Orthogonal-flow ion trap array
10651025 ยท 2020-05-12
Assignee
Inventors
- Joshua A. Silveira (San Jose, CA, US)
- Viatcheslav V. KOVTOUN (Santa Clara, CA, US)
- Eloy R. Wouters (San Jose, CA, US)
Cpc classification
H01J49/068
ELECTRICITY
H01J49/4225
ELECTRICITY
International classification
Abstract
An ion separation device comprising a plurality of electrodes arranged in a two-dimensional grid, a gas supply configured to provide a gas flow along the first direction, and an ion inlet arranged to receive ions. The plurality of electrodes is configured to create one or more pseudopotential barriers of increasing magnitude along a first direction. A drag force is applied to the ions by the gas flow is opposed by a pseudopotential gradient of the plurality of electrodes.
Claims
1. An ion separation device comprising: a plurality of electrodes arranged in a two-dimensional grid, wherein the plurality of electrodes is configured to create pseudopotential barriers separating a plurality of pseudopotential wells, the pseudopotential barriers increasing in magnitude along a first direction; a gas supply configured to provide a gas flow along the first direction; and an ion inlet arranged to receive ions, wherein a drag force applied to the ions by the gas flow is opposed by a pseudopotential gradient of the plurality of electrodes.
2. The ion separation device of claim 1, wherein the ion inlet is positioned to receive ions orthogonal to the first direction.
3. The ion separation device of claim 1, wherein the ion inlet is positioned to receive ions aligned with the first direction.
4. The ion separation device of claim 1, wherein the plurality of electrodes are further configured to receive RF voltages from an RF supply.
5. The ion separation device of claim 4, wherein the RF supply is configured to supply RF voltages of increasing amplitude along the first direction.
6. The ion separation device of claim 1, wherein the spacing between electrodes in the first direction, the spacing between rows of the two-dimensional grid, the pitch of the electrodes, the width of the electrodes, or any combination thereof changes along the first direction to achieve the increasing magnitude of the pseudopotential barriers.
7. The ion separation device of claim 1, wherein an operating gas pressure is between about 10.sup.4 Torr and about 10.sup.2 Torr.
8. The ion separation device of claim 1, wherein the ions are continuously transmitted through the two-dimensional array.
9. The ion separation device of claim 1, wherein the ions equilibrate within the ion separation device such that the ions migrate to a pseudopotential well where the pseudopotential barrier has a magnitude sufficient to trap the ions against the drag force generated from the gas flow.
10. The ion separation device of claim 1, further comprising guard electrodes configured to confine the ions and the gas flow within the two-dimensional array.
11. A mass spectrometer system comprising: an ion source configured to produce ions; an ion separation device including a plurality of electrodes arranged in a two-dimensional grid, wherein the plurality of electrodes is configured to create pseudopotential barriers separating a plurality of pseudopotential wells, the pseudopotential barriers increasing in magnitude along a first direction; a gas supply configured to provide a gas flow along the first direction; and an ion inlet arranged to receive the ions, wherein a drag force applied to the ions by the gas flow is opposed by a pseudopotential gradient of the plurality of electrodes; and a mass analyzer configured to measure a mass to charge ratio of the ions.
12. The mass spectrometer system of claim 11, further comprising an RF supply configured to provide RF voltages to the plurality of electrodes.
13. The mass spectrometer system of claim 12, wherein the RF supply is configured to supply RF voltages of increasing amplitude along the first direction.
14. The mass spectrometer system of claim 11, wherein the spacing between electrodes in the first direction, the spacing between rows of the two-dimensional grid, the pitch of the electrodes, the width of the electrodes or any combination thereof changes along the first direction to achieve the increasing magnitude of the pseudopotential barriers.
15. The mass spectrometer system of claim 11, wherein the ions equilibrate within the ion separation device such that the ions migrate to a pseudopotential well where the pseudopotential barrier has a magnitude sufficient to trap the ions against the drag force generated from the gas flow.
16. The mass spectrometer system of claim 11, wherein the ion separation device further includes guard electrodes configured to confine the ions and the gas flow within the two-dimensional array.
17. The mass spectrometer system of claim 16, wherein the guard electrodes are further configured to eject ions from the two-dimensional array in a direction parallel to a major axis of the electrodes and orthogonal to the gas flow by applying a DC pulse.
18. The mass spectrometer system of claim 11, further comprising a DC supply configured to provide a DC voltage to the plurality of electrodes.
19. The mass spectrometer system of claim 18, wherein the DC supply is configured to apply a DC gradient to eject ions from the two-dimensional array.
20. A method of separating ions comprising: providing RF potentials to a plurality of electrodes arranged in a two-dimensional grid such that pseudopotential barriers separating a plurality of pseudopotential wells are formed, the pseudopotential barriers increasing in magnitude along a first direction; supplying a gas flow through the two-dimensional grid in the first direction; injecting ions into the two-dimensional grid; and separating the ions within the two-dimensional grid wherein a drag force applied by the gas flow is opposed by a pseudopotential gradient of the plurality of electrodes.
21. The method of claim 20, further comprising equilibrating ions within the two-dimensional grid such that ions become trapped in one of the pseudopotential wells where the pseudopotential barrier has a magnitude sufficient to trap the ions against the drag force generated from the gas flow.
22. The method of claim 20, further comprising maintaining an operating gas pressure within the two-dimensional grid of between about 10.sup.4 Torr and about 10.sup.2 Torr.
23. The method of claim 20, wherein the drag force is a function of the collisional cross section of the ions.
24. The method of claim 20, wherein the gas velocity is between about 10 m/s and about 200 m/s.
25. The method of claim 20 wherein the pseudopotential barrier is a function of the mass-to-charge ratio.
26. The method of claim 20, wherein movement of the ions through the two-dimensional grid is a function of collisional cross section and mass-to-charge ratio.
27. The method of claim 26, wherein movement of the ions through the two-dimensional grid is further dependent upon a gas velocity and a gas viscosity.
28. The method of claim 20, further comprising ejecting the ions from the two-dimensional grid in a direction parallel to a major axis of the electrodes and orthogonal to the gas flow.
29. The method of claim 28, wherein ejecting the ions includes ejecting the ions substantially simultaneously from two or more the plurality of pseudopotential wells.
Description
DRAWINGS
(1) For a more complete understanding of the principles disclosed herein, and the advantages thereof, reference is now made to the following descriptions taken in conjunction with the accompanying drawings, in which:
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(10) It is to be understood that the figures are not necessarily drawn to scale, nor are the objects in the figures necessarily drawn to scale in relationship to one another. The figures are depictions that are intended to bring clarity and understanding to various embodiments of apparatuses, systems, and methods disclosed herein. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts. Moreover, it should be appreciated that the drawings are not intended to limit the scope of the present teachings in any way.
DESCRIPTION OF VARIOUS EMBODIMENTS
(11) Embodiments of systems and methods for transporting ions are described herein.
(12) The section headings used herein are for organizational purposes only and are not to be construed as limiting the described subject matter in any way.
(13) In this detailed description of the various embodiments, for purposes of explanation, numerous specific details are set forth to provide a thorough understanding of the embodiments disclosed. One skilled in the art will appreciate, however, that these various embodiments may be practiced with or without these specific details. In other instances, structures and devices are shown in block diagram form. Furthermore, one skilled in the art can readily appreciate that the specific sequences in which methods are presented and performed are illustrative and it is contemplated that the sequences can be varied and still remain within the spirit and scope of the various embodiments disclosed herein.
(14) All literature and similar materials cited in this application, including but not limited to, patents, patent applications, articles, books, treatises, and internet web pages are expressly incorporated by reference in their entirety for any purpose. Unless described otherwise, all technical and scientific terms used herein have a meaning as is commonly understood by one of ordinary skill in the art to which the various embodiments described herein belongs.
(15) It will be appreciated that there is an implied about prior to the temperatures, concentrations, times, etc. discussed in the present teachings, such that slight and insubstantial deviations are within the scope of the present teachings. In this application, the use of the singular includes the plural unless specifically stated otherwise. Also, the use of comprise, comprises, comprising, contain, contains, containing, include, includes, and including are not intended to be limiting. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the present teachings.
(16) As used herein, a or an also may refer to at least one or one or more. Also, the use of or is inclusive, such that the phrase A or B is true when A is true, B is true, or both A and B are true. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.
(17) A system sets forth a set of components, real or abstract, comprising a whole where each component interacts with or is related to at least one other component within the whole.
(18) Mass Spectrometry Platforms
(19) Various embodiments of mass spectrometry platform 100 can include components as displayed in the block diagram of
(20) In various embodiments, the ion source 102 generates a plurality of ions from a sample. The ion source can include, but is not limited to, a matrix assisted laser desorption/ionization (MALDI) source, electrospray ionization (ESI) source, inductively coupled plasma (ICP) source, electron ionization source, photoionization source, glow discharge ionization source, thermospray ionization source, and the like.
(21) In various embodiments, the mass analyzer 104 can separate ions based on a mass to charge ratio of the ions. For example, the mass analyzer 104 can include a quadrupole mass filter analyzer, a time-of-flight (TOF) analyzer, a quadrupole ion trap analyzer, an electrostatic trap mass analyzer (such as an ORBITRAP mass analyzer), and the like. In various embodiments, the mass analyzer 104 can also be configured to fragment the ions and further separate the fragmented ions based on the mass-to-charge ratio.
(22) In various embodiments, the ion detector 106 can detect ions. For example, the ion detector 106 can include an electron multiplier, a Faraday cup, and the like. Ions leaving the mass analyzer can be detected by the ion detector. In various embodiments, the ion detector can be quantitative, such that an accurate count of the ions can be determined.
(23) In various embodiments, the controller 108 can communicate with the ion source 102, the mass analyzer 104, and the ion detector 106. For example, the controller 108 can configure the ion source or enable/disable the ion source. Additionally, the controller 108 can configured the mass analyzer 104 to select a particular mass range to detect. Further, the controller 108 can adjust the sensitivity of the ion detector 106, such as by adjusting the gain. Additionally, the controller 108 can adjust the polarity of the ion detector 106 based on the polarity of the ions being detected. For example, the ion detector 106 can be configured to detect positive ions or be configured to detected negative ions.
(24) Various embodiments of mass spectrometry system 100 can include an orthogonal-flow ion trap array 200 as illustrated in the block diagram of
(25) In various embodiments, rows 214A and 214B can extend in a first direction (X), rows 214A and 214B can be spaced apart from one another in a second direction (Y), and the electrodes can extend in a third direction (Z). In various embodiments, guard electrodes 218A and 218B can be positioned at each end of the plurality of electrodes 202A-212A and 202B-212B. A DC voltage can be applied to the guard electrodes 218A and 218B to confine the ions in the Z direction. In alternate embodiments, each of the plurality of electrodes can be segmented (not shown) and DC potentials can be applied to each segment to confine the ions in the Z direction. Additionally, changes to the DC voltages can be used to eject ions in the Z direction. The ions can be ejected simultaneously from multiple pseudopotential wells. Alternatively, the pseudopotential wells can be individually addressed either with segmented electrodes 202A-212A and 202B-212B or by segmenting the guard electrodes 218A and 218B.
(26) In various embodiments, the amplitude of the RF potentials applied to the electrodes can increase along the direction of gas flow (X direction). Specifically, the RF amplitude of electrode 212A>210A>208A>206A>204A>202A.
(27) In various embodiments, the electrode can have a planar electrode geometry to allow for a non-turbulent laminar gas flow to propagate across the entire channel.
(28) In alternate embodiments, the RF amplitude can be constant along the X direction but the electrode geometry can change, such as by altering the spacing in the X and/or Y directions, to achieve the increasing pseudopotential barrier.
(29) The pseudopotential barrier can result in a force on the ions that pushes in the negative X direction. The pseudopotential is both a function of mass-to-charge ratio (m/z) of the ion and the amplitude of the RF voltage (V.sub.RF). The pseudopotential, V*, can be defined according to Equation 1 where z is the ion charge state, e is the elementary charge, E.sub.RF is the RF electric field, and w is the angular RF frequency.
V*=eE.sub.RF.sup.2/(4(m/z).sup.2)Equation 1
(30) The interaction of the ions with the gas flow can result in a drag force that acts to move the ions in the positive X direction. The drag force is related to collisional cross section or projection area A, and is a function of the gas number density n, the molecular mass of the gas m.sub.2, and the particle velocity v.
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In the context of ion mobility, the drag force is proportional to the ratio of the gas velocity to the mobility coefficient K. Both expressions follow a similar form since the cross section is proportional to z/K.
F.sub.Drag=zev.sub.gas/KEquation 3
(32) In a quadrupolar field, ions are confined radially in a pseudopotential well, such as at 216. Using a gas flow, ions of low mobility can be forced across the pseudopotential barrier from one well to the next. Because Equation 3 shows that the drag force exerted on ions of low mobility is greater, these ions can be forced further up the confining potential. It is important to note that ions of low mobility can experience not only a greater drag force, but can be trapped by lower pseudopotential barriers. Together, these factors can allow for ions of high m/z and/or low K ions to overcome the pseudopotential barriers and move laterally into an adjacent well in the trap. Importantly, the magnitude of the pseudopotential barriers can increase laterally as a result of increasing the RF voltage or changing geometry. This can allow high m/z and/or low K ions to eventually become confined when the drag force cannot overcome the confining potential. This can also allow for better confinement of high mass ions by increasing their q, stability parameter. Conversely, ions of high mobility may not be as affected by the gas flow and thus, may not migrate laterally or may migrate laterally to a lesser extent.
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(34) At 506, the ions can be injected into the orthogonal flow ion trap array. In various embodiments, the ions can be injected into the trap array as an ion packet rather than as a continuous stream of ions. In various embodiments, the ions can be injected into the first ion trap in a direction parallel to the electrodes and perpendicular to the gas flow.
(35) At 508, a time delay can allow the ions to reach an equilibrium position. In various embodiments, the time delay can be not greater than about 1000 milliseconds. Although, a shorter time delay can be desirable when separating ions with the larger m/z.
(36) In various embodiments, the equilibration time can be influenced by the RF voltage increase as a function of the lateral position. The simulations contained in FIGS. 9A-9I utilize a linear RF voltage increase which produces a trapping potential that increases with the square of distance. Varying the pseudopotential profile as a function of position can allow for the relative separation timescale to be adjusted, and can also allow for the charge capacity in each well to be altered. Another means for changing the separation timescale may involve changing the geometry of the device. Geometry changes may include changing the height of the trap and/or changing the height along the separation dimension (i.e.: placing the two planes of the array at a small angle with respect to one another), changing the width and spacing of the electrodes, varying the height along the axial direction to speed up ejection from the trap, or any combination thereof.
(37) At 510, the ions can be ejected from the traps. In various embodiments, the ions can be ejected in a direction parallel to the electrodes and perpendicular to the gas flow. In various embodiments, the ions can be ejected from a trap by applying a DC gradient or DC pulse. This can be accomplished by lowering the DC potential of one of the end electrodes and/or raising the DC potential of the other end electrode. Alternatively, when using a segmented electrode, a DC gradient can be applied to the segmented electrode by applying a high voltage to the segment on one end and a lower voltage to a segment on the other end of the electrode. In various embodiments, the ions can be ejected from the traps of the orthogonal flow ion trap array substantially simultaneously, such as into a storage cell array. When using a storage cell array, the ions can be temporarily stored and each individual ion packet can be released and analyzed sequentially. At 512, the ions can be analyzed.
(38) In various embodiments, the orthogonal flow ion trap array can be used in conjunction with a storage cell array.
(39) In various embodiments, different ion species can have different abundance in the sample, such that a first well include one or more low abundance ion species while a second well can include a higher abundance ion species. Using the storage cell to accumulate ions and different numbers of transfers depending on the well can compensate for the initial differences in ion abundance. For example, the high abundance ion of the second well can substantially fill the corresponding cell of the storage cell array in one or two cycles while the low abundance ions of the first well may take more cycles to reach the capacity of the corresponding cell of storage cell array. The system can reduce the number of accumulations for the second well while increasing the number of accumulations for the first well.
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(41) At 706, the ions can be injected into the orthogonal flow ion trap array. In various embodiments, the ions can be injected into the trap array as an ion packet rather than as a continuous stream of ions. In various embodiments, the ions can be injected into the first ion trap in a direction parallel to the electrodes and perpendicular to the gas flow.
(42) At 708, the ions moving along the length of the trap array and exit with the gas flow. In various embodiments, the gas flow may be large enough that the ions are not trapped by the increasing pseudopotential barrier, but rather differentially slowed. Ions with a larger mobility coefficient and/or a larger m/z may leave the trap array first and other ions with a smaller mobility coefficient and/or smaller m/z may leave the trap later (with a greater delay). The ions exiting the trap array can then be focused and directed for further processing.
(43) Optionally, at 710, any remaining ions can be ejected from the traps. In various embodiments, the ions can be ejected in a direction parallel to the electrodes and perpendicular to the gas flow. In various embodiments, the ions can be ejected from a trap by applying a DC gradient or DC pulse. This can be accomplished by lowering the DC potential of one of the end electrodes and/or raising the DC potential of the other end electrode. Alternatively, when using a segmented electrode, a DC gradient can be applied to the segmented electrode by applying a high voltage to the segment on one end and a lower voltage to a segment on the other end of the electrode. Alternatively, the ions can be ejected from the traps radially.
(44) At 712, the ions can be analyzed.
(45) Computer-Implemented System
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(47) In various embodiments, computer system 800 can be coupled via bus 802 to a display 812, such as a cathode ray tube (CRT) or liquid crystal display (LCD), for displaying information to a computer user. An input device 814, including alphanumeric and other keys, can be coupled to bus 802 for communicating information and command selections to processor 804. Another type of user input device is a cursor control 816, such as a mouse, a trackball or cursor direction keys for communicating direction information and command selections to processor 804 and for controlling cursor movement on display 812. This input device typically has two degrees of freedom in two axes, a first axis (i.e., x) and a second axis (i.e., y), that allows the device to specify positions in a plane.
(48) A computer system 800 can perform the present teachings. Consistent with certain implementations of the present teachings, results can be provided by computer system 800 in response to processor 804 executing one or more sequences of one or more instructions contained in memory 806. Such instructions can be read into memory 806 from another computer-readable medium, such as storage device 810. Execution of the sequences of instructions contained in memory 806 can cause processor 804 to perform the processes described herein. In various embodiments, instructions in the memory can sequence the use of various combinations of logic gates available within the processor to perform the processes describe herein. Alternatively hard-wired circuitry can be used in place of or in combination with software instructions to implement the present teachings. In various embodiments, the hard-wired circuitry can include the necessary logic gates, operated in the necessary sequence to perform the processes described herein. Thus implementations of the present teachings are not limited to any specific combination of hardware circuitry and software.
(49) The term computer-readable medium as used herein refers to any media that participates in providing instructions to processor 804 for execution. Such a medium can take many forms, including but not limited to, non-volatile media, volatile media, and transmission media. Examples of non-volatile media can include, but are not limited to, optical or magnetic disks, such as storage device 810. Examples of volatile media can include, but are not limited to, dynamic memory, such as memory 806. Examples of transmission media can include, but are not limited to, coaxial cables, copper wire, and fiber optics, including the wires that comprise bus 802.
(50) Common forms of non-transitory computer-readable media include, for example, a floppy disk, a flexible disk, hard disk, magnetic tape, or any other magnetic medium, a CD-ROM, any other optical medium, punch cards, paper tape, any other physical medium with patterns of holes, a RAM, PROM, and EPROM, a FLASH-EPROM, any other memory chip or cartridge, or any other tangible medium from which a computer can read.
(51) In accordance with various embodiments, instructions configured to be executed by a processor to perform a method are stored on a computer-readable medium. The computer-readable medium can be a device that stores digital information. For example, a computer-readable medium includes a compact disc read-only memory (CD-ROM) as is known in the art for storing software. The computer-readable medium is accessed by a processor suitable for executing instructions configured to be executed.
(52) In various embodiments, the methods of the present teachings may be implemented in a software program and applications written in conventional programming languages such as C, C++, G, etc.
(53) While the present teachings are described in conjunction with various embodiments, it is not intended that the present teachings be limited to such embodiments. On the contrary, the present teachings encompass various alternatives, modifications, and equivalents, as will be appreciated by those of skill in the art.
(54) Further, in describing various embodiments, the specification may have presented a method and/or process as a particular sequence of steps. However, to the extent that the method or process does not rely on the particular order of steps set forth herein, the method or process should not be limited to the particular sequence of steps described. As one of ordinary skill in the art would appreciate, other sequences of steps may be possible. Therefore, the particular order of the steps set forth in the specification should not be construed as limitations on the claims. In addition, the claims directed to the method and/or process should not be limited to the performance of their steps in the order written, and one skilled in the art can readily appreciate that the sequences may be varied and still remain within the spirit and scope of the various embodiments.
(55) The embodiments described herein, can be practiced with other computer system configurations including hand-held devices, microprocessor systems, microprocessor-based or programmable consumer electronics, minicomputers, mainframe computers and the like. The embodiments can also be practiced in distributing computing environments where tasks are performed by remote processing devices that are linked through a network.
(56) It should also be understood that the embodiments described herein can employ various computer-implemented operations involving data stored in computer systems. These operations are those requiring physical manipulation of physical quantities. Usually, though not necessarily, these quantities take the form of electrical or magnetic signals capable of being stored, transferred, combined, compared, and otherwise manipulated. Further, the manipulations performed are often referred to in terms, such as producing, identifying, determining, or comparing.
(57) Any of the operations that form part of the embodiments described herein are useful machine operations. The embodiments, described herein, also relate to a device or an apparatus for performing these operations. The systems and methods described herein can be specially constructed for the required purposes or it may be a general purpose computer selectively activated or configured by a computer program stored in the computer. In particular, various general purpose machines may be used with computer programs written in accordance with the teachings herein, or it may be more convenient to construct a more specialized apparatus to perform the required operations.
(58) Certain embodiments can also be embodied as computer readable code on a computer readable medium. The computer readable medium is any data storage device that can store data, which can thereafter be read by a computer system. Examples of the computer readable medium include hard drives, network attached storage (NAS), read-only memory, random-access memory, CD-ROMs, CD-Rs, CD-RWs, magnetic tapes, and other optical and non-optical data storage devices. The computer readable medium can also be distributed over a network coupled computer systems so that the computer readable code is stored and executed in a distributed fashion.
(59) Results
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