Ion interface device having multiple confinement cells and methods of use thereof
09831076 · 2017-11-28
Assignee
Inventors
Cpc classification
H01J49/009
ELECTRICITY
International classification
Abstract
A device and associated method are disclosed for interfacing an ion trap to a pulsed mass analyzer (such as a time-of-flight analyzer) in a mass spectrometer. The device includes a plurality of separate confinement cells and structures for directing ions into a selected one of the confinement cells. Ions are ejected from the ion trap in a series of temporally successive ion packets. Each ion packet (which may consist of ions of like mass-to-charge ratio), is received by the ion interface device, fragmented to form product ions, and then stored and cooled in the selected confinement cell. Storage and cooling of the ion packet occurs concurrently with the receipt and storage of at least one later-ejected ion packet. After a predetermined cooling period, the ion packet is released to the mass analyzer for acquisition of a mass spectrum.
Claims
1. A mass spectrometer, comprising: an ion trap configured to eject first and second packets of ions in temporal succession; at least one pulsed mass analyzer for separating ions according to their mass-to-charge ratios to acquire a mass spectrum; and an ion interface device having a transport/collision region and a plurality of spatially separated ion confinement cells, the ion interface device being configured to: receive the first packet of ions ejected from the ion trap, to cause at least a portion of the ions in the first ion packet to undergo fragmentation or reaction, and to route the first ion packet to a first ion confinement cell of the plurality of ion confinement cells; and while the first ion packet is still confined within the first ion confinement cell, to receive the second packet of ions ejected from the ion trap, to cause at least a portion of the ions in the second ion packet to undergo fragmentation or reaction, and to route the second ion packet to a second ion confinement cell of the plurality of ion confinement cells; wherein the first packet of ions is routed to the first ion confinement cell without passing through the second confinement cell, and further wherein the second packet of ions is routed to the second confinement cell without passing through the first confinement cell; the ion interface device being configured to release each ion packet to the at least one pulsed mass analyzer after the packet has been confined in the ion confinement cell for a prescribed confinement period, wherein the first and second ion confinement cells release ions to a common pulsed mass analyzer.
2. The mass spectrometer of claim 1, wherein the ion interface device includes at least four confinement cells.
3. The mass spectrometer of claim 1, wherein the ion interface device is formed as an integrated structure comprising the transport/collision section and a distribution section.
4. The mass spectrometer of claim 1, wherein the at least one pulsed mass analyzer includes a time-of-flight (TOF) mass analyzer.
5. The mass spectrometer of claim 1, wherein the ion interface device includes a distribution section having an array of rod electrodes each extending transversely to a longitudinal axis of the ion interface device, and the confinement cells are disposed laterally outwardly of the rod electrodes.
6. The mass spectrometer of claim 5, wherein at least a portion of the rod electrodes are segmented, and further comprising a DC voltage source for applying DC offsets to the rod electrode segments to establish a transverse DC field of controllable direction to cause ion packets to pass to a selected one of the plurality of confinement cells.
7. The mass spectrometer of claim 1, wherein the plurality of confinement cells are arranged such that ions directed to at least one of the confinement cells pass through another one of the confinement cells.
8. The mass spectrometer of claim 1, wherein the ion trap comprises a two-dimensional quadrupole ion trap configured for orthogonal mass-selective ejection of ion packets.
9. The mass spectrometer of claim 1, wherein the ion trap comprises a two-dimensional quadrupole ion trap configured for axial mass-selective ejection of ion packets.
10. The mass spectrometer of claim 1, wherein the product of the ion confinement period and a pressure within the confinement cell is at least 1 ms.Math.mTorr.
11. The mass spectrometer of claim 4, wherein the TOF mass analyzer includes a first flight path having an entrance region positioned proximate to a first set of confinement cells, and a second flight path having an entrance region positioned proximate to a second set of confinement cells.
12. The mass spectrometer of claim 11, wherein the first and second flight paths terminate at a common detector system.
13. The mass spectrometer of claim 1, wherein each ion packet consists of ions having a range of mass-to-charge ratios that is narrow relative to the mass-to-charge ratios of the initial ion population within the ion trap.
14. A method of performing mass spectrometry analysis, comprising: storing ions in an ion trap; ejecting first and second packets of ions from the ion trap in temporal succession; providing an ion interface device having a transport/collision section and a plurality of spatially separate confinement cells, the plurality of confinement cells including first and second confinement cells; receiving a first ion packet in the ion interface device, fragmenting or reacting at least a portion of the ions in the transport/collision section, and routing the first ion packet to the first confinement cell; concurrently with confinement of the first ion packet in the first confinement cell, receiving a second ion packet in the ion interface device, fragmenting or reacting at least a portion of the ions in the transport/collision section, and routing the second ion packet to the second confinement cell; and releasing each ion packet to a pulsed mass analyzer after the packet has been confined in the ion confinement cell for a prescribed confinement period, wherein the first and second confinement cells release ions to a common pulsed mass analyzer; wherein the first packet of ions is routed to the first ion confinement cell without passing through the second confinement cell, and further wherein the second packet of ions is routed to the second confinement cell without passing through the first confinement cell.
15. The method of claim 14, wherein the ion interface device includes at least four confinement cells.
16. The method of claim 14, wherein the product of the cooling period and a pressure within the confinement cell is at least 1 ms.Math.mTorr.
17. The method of claim 14, wherein each ion packet consists of ions having a narrow range of mass-to-charge ratios relative to the initial population of ions in the ion trap.
18. The method of claim 14, wherein the pulsed mass analyzer is a time-of-flight mass analyzer.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
(1) In the accompanying drawings:
(2)
(3)
(4)
(5)
(6)
(7)
DETAILED DESCRIPTION OF EMBODIMENTS
(8)
(9) Ion interface device 105 is provided with a plurality of separate confinement cells. As will be discussed in greater detail below, ion interface device 105 receives individual packets of ions ejected from ion trap 110 and directs each ion packet to a selected confinement cell. The ion packet is held within the confinement cell for confinement period, during which time the ions undergo energetic cooling. As the ions in one ion packet cool in the associated confinement cell, one or more successively ejected ion packets are received by ion interface 105 and directed to other ones of the plurality of confinement cells. In a preferred embodiment, ion interface 105 includes a transport/collision section in which some or all of the ions in the incoming ion packet undergo fragmentation by collision activated dissociation (CAD) or other mechanism of dissociation to yield product ions.
(10) After cooling for a predetermined confinement period, an ion packet is released from the associated confinement cell of ion interface device 105 to the inlet of TOF analyzer 115. As depicted in
(11) The operation of the various components of mass spectrometer 100 is directed by a control and data system (not depicted in
(12) While mass spectrometer 100 is depicted as being configured for an electrospray ion source, it should be noted that other implementations may utilize any number of pulsed or continuous ion sources (or combinations thereof), including without limitation a matrix assisted laser desorption/ionization (MALDI) source, an atmospheric pressure chemical ionization (APCI) source, an atmospheric pressure photo-ionization (APPI) source, an electron ionization (EI) source, or a chemical ionization (CI) ion source. Furthermore, while embodiments of the invention are described herein with reference to a TOF mass analyzer, those of ordinary skill will appreciate that the interface device and method described herein may be beneficially utilized in connection with other types of pulsed mass analyzers, including but not limited to Orbitrap and other electrostatic trap mass analyzers, and Fourier Transform/Ion Cyclotron Resonance (FTICR) mass analyzers.
(13)
(14) Electrodes 205,a,b,c,d (or a portion thereof) are coupled to an RF trapping voltage source, excitation voltage source, and DC voltage source (not depicted), all of which communicate with and operate under the control of a controller that forms part of the control and data system. The RF trapping voltage source is configured to apply RF voltages of adjustable amplitude in a prescribed phase relationship to pairs of electrodes 205a,b,c,d to generate a trapping field that radially confines ions within the interior of ion trap 110. The DC voltage source is operable to apply DC potentials to electrodes 205a,b,c,d or sections thereof to, for example, generate a potential well that axially confines ions within ion trap 110. The excitation voltage source applies an oscillatory excitation voltage of adjustable amplitude and frequency across at least one pair of opposed electrodes to create a dipolar excitation field that resonantly excites ions for the purposes of isolation of selected species, collision induced dissociation, and mass-sequential scanning. During a mass-sequential scan, the RF trapping voltage amplitude is progressively increased from a first value to a second value, which respectively correspond to the lowest and highest m/z ions to be ejected, while a resonant excitation voltage is applied across electrodes 205b,d. This causes the ions to become resonantly excited and ejected from ion trap 110 (via aperture 207) in order of their m/z's. For all-mass MS/MS operation, the mass sequential scan is broken into a number of scan periods or windows, during each of which a packet of ions within a relatively narrow range of m/z's is ejected to ion transfer device 105. In one illustrative example, a mass sequential scan representing a total interval (difference between lightest and heaviest ions ejected) of 600 Th may be broken into 100 component scan windows, each representing an m/z range of 6 Th. For a typical mass-sequential scan rate of 16,000 Th/s, each scan window requires 6/16,000=375 μs to complete. Since this time may be significantly shorter than the time required for fragmentation and cooling (at typical operating pressures) of the ejected ions prior to analysis in a TOF mass analyzer, delaying the ejection of a packet of ions until the previously ejected group is fully cooled and fragmented would substantially increase the total analysis cycle time and reduce throughput. The utilization of ion interface device 105 avoids the need to delay ejection of a packet of ions pending completion of cooling and fragmentation of a previous group, as described below.
(15) The design and operation of the ion trap described above is presented only by way of example, and should not be construed as limiting the scope of the invention. Other ion trap configurations (including two-dimensional quadrupole ion traps adapted for mass-selective axial ejection of ions through a barrier field, an example of which is described in U.S. Pat. No. 6,177,668 to Hager) may be used in place of the radial-ejection two-dimension ion trap disclosed above and depicted in the drawings.
(16) Generally described, ion interface device 105 includes a transport/collision section 210, a distribution section 220, and four separate confinement cells 230a, 230b, 230c and 230d. An ion packet ejected from ion trap 110 enters ion interface device 105 through an inlet to transport/collision section 210. Transport/collision section 210 may be filled with a neutral collision/damping gas, such as argon, to induce fragmentation (which results from the collisions of energetic ions with atoms or molecules of the collision/damping gas, causing transfer of kinetic energy to excited vibrational modes of the ions). Concurrently, collisions remove kinetic energy from the incoming ions and product ions derived therefrom. If fragmentation of the incoming ions is desired, the conditions at which ions are resonantly ejected from ion trap 110, the DC potentials applied to electrodes of ion trap 110 and interface device 105 (as well as any intermediate lenses or other ion optics) and the composition of the collision/damping gas are selected such that the kinetic energies of the ions are sufficiently high to cause a substantial portion of the ions to undergo collisionally activated dissociation and produce product ions. In alternative implementations, product ions may be formed by filling transport/collision section 210 with reagent ions or molecules that react with sample ions in the ion packet. Typical collision/damping gas pressure within transport/collision section 210 will be in the range of 10-15 mTorr.
(17) While
(18) The ion packet (inclusive of any product ions) traverses transport/collision section 210 and enters distribution section 220. Movement of ions through transport/collision section 210 into distribution section 220 may be assisted by use of a longitudinal DC gradient, which may be established by the application of suitable DC potentials to electrodes of interface device 105 (including the main RF electrodes and/or any auxiliary electrodes). Within distribution section 220, ions of the ion packet are routed to an available (i.e., empty) confinement cell. Generally, routing of ions to a selected confinement cell will occur in a repeated fixed sequence. For example, a first-in-time ion packet may be routed to confinement cell 230a, a second-in-time ion packet may be routed to confinement cell 230b, a third-in-time ion packet may be routed to confinement cell 230c, and a fourth-in-time ion packet may be routed to confinement cell 230d. The timing and sequence of filling and emptying the confinement cells is discussed below in greater detail in connection with
(19) Routing of an ion packet to the destination confinement cell may be effected by the application of suitable DC potentials to electrodes within distribution region 220 to produce DC fields in the longitudinal and transverse dimensions that urge the ions toward the confinement cell. In a particular implementation, DC potentials may be applied to electrodes of distribution section 220 to establish a longitudinal potential well that confines ions to the front portion 240a or rear portion 240b of distribution section 220. A transverse DC field may be generated to cause the ions to travel in the transverse direction leading toward the selected confinement cell. As will be discussed in further detail below in connection with
(20) Each ion packet is confined in the corresponding confinement cell for a confinement period of adequate duration to reduce the ions' kinetic energies to values that permit acquisition of a mass spectrum at high resolution and mass accuracy. As set forth in the background section, the amount of ion cooling will be a function of the product of confinement cell pressure and confinement period. In exemplary implementations, ion interface device is operated to provide a product of confinement cell pressure and confinement period of at least 1 ms.Math.mTorr, and more preferably in the range of 2-5 ms.Math.mTorr. For a typical confinement cell pressure of about 1.5 mTorr, the foregoing values translate to a confinement period of at least approximately 650 μs, and more preferably in the range of about 1300-3300 μs. After an ion packet has been confined in the confinement cell for the prescribed confinement period, the ion packet is released through the confinement cell outlet to TOF mass analyzer 115. Release of an ion packet from the confinement cell may be performed by applying or changing DC potentials on electrodes associated with the confinement cell. As depicted in
(21)
(22)
(23)
(24)
(25)
(26) While ion interface 105 is described and depicted as having four confinement cells, other implementations may utilize a lesser or greater number of confinement cells. In particular, the maximum confinement period of an ion packet in the ion interface device can be extended by increasing the number of confinement cells.
(27) Following the emptying and refilling of confinement cell 230a, each of the other confinement cells is emptied and refilled in the sequence described above. This sequence is repeated until the analytical scanning of the ion trap is terminated (or until another specified termination point has been reached), and all ion packets have been mass analyzed in TOF mass analyzer 115.
(28) It will be recognized that each transfer of ion packets within ion interface is not instantaneous, but instead will require a finite time to complete. However, the applicant has found (via detailed computer modeling of ion motion during transfer operations), that the aggregate transfer time is significantly shorter than the confinement period required for adequate energetic cooling, and will typically comprise about ten percent of the total residence time within interface device 105.
(29)
(30) Another set of rod electrodes 610, oriented transversely to the major longitudinal axis of ion interface device 105, is positioned within distribution section 220. Each electrode 610 receives an RF potential of a phase opposite to the adjacent and opposing electrodes to establish the confining RF field. Certain rod electrodes 615a,b,c,d (which also receive RF potentials) are segmented to allow different DC potentials to be applied to discrete segments of each rod, such that a DC potential gradient may be created along the transverse axis defined by the dimension of elongation of the rod electrodes. The transverse DC potential gradient is controlled (by adjustment of the potentials applied to the segments) to cause an ion packet to travel in the direction of the destination confinement cell; for example, DC potentials may be applied to segments of rod electrodes 615a and 615b to produce a DC gradient that directs ions toward confinement cell 230c or 230d. Of course, the segments may all be maintained at the same DC potential if no transverse DC field is to be established; for example, in the case where an ion packet is to be directed to one of confinement cells 230a or 230b, the segments of rod electrodes 615a and 615b may be maintained at the same DC potential such that ions passing through the region defined by these rods are not transversely deflected toward confinement cell 230c or 230d.
(31) Those skilled in the art will recognize that the transverse DC potential gradients may be controllably established using techniques other than segmentation of the rod electrodes. For example, the rod electrodes may be surface coated with a resistive material, with different DC potentials applied to opposite ends of the rod electrodes, as described in U.S. Pat. No. 5,847,386 to Thomson et al. (the disclosure of which is hereby incorporated by reference). Alternatively, as also described in the aforementioned Thomson et al. patent DC potentials may be applied to auxiliary electrodes positioned around or between the rod electrodes. In another alternative, a helical conductive path may be disposed on the surface of the rod electrodes, with different DC potentials applied to the ends of the helical path, as described in U.S. Pat. No. 7,067,802 to Kovtoun, which is also incorporated by reference.
(32) Ions travel from distribution section 220 to the destination confinement cell through an intermediate chamber in which are disposed rod electrodes 625, which are grouped into multipole structures having central axes extending between an outlet of distribution section 220 and a corresponding confinement cell. RF potentials may be applied to rod electrodes 625 in an alternating phase pattern, such that each multipole acts as an RF ion guide and radially confine the movement as ions as they travel therethrough.
(33) Electrostatic lenses 630, 635 and 640, which may take the form of plate lenses, are located at (respectively) the outlet apertures of distribution section 220 and the inlet and outlet apertures of confinement cells 230a,b,c,d. Suitable DC voltages may be applied to the electrostatic lenses (from the not-depicted DC source) to selectively block or permit the movement of ion packets out of distribution section 220 and into the destination confinement cell, to axially confine ions within a confinement cell, and to eject ions from the confinement cell to the mass analyzer.
(34) Each confinement cell is provided with a set of rod electrodes 650. Ions may be axially confined within the confinement cell by applying appropriate DC potentials to the corresponding lenses located at the inlet and outlet of the confinement cell. Following completion of the prescribed confinement period, the ion packet is ejected from its confinement cell by adjusting the DC potentials applied to outlet lens 640 and/or to rod electrodes 650.
(35) Gas is controllably supplied to the interior of ion interface device 105 from a not-depicted external source through conduit 660. The gas, which will typically comprise an inert gas such as argon, removes kinetic energy from the incoming ions via collisions and induces (if desired) collisionally activated dissociation. Ion interface device 105 is located in one or more vacuum chambers that are evacuated by means of a suitable pump. The distribution outlet apertures (at which lenses 630 are located) and confinement cell inlet and outlet apertures (at which lenses 635 and 640 are respectively located) may be conductance limiting to allow the confinement cells to be maintained at a reduced pressure relative to the transport/collision and distribution sections. In an illustrative implementation, transport/collision section 210 and distribution section 220 are maintained at a pressure of about 13 mTorr, the intermediate section (interposed between distribution section 220 and the confinement cells) is maintained at a pressure of about 6 mTorr, and confinement cells 230a,b,c,d are maintained at a pressure of about 1.5 mTorr.
(36) 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.