Patent Application
20100176295
1. Field of the Invention
The present invention relates to the field of mass spectrometry, and more particularly to a mass spectrometer multipole device that enables the merging of ion beams from separate sources and/or for directing a single ion beam into a plurality of directions for collection and/or analysis.
2. Discussion of the Related Art
Mass spectrometry is an analytical technique that enables the identification of chemical compositions of a sample based on the mass-to-charge ratio of charged particles. Generally, analytes in a sample are ionized and thereafter separated via their mass wherein the ratio of a respective charge to mass is determined by passing them through electric and magnetic fields so as to result in a desired mass spectrum.
In particular, the design of a mass spectrometer to enable separation and detection most often includes: an ion source to transform introduced molecules in a sample into ionized particles; an analyzer to separate such ionized particles by their masses by applying electric and magnetic fields; and a detector to measure and thus provide data for calculating the abundances of each ion present.
As known to those skilled in the art, in the design of such a spectrometer system, the ionized particles resulting from the ion source are often directed along an ion path using ion steering optics, such as, but not limited to cylindrical lenses, einzel structures, skimmers, and multipole rod configurations, etc. In the multipole rod configuration, the number of rods can be any even number, such as four, six, or eight with high-frequency voltages having inverted phases applied to electrodes adjacent to each and often in electrical cooperation with additionally applied direct current (DC) voltages. Accordingly, ions introduced along a longitudinal direction into such structures proceed by oscillation in a predetermined cycle due to a high frequency electric field caused by the aforementioned voltages so as to direct a desired amount of ions to a subsequent stage.
While such ion steering optics, and in particular, the mutipole rod configurations, beneficially enable the desired ions to be directed along predetermined paths, such designs do not provide for the merging of ion beams from two distinct sources, or for redirecting a single ion beam in one direction or another as disclosed by the novel and beneficial configurations of the present invention.
To give the reader an idea of the technical capabilities presently in the field, one can look to background information for a system that uses movably mounted multipoles to couple one or more ion sources to a mass spectrometer, which is described and claimed in U.S. Pat. No. 5,825,026, entitled “Introduction of Ions from Ion sources Into Mass Spectrometers,” issued Oct. 20, 1998, to Baykut, including the following, “The basic idea of the invention is to movably position one or several curved multipole ion guides, so that in a system of multiple stationary ion sources, each source can be used one after another by adjusting the movable multipole. The ions originating from various ion sources, which however are directed toward a common point, can be introduced into the mass spectrometer, using a rotatable multipole ion guide arrangement. The ions can be transferred directly into an rf ion trap or into a quadrupole or sector mass spectrometer, or also an ion transfer line of a FTICR spectrometer. For this purpose, a multipole (e.g. a hexapole or octopole) is positioned adjustably around the axis of the ion trap or around of the axis of the ion transfer path of the FTICR mass spectrometer. The curved longitudinal axis of the multipole on the mass spectrometer side (injection side) is identical to the rotation axis of the rotatably positioned multipole. During a rotation, the other end of the multipole moves in a circle passing various ion sources. The rotation position of the multipole determines from which ion source the ions are transferred into the mass spectrometer.”
Moreover, background information for a system that utilizes a deflecting means to steer ions produced from a plurality of ion sources to a mass spectrometer, is described and claimed in U.S. Pat. No. 6,596,989 B2, entitled, Mass Analysis Method and Apparatus for Mass Analysis,” issued Jul. 22, 2003, to Kato, including the following, “A mass analysis system is capable of performing a plurality of measurements in parallel by mounting a plurality of ion sources onto one mass spectrometer and speedily switching the ion sources. The mass analysis apparatus comprises a plurality of ion sources; and a deflecting means for deflecting ions from at least one ion source among the plurality of ions sources so that the ions travel toward the mass spectrometer by producing an electric field.”
Background information for an ion funnel to merge ions is described and claimed in U.S. Pat. No. 6,979,816 B2, entitled, “Multi-Source Ion Funnel,” issued Dec. 27, 2005, to Tang et al., including the following, “A method for introducing ions generated in a region of relatively high pressure into a region of relatively low pressure by providing at least two electrospray ion sources, providing at least two capillary inlets configured to direct ions generated by the electrospray sources into and through each of the capillary inlets, providing at least two sets of primary elements having apertures, each set of elements having a receiving end and an emitting end, the primary sets of elements configured to receive a ions from the capillary inlets at the receiving ends, and providing a secondary set of elements having apertures having a receiving end and an emitting end, the secondary set of elements configured to receive said ions from the emitting end of the primary sets of elements and emit said ions from said emitting end of the secondary set of elements. The method may further include the step of providing at least one jet disturber positioned within at least one of the sets of primary elements, providing a voltage, such as a dc voltage, in the jet disturber, thereby adjusting the transmission of ions through at least one of the sets of primary elements.”
Background information on a branched device to alternatively direct ions is described and claimed in U.S. Pat. No. 7,420,161 B2, entitled “Branched Radio Frequency Multipole,” issued Sep. 2, 2008, to Kovtoun, including the following, “Systems and methods of the invention include a branched radio frequency multipole configured to act, for example, as an ion guide. The branched radio frequency multipole comprises multiple ion channels through which ions can be alternatively directed. The branched radio frequency multipole is configured to control which of the multiple ion channels ions are directed, through the application of appropriate potentials. Thus, ions can alternatively be directed down different ion channels without the use of a mechanical valve.”
Additional background information for a system that uses an electrical lens to merge ion beams, is described and claimed in U.S. Pat. No. 7,372,042 B2, entitled “Lens Device For Introducing A Second Ion Beam Into a Primary Ion Path,” issued May 13, 2008, to Mordehai et al., including the following, “The invention provides a device for introducing a second ion beam into the primary ion path of a mass spectrometry system. In general, the device contains an electrical lens having a primary ion passageway and a secondary ion passageway that merges with the primary ion passageway. In certain embodiments, the electrical lens contains a first part and a second part that, together, form the primary ion passageway. The first part of the lens may contain the secondary ion passageway. A device for delivering ions to a mass analyzer and a mass spectrometer system containing the subject electric lens are also provided. Also provided by the invention are methods for introducing a second ion beam into a primary ion path using the subject electric lens, and methods of sample analysis.”
Finally, background information for a system that interfaces one or more ion sources via multipole rod configurations, is described and claimed in U.S. Pat. No. 7,358,488 B2, entitled “Mass Spectrometer Multiple Device Interface For Parallel Configuration of Multiple Devices,” issued Apr. 15, 2008, to Chernushevich et al., including the following, “A multi-device interface for use in mass spectrometry for interfacing one or more ion sources to one or more downstream devices. The multi-device interface comprises three or more multipole rod sets configured as either an input rod set or an output rod set depending on potentials applied to the multipole rod sets. The multipole rod sets configured as an input rod set are connectable to the one or more ion sources for receiving generated ions therefrom and sending the ions to at least one multipole rod set configured as an output multipole rod set. The output multipole rod sets are connectable to a downstream device for sending the generated ions thereto. At least two of the multipole rod sets are configured as input rod sets or at least two of the multipole rod sets are configured as output rod sets.”
Accordingly, while the above described inventions have beneficial applications, a large customer need exists for a mass spectrometer system that utilizes multipole ion optics in a novel interlaced configuration, as disclosed herein, which can not only merge ion beams from two separate sources but can also be used to direct a single ion beam into a plurality of desired directions. The present invention is thus directed to such a need.
Accordingly, the present invention provides for an interlaced ion guide apparatus to enable ions from two separate sources to be merged along a predetermined longitudinal direction for collection and/or analysis but also enables in the reverse path, predetermined ions to be sequentially directed along a selected ion channel to also enable, for example, collection and/or analysis by predetermined downstream instruments.
As another aspect of the present invention, there is provided a mass spectrometer system that incorporates the aforementioned interlaced ion guide apparatus to enable the merging of produced ions or if desired to direct ions produced from a desired ion source sequentially to a pair of predetermined downstream instruments.
In accordance with another aspect, as disclosed herein, the present invention provides for a method of operating a mass spectrometer having an interlaced rod set, that includes: receiving ions within an interlaced set of ion guide electrodes; the interlaced set of electrodes being configured from a first and a second set of ion guide electrodes that respectively defines a first and a second ion channel path; providing an RF field within the first and the second set of ion guide electrodes to radially confine the desired ions within the first and the second ion channel paths; and providing a DC voltage gradient to induce DC axial forces that act on the received ions so that the received ions can be sequentially directed along either of the first ion channel or the second ion channel paths.
In accordance with a final aspect of the present invention, there is provided a method of operating a mass spectrometer having an interlaced ion guide rod set that includes: receiving ions within a first and a second set of ion guide electrodes interlaced to provide for a resultant multipole ion channel; wherein the first and said second ion channels further define a first and a second ion channel path; providing an RF field to radially confine the desired received ions within the first and the second ion channel paths; and providing a DC voltage gradient to induce DC axial forces that act on the received ion so that the received ions can be directed to the resultant multipole ion channel.
Accordingly, the present invention provides for an apparatus that combines two independent sets of electrodes (i.e., multipoles) in an interlaced fashion to form a resultant multipole structure. In such a novel structure, ions originating from different sources can be measured for separate or conjunctive ion calibration and/or (m/e) ion analysis without the cost of ion source switching inefficiency. Additionally, by operating the Y-multipole device of the present invention in a reverse mode enables produced ions to be sequentially directed to one or more downstream analyzing instruments also without the cost of analyzing switching inefficiency.
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. Moreover, it is to be appreciated that the figures, as shown herein, are not necessarily drawn to scale, wherein some of the elements may be drawn merely for clarity of the invention. Also, reference numerals may be repeated among the various figures to show corresponding or analogous elements. 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.
In addition, 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 numerical values, however, inherently contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
The present invention is directed to a Y-multipole apparatus and method approach designed to merge ion beams from at least two separate ion sources or as another beneficial arrangement, direct a single ion beam source into separate optical paths to enable collection and/or manipulation by one or more desired mass to charge selection mode instruments, such as, for example, by a mass analyzer.
To reiterate, it is known that mass spectrometer systems most often provide ions from a desired single ion source along a directed ion path so as to be received by an analyzer for mass/charge (m/z) ratio interrogation. Generally, four, six, eight, or more equally spaced rods can be configured in an often substantially spherical arrangement to urge (i.e., guide) the ions along a single ion path to enable high efficiency capture, transmission, and/or storage of ions in a variety of instruments. While such configurations have provided the mass spectroscopy community a valuable tool, the resultant interlaced configurations of the present invention additionally enable introduced ions not just from a single ion source to be directed along a desired ion path but also enable ions from a separate distinct ion source to be introduced either in series or simultaneously into a first ion path. Such a novel design enables ions to be introduced if and when desired, for separate or conjunctive ion calibration and/or (m/e) ion analysis without the cost of ion source switching inefficiency that includes, but is not just limited to, disassembly and reassembly downtime. Another beneficial aspect of the present invention is provided by operating the Y-multipole device of the present invention in the reverse direction so as to enable ions from a single source to be sequentially directed off of the interlaced split to one or more stages, such as, for example, a separate pair of desired analyzers.
To enable a directional guidance of the ions in either of the above discussed operating modes, a RF voltage of adjustable phase and/or amplitude of up to about several kilovolts with a frequency from about 500 kHz up to about 2.5 MHz is applied to the alternating rods at 180 degrees out of phase from each other throughout the assembly. While such an arrangement is beneficial RF voltages having fixed RF phase relationships and amplitudes to the alternating rods can also be utilized. As an optional beneficial configuration, an applied distinct DC offset axial voltage gradient(s) (e.g., a voltage gradient from about +1V up to about +30V) can also be dynamically applied in conjunction with the RF to manipulate ions along desired directions. Moreover, ion traffic control can also be assisted via ion diffusion and/or gas flow methods as known and as understood by those of ordinary skill in the art. It is to be appreciated that the aforementioned distinct applied DC offset voltage gradient(s) can be implemented preferably using one or more DC axial field electrodes, as known and understood in the art, which can be situated external to or integrated with or between the electrode structures that make up the Y-multipole devices described herein. Example DC axial field electrode configurations can include, coupling DC voltages to segmented portions of the Y-multiple structures, providing a set of conductive metal bands spaced along each rod with a resistive coating between the bands, providing resistive coatings to tube structures, resistive or coated auxiliary electrodes, finger electrodes, curved thin plates contoured to match the curvature of the electrode set structures, and/or other means known to one of ordinary skill in the art to move ions via induced DC axial forces along desired ion paths.
To assist in the production of such RF and DC fields, known components and circuitry, such as, computers, RF and DC voltage supplies, RF and DC controllers, digital to analog converters (DACS), and programmable logic controllers for dynamic control of the applied DC voltages are integrated into the present invention so as to move ions along desired ion paths within the Y-multipole apparatus and/or other components integrated into the systems described herein. Moreover, because voltage supplies required to provide the various RF and DC voltage levels are capable of being dynamically controlled via, for example, a computer, the magnitude and range of voltages may be adjusted and changed to meet the needs of a particular sample or set of target ions to be analyzed.
It is also to be appreciated that within the systems disclosed herein, one or more ion lenses known by those of ordinary skill in the art can also be introduced to guide desired ions along a predetermined ion path. Such ion lenses can include, but are not limited to, lens stacks (not shown), inter-pole lenses, conical skimmers, gating means, (e.g., split gate lenses), etc., to cooperate with the Y-multipole devices of the present invention so as to direct predetermined ions along either longitudinal direction in order to be received by other subsequent sections and/or downstream instruments such as, for example, a mass analyzer.
Accordingly, by providing the configurations and approaches of the present invention, the resultant merged or separated ion beams can be interrogated and/or manipulated by the interlaced (i.e., the combined) Y-multipole structures disclosed herein. In particular, if configured to operate in the merged configuration, ions from either of the separate sources can be operated solely for sole ion calibration and/or (m/e) ion analysis but beneficially separate sources are more often simultaneously merged by directing ions from a second beam path into a first beam path to enable, for example, conjunctive ion calibration and/or (m/e) ion analysis with ions resulting from the source as received along the first beam path. Also beneficially, if the multipole device of the present invention is configured to operate in the reverse direction, the present invention enables ions resulting from a single source to be directed sequentially to a pair of instruments, such as, but not limited to, a Time of Flight (TOF) mass analyzer and a triple quadrupole (Q3)/linear trap hybrid configured with a switching functionality of the present interlaced device near the collision cell to enable analysis with either the (Q3) or the linear trap.
Turning now to the drawings,
Specifically, the Y-multipole 10 of
Generally described, the Y-multipole 10, 20 device(s) of the present invention itself is often a configured pair of multipole devices having an equivalent set of electrodes, wherein each of the configured electrodes is capable of being configured to have operating lengths of up to about 20 cm that are interlaced (combined) to produce a resultant multipole structure. For example, the Y-multipole 10, 20 devices disclosed herein can result from a pair of tripoles interlaced (i.e., combined in a manner) to form a hexapole, a pair of quadrupoles interlaced (i.e., combined in a manner) to form an octupole, or a pair of hexapoles interlaced to form a dodecapole, or as another beneficial example, a pair of octupoles interlaced to produce a hexadecapole configuration. Alternatively, while the above mentioned configurations are preferable in arrangement, the resultant multipoles of the present invention can also be configured from multipole devices having a non-equivalent number of electrodes, such as, for example, a quadrupole interlaced (i.e., combined in a manner) with a hexapole to provide a decapole or an octapole interlaced with a quadrupole to provide, for example, a dodecapole.
Moreover, while a desired shape of the electrodes that make up the Y-multipole 10, 20 device(s), as disclosed herein, are often hyperbolic, it is to be appreciated that flat or circular cross sectioned rods also having lengths of greater than about 2.4 cm, more often from about 2.4 cm up to about 20 cm, can also be used to generate RF electric field lines similar to the theoretically ideal hyperbolic field lines between the rods without departing from the scope and spirit of the invention.
Beneficially, example ion beam sources that can be singly or simultaneously coupled to the configurations of the Y-multipole devices 10, 20 of the present invention can include a variety of sources known and understood by those in the field of mass spectroscopy, such as, but not limited to, an Electrospray Ionization Source (ESI), a Nanoelectrospray Ionization source (NanoESI), an Atmospheric Pressure Ionization source (API), an electron impact (EI) ionization source, a chemical ionization (CI) source, an EI/CI combination ionization source, a Surface-Enhanced Laser Desorption/Ionization (SELDI), a Laser Desorption Ionization (LDI) ion source, and a Matrix Assisted Laser Desorption/Ionization (MALDI) source. With respect to simultaneously coupling two ion sources, an application can include merging ions resultant from an API source and a MALDI source to eliminate the time from switching from one source to another. Another beneficial application would be to couple an API source and an EI/CI source for generating Electron-Transfer Disassociation (ETD) reagents.
It is also to be appreciated that a number devices configured as analyzers (any device capable of separating ions based on one or more of m/z, charge, species, ion mobility and combinations thereof, can also be coupled to the Y-multipole device(s) described herein and can include systems having single stage devices, e.g., linear ion traps (LIT), an ion cyclotron resonance (ICR), an orbitrap, a Fourier Transform Mass Spectrometer (FTMS), or dual stage mass analyzers, such as, a quadrupole/orthogonal acceleration time of flight (oa-TOF), a linear ion trap-time of flight (LIT-TOF), a linear ion trap (LIT)-orbitrap, a quadrupole-ion cyclotron resonance (ICR), an ion trap-ion cyclotron resonance (IT-ICR), a linear ion trap-off axis-time of flight (LIT-oa-TOF), or a linear ion trap (LIT)-orbitrap mass analyzer.
When operating the device 300 of
The example branched portions 33 themselves, as shown in
To illustrate a method of operation so as to alternatively separate ions into desired downstream instruments and/or other coupled sections of a mass spectrometer, the reader of the present application is directed to the set of plots shown in
In particular,
Specifically, to direct ions received at the interlaced multipole junction III into ion path 11″ of electrode set II (i.e., Multipole 2), relative DC voltage gradients are desirably applied to the DC electrodes 30, 31, and 32 of
Following along in the discussion of example reverse mode operations of the Y-multipole device of the present invention, to direct ions received at the interlaced multipole junction III into ion path 11′ of electrode set I (i.e., Multipole 1), relative DC voltage gradients are again desirably applied to the DC electrodes 30, 31, and 32 of
In this example arrangement however, simultaneously applied relative decreasing and increasing voltage levels, as shown in the top plot of
Turning now to a forward method of operation of the Y-multipole of the present invention so as to direct ions provided by one or more ions sources into desired downstream instruments and/or other coupled sections of a mass spectrometer, the reader of the present application is now directed to the set of plots shown in
To illustrate such a mode of operation,
As an example of operation so as to direct ions either alone or simultaneously into the interlaced multipole junction III via the aforementioned electrode sets I and II, as shown in
In particular, to direct ions along electrode set I (alone or simultaneously along with ions directed by electrode set II) so as to be received by the interlaced multipole junction III of
In addition, to direct ions along electrode set II (alone or simultaneously along with ions directed by electrode set I) to be received by the interlaced multipole junction III of
Accordingly such example DC voltage gradients, as illustrated in
In particular, the example mass spectrometer 700 depicted in
In this beneficial configuration, the example mass spectrometer 800 depicted in
It is to be noted that he generally depicted mass spectrometer systems 600, 700, and 800, as discussed above, may also include an electronic controller and one or more power sources for supplying RF (e.g., fixed voltage amplitudes and phases or controllably adjustable amplitudes and phases to the Y-multipole electrodes for ion radial confinement) as well as DC voltages to predetermined electrodes and devices, such as, for example, DC electrodes 30, 31, and 32 operably coupled with the Y-multipole 10 configurations of the present invention, trapping devices/analyzers, and other electrode structures, ion traps, etc., of the present invention.
Moreover, an electronic controller configured with embodiments of the present invention is also often operably coupled to various other devices known to be implemented in such systems, e.g., pumps, sample plates, illumination sources, sensors, lenses 35, 40 gating lenses 36, 38, ion guides, 16, 42, and detectors, etc., so as to control such devices/instruments and conditions at the various locations throughout a configured system, as well as to receive and send signals representing the particles being analyzed. As also known to those skilled in the art, any number of vacuum stages may also be implemented to enclose and maintain any of such devices/instruments along the ion paths to provide for predetermined pressures, such as, and often at, a lower than atmospheric pressure.
In addition, it is to also be appreciated that in being directed to such example mass analyzers, the resultant ions can and often are transported through a series of chambers of progressively reduced pressure by a set of ion optic components, e.g., ion apertures, skimmer cones, electrostatic lenses, and multipoles selected from radio-frequency RF multipole ion guides, e.g., octupoles, quadrupoles, that restrict, guide and focus ions to provide good transmission efficiencies. The various chambers communicate with corresponding ports as known in the art (not shown) that are coupled to a set of pumps (not shown) to maintain the pressures at the desired values. The operation of a configured mass spectrometer, such as, the systems shown in either of
It is also to be appreciated that instructions to start any of the operations inherent in the systems disclosed herein, such as, for example, the identifying of a set of m/z values, the merging of data, the exporting/displaying of results, etc., may be executed under instructions stored on a machine-readable medium (e.g., a computer readable medium) coupled a particular mass spectrometer. A computer-readable medium, in accordance with aspects of the present invention, refers to mediums known and understood by those of ordinary skill in the art, which have encoded information provided in a form that can be read (i.e., scanned/sensed) by a machine/computer and interpreted by the machine's/computer's hardware and/or software. When, for example, mass spectra data of a mass spectrum is received by the apparatus/system disclosed herein, the information embedded in a computer program of the present invention can be utilized, for example, to extract data from the mass spectral data, which corresponds to a selected set of mass-to-charge ratios. In addition, the information embedded in a computer program of the present invention can be utilized to carry out methods for normalizing, shifting data, or extracting unwanted data from a raw file in a manner as and as understood by those of ordinary skill in the art.
It is to be understood that features described with regard to the various embodiments herein may be mixed and matched in any combination without departing from the spirit and scope of the invention. Although different selected embodiments have been illustrated and described in detail, it is to be appreciated that they are exemplary, and that a variety of substitutions and alterations are possible without departing.
