Patent Grant
11728153
The present disclosure relates generally to tandem mass spectrometers of the kind having a collision cell with an elongated conductor set. More particularly, the present disclosure relates to apparatuses and methods for re-focusing an ion beam via exposure to RF-only potential during transmission through such a collision cell.
In tandem mass spectrometers such as triple quadrupole mass spectrometers, and also in other mass spectrometers, gas within the volumes defined by the RF rod sets in ion guides and collision cells improves the sensitivity and mass resolution of the instrument by a process known as collisional focusing. Collisions between the gas and the ions cause the velocities of the ions to be reduced and the ions become focused near the longitudinal axis. Although the ion focusing effect is desirable, unfortunately the slowing of the ion velocities also produces other, undesirable effects.
One such undesirable effect is that after product (daughter) ions have been formed in a collision cell downstream of a first mass filter, for example, the ions may drain slowly out of the collision cell because of their very low velocity after many collisions. The ion clear-out time (typically several tens of milliseconds) can cause tailing in the chromatogram and other spurious readings due to interference between adjacent channels when monitoring several parent/fragment pairs in rapid succession. To avoid this, a fairly substantial pause time is needed between measurements. The tailing also requires a similar pause. This required pause time between measurements reduces the productivity of the instrument.
It is known to create an axial field, sometimes referred to as a drag field, in order to move ions axially through the multipoles forming ion guides and collision cells. Several different approaches have been described for creating such axial fields.
U.S. Pat. No. 5,847,386, entitled, “Spectrometer with Axial Field,” issued Dec. 8, 1998, to Thompson et al., discusses the creation of an axial field using tapered main rods, or arranging the main rods at angles with respect to each other, or segmenting the main rods. Additionally, U.S. Pat. No. 5,847,386 discusses providing resistively coated or segmented auxiliary rods, providing a set of conductive metal bands spaced along each rod with a resistive coating between the bands, forming each rod as a tube with a resistive exterior coating and a conductive inner coating, and other methods.
U.S. Pat. No. 7,675,031 to Konicek et al. discusses the creation of an axial field using auxiliary electrodes, configured with a number of finger electrodes, designed to be disposed between adjacent pairs of main electrodes. In an alternative implementation, vanes of a thin semi-conductive material such as, but not limited to, silicon dioxide are disposed between adjacent pairs of main electrodes. These so-called drag vanes can be configured to have a resistance in a direction along their lengths for creating a DC axial field when an electrical potential is applied. Straight and flat auxiliary electrodes are described for use with linear main electrodes, as well as curved auxiliary electrodes for use with curved main electrodes.
In each of the examples described above, the DC axial field extends along the entire length of the collision cell between an ion inlet end and an ion outlet end thereof. Ions experience the DC axial field immediately upon introduction into the collision cell and they continue to experience the DC axial field until they are extracted from the collision cell. During this entire time, the ions may undergo collisions with gas molecules inside the collision cell and drift away from the longitudinal axis. This effect defocuses the ions and tends to increase ion losses, which in turn leads to reduced instrumental sensitivity. In order to offset this effect, it is necessary to precisely axially align of the various sections of the instrument and provide complex lens systems between the adjacent sections. Unfortunately, these solutions increase the cost and complexity of the instrument and also necessitate rigorous set-up and maintenance procedures.
It would therefore be beneficial to provide methods and apparatuses that overcome at least some of the disadvantages and/or limitations that are mentioned above.
In accordance with an aspect of at least one embodiment there is provided a method, comprising: providing a multipole ion guide device comprising a plurality of electrodes, the electrodes being arranged one relative to another so as to define a space therebetween for transmitting ions, the multipole ion guide device having a length extending between an ion inlet end and an opposite ion outlet end thereof; introducing a population of ions into the ion inlet end of the multipole ion guide device; transmitting at least some of the ions of the population of ions along the entire length of the multipole ion guide device to the ion outlet end thereof; and during the step of transmitting, exposing the at least some of the ions to an RF-only field extending along a first portion of the length and exposing the at least some of the ions to a DC axial field extending along a second portion of the length.
In accordance with an aspect of at least one embodiment there is provided a multipole ion guide device, comprising: providing a multipole ion guide device comprising a plurality of electrodes, the electrodes being arranged one relative to another so as to define a space therebetween for transmitting ions, the multipole ion guide device having a length extending between an ion inlet end and an opposite ion outlet end thereof; applying voltages to electrodes of the plurality of electrodes and thereby forming: i) an RF-only field along a first portion of the length of the device; and ii) a DC axial field along a second portion of the length of the device; and transmitting ions through the first and second portions of the length of the multipole ion guide device, such that the ions are exposed to both the RF-only field and the DC axial field during a single pass through the device.
In accordance with an aspect of at least one embodiment there is provided a multipole ion guide device, comprising: multipole ion guide device, comprising: a plurality of electrodes disposed about a longitudinal axis of said device and being arranged one relative to another so as to define an ion transmission volume therebetween for transmitting ions along a length of said device between an ion inlet end and an opposite ion outlet end thereof; an electronic controller operably connected to an RF power source and at least some electrodes of the plurality of electrodes and being configured to apply at least an RF potential to said at least some electrodes, wherein said plurality of electrodes is configured to generate an RF-only field along a first portion of the length of said device and to generate an axial DC field along a second portion of the length of said device when said electronic controller is applying said at least an RF potential to said at least some electrodes, and wherein, during use, ions are focused radially inward toward the longitudinal axis of said device within the first portion of the length of said device.
The instant invention will now be described by way of example only, and with reference to the attached drawings, wherein similar reference numerals denote similar elements throughout the several views, and in which:
The following description is presented to enable a person skilled in the art to make and use the invention and is provided in the context of a particular application and its requirements. Various modifications to the disclosed embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be applied to other embodiments and applications without departing from the scope of the invention. Thus, the present invention is not intended to be limited to the embodiments disclosed but is to be accorded the widest scope consistent with the principles and features disclosed herein.
In the description of the invention herein, it is understood that a word appearing in the singular encompasses its plural counterpart, and a word appearing in the plural encompasses its singular counterpart, unless implicitly or explicitly understood or stated otherwise. Furthermore, it is understood that for any given component or embodiment described herein, any of the possible candidates or alternatives listed for that component may generally be used individually or in combination with one another, unless implicitly or explicitly understood or stated otherwise. Additionally, it will be understood that any list of such candidates or alternatives is merely illustrative, not limiting, unless implicitly or explicitly understood or stated otherwise. It is also to be understood, where appropriate, like reference numerals may refer to corresponding parts throughout the several views of the drawings for simplicity of understanding.
Moreover, unless otherwise indicated, numbers expressing quantities of ingredients, constituents, reaction conditions and so forth used in the specification and claims are to be understood as being modified by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the subject matter presented herein. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the subject matter presented herein are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any measured numerical values, however, inherently contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
Turning now to the drawings,
In other example arrangements, mass spectrometer 12 often may be configured with an ion source and an inlet section 24 known and understood to those of ordinary skill in the art, of which, such sections can include, but are not limited to, electrospray ionization, chemical ionization, photo ionization, thermal ionization, and matrix assisted laser desorption ionization sections. In addition, mass spectrometer 12 may also include any number of ion guides)(q0) 27, (q4) 30, mass filters (Q1) 33, collision cells (q2) 36, and/or mass analyzers (Q3) 39, (Qn) 42, wherein the mass analyzers 39, 42, may be of any type, including, but not limited to, quadrupole mass analyzers, two dimensional ion traps, three dimensional ion traps, electrostatic traps, and/or Fourier Transform Ion Cyclotron Resonance analyzers.
The ion guides 27, 30, collision cells 36, and analyzers 39, 42, as known to those of ordinary skill in the art, can form an ion path 45 from the inlet section 24 to at least one detector 48. Any number of vacuum stages may be implemented to enclose and maintain any of the devices along the ion path at a lower than atmospheric pressure. The electronic controller 15 is operably coupled to the various devices including the pumps, sensors, ion source, ion guides, collision cells and detectors to control the devices and conditions at the various locations throughout the mass spectrometer 12, as well as to receive and send signals representing the particles being analyzed. Specific and non-limiting examples of geometries that are appropriate for the ion guides 27, 30, collision cells 36 include quadrupole (set of four main electrodes), hexapole (set of six main electrodes) and octupole (set of eight main electrodes). The following discussion assumes a quadrupole geometry; however, it is to be understood that the same principles may be applied using either hexapole or octupole geometries.
As described above, many ion guides and collision cells suffer from the trade-off of slowing the ions down during ion transport when a gas is used to cool the ions and move them toward a central axis. Auxiliary electrodes or drag vanes have been utilized to create a DC axial field along the length of the ion guides and collision cells, which speeds up the transport of the ions but also imposes strict alignment and inter-stage focusing requirements, which in turn increases instrumental complexity and cost.
Referring now to
Referring again to
A structural element for receiving and supporting metallization may be a substrate 99, as shown in
In an alternative embodiment, one or more of the auxiliary electrodes can be provided by an auxiliary electrode that has dynamic voltages applied to one or more finger electrode of the array of finger electrodes 71. In this example arrangement, the controller 15, as shown in
As shown in
Optionally, the auxiliary electrodes 54, 55, 56, 57 may be dimensioned and positioned relative to the main rod electrodes 60, 61, 62, 63 so as to form an RF-only region proximate each end of the multipole ion guide. In this case, ions introduced into the right-hand side of the multipole ion guide of
Further optionally, the lengths of the regions within which there is no DC axial field may be different at the opposite ends of the multipole ion guide. For instance, the auxiliary electrodes 54, 55, 56, 57 may be dimensioned and positioned relative to the main rod electrodes 60, 61, 62, 63 so as to provide a longer region within which there is no DC axial field at the ion outlet end of the multipole ion guide, such that the ions are well focused prior to being extracted.
By way of a specific example, the auxiliary electrodes 54, 55, 56, 57 may be shortened, relative to each end of the main rod electrodes 60, 61, 62, 63, by between 2.5 ro and 5 ro, where ro is the inscribed radius of the RF electrodes main rod electrodes 60, 61, 62, 63. As discussed above, the auxiliary electrodes 54, 55, 56, 57 may be shortened by this amount at one end or at both ends of the multipole ion guide, in either a symmetric or asymmetric fashion. However, when implemented in a collision cell the resulting length of the DC axial field must still be long enough to allow for sufficient ion fragmentation.
Referring now to
Auxiliary electrodes 111, 112, 113, 114 are inserted between the main electrodes 105, 106, 107, 108 and DC voltages are applied to the auxiliary electrodes 111, 112, 113, 114, as has been described with regard the embodiments of
In the end view perspective of
As may be appreciated from
As with the other example embodiments, the array of finger electrodes 128 is disposed on opposite sides of the circuit board material that forms each of the substrates. Similar to the other example embodiments described above, the array of finger electrodes 128 may include a printed or otherwise applied conductive material on an edge of the printed circuit board material that joins the conductive material on opposite sides of the circuit board material. In this way, the array of finger electrodes presents the conductive material on a majority of a radially innermost edge surface of the auxiliary electrode. Also similar to the other embodiments, there are recesses 92 in the edges of the circuit board material between respective finger electrodes 128 of the finger electrode array. Thus, available sites for ion deposit on an insulative material surface of the circuit board material are recessed radially outward away from the ion beam or path.
As with the other embodiments, the printed circuit board material utilized in forming the auxiliary electrodes for the embodiment of
Alternatively, a DAC may be connected to a group of finger electrodes 128, which are in turn connected to each other by resistors 126 as shown and described with regard to the embodiment of
The embodiments that have been discussed with reference to
Alternatively, embodiments may be envisaged that do not utilize auxiliary electrodes positioned between the main rod electrodes to create a DC axial field within a predetermined region of the multipole ion guide but not within other regions of the multipole ion guide. In these embodiments, the main rod electrodes are suitably configured to produce a RF-only potential at one or both ends and a DC axial field within a predetermined region.
The different electrode configurations described above result in several advantages including more forgiving mechanical geometry and less sensitive to axial alignment of q2, Q1 and Q3 in terms of instrument sensitivity. For instance, the sensitivity is enhanced due to reduction of ion the loss processes that occur after ions are introduced into the multipole ion guide as well as when the ions are extracted from the multipole ion guide. Further, the design ion optic systems between stages of the mass spectrometer may be simplified and DC ion focusing elements can be reduced and or eliminated because transmission between the stages is facilitated by RF only lensing. By way of an example, two of the three DC lenses that are typically provided between the different stages could be eliminated. Alternatively, the instrument could be run at a higher pressure.
As already discussed above, the RF-only focusing of the ions that are introduced into a collision cell leads to improved transmission into the drag region of the collisions cell and allows for more uniform distributions of ion kinetic and internal energies, resulting in richer and more consistent fragmentation spectra. Further, improvements to the observance of low abundance fragment ions and improvements to the consistency of daughter ion abundance ratios may be observed.
Specific and non-limiting examples have been illustrated and described herein in order to clearly explain the subject-matter that is considered to be inventive. Additional modifications may be made to the various examples without departing from the scope of the invention. For instance, specific examples have been shown in which the main RF electrodes are generally circular or square/rectangular in a cross-sectional view taken in a plane normal to the electrode length. However, any other suitably shaped electrode may be used instead, such as for instance RF electrodes that are true hyperbolic shape in cross-section.
Additional advantages may include more consistent instrument to instrument performance and simpler and faster instrument tuning.
As used herein, including in the claims, unless the context indicates otherwise, singular forms of the terms herein are to be construed as including the plural form and vice versa. For instance, unless the context indicates otherwise, a singular reference, such as “a” or “an” means “one or more”.
Throughout the description and claims of this specification, the words “comprise”, “including”, “having” and “contain” and variations of the words, for example “comprising” and “comprises” etc., mean “including but not limited to”, and are not intended to (and do not) exclude other components.
It will be appreciated that variations to the foregoing embodiments of the invention can be made while still falling within the scope of the invention. Each feature disclosed in this specification, unless stated otherwise, may be replaced by alternative features serving the same, equivalent or similar purpose. Thus, unless stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.
The use of any and all examples, or exemplary language (“for instance”, “such as”, “for example”, “e.g.” and like language) provided herein, is intended merely to better illustrate the invention and does not indicate a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.
Any steps described in this specification may be performed in any order or simultaneously unless stated or the context requires otherwise.
All of the features disclosed in this specification may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive. In particular, the preferred features of the invention are applicable to all aspects of the invention and may be used in any combination. Likewise, features described in non-essential combinations may be used separately (not in combination).
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| Number | Date | Country | |
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| 20200194244 A1 | Jun 2020 | US |
