Patent Application
20050242281
The invention relates generally to multipole devices such as quadrupoles, which are useful in analysis of ions, and other applications. More specifically, the invention relates to segmented multipoles.
Mass spectrometry systems are analytical systems used for quantitative and qualitative determination of the compositions of materials, which include chemical mixtures and biological samples. In general, a mass spectrometry system uses an ion source to produce electrically charged particles (e.g., molecular or polyatomic ions) from the material to be analyzed. Once produced, the electrically charged particles are introduced to the mass spectrometer and separated by mass analyzer based on their respective mass-to-charge ratios. The abundance of the separated electrically charged particles are then detected and a mass spectrum of the material is produced. The mass spectrum provides information about the mass-to-charge ratio of a particular compound in a mixture sample and, in some cases, information about the molecular structure of that component in the mixture.
For determining molecular weight of a compound, mass spectrometry systems employing a single mass analyzer are widely used. These analyzers include a quadrupole (Q) mass analyzer, a time-of-flight mass analyzer (TOFMS), ion trap (IT-MS), and etc. For more complicated molecular structure analysis, however, tandem mass spectrometers (Tandem-MS or MS/MS) are often needed. Tandem mass analyzers typically consist of two mass analyzer of the same or of different types, for instance TOF-TOF MS or Q-TOF MS. In a tandem MS analysis, ionized particles are sent to the first mass analyzer and an ion of particular interest is selected. The selected ion is typically transmitted to a collision cell where the selected ion is fragmented. The fragment ions are transmitted to the second mass analyzer for mass analysis. The fragmentation pattern obtained from the second mass analyzer can be used to determine the structure of the corresponding molecules.
For example, in a triple quadrupole mass spectrometer an ionization source produces a plurality of parent ions. The first quadrupole is used as a mass analyzer to select a particular parent ion. Then, the selected parent ion is dissociated into daughter ions in the second quadrupole via photodissociation and/or collisionally induced dissociation. Subsequently, the third quadrupole is used as a mass analyzer to separate the daughter ions based on their respective mass-to-charge ratios. The resulting mass spectrum can be used to identify the daughter ions, which can be useful in identifying the structure of the selected parent ion.
In the example described above, the second quadrupole can be used as a collision cell to facilitate collision induced dissociation of the selected parent ion. In such a collision cell, the selected parent ions are sent into an RF quadrupole field which is pressurized up to approximately 1 to 10 mbar with a background gas (normally an inert gas such as argon). When the parent ions collide with the background gas, a portion of the translation energy of the parent ions is converted into activation energy that is sufficiently high to break certain molecular bonds to form daughter ions. The RF quadrupole field facilitates confinement of the daughter ions and the remaining parent ions until further mass analysis. The fragment pattern produced characterizes the original molecule and provides information about its structure.
In combination with other ion optic elements, an RF quadrupole can also be used as an ion trap for storage of ions. A potential gradient is formed along the axis of the quadrupole, and ions are trapped in a potential well. The ion trapping provides a possibility for performing ion accumulation, charge reduction, and ion-ion chemistry. In some tandem mass spectroscopy applications, an ion collision cell/linear ion trap is also used as a mass selective device. A molecular ion of a given mass is selected, isolated, and stored. Ion-gas collisions and/or ion-ion reactions are then performed.
When the quadrupole is used as a linear ion trap or as a collision cell, specific potential distributions are formed along the axis of the quadrupole. In a linear ion trap, a potential well is formed for confining ions (which may be either positively or negatively charged). The potential well typically is formed by using a quadrupole with gate electrodes at each end of the quadrupole. Holding the gate electrodes at a relatively “high” potential (at “trapping potential”) and the quadrupole at a relatively “low” potential provides the potential well that confines the ions. In a collision cell, a potential gradient is necessary for accelerating ions along the axis of the quadrupole. This potential distribution is typically formed by using an evenly segmented quadrupole and applying a DC potential gradient to the different segments of the quadrupole.
Each of the described uses of a quadrupole structure in a mass spectrometer is dependent upon the application of specific RF and/or DC potentials to manipulate the ions. What is needed is a quadrupole that provides for the needed RF and/or DC potential distributions.
The invention addresses the aforementioned technology, and provides a multipole useful for, e.g. manipulating ions in a mass spectrometer, wherein the multipole has segments of differing length. The multipole includes a rod set having 2N rods, where N is an integer selected from the range of 2 to about 8. The rods are disposed around a long axis of the multipole. Each rod includes a rod-shaped support and a plurality of conductive segments disposed along the rod-shaped support. The conductive segments are separated from each other by non-conductive areas of the rod-shaped support. In particular embodiments, at least one of the segments of each rod is relatively long compared to the remaining segments. In some embodiments, two or even three of the segments are relatively long compared to the other remaining segments. For a multipole having length L, a relatively long segment typically has a length in the range from about 14% L to about 90% L. In certain embodiments, at least three of the segments of each rod are relatively short compared to the relatively long segments. A relatively short segment typically has a length in the range from about 1% L to about 12% L. In some embodiments, at least four of the segments of each rod are relatively short. In certain embodiments, at least five of the segments of each rod are relatively short. Each segment is adapted to be in electrical communication with a potential source for applying a DC potential, an RF potential, or both to the segment, thereby producing a potential distribution for manipulating ions in a mass spectrometer. In a typical embodiment, the segments on each rod of the rod set are disposed similarly on each of the rods such that the pattern of relatively long segments and relatively short segments is the same for each rod.
In a particular embodiment, N is 2 and the multipole is a quadrupole. In another embodiment, N is 3 and the multipole is a hexapole. In yet another embodiment, N is 4 and the multipole is an octopole. In still another embodiment, N is 5 and the multipole is a decapole. In another embodiment, N is 8 and the multipole is denoted a “16-pole”.
The invention further provides a mass spectrometer which includes such a multipole and methods of analyzing ions in a mass spectrometer using such a multipole. A method in accordance with the invention includes obtaining a sample, ionizing the sample to provide ions, directing the ions into a multipole having at least four segments, wherein the segments include at least one relatively long segment and at least three relatively short segments. The method in accordance with the invention further includes applying potentials to the segments of the multipole to manipulate ions in the mass spectrometer, thereby resulting in manipulated ions, and detecting the manipulated ions.
Additional objects, advantages, and novel features of this invention shall be set forth in part in the descriptions and examples that follow and in part will become apparent to those skilled in the art upon examination of the following specifications or may be learned by the practice of the invention. The objects and advantages of the invention may be realized and attained by means of the instruments, combinations, compositions and methods particularly pointed out in the appended claims.
These and other features of the invention will be understood from the description of representative embodiments of the method herein and the disclosure of illustrative apparatus for carrying out the method, taken together with the Figures, wherein
To facilitate understanding, identical reference numerals have been used, where practical, to designate corresponding elements that are common to the Figures. Figure components are not drawn to scale.
Before the invention is described in detail, it is to be understood that unless otherwise indicated this invention is not limited to particular materials, reagents, reaction materials, manufacturing processes, or the like, as such may vary. It is also to be understood that the terminology used herein is for purposes of describing particular embodiments only, and is not intended to be limiting. It is also possible in the present invention that steps may be executed in different sequence where this is logically possible. However, the sequence described below is preferred.
It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a segment” includes a plurality of segments. Similarly, a “set” of an item as recited in the description includes embodiments where the set includes a single item and also embodiments in which a plurality of the items are in the set.
Referring now to
Ion source 106 is located in chamber 104. From ion source 106, ions are directed through an orifice 110 in orifice plate 112 and into a first stage vacuum chamber 114 pumped e.g. to a pressure of about 1 torr by a vacuum pump 116. The ions then travel through a skimmer opening 120 in a skimmer 122 and into a vacuum chamber 124. Vacuum chamber 124 is pumped e.g. down to a pressure of about 1 to about 10 millitorr by pump 126, and a further vacuum chamber 134 is pumped e.g. to a pressure of about 10{circumflex over ( )}−5 millitorr to about 10{circumflex over ( )}−4 millitorr by pump 136. An orifice 130 in plate 132 connects vacuum chambers 124, 134.
Mass spectrometer 100 contains four sets of quadrupole rods, indicated as Q0, Q1, Q2 and Q3. The four sets of rods extend tandem to each other along a common central axis 140 and are spaced slightly apart end to end so that each defines an elongated interior volume 142, 144, 146, 148. Rod set Q2 has collision gas from a collision gas source 156 injected into its interior volume 146 and is largely enclosed in a grounded metal case 152, to maintain adequate gas pressure (e.g. about 8 millitorr) therein. Apertures 150 in the metal case 152 permit entry and exit of ions.
Appropriate RF and DC potentials are applied to opposed pairs of rods of the rod sets Q0 to Q3, and to the various ion optical elements 112, 122, and 132 by a power supply 158 which is part of a controller 160. Appropriate DC offset voltages are also applied to the various rod sets by power supply 158. A detector 154 detects ions transmitted through the last set of rods Q3.
In use, normally a RF potential is applied to rod set Q0, plus a DC rod offset voltage which is applied uniformly to all the rods. This rod offset voltage delivers the electric potential inside the rod set (the axial potential). Because the rods have conductive surfaces, and the rod offset potential is applied uniformly to all four rods, the potential is constant throughout the length of the rod set, so that the electric field in an axial direction is zero (i.e. the axial field is zero). Rod set Q0 acts as an ion transmission device, transmitting ions axially therethrough while permitting gas entering rod set Q0 from orifice 120 to be pumped away. Therefore the gas pressure in rod set Q0 can be relatively high, particularly when chamber 104 is at atmospheric pressure. The gas pressure in rod set Q0 is in any event kept fairly high to obtain collisional focusing of the ions, e.g. it can be about 8 millitorr. By way of typical example, the offsets applied may be in the range from about 100 to about 1,000 volts DC on plate 112, 0 volts on the skimmer 122, and −20 to −30 volts DC offset on Q0 (this may vary depending on the ions of interest).
The rod offsets for Q1, Q2 and Q3 depend on the mode of operation, as is well known. Rod set Q1 normally has both RF potential and DC potential applied to it, so that it acts as an ion filter, transmitting ions of desired mass (or in a desired mass range), as is conventional. Rod set Q2 typically has an RF potential applied to it, plus (as mentioned) a rod offset voltage which defines the electric potential in the volume 144 of the rod set. The rod offset voltage is used to control the collision energy in an MS/MS mode, where Q2 acts as a collision cell, fragmenting the parent ions transmitted into it through rod sets Q0 and Q1.
The daughter ions formed in the collision cell constituted by rod set Q2 are scanned sequentially through rod set Q3, to which both RF potential and DC potential are applied. Ions transmitted through rod set Q3 are detected by detector 154. The detected signal is processed and stored in memory and/or is displayed on a screen and printed out.
A multipole according to the present invention includes a rod set having 2N rods, where N is an integer in the range 2 to about 8, typically in the range from 2 to 4. In a particular embodiment, N is 2 and the multipole is a quadrupole. In another embodiment, N is 3 and the multipole is a hexapole. In yet another embodiment, N is 4 and the multipole is an octopole. In still another embodiment, N is 5 and the multipole is a decapole. In another embodiment, N is 8 and the multipole is denoted a 16-pole. In the embodiments described in the figures, herein, the multipoles described are quadrupoles; however, it will be appreciated that multipoles having features described herein may have more than four rods and such multipoles are within the scope of the invention.
Each rod in a multipole according to the present invention typically has a rod-shaped support and a plurality of conductive segments (sometimes referenced herein as just “segments”) disposed along the rod-shaped support. The plurality of conductive segments of each rod typically includes one relatively long segment, although in some embodiments, two relatively long segments may be included, or, in some embodiments three relatively long segments are included. In certain embodiments four relatively long segments are included. For a multipole having length L (measured as the length of a rod from tip to opposing tip along the long axis of the rod), a relatively long segment typically has a length in the range from about 14% L to about 90% L, or, in certain embodiments, in the range from about 14% to about 75%, or, in certain embodiments, in the range from about 14% to about 60%, or, in some embodiments, in the range from about 14% to about 45%. In certain embodiments, at least three of the segments of each rod are relatively short segments (compared to the relatively long segments). In some embodiments, at least four of the segments of each rod are relatively short segments (compared to the relatively long segments). In certain embodiments according to the present invention, each rod of the multipole includes at least five relatively short segments, or at least six relatively short segments, or at least seven relatively short segments, or at least eight relatively short segments. A relatively short segment typically has a length in the range from about 1% L to about 10% L, or, in certain embodiments, a relatively short segment has a length in the range from about 2% to about 8%.
Referring now to
Continuing with
In a typical embodiment, the segments on each rod of the rod set are disposed similarly on each of the rods such that the pattern (spatial configuration, or format) of relatively long segments and relatively short segments is the same for each rod. Typically, each rod in the multipole will have up to about ten conductive segments, in some instances up to about a dozen, or up to about 15, more typically up to about 20, or up to about 25, or in some embodiments up to about 30 conductive segments, or even more.
As shown in
In typical embodiments, the number and format of conductive segments 212 will typically be selected based on desired operational characteristics of the multipole (e.g. quadrupole). In this regard, “unevenly segmented” references a rod, rod set, or multipole comprising a rod set that has both relatively long conductive segments and relatively short conductive segments. Having different length conductive segments provides the opportunity to shape the potential fields used for manipulating ions in the multipoles of the present invention. This may provide advantages in manipulating ions. The selection and configuration of rods sets with conductive segments will be based on design and desired performance characteristics of the device employing the unevenly segmented multipoles of the present invention. In theory, it is advantageous if the segments of the quadrupole are made short, i.e., there are more segments in a given collision cell/linear ion trap length. Short segments would allow a more finely adjustable, more continuous potential distribution with the quadrupole. However, short segments also require more skill (and more cost) to manufacture, e.g. more electrical connection and isolation of segments and components is necessary. So the actual number of the segments is typically a compromise between performance and cost. On the other hand, a non-segmented quadrupole is desired if it is used as a mass filter: a non-segmented quadrupole provides better performance (resolution, transmission) and is less complicated to manufacture in comparison to one of segmented. Given the disclosure herein, those of ordinary skill in the art will be able to build and use unevenly segmented multipoles according to the current invention without undue experimentation. In particular embodiments of unevenly segmented quadrupoles according to the present invention, the quadrupole is only segmented where a specific potential distribution is required due to design and function considerations.
Each conductive segment 212 is adapted to be in electrical communication with a potential source for applying a DC potential, an RF potential, or both to the conductive segment, thereby producing a potential distribution for manipulating ions in a mass spectrometer. Each conductive segment 212 is in communication with a potential source in a manner well known in the art to provide a potential to the conductive segment during operation of the quadrupole. In certain embodiments, two or more conductive segments may be electrically connected via, e.g. a direct connection, resistor(s), capacitor(s), or other method well known in the art to reduce the complexity of the overall apparatus (e.g. to reduce the number/complexity of power supply(ies)).
Rods may be made by depositing or otherwise forming a layer of metal on a rod-shaped support. The support may be any suitable material or combination of materials that provides a non-conductive surface for the metal layer, such as ceramic. The metal layer may be formed over the full length of the rod and then portions removed to give the conductive segments. Another method involves forming metal bands or rings in the desired format to give the conductive segments; subsequent removal of material is then unnecessary. Any other suitable method of manufacture of the rods may be used, such as is known in the art.
It will be apparent to one of skill in the art given the disclosure herein that quadrupoles having unevenly segmented rods in accordance with the present invention will be useful in a variety of mass spectrometers which employ quadrupoles. A mass spectrometer such as the one shown in
One embodiment of an unevenly segmented quadrupole is shown in
Another embodiment, shown in
In another embodiment, one end of the quadrupole has a series of relatively short segments 216 as shown in
The invention further provides methods of analyzing ions in a mass spectrometer using such a multipole. A method in accordance with the invention includes obtaining a sample, ionizing the sample to provide ions, directing the ions into a multipole having at least four segments per rod, wherein the at least four segments include at least one relatively long segment and at least three relatively short segments. The method in accordance with the invention further includes applying potentials to the segments of the multipole to manipulate ions in the mass spectrometer, thereby resulting in manipulated ions, and detecting the manipulated ions. The manipulation of the ions can include such processes as, e.g. mass selection, ion-ion reaction, fragmentation, collisional focusing, ion transport, collision induced dissociation, charge reduction, and other techniques of ion manipulation in multipoles as known in the art, and combinations thereof.
The practice of the present invention will employ, unless otherwise indicated, conventional techniques of analytical chemistry, analytical instrumentation design, and mass spectrometry instruments and methods, and the like, which are within the skill of the art. Such techniques are explained fully in the literature.
The examples described herein are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to perform the methods and use the compositions disclosed and claimed herein. Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.) but some errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, temperature is in ° C. and pressure is at or near atmospheric. Standard temperature and pressure are defined as 20° C. and 1 atmosphere.
While the foregoing embodiments of the invention have been set forth in considerable detail for the purpose of making a complete disclosure of the invention, it will be apparent to those of skill in the art that numerous changes may be made in such details without departing from the spirit and the principles of the invention. Accordingly, the invention should be limited only by the following claims.
All patents, patent applications, and publications mentioned herein are hereby incorporated by reference in their entireties.
