Patent Application
20220068624
The teachings herein relate to single electrostatic linear ion trap (ELIT) for a mass spectrometer that can selectively mass analyze a wide mass-to-charge ratio (m/z) range with a low resolution or a narrower m/z range with a higher resolution. More specifically, an ELIT includes additional axial electrode plates so that applying voltages selectively to one of two or more different groups of axially aligned electrode plates causes ions to be trapped along one of two or more different ion path lengths.
The apparatus and methods disclosed herein can be performed in conjunction with a processor, controller, microcontroller, or computer system, such as the computer system of
An electrostatic linear ion trap mass spectrometer (ELIT-MS) is a type of mass spectrometer. An ELIT-MS includes an ELIT for performing mass analysis of ions. In an ELIT, electric current induced by oscillating ions in the trap is detected. The measured frequency of oscillation of the ions is used to calculate the m/z of the ions. For example, a Fourier transform is performed on the measured induced current.
Dziekonski et al., Int. J. Mass Spectrom. 410 (2016) p 12-21, (the “Dziekonski Paper”) describes an exemplary ELIT. The Dziekonski Paper is incorporated by reference herein.
In ELIT 200, ions are introduced axially and oscillate axially between first set of electrode plates 210 and second set of electrode plates 220. Pickup electrode 215 is used to measure the induced image current or image charge produced by the oscillating ions. A Fourier transform (FT) is performed on the digitized signal measured from pickup electrode 215 to obtain the oscillation frequency. From the oscillation frequency or frequencies, the m/z of one or more ions is calculated. Detection can also be performed on the electrode plates, using multiple electrodes, or shaped electrodes.
The axial length of an ELIT is directly related to the accepted time-of-flight distance of the ELIT. For traps of reasonable proportions, i.e. less than 10 meters, and for a fixed low-mass cutoff, a longer ELIT can be used to analyze ions across a wider m/z range. However, the axial length of an ELIT is inversely related to resolution for a fixed acquisition time and ion kinetic energy. In other words, a longer ELIT has a lower mass analysis resolution for a given acquisition time and ion kinetic energy. So, it is better to use a longer ELIT to analyze a wider m/z mass range, but it is better to use a shorter ELIT to obtain a higher resolution.
This dichotomy between m/z range and resolution originates from the fact that both ion injection (external) and ion detection occur in the axial dimension. In general, the average kinetic energy (average velocity) of ions injected into an ELIT is fixed by the injection method, electrode geometries, and trapping potentials. As a result, ions in the ELIT oscillate back and forth along the axis from end to end with an m/z-specific average velocity. If similar ion energies and plate potentials are used with a longer ELIT, ions will require a longer time to traverse the longer path length. Consequently, the frequency of oscillation is lower. The FT frequency resolution is directly proportional to the frequency of oscillation. Thus, the lower frequency of oscillation produces a lower resolution for a fixed acquisition time. Note that the plate potentials are slightly different in different sized ELITs as the temporal and radial focal points will not be in the same position. Also note that it is possible to offset certain electrodes to compensate for the longer path length.
Therefore, a longer trap is beneficial for generating mass spectra of a broad m/z range, while a smaller trap is beneficial for resolving isobaric compounds, resolving isotopic envelopes for charge states determination, etc. Generally, the only solution to this problem has been to physically remove one trap and replace it with a trap that is appropriately sized to best answer the analytical question of interest. This, however, requires breaking vacuum, days of downtime, and a skilled person.
Another possible solution is to place ELITs of different sizes in parallel. This solution, however, also has a number of downsides. For example, more elements are needed such as multiple deflectors to offset the beam of ions, a preamplifier is needed for each ELIT, and more ion loss is likely.
As a result, additional systems and methods are needed to provide a single ELIT that can selectively analyze a wide m/z range with low resolution or a narrower m/z range with higher resolution.
An ELIT with a selectable ion path length is disclosed. In addition, a method and a computer program product are disclosed for selecting different ion path lengths in an ELIT.
The ELIT includes one or more voltage sources, a first set of electrode plates, a second set of electrode plates, and one or more switches. The first set of electrode plates is aligned along a central axis. The second set of electrode plates also includes holes in the center and is aligned with the first set along the central axis.
A first group of plates of the first set of plates and the second set of plates is positioned along the central axis to trap ions within a first path length of the central axis. A second group of plates of the first set of plates and the second set of plates is positioned along the central axis to trap ions within a second path length of the central axis that is shorter than the first path length.
The one or more switches select the first path length by applying voltages from the one or more voltage sources to the first set of plates and the second set of plates that cause the first group of plates to trap ions within the first path length. Alternatively, the one or more switches can select the second path length by applying voltages from the one or more voltage sources to the first set of plates and the second set of plates that cause the second group of plates to trap ions within the second path length.
These and other features of the applicant's teachings are set forth herein.
The skilled artisan will understand that the drawings, described below, are for illustration purposes only. The drawings are not intended to limit the scope of the present teachings in any way.
Before one or more embodiments of the present teachings are described in detail, one skilled in the art will appreciate that the present teachings are not limited in their application to the details of construction, the arrangements of components, and the arrangement of steps set forth in the following detailed description or illustrated in the drawings. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting.
Computer system 100 may be coupled via bus 102 to a display 112, such as a cathode ray tube (CRT) or liquid crystal display (LCD), for displaying information to a computer user. An input device 114, including alphanumeric and other keys, is coupled to bus 102 for communicating information and command selections to processor 104. Another type of user input device is cursor control 116, such as a mouse, a trackball or cursor direction keys for communicating direction information and command selections to processor 104 and for controlling cursor movement on display 112. 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.
A computer system 100 can perform the present teachings. Consistent with certain implementations of the present teachings, results are provided by computer system 100 in response to processor 104 executing one or more sequences of one or more instructions contained in memory 106. Such instructions may be read into memory 106 from another computer-readable medium, such as storage device 110. Execution of the sequences of instructions contained in memory 106 causes processor 104 to perform the process described herein. Alternatively, hard-wired circuitry may be used in place of or in combination with software instructions to implement the present teachings. Thus, implementations of the present teachings are not limited to any specific combination of hardware circuitry and software.
In various embodiments, computer system 100 can be connected to one or more other computer systems, like computer system 100, across a network to form a networked system. The network can include a private network or a public network such as the Internet. In the networked system, one or more computer systems can store and serve the data to other computer systems. The one or more computer systems that store and serve the data can be referred to as servers or the cloud, in a cloud computing scenario. The one or more computer systems can include one or more web servers, for example. The other computer systems that send and receive data to and from the servers or the cloud can be referred to as client or cloud devices, for example.
The term “computer-readable medium” as used herein refers to any media that participates in providing instructions to processor 104 for execution. Such a medium may take many forms, including but not limited to, non-volatile media, volatile media, and transmission media. Non-volatile media includes, for example, optical or magnetic disks, such as storage device 110. Volatile media includes dynamic memory, such as memory 106. Transmission media includes coaxial cables, copper wire, and fiber optics, including the wires that comprise bus 102.
Common forms of computer-readable media or computer program products include, for example, a floppy disk, a flexible disk, hard disk, magnetic tape, or any other magnetic medium, a CD-ROM, digital video disc (DVD), a Blu-ray Disc, any other optical medium, a thumb drive, a memory card, 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.
Various forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to processor 104 for execution. For example, the instructions may initially be carried on the magnetic disk of a remote computer. The remote computer can load the instructions into its dynamic memory and send the instructions over a telephone line using a modem. A modem local to computer system 100 can receive the data on the telephone line and use an infra-red transmitter to convert the data to an infra-red signal. An infra-red detector coupled to bus 102 can receive the data carried in the infra-red signal and place the data on bus 102. Bus 102 carries the data to memory 106, from which processor 104 retrieves and executes the instructions. The instructions received by memory 106 may optionally be stored on storage device 110 either before or after execution by processor 104.
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.
The following descriptions of various implementations of the present teachings have been presented for purposes of illustration and description. It is not exhaustive and does not limit the present teachings to the precise form disclosed. Modifications and variations are possible in light of the above teachings or may be acquired from practicing of the present teachings. Additionally, the described implementation includes software but the present teachings may be implemented as a combination of hardware and software or in hardware alone. The present teachings may be implemented with both object-oriented and non-object-oriented programming systems.
ELIT within an ELIT
As described above, the axial length or size of an ELIT is directly related to the accepted m/z range. However, the axial length of an ELIT is inversely related to resolution. As a result, a longer ELIT is better for analyzing a wide mass range with a low resolution, while a shorter ELIT is better for analyzing a narrower mass range with a higher resolution.
One solution to this problem has been to physically remove one trap and replace it with a trap that is appropriately sized to best answer the analytical question of interest. This, however, requires breaking vacuum, days of downtime, and a skilled person. Another possible solution is to place ELITs of different sizes in parallel. This solution, however, also has a number of downsides. For example, more elements are needed such as multiple deflectors to offset the beam of ions, a preamplifier is needed for each ELIT, and more ion loss is likely.
As a result, additional systems and methods are needed to provide a single ELIT that can selectively analyze a wide m/z range with low resolution or a narrower m/z range with higher resolution.
In various embodiments, an ELIT is placed coaxially within an ELIT to provide a single ELIT that can selectively analyze a wide m/z range with low resolution or a narrower m/z range with higher resolution. Both ELITs share the same pickup electrode, although separate detection systems could be used to match the frequency response of the preamplifier to that of the different traps.
A second group of plates includes first set of electrode plates 410 and second set of electrode plates 420. Voltages are applied to the second group of plates so that ions 605 pass through the plates along a stable trajectory. The voltages applied to the second group of plates can be used to alter the time-averaged kinetic energy of ions 605, either increasing or decreasing the oscillation frequency.
A first group of plates includes first set of electrode plates 310 and second set of electrode plates 320. Voltages are applied to the first group of plates so that they do not participate in the analysis of ions 705. However, the outer plates of the first group of plates can be used to focus ions 705.
The first group of plates and the second group of plates of
A comparison of
The operation of the ELIT of
The operation of the ELIT of
It is important to note that although only six plates were added to generate two unique ELIT structures in the ELIT of
Also, to ease tuning, in various embodiments, the axial spacings of each ELIT structure are proportional to one another. In addition, while as indicated in
ELIT with a Selectable Ion Path Length
First set of electrode plates 1110 is aligned along central axis 1105. Second set of electrode plates 1120 also includes holes in the center and is aligned with first set of electrode plates 1110 along central axis 1105.
A first group of plates of first set of plates 1110 and second set of plates 1120 is positioned along central axis 1105 to trap ions within a first path length of central axis 1105. A first group of plates positioned to trap ions within a first path length is shown, for example, in bold in
Returning to
Returning to
In various embodiments, the first group of plates and the second group of plates do not share any plates. For example, the first group of plates, shown in bold in
Returning to
Returning to
Returning to
As described above, tuning is simplified if locations of the plates in the second group of plates are proportional to the plates in the first group of plates. Specifically, this means that the same voltages can be applied to most of the plates in the two groups. The trapping plates and the plates to change the curvature of the electric field near a turning point only focus the kinetic energy distribution, which is constant when a longer ELIT is used or when a shorter ELIT is used. As a result, if the locations of the plates in the second group of plates are proportional to the plates in the first group of plates, only the voltages of the plates used to radially confine ions should need to be drastically changed when switching between the first group of plates and the second group of plates.
Therefore, in various embodiments, if the locations of the plates in the second group of plates are proportional to the plates in the first group of plates, a voltage applied to a trapping plate of the first group of plates to trap ions within the first path length is the same (or very similar) voltage applied to a corresponding trapping plate of the second group of plates to trap ions within the second path length. Similarly, if the locations of the plates in the second group of plates are proportional to the plates in the first group of plates, a voltage applied to a plate to change the curvature of an electric near a turning point of the first group of plates to trap ions within the first path length is the same (or very similar) voltage applied to a corresponding plate to change the curvature of an electric near a turning point of the second group of plates to trap ions within the second path length.
If the locations of the plates in the second group of plates are proportional to the plates in the first group of plates, only the voltages of the plates used to radially confine ions need to be drastically changed. Specifically, if the locations of the plates in the second group of plates are proportional to the plates in the first group of plates, a voltage applied to a plate to radially confine ions of the first group of plates to trap ions within the first path length is different from a voltage applied to a corresponding plate to radially confine ions of the second group of plates to trap ions within the second path length.
As described above, when the second group of plates is selected to trap ions within a shorter second path length, voltages applied to the outermost electrodes of the first group of plates are applied so that they do not participate in the analysis of ions. In various embodiments, however, these plates can be used to focus ions. Specifically, returning to
In various embodiments, switching between ELITs is done between sample experiments. Specifically, one or more switches 1102 switch between the first path length and the second path length between samples analyses.
In various embodiments, switching between ELITs is done dynamically or in real-time within a single sample experiment. Specifically, one or more switches 1102 switch between the first path length and the second path length within a sample analysis. For example, in a targeted scan, it may be known that a peak of interest is located in a narrow m/z range. If the peak of interest is not resolved using the longer first path length, one or more switches 1102 can switch from the first path length to the second path length to increase the resolution to locate the peak of interest.
In various embodiments, near each trapping point, one trapping plate is needed and a minimum of three plates is needed for changing the curvature of the electric and radially confining ions. As a result, the first group of plates includes at least four plates from the first set and at least four plates from second set, and the second group of plates includes at least four plates from the first set and at least four plates from second set. In various embodiments, it is be possible to use less electrodes if the electrodes are shaped, i.e. they are not represented by a simple cylindrical structure as described, for example, by Hogan, J. A.; Jarrold, M. F. J. Am. Soc. Mass Spectrom. 2018, 1-10.
As described above, in various embodiments, any number of plates can be added to an ELIT to create one or more additional ELITs within the ELIT. For example, a third group of plates (not shown) of the first set of plates 1110 and the second set of plates 1120 can be positioned along central axis 1105 to trap ions within a third path length of central axis 1105 that is shorter than the second path length. One or more switches 1102 can select the third path length by applying different separate voltages from one or more voltage sources 1101 to the first set of plates 1110 and the second set of plates 1120 that cause the third group of plates to trap ions within the third path length.
In various embodiments, processor 1104 is used to control or provide instructions to one or more switches 1102 and to one or more voltage sources 1101 and to analyze data collected. Processor 1104 controls or provides instructions by, for example, controlling one or more voltage, current, or pressure sources (not shown) or by applying currents or voltages. Processor 1104 can be a separate device as shown in
In step 1210 of method 1200, one or more switches are instructed to select a first path length by applying voltages from one or more voltage sources to a first set of electrode plates and a second set of electrode plates that cause a first group of plates of the first set of plates and the second set of plates to trap ions within the first path length using a processor. The plates of the first set include holes in center and are aligned along a central axis. The plates of the second set include holes in center and are aligned along the central axis with the first set. The first group of plates is positioned along the central axis to trap ions within the first path length of the central axis. A second group of plates of the first set of plates and the second set of plates is positioned along the central axis to trap ions within a second path length of the central axis that is shorter than the first path length.
In step 1210, the one or more switches are instructed to select a second path length by applying voltages from the one or more voltage sources to the first set of plates and the second set of plates that cause the second group of plates to trap ions within the second path length using the processor.
In various embodiments, computer program products include a tangible computer-readable storage medium whose contents include a program with instructions being executed on a processor so as to perform a method for selecting different ion path lengths in an ELIT. This method is performed by a system that includes one or more distinct software modules.
Control module 1310 instructs one or more switches to select a first path length by applying voltages from one or more voltage sources to a first set of electrode plates and a second set of electrode plates that cause a first group of plates of the first set and the second set to trap ions within the first path length. The plates of the first set include holes in center and are aligned along a central axis. The plates of the second set include holes in center and are aligned along the central axis with the first set. The first group of plates is positioned along the central axis to trap ions within the first path length of the central axis. A second group of plates of the first set and the second set is positioned along the central axis to trap ions within a second path length of the central axis that is shorter than the first path length.
Control module 1310 instructs the one or more switches to select the second path length by applying voltages from the one or more voltage sources to the first set and the second set that cause the second group of plates set to trap ions within the second path length.
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.
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.
This application claims the benefit of U.S. Provisional Patent Application Ser. No. 62/779,363, filed on Dec. 13, 2018, the content of which is incorporated by reference herein in its entirety.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/IB2019/060573 | 12/9/2019 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 62779363 | Dec 2018 | US |
