions.

[0039] Therefore, methods for reducing ion transit time are needed to address problems such as insufficient time for refilling the ion guide that supplies ions before they reach the downstream mass filter when operating a mass spectrometer in any scan mode, which can be obtained on any mass spectrometer analyzer, including but not limited to quadrupole, triple quadrupole, ion trap, and time-of-flight instruments.

[0040] As discussed in more detail below, in some embodiments, the present teachings provide for filtering ions in a first region of an ion guide and utilizing an axial electric field in a second region downstream of the first region to receive unfiltered ions so as to accelerate the unfiltered ions and thereby speed up their transport through the ion guide. As discussed in more detail below, in the following embodiments, a set of LINACs is employed. TM The electrodes are arranged to produce a voltage drop across the propagation axis of the ion guide. By way of example and not limitation, a voltage in the range of about -2000 volts to about +2000 volts may be applied to the LINAC TM By way of example and not limitation, in some embodiments, the LINAC may be electrically conductive by applying a voltage in the range of about -100 volts to about -150 volts to the LINAC. TM The electrodes are provided to achieve an axial potential drop in the range of about 0.9 V to about 1.3 V. This voltage drop should be added to the potential difference that would normally exist between the Q0 rod and the remainder of the ion path downstream of the Q0 rod, so that in the absence of the LINAC TM In some embodiments, rather than reducing the potential of the ion path downstream of Q0, the Q0 offset voltage is increased to maintain a similar potential difference when the Q0-LINAC is applied. TM In general, the Q0 offset voltage can be varied based on the LINAC TM Voltage varies, and the Q0 offset voltage is preferably configured to maintain ion transmission, so that comparable ion transmission with or without the LINAC accelerating voltage applied can be achieved. For example, in some embodiments in which the ions under mass analysis have positive polarity, the Q0 offset voltage can be generated by keeping the multipole at a more positive voltage relative to the voltage applied to the accelerating electrode. In some embodiments in which the ions under mass analysis have negative polarity, the Q0 offset voltage can be generated by keeping the multipole at a less positive voltage relative to the voltage applied to the accelerating electrode. For the sake of brevity and without limitation, this relative voltage of the multipole relative to the accelerating electrode is referred to herein as being achieved by keeping the multipole at a higher DC potential relative to the accelerating electrode.

[0041] U.S. Patent Nos. 5,847,386 and 6,111,250 (incorporated herein by reference in their entireties) provide information regarding auxiliary LINAC TM Additional information on electrodes, these auxiliary LINAC TM Electrodes may be utilized in accordance with the present teachings to generate an accelerating field along the axis of propagation of ions.

[0042] refer to Figure 1A , Figure 1B , Figure 1C and Figure 1D, an ion guide 100 according to an embodiment of the present teachings includes an inlet 100a and an outlet 100b. The inlet 100a is for receiving ions generated by an upstream ion source (not shown), and the ions can leave the ion guide through the outlet 100b.

[0043] The ion guide 100 includes a set of rods 104. The set of rods 104 is arranged according to a multipole configuration and spaced apart from each other to provide an ion channel through which ions can pass. In this embodiment, the rod set 104 includes four rods 104a, 104b, 104c, and 104d, which are arranged according to a quadrupole configuration. In this embodiment, each rod 104 extends as a continuous element from a proximal end (e.g., the proximal end depicted as PE with respect to rod 104a) to a distal end (e.g., the distal end depicted as DE with respect to rod 104a). The proximal ends of the quadrupole rods are located at or near the inlet 100a of the ion guide, while the distal ends of the quadrupole rods are located at or near the outlet 100b of the ion guide. For example, the distance between the proximal end of the rod 104 and the inlet of the ion guide chamber (which is defined herein as the orifice of the lens IQ0 located at the inlet of the ion guide) can be, for example, in the range of about 0.5 mm to about 6 mm, such as in the range of about 1 mm to about 5 mm, or in the range of about 2 mm to about 4 mm. Similarly, the distance between the distal end of the rod 104 and the outlet of the ion guide (which is defined herein as the orifice of the lens IQ1 located at the outlet of the ion guide chamber) can be, for example, in the range of about 0.5 mm to about 6 mm, such as in the range of about 1 mm to about 5 mm, or in the range of about 2 mm to about 4 mm. Thus, the rods of the quadrupole rod set extend continuously from the inlet of the ion guide (or from a point near the inlet of the ion guide chamber) to the outlet of the ion guide chamber (or to a point near the outlet), thereby ensuring the radial focusing of at least a portion of the ions along the entire length of the ion guide. In other words, the rods of the quadrupole rod set are not in the form of multiple segments positioned relative to each other with gaps separating adjacent segments, where continuous radial focusing of ions from the inlet to the outlet of the ion guide would not be feasible.

[0044] An RF voltage source 200 operating under the control of a controller 202 applies an RF voltage to the rods of the quadrupole rod set to generate an electromagnetic field within the ion channel for providing radial confinement of the ions as they travel through the ion guide.

[0045] The quadrupole rods can be characterized by including multiple pairs of poles, where the RF voltage applied to the rods of each pole is substantially equal (the rods of each pole are equipotential), while the phase of the voltage applied to one pole is opposite to the phase of the voltage applied to another pole.

[0046] The RF voltage applied to the quadrupole rods can generate a quadrupole electromagnetic field within the ion channel, which can contribute to the radial confinement of the ions.

[0047] In some embodiments, the RF voltage applied to the multipole rod may have a frequency in the range of from about 0.1 MHz to about 5 MHz, for example, in the range of from about 1 MHz to about 3 MHz, or in the range of from about 3 MHz to about 5 MHz. In some such embodiments, the RF voltage may have an amplitude in the range of from about 10 volts to about 5 kilovolts (V 0-p ) range, for example, in the range of from about 100 to 2000 V o-p .

[0048] A DC voltage source 204, which is also operated under the control of the controller 202, may apply an offset DC voltage to the quadrupole rod to provide an offset DC voltage between the quadrupole rod and the upstream and / or downstream ion optics (e.g., a downstream ion mass filter).

[0049] Continuing to refer to Figure 1A , Figure 1B , Figure 1C and Figure 1D , a plurality of auxiliary electrodes 300a, 300b, 300c, and 300d (collectively referred to herein as the T-shaped auxiliary electrodes or the T-shaped electrodes or the T-strip 300) are interspersed between the quadrupole rod sets such that each auxiliary electrode is interposed between two of the quadrupole rods. In this embodiment, the auxiliary electrodes have a T-shaped configuration characterized by a base extending parallel to the quadrupole rods and a stem extending orthogonally from the base towards the ion channel. In this embodiment, the auxiliary electrodes 300 may be grouped into two pairs, herein referred to as T-strip A and T-strip B.

[0050] The pair of auxiliary electrodes 300a / 300b forms one pole of the auxiliary electrode (referred to herein as the B pole), and the pair 300c / 300d (referred to herein as the A pole) forms the other pole of the auxiliary electrode.

[0051] In this embodiment, the auxiliary electrodes 300 do not extend across the entire length of the ion guide. In other words, the length of the base of the T-shaped electrode is less than the longitudinal length of the ion guide. The auxiliary electrodes 300 may be positioned in a region of the ion guide closer to the inlet of the ion guide rather than its outlet.

[0052] As mentioned above, the ions entering the ion guide pass through only the first region 1000 of the radial confinement field generated by the (one or more) voltages applied to the multipole, which is the ion guide. The DC voltage source can apply a DC voltage to the T-shaped auxiliary electrode such that the DC potential difference between the auxiliary electrodes (and the potential difference between the auxiliary electrode and the quadrupole) can generate a DC field (e.g., an octupole DC field distribution) within the second region 2000 of the ion channel. This DC field can cause a subset of the ions (also referred to herein as the first subset) received by the ion guide having an m / z ratio within the target range to experience a reduction in ion confinement, thereby suppressing the passage of these ions through the ion guide while allowing other ions received by the ion guide to continue to propagate in the ion channel. For example, the reduction in ion confinement of the ions in the first subset can cause these ions to follow trajectories that result in the ions being attracted to the auxiliary electrodes and striking those electrodes, thus being removed from the ions propagating towards the exit of the ion guide. The T-strip electrodes can be used to establish a high mass cut-off (HMCO), and the RF voltage applied to the multipole can be used to establish a low mass cut-off (LMCO) such that the combination of the HMCO and the LMCO provides a bandpass filter that allows the transmission of ions having an m / z ratio within the m / z range while suppressing the passage of ions having an m / z ratio outside of this m / z range.

[0053] By way of example, the DC bias voltage applied to the T-shaped auxiliary electrode can be in the range of about -1000 volts to about +1000 volts. In some embodiments, the DC bias voltage can be distributed across the two poles of the T-strip, with the Q0 DC offset being at zero (reference) point. The remaining ions (referred to herein as the second subset of ions) continue to propagate along the ion guide. The voltage applied to the T-shaped auxiliary electrode can establish an HMCO, which in combination with the LMCO established by the RF voltage applied to the multipole produces a bandpass filter that suppresses the passage of one subset of ions but allows the passage of another subset.

[0054] Specific reference Figure 1A and Figure 1C , in this embodiment, the LINAC TM (linear accelerator) electrode set 400 is positioned downstream of the T-shaped electrode. In this embodiment, the LINAC TM electrode set includes four electrodes (two of which 400a / 400b are visible in Figure 1C ), and each electrode is interposed between two of the quadrupoles. As Figure 1D shown, in this embodiment, each LINAC TMThe electrodes have a tapered profile such that applying a DC voltage to those electrodes results in an axial electric field being generated within a third region 3000 of the ion guide, which third region 3000 is positioned downstream of a second region 2000 and substantially corresponds to the portion of the ion channel surrounded by the LINAC TM electrodes to axially accelerate ions passing through the bandpass filter towards the exit of the ion guide.

[0055] By way of example but not limitation, the DC voltage applied to the T-shaped electrodes can be in the range of from about -1000 volts to about +1000 volts.

[0056] In some embodiments, generating an axial electric field in region 3000 of the ion guide can reduce the transit time of ions passing through the ion guide by a factor in the range of from about 2-fold to about 30-fold. For example, in some embodiments, due to the use of the axial acceleration field, the transit time of ions through the ion guide can be, for example, equal to or less than about 5 ms, e.g., in the range of from about 1 ms to about 5 ms. This can in turn allow for rapid refilling of the ion guide. In this way, the bandpass filter provided by the combination of the multipole rods and the T-shaped electrodes can significantly reduce the contamination of downstream ion optics, while the axial electric field provided by the LINAC TM electrodes allows for rapid refilling of the ion guide with those ions removed by the bandpass filter.

[0057] The following examples are provided to further clarify various aspects of the present teachings and are not intended to indicate the necessarily optimal way of practicing the present teachings and / or the optimal results that may be achieved.

[0058] Examples

[0059] Example 1

[0060] Figure 2 An example of the ion transit time of ions having an m / z of 922 through the Q0 ion guide of a prototype mass spectrometer is shown. The T-strip electrodes are integrated into the Q0 ion guide to create a controllable high-mass cut-off (HMCO), which can prevent unwanted ions from being transmitted to downstream ion optics to reduce and preferably eliminate the contamination of downstream ion optics caused by such ions.

[0061] Figure 2 The data presented were obtained on a system that does not include LINAC TM electrodes (such as those mentioned above) and includes a 12 cm Q0 ion guide. As the pressure in the Q0 region increases, a longer time frame is required to refill the ion optics.

[0062] To obtain Figure 2For the data depicted, the T-strip voltage is set to produce an HMCO that is approximately 100 Da higher in m / z ratio than the precursor ions selected by the downstream mass filter (Q1). A calibration table is established to correlate the T-strip voltage with the Q1 filter (i.e., with the m / z ratio of the ions passing through the Q1 filter).

[0063] The above data indicate that when using a 12 cm Q0 with various pressures, ions require at least about 5 - 10 ms to traverse the Q0 region. When using a longer Q0 component (such as a Q0 component with a length in the range of 15 - 18 cm), the transit time can be further slowed down to 10 - 30 ms. For example, in Figure 2 the data depicted, as the pressure within Q0 increases, the time required to refill the Q0 ion guide also increases.

[0064] Example 2

[0065] Figure 3 Shows the offset potential of Q0 relative to the ion path as a result of the LINAC TM electrode as a function of the DC offset voltage between the LINAC Figure 1A electrode and the quadrupole, according to an embodiment having a quadrupole, T-strip, and LINAC TM electrode as depicted in TM The potential drop varies from about 0.9 V to about 1.3 V as the offset voltage between the LINAC TM electrode and Q0 varies from about -100 volts to about -150 volts.

[0066] In the absence of the Q0 LINAC electrode, to maintain the desired potential difference, the offset voltage between the LINAC TM electrode and the Q0 rod should be added to the potential difference that normally exists between Q0 and the rest of the ion path downstream of Q0. In some cases, instead of reducing the voltage on the ion path downstream of Q0, the Q0 offset voltage is increased to maintain the desired potential difference when applying the Q0 - LINAC TM offset voltage. This allows for comparable ion transport with and without LINAC acceleration.

[0067] Example 3

[0068] Figure 4 Shows various LINACs with the T-strip and 15 cm Q0 enabled TMComparison of the transit time of an ion with m / z of 829.5 through an exemplary ion guide according to the present teachings at 200 MHz and 100 MHz. The transit time was measured by monitoring the total ion current using a time-of-flight (ToF) instrument. The data show that without using LINAC TM When the electrode is used to accelerate ions, the refill time required is about 20-25ms, while in LINAC TM A LINAC of -50 and -250 is applied between the electrode and the Q0 rod. TM The required refill time is less than about 5 ms for a voltage of 1.5 Ω. Similar improvements have been measured on triple quadrupole systems.

[0069] By way of further illustration, Figure 5 The figure shows the relative intensity of ions passing through the ion guide as Q0 multipole and LINAC TM Data as a function of the offset voltage between the electrodes for the following three cases: (1) T-bar off (T-bar passband disabled), (2) T-bar on B (T-bar passband enabled, where filtered ions are deposited on the T-bar B electrode), (3) T-bar on A (T-bar passband enabled, where filtered ions are deposited on the T-bar A electrode). Signals for relatively low m / z (829.5) compounds and high m / z (1446.7) compounds were measured using a TOF / MS / MS spectrometer in which a 15 cm Q0 ion guide according to the present teachings was combined with a 10 ms integration measurement time and a 2 ms dwell time. Figure 5 A comparison of the signal for a high m / z ion (m / z 1446.7) is shown. With the T-bar bandpass disabled (T-bar off), there is a continuous ion flow through Q0 and therefore no transmission difference for m / z 1446.7 is observed as the LINAC voltage is gradually increased.

[0070] Applying a DC bias voltage to the T-bar electrode during the first TOFMSMS of m / z 829.5 to produce HMCO at m / z 929.5 results in the ion of m / z 1446.7 not being within the transmission window, while the ion of m / z 829.5 passes through Q0. Therefore, when the T-bar passband is changed to allow the ion of m / z 1446.7 to pass through Q0, the ion of m / z 1446.7 must be refilled into Q0. When a LINAC voltage in the range of -100V to -300V is adopted, the ions can be refilled into Q0 quickly. In contrast, with the Q0-LINAC voltage set to zero, a signal loss of 30%-40% is observed for m / z 1446.7, indicating that Q0 is not sufficiently refilled with ions at this 12ms time scale (10ms measurement time + 2ms pause time).

[0071] Example 4

[0072] In some embodiments, a LINAC is applied in the range of about -100V to about -150V TM The offset voltage can significantly reduce the fill time of the Q0 ion guide. The reduction in the fill time of the Q0 ion guide can be important, especially when rapid refilling of Q0 with ions having an m / z ratio in the T-strip passband is required.

[0073] By way of further illustration, Figure 6 Data is shown indicating that ion signal loss can be restored by applying an acceleration voltage to the LINAC TM electrode on a triple quadrupole mass spectrometer system. The experiment included monitoring the signals for m / z 133 and m / z 1522 with the T-strip passband enabled. Data was collected using a 2-ms dwell time and a 3-ms pause time. The baseline was obtained with the T-strip passband disabled (T-strip off, LINAC TM off), where there was a continuous ion flow through Q0. During the first MRM transition (m / z 133), a DC bias voltage was applied to the T-strip electrode to cause ions at m / z 233 to result in ions at m / z 1522 outside the transmission window, while ions at m / z 133 passed through Q0. Without LINAC TM acceleration (LINAC TM off, T-strip on), a 4-fold signal loss was observed for m / z 1522 due to insufficient refill time. When an offset between the LINAC electrode and the Q0 electrode of -150V was employed (LINAC TM on, T-strip on), ions at m / z1522 could be rapidly refilled into Q0 and the signal was restored.

[0074] The foregoing description of the embodiments is presented for purposes of illustration only. It is not exhaustive and does not limit the embodiments to the precise forms disclosed. While several exemplary embodiments and features have been described, modifications, adaptations, and other implementations are possible without departing from the spirit and scope of the embodiments. For example, the presented data was obtained using infusion, but any sample introduction mode can be used, including LC. Thus, unless otherwise explicitly stated, the description pertains to one or more embodiments and should not be construed as limiting the overall embodiments. This is true whether the disclosure indicates that a feature relates to "a," "the," "one," "one or more," "some," or "various" embodiments. As used herein, the singular forms "a / an" and "the" may include the plural forms unless the context clearly dictates otherwise. Additionally, the term "coupled" does not exclude the presence of intermediate elements between the coupled items. Similarly, indicating that a feature may be present indicates that the feature may be present in one or more embodiments.

[0075] In the present disclosure, the terms "comprising," "including," "containing," and "having," when used after a set or system, mean open inclusion and do not exclude adding other non-listed members to the set or system. Additionally, unless otherwise stated or inferred from the context, if the conjunction "or" is used, it is not exclusive but inclusive, meaning and / or. Moreover, if these terms are used, a subset of a set can include one or more than one (including all) members of the set.

[0076] Furthermore, if used in the present disclosure and unless otherwise stated or inferred, if a first variable generally increases rather than decreases as a second variable increases, then the first variable is an increasing function of the second variable. On the other hand, if the first variable generally decreases rather than increases as the second variable increases, then the first variable is a decreasing function of the second variable. In some embodiments, if the first variable is directly or inversely proportional to the second variable, respectively, then the first variable can be an increasing or decreasing function of the second variable.

[0077] The disclosed systems, methods, and devices are not limited to any particular aspect or feature or combination thereof, nor do they require the presence of any one or more particular advantages or the solution of any problems. Any theory of operation is for ease of explanation, but the disclosed systems, methods, and devices are not limited to such a theory of operation.

[0078] In view of the foregoing teachings, modifications and variations are possible, or may be obtained from practicing the embodiments. For example, the described steps need not be performed in the same order as discussed or with the same degree of separation. Also, various steps may be omitted, repeated, combined, or performed in parallel as needed to achieve the same or similar objectives. Similarly, the described system need not include all of the components described in the embodiments and may also include other components not described in the embodiments. Accordingly, the embodiments are not limited to the above details but are defined by the appended claims in their full scope of equivalents. Further, the present disclosure is directed to all novel and non-obvious features and aspects of the various disclosed embodiments, individually and in various combinations and sub-combinations with each other.

[0079] Although the present disclosure has been specifically described in connection with specific embodiments, many alternatives, modifications, and variations will be apparent from the foregoing description. Accordingly, it is expected that the appended claims will cover any such alternatives, modifications, and variations that fall within the true spirit and scope of the present disclosure.

[0080] Those of ordinary skill in the art will recognize that various changes may be made to the above embodiments without departing from the scope of the present teachings.

Claims

1. A method for transporting ions through an ion guide in a mass spectrometer, comprising: using a plurality of rods arranged in a multipole configuration and each rod extending continuously from near the entrance of the ion guide to near the exit of the ion guide to generate a radially confining electromagnetic field for radially confining ions received via the entrance of the ion guide into the space between the rods, using a plurality of auxiliary electrodes positioned between the rods to generate an electric field in a first region of the ion guide to reduce the radial confinement of a first subset of ions received in the first region to inhibit them from reaching a second region downstream of the ion guide while allowing a second subset of ions to reach the second region downstream of the ion guide, and axially accelerating the second subset of ions in the second region downstream of the ion guide to facilitate the exit of the second subset of ions from the ion guide.

2. The method according to claim 1, wherein The step of using the multipole rods to generate the radially confining electromagnetic field includes applying one or more RF voltages to the plurality of rods in the multipole rods.

3. The method according to any one of claims 1 or 2, wherein The step of using the plurality of auxiliary electrodes to generate the electric field includes applying a DC bias voltage to at least one of the auxiliary electrodes to generate a DC electric field.

4. The method according to claim 3, wherein, The DC bias voltage is in the range of about -1000 volts to about +1000 volts.

5. The method according to any one of the preceding claims, wherein, The DC electric field is generated along a direction substantially orthogonal to the longitudinal axis of the ion guide.

6. The method according to any one of the preceding claims, wherein, The step of axially accelerating the second subset of ions includes applying a DC offset voltage between an ion acceleration electrode set positioned in the second region downstream of the ion guide and the multipole rods.

7. The method according to claim 6, wherein The DC offset voltage is in the range of about -2000 volts to about +2000 volts.

8. The method according to any one of the preceding claims, wherein, The multipole configuration includes any one of a quadrupole, hexapole, and octapole configuration.

9. The method according to claim 6, further comprising adjusting the DC offset voltage between the multipole rods and the ion acceleration electrodes to obtain a desired transmission rate of ions through the ion guide.

10. The method according to claim 6, wherein, The DC offset voltage is generated by maintaining the multipole rods at a higher DC electric potential relative to the acceleration electrodes.

11. An ion guide for use in a mass spectrometer, comprising: an entrance for receiving ions and an exit through which ions can leave the ion guide, a plurality of rods arranged in a multipole configuration and extending continuously from near the entrance to near the exit, and the plurality of rods being configured to have an RF voltage applied thereto to generate a radially confining electromagnetic field within the space between the rods, a plurality of auxiliary electrodes positioned between the rods, and the plurality of auxiliary electrodes being configured to have at least one DC voltage applied thereto for generating an electric field in a first region of the ion guide for reducing the radial confinement of a first subset of ions in the first region to inhibit them from reaching a second downstream region of the ion guide while allowing a second subset of ions to reach the second downstream region, and An ion acceleration electrode set positioned in the ion guide for generating an axial acceleration electric field in the second downstream region of the ion guide for accelerating a second subset of the ions to facilitate their exit from the ion guide via the outlet of the ion guide.

12. The ion guide according to claim 11, wherein The auxiliary electrode has a T-shaped configuration characterized by a stem extending from a base towards the space between the plurality of rods.

13. The ion guide according to any one of claims 11 and 12, further comprising an RF voltage source for generating an RF voltage to be applied to the plurality of rods of the multipole rods.

14. The ion guide according to claim 13, further comprising a DC voltage source for generating a DC voltage to be applied to any one of the auxiliary electrode and the LINAC electrode.

15. The ion guide according to claim 14, wherein, The DC voltage source is configured to apply a DC voltage to the ion acceleration electrode so as to generate a DC offset voltage in the range of approximately -2000 volts to approximately +2000 volts between the ion acceleration electrode and the multipole rods.

16. The ion guide according to any one of claims 13-15, wherein The RF voltage has a frequency in the range of approximately 0.1 MHz to approximately 5 MHz.

17. The ion guide according to any one of the preceding claims, further comprising an ion mass filter positioned downstream of the ion guide for receiving ions exiting the ion guide.

18. A method for transporting ions through an ion guide in a mass spectrometer, comprising: A plurality of rods arranged in a multipole configuration and configured to have an RF voltage applied thereto to generate a radial confinement electromagnetic field within the space between the rods, wherein the shape and size of the rods are such that the radial confinement electromagnetic field extends from near the inlet of the ion guide through which ions can enter the ion guide to the outlet of the ion guide through which ions can exit the ion guide, A plurality of auxiliary electrodes positioned between the rods and configured to have at least one DC voltage applied thereto for generating an electric field within a first region of the ion guide for reducing the radial confinement of a first subset of the ions in the first region to inhibit their passage to a second downstream region of the ion guide while allowing a second subset of the ions to reach the second downstream region, and An ion acceleration electrode set positioned in the ion guide for generating an axial acceleration electric field in the second downstream region to facilitate the exit of a second subset of the ions from the ion guide via the outlet of the ion guide.

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