Patent Application
20110049360
The present invention relates generally to structures for controllably fragmenting ions in a mass spectrometer, and more particularly to collision/reaction cells utilizing radio frequency multipole structures.
Radio frequency (RF) multipoles are commonly used in mass spectrometers and similar instruments to efficiently transportions within vacuum regions. Typically, an RF multipole consists of a set of parallel elongated electrodes arranged around a central longitudinal axis. RF voltages are applied to the electrodes in a prescribed phase relationship to generate an oscillatory field that radially confines ions within the multipole interior volume while the ions traverse the RF multipole from an inlet end to an outlet end.
Certain mass spectrometers utilize collision cells, in which an RF multipole is placed within an enclosure pressurized with a collision gas, such as nitrogen or argon. Precursor ions that enter the collision cell collide with molecules or atoms of collision gas and undergo dissociation to yield product ions. The degree and pattern of fragmentation may be controlled by adjusting the kinetic energy at which the precursor ions enter the collision cell as well as the collision gas pressure. The resultant product ions are transported along the central axis of the multipole to the outlet end thereof, and are thereafter passed to downstream regions of the mass spectrometer for further processing and/or mass analysis.
It is known that product ions having low mass-to-charge ratios (m/z's) may tend to develop unstable trajectories in collision cells, causing them to be lost via contact with electrode surfaces or ejection from the multipole interior volume. Loss of low-m/z ions in the collision cell is undesirable, since they may carry information useful for identification or structural elucidation of analyte molecules. The stability of an ion in an RF quadrupole (the most commonly employed multipole in collision cells) is governed by the value of the Mathieu stability parameter q, which is proportional to the amplitude of the applied RF voltage and inversely proportional to the m/z of the ion. Typically, the RF voltage amplitude is selected such that the q of the precursor ions entering the quadrupole is about 0.2. Under these conditions, product ions having m/z's of less than 0.22 times the precursor m/z will have q's greater than 0.908 (the stability limit for an RF-only quadrupole) and will develop unstable trajectories. For example, if the RF voltage amplitude is tuned to set q=0.2 for a precursor m/z of 500, product ions having m/z's of less than 110 will be lost in the quadrupole and will not be available for detection in the downstream mass analyzer. The value of m/z below which ions are unstable (referred to in the art as the low mass cut-off, or LMCO) may be reduced by decreasing the RF voltage amplitude, but doing so will tend to reduce the transmission efficiency of heavier ions.
Another problem associated with prior art multipoles is that a small manufacturing error, such as a slight bowing or angular misalignment of an electrode, may produce trapping regions within the multipole interior volume that retain ions or impede their axial movement. This unintended trapping phenomenon, which may also arise from the accumulation of contaminants on electrode surfaces during operation of the mass spectrometer, reduces the rate at which ions may be removed from the multipole interior, which is particularly problematic for tandem mass spectrometry applications where it is highly desirable to remove ions from the collision cell quickly so that a large number of experiments (for example, multiple MRM transitions) may be performed across an elution peak. The rate at which ions are drawn through a multipole may be increased by superimposing an axial DC field (sometimes referred to as a “drag field”), which is described in U.S. Pat. Nos. 5,847,386 by Thomson et al. and 7,067,802 by Kovtoun. However, incorporating the additional structures and electronics required for producing the DC axial field may significantly increase manufacturing cost and complexity.
Roughly described, a multipole constructed in accordance with an embodiment of the present invention includes at least four elongated electrodes arranged around a longitudinal axis, and an RF voltage source for applying RF voltages to the electrodes in a prescribed phase relationship. The electrodes are formed and positioned such that the value of the radial spacing r0 (the distance from the axis to the inner surface of each of the electrodes) increases from the inlet end to the outlet end of the multipole. In one implementation, the electrodes have uniform cross-sections, and are angled outwardly from the inlet end. In a second implementation, electrodes having tapered cross sections are positioned in mutually parallel relation.
RF multipoles constructed in accordance with embodiments of the present invention may be particularly useful for implementation in a collision/reaction cell, wherein the electrodes are disposed within an enclosure to which collision/reaction gas is added. By increasing r0 from the inlet end to the outlet end of the RF multipole, the value of the Mathieu parameter q of an ion is progressively reduced in the direction of ion travel, resulting in a reduced effective low-mass cutoff and the availability of greater numbers of low-m/z ions for mass analysis. In addition, the RF multipoles may have decreased sensitivity to manufacturing or assembly errors and may promote higher ion transmission rates.
In the accompanying drawings:
First QMF 145 and second QMF 150 each consist of four elongated electrodes to which RF and resolving DC voltages are applied. As is known in the art, the m/z ranges of the transmitted ions are determined by the amplitudes of the RF and resolving DC voltages (respectively designated as U and V), and ions having a desired range of m/z values may be selected for transmission by appropriately adjusting the values of U and V. Each QMF may be “parked” by temporally fixing the values of U and V such that only a single ion species is transmitted, or may instead be “scanned” by progressively changing U and/or V such that the m/z of the transmitted ions varies in time.
Collision/reaction cell 105 includes a multipole 110, constructed in accordance with embodiments of the present invention, located within an interior region 185 to which a collision/reaction gas is controllably supplied via a suitable collision gas source, such as a conduit 190 that receives gas from a suitable supply arrangement. The interior region 185 is defined by enclosure 192, which may be partially formed by entrance and exit lenses 194 and 196, and which enables development of an elevated pressure relative to the pressure of the vacuum chamber 140 which collision/reaction cell 105 is located. When configured as a collision cell, collision/reaction cell 105 is filled with a collision gas conventionally consisting of one or a mixture of generally unreactive or inert gases, such as nitrogen or argon, and the collision gas pressure within collision/reaction cell 105 is typically in the range of 0.5-10 millitorr. In an alternative reaction cell configuration, collision/reaction cell is filled with gas and/or reagent ions selected to react with the sample ions.
In operation as a conventional triple quadrupole mass spectrometer, a subset of ions entering vacuum chamber 140 is selectively transmitted by first QMF 145. The transmitted ions (“precursor ions”) enter collision cell 105, and a portion of the ions undergo energetic collisions to produce fragments (“product ions”). The product ions and residual precursor ions are passed to second QMF 150, which transmits ions within a selected range determined by the amplitudes of the applied RF and resolving DC voltages. The ions transmitted by second QMF 150 strike detector 198, which generates a signal representative of the numbers of ions impinging thereon. The detector signal is received and processed by control and data system (not depicted), which may be implemented as any one or combination of application-specific circuitry, general purpose and/or specialized processors, and software logic.
The arrangement of electrodes in multipole 110 may be more clearly explained with reference to
r
0
=r
0,inlet
+x/L*(r0,outlet−r0,inlet)
where x is the distance from inlet end 210, L is the multipole length, and r0,inlet and r0,outlet are the values of the inscribed circle radius at inlet end 210 and outlet end 215, respectively. The electrodes may be precisely fixed in the desired geometry and spacing using ceramic holders or suitable equivalent, in a manner known in the art.
In alternative embodiments of the invention (such as the one discussed below), the variation of r0 with distance along the multipole may follow a non-linear relation, such as a polynomial or logarithmic function. In order to avoid creating undesirable trapping regions, the increase of r0 with distance along the multipole should be monotonic. It is further noted that although electrodes having rectangular cross-sections are depicted in
As known in the art and described above, an RF field that radially confines ions within multipole 110 is established by applying RF voltages in a prescribed phase relationship to electrodes 205a,b,c,d.
Selection of an appropriate splay angle at which to arrange the electrodes will depend on the desired reduction in q and various operational and design considerations, primarily determined by the range product to precursor mass difference and the expected manufacturing tolerances. Typically, a splay angle and electrode length will be selected to yield a ratio of r0 at the outlet end to r0 at the inlet end that is at least 1.1, and more preferably at least 1.2. According to one illustrative implementation, each electrode 205a,b,c,d has a square cross section of 0.157 in.×0.157 in. (4 mm×4 mm) and a length of 8 in. (203.2 mm). Electrodes 205a,b,c,d are arranged at a radial spacing of 0.081 in. (2.06 mm) at inlet end 210 and are angled outwardly at a splay angle of about 0.19° so that the radial spacing at outlet end 215 is increased to 0.107 in. (2.72 mm). In this implementation, the q for an ion of a given m/z at outlet end 215 is (0.081/0.107)2=57% of its q at inlet end 210.
In addition to reducing q at and adjacent to outlet end 215 and lowering the low mass cutoff, increasing r0 with distance along the multipole provides other benefits. As alluded to above, manufacturing errors or tolerances associated with the formation and positioning of electrodes in conventional multipoles having an invariant r0 may create small convergent regions in which ions may be unintentionally trapped. Such convergent regions may also be created during operation of a mass spectrometer by deposition of contaminants on electrode surfaces. The unintended and undesirable creation of trapping regions in multipoles is avoided or minimized by outwardly angling the electrodes or otherwise increasing the electrode radial spacing with distance along the multipole (such as by tapering the electrodes, discussed below in connection with
It is has been further noted by the applicant that increasing r0 in the direction of ion travel produces a pseudo-potential gradient that urges ions towards outlet end 215 of multipole 110. This effect may increase the rate at which ions are transported through multipole 110 and prevent stalling and unintended trapping of ions, particularly when collision cell 105 is operated at a relatively high pressure. Furthermore, the creation of a motive force arising from the pseudo-potential gradient may avoid the need (and associated cost and complexity) to provide structures for establishing an axial DC field.
Multipoles constructed in accordance with the present invention, i.e., having axially increasing r0, may be utilized in other environments and for other purposes than collision/reaction cells. For example, multipoles of this general description may be employed as RF ion guides to transportions through regions of a mass spectrometer. In this implementation, ion transport efficiency may be advantageously increased by establishment of a pseudo-potential gradient that moves ions toward the outlet, as discussed above.
Although each of the multipoles described and depicted herein are quadrupoles (i.e., have exactly four electrodes), the concept of arranging or forming electrodes in an RF multipole to establish increasing r0 may be extended to multipoles having a larger number of electrodes (e.g., hexapoles or octopoles). Furthermore, while the multipoles described and depicted herein have substantially straight axially centerlines, other embodiments may have a curved axial centerline, such as collision/reaction cells or ions guides that describe a 90-degree bend or are U-shaped.
In certain implementations of the invention, the multipole electrodes may be specially adapted (e.g., with a resistive coating) to enable application of a DC potential difference to ends of the electrodes in order to create a DC axial field. A desired DC axial field may also be established using a set of supplemental electrodes arranged adjacent to or around the main electrodes, as known in the prior art.
It should also be appreciated that RF multipoles constructed according to the present invention, i.e., with increasing r0 from the inlet end to the outlet end, may be employed for purposes and in environments other than in a collision cell. For example, an RF multipole of this general description may be employed to efficiently transportions within an intermediate pressure region of the mass spectrometer located between the ion source and the mass analyzer(s). Other beneficial uses may occur to those of ordinary skill in the art.
Finally, it is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.
