Patent Grant
11990328
The present invention relates to a mass spectrometer, and more specifically, to an ion trap time-of-flight mass spectrometer (IT-TOFMS).
An IT-TOFMS includes an ion trap configured to capture ions and a time-of-flight mass spectrometer (TOFMS) configured to detect ions after separating them based on their times of flight which correspond to their respective mass-to-charge ratios m/z (for example, see Patent Literatures 1 and 2). The ion trap and TOFMS are arranged within a vacuum container. The ion trap has a plurality of electrodes as well as an ion introduction port for introducing ions into the inner space and an ion ejection port for ejecting ions from the inner space toward the TOFMS. By creating an electric field within the space surrounded by those electrodes, the ion trap captures ions introduced within that space and then ejects only a specific kind of ion at a predetermined timing. The ion trap is electrically insulated from the wall of the vacuum container by an insulating spacer (see Patent Literature 2).
The ions ejected from the ion ejection port at a predetermined timing are introduced into the flight space in the TOFMS. Ions which have completed their flight in the flight space are detected by a detector. A time-of-flight spectrum which shows the relationship between the time of flight and the detection intensity is created, and the time of flight in the time-of-flight spectrum is converted into m/z to obtain a mass spectrum.
During the period of time from the capturing of ions within the ion trap to the ejection of the ions, an inert gas, such as argon gas, is introduced into the ion trap. This gas is called the “cooling gas” in Patent Literature 1. The cooling gas thus introduced cools the ions and lowers the kinetic energy of the ions. Lowering the kinetic energy of the ions in this manner before ejecting them from the ion trap reduces the variation in the speed of the ions of the same m/z value at the time of the ejection of the ions. This in turn reduces the variation in the time of flight for the ions to reach the detector, so that the m/z resolving power is improved.
The cooling gas introduced into the ion trap flows out of the ion ejection port of the ion trap. Therefore, the ions within the ion trap collide with the molecules of the cooling gas not only while the ions are being cooled (i.e., while they are captured within the ion trap) but also when the ions are ejected from the ion ejection port. Due to this collision, some of the ions are prevented from entering the flight space in the TOFMS, while some other ions enter the flight space yet deviate from the intended flight path. In both cases, the ions cannot reach the detector, so that the detection intensity of the ions will be lowered.
The problem to be solved by the present invention is to provide an IT-TOFMS which can reduce the decrease in the detection intensity of the ions caused by the cooling gas.
The mass spectrometer according to the present invention developed for solving the previously described problem includes:
In the mass spectrometer according to the present invention, the cooling gas introduced from the gas introduction tube into the ion-capturing space in the ion trap flows through the gap between the plurality of electrodes forming the ion-capturing space, as well as through the cooling-gas discharge port in the ion trap holder, into the space which is outside the ion trap holder yet inside the first chamber, from which the cooling gas is further discharged to the outside of the first chamber due to the evacuation of the inner space of the first chamber. This configuration reduces the amount of cooling gas flowing to the ion ejection port, so that the decrease in the detection intensity of the ions is reduced.
An IT-TOFMS 1 as one embodiment of the mass spectrometer according to the present invention is hereinafter described using
As shown in
The ion source 2 is a device for ionizing components in a sample to be analyzed. For example, a liquid sample whose components have been temporally separated by a column in a liquid chromatograph (LC) is used as the sample. When this type of liquid sample is used, an atmospheric pressure ion source which ionizes components in a sample liquid in an ambience of atmospheric pressure, such as an electrospray ion source, can be used as the ion source 2. However, there is no specific limitation on the configuration of the ion source 2 in the present invention; any type of ion source commonly used in mass spectrometers can be appropriately used.
As for the ion trap 3, a parallel-plate linear ion trap is used in the present embodiment. As shown in
The main electrode 31 consists of a first main plate electrode 311 and a third main plate electrode 313 which are two plate electrodes arranged parallel to each other with the linear central axis C in between, as well as a second main plate electrode 312 and a fourth main plate electrode 314 which are two plate electrodes arranged perpendicularly to the first main plate electrode 311 and the third main plate electrode 313 with the central axis C in between. The space surrounded by these first through fourth main plate electrodes 311-314 functions as the ion-capturing space 315 (see
The ion introduction-side end electrode 32 includes a first introduction-side end plate electrode 321, second introduction-side end plate electrode 322, third introduction-side end plate electrode 323 and fourth introduction-side end plate electrode 324 which are arranged as if the main electrode 31 has been translated parallel to the central axis C. No ion ejection port is formed in the first through fourth introduction-side end plate electrodes 321-324. In the space surrounded by the first through fourth introduction-side end plate electrodes 321-324, the end portion of the ion introduction-side end electrode 32 opposite to the main electrode 31 functions as an ion introduction port 326. The aforementioned space functions as an ion passage space 325 (see
The ion non-introduction-side end electrode 33 includes a first non-introduction-side end plate electrode 331, second non-introduction-side end plate electrode 332, third non-introduction-side end plate electrode 333 and fourth non-introduction-side end plate electrode 334 which are arranged as if the main electrode 31 has been translated parallel to the central axis C in the opposite direction to the ion introduction-side end electrode 32. Neither the ion introduction port nor the ion ejection port is formed in the first through fourth non-introduction-side end plate electrodes 331-334.
An extraction electrode 34 is located on the outside of the ion-capturing space 315 as viewed from the ion ejection port 316. The extraction electrode 34 includes a plurality of plate electrodes arranged parallel to each other, in which a hole 346 facing the ion ejection port 316 is formed at the center of each plate electrode.
As shown in
An ion trap holder 60 is fixed to the bottom plate 511 of the first chamber 51. The ion trap holder 60 has a wall 61 made of an insulator. An ion-trap-holding space 610 surrounded by the wall 61 is formed in the ion trap holder 60. The ion trap 3 (main electrode 31, ion introduction-side end electrode 32 and ion non-introduction-side end electrode 33) is held within this ion-trap holding space 60 and fixed to the wall 61. The extraction electrode 34 is fixed to a supporting part 65 made of an insulator extending from the wall 61.
The wall 61 has an introduction-side ion passage port 62 connected to the ion introduction port 326, as well as an ejection-side ion passage port 63 located between the ion ejection port 316 and the second opening 54 (and furthermore, between the hole 346 in the extraction electrode 34 and the second opening 54).
In the portions of the wall 61 corresponding to the bottom portion 611 and the side wall of the ion trap holder 60, a number of cooling-gas discharge ports 64 each of which is a hole are formed. Each cooling-gas discharge port 64 is a hole which connects the ion-trap holding space 610 to a space which is outside the ion-trap holding space 610 yet inside the first chamber 51. The bottom portion 611 of the ion trap holder 60 is supported by a pillar 612 made of an insulator above the bottom plate 511 of the first chamber 51. By this structure, a space 613 which allows a flow of gas to pass through is formed between the bottom portion 611 of the ion trap holder 60 and the bottom plate 511 of the first chamber 51.
An ion trap holder formed by a wall made of an insulator for holding an ion trap has also been used in conventional IT-TOFMSs. However, the conventional ion trap holder is not provided with the cooling-gas discharge ports.
Within the ion-capturing space 315, one end of a gas introduction tube 36 is located. This tube extends from outside the vacuum container 5 and penetrates the wall of the vacuum container 5, the wall 61 of the ion trap holder 60, and the third main plate electrode 313. The gas introduction tube 36 is used for supplying the ion-capturing space 315 with an inert gas (e.g., argon, helium or nitrogen gas) from a gas supply source (gas cylinder) 361 located outside the vacuum container 5.
In the present embodiment, a multiturn TOFMS (MT-TOFMS) is used as the TOFMS 4. As shown in
The outer and inner electrodes 41 and 42 are formed by three partial-electrode pairs S1, S2 and S3 each of which consists of a pair of electrodes having a curved shape in the ZX plane and facing each other, combined with four partial-electrode pairs L1, L2, L3 and L4 each of which consists of a pair of electrodes having a linear shape in the ZX plane and facing each other. The partial-electrode pair S2 as viewed on the ZX plane is located at both ends of the main electrode 31 in the Z direction and has a symmetrical shape with respect to the Z axis. The partial-electrode pair S1 is located on the positive side of the Z direction as viewed from the partial-electrode pair S2. The partial-electrode pair S3 is located on the negative side of the X direction as viewed from the partial-electrode pair S2 and is symmetrical to the partial-electrode pair S1 with respect to the Z axis. The partial-electrode pair L2 is located between the partial-electrode pairs S1 and S2. The partial-electrode pair L3 is located between the partial-electrode pairs S2 and S3, having a symmetrical shape to the partial-electrode pair L2 with respect to the Z axis. The partial-electrode pair L1 is shaped like a doughnut plate perpendicular to the X axis and is located on the positive side of the X direction as well as inside the partial-electrode pair S1 when projected onto the XY plane. The partial-electrode pair L4 is located on the negative side of the X direction, having a symmetrical shape to the partial-electrode pair L1 with respect to the Z axis. The combination of those partial-electrode pairs gives each of the outer and inner electrodes 41 and 42 a substantially spheroidal shape in their entirety.
A MT-TOF voltage application unit 45 is connected to the partial-electrode pairs S1, S2 and S3 among the partial-electrode pairs constituting the outer and inner electrodes 41 and 42. The MT-TOF voltage application unit 45 is configured to give potentials to the partial-electrode pairs S1, S2 and S3, respectively, so as to create an electric field directed from the outer electrode 41 toward the inner electrode 42. Thus, within an ion flight space 40 which is the space between the outer and inner electrodes 41 and 42, a loop-flight electric field is created which makes ions fly in an orbit within the flight space 40.
The partial-electrode pair S3 in the outer electrode 41 is provided with a MT-TOF ion inlet 401 for introducing ions exiting from the second opening 54 into the flight space 40. The MT-TOF ion inlet 401 is located at a position slightly displaced from the Z axis toward the positive side of the Y direction, and is arranged so that the ions from the ion source 2 are injected substantially parallel to the Z axis. The ions undergo a centripetal force from the loop-flight electric field created by the partial-electrode pair S1 at a position immediately after the point of injection from the MT-TOF ion inlet 401 into the flight space 40. Additionally, due to the displacement of the MT-TOF ion inlet 401 from the Z axis toward the positive side of the Y direction, the ions also undergo a force directed toward the Z-axis direction.
Consequently, the ions fly in an orbit 403 (see
The partial-electrode pair S1 in the outer electrode 41 is provided with a MT-TOF ion outlet 402 for making ions exit from the flight space 40 after the ions have turned within the flight space 40 a plurality of times (typically, tens of times). The ions which have exited from the MT-TOF ion outlet 402 fly in a linear path. The ion detector 43 is placed on this linear path.
Additionally, the IT-TOFMS 1 includes a control unit 7, which is configured to control the operations of the components of the IT-TOFMS 1, such as the ion source 2, ion-trap voltage application unit 35, MT-TOF voltage application unit 45 and ion detector 43.
An operation of the IT-TOFMS 1 according to the present embodiment is hereinafter described using
The ion source 2 ionizes a sample into positive ions by a commonly known method. The positive ions P generated in the ion source 2 are sequentially introduced into the ion trap 3 through the introduction-side ion passage port 62 and the ion introduction port 326. In the ion trap 3, the three steps of (i) accumulation, (ii) cooling and (iii) ejection are performed, as will be hereinafter described.
(2-1) Operation of Ion Trap 3
(i) Accumulation of Ions
In the ion accumulation step, as shown in the lower diagram in
(ii) Cooling of Ions
After the accumulation of the positive ions P has been continued for a predetermined period of time, the ion-trap voltage application unit 35 applies a voltage between the ion introduction-side end electrode 32 and the ground so that the ion introduction-side end electrode 32 (or more specifically, the first through fourth introduction-side end plate electrodes 321-324) has a positive potential, while maintaining the potentials of the main electrode 31 and the ion non-introduction-side end electrode 33 (at 0 and a positive value, respectively; see the lower diagram in
In this state, the cooling gas is supplied from the gas supply source 361 into the ion-capturing space 315 through the gas introduction tube 36. The positive ions P are thereby cooled, and the kinetic energy of the positive ions P is lowered.
Most of the cooling gas supplied into the ion-capturing space 315 exits from the ion-capturing space 315 through the gap between the plate electrodes of the main electrode 31 as well as the gap between the main electrode 31 and the ion introduction-side end electrode 32 or ion non-introduction-side end electrode 33. The cooling gas which has exited from the ion-capturing space 315 further flows through the cooling-gas discharge ports 64 into the first chamber 51 due to the pressure reduction by the first-chamber vacuum pump 551, and is ultimately discharged from the first chamber 51 to the outside (as for the flow of the cooling gas described in this paragraph, see the broken arrows in
Meanwhile, a portion of the cooling gas within the ion-capturing space 315 flows through the ion ejection port 316 into an area near the extraction electrode 34, from which the gas further flows through the hole 346 and the ejection-side ion passage port 63 into the second chamber 52, to be ultimately discharged to the outside of the second chamber 52 by the second vacuum pump 552. Since the second chamber 52 is evacuated to a higher degree of vacuum (and a lower pressure) than the first chamber 51 by the second-chamber pump 552, the cooling gas near the extraction electrode 34 is quickly discharged.
(iii) Ejection of Ions
After the ions have been sufficiently cooled, the supply of the cooling gas is stopped. Then, the ion-trap voltage application unit 35 applies a voltage between the main electrode 31 and the ground so that the potential of the main electrode 31 becomes a positive potential that is lower than the potentials of the ion introduction-side end electrode 32 and the ion non-introduction-side end electrode 33, while maintaining the potentials of the ion introduction-side end electrode 32 and the ion non-introduction-side end electrode 33 (see the lower diagram in
In a conventional IT-TOFMS, the cooling gas introduced into the ion trap holder cannot be discharged from the ion trap holder without passing through the introduction-side ion passage port or the ejection-side ion passage port. Due to the gas-discharging resistance at these two passage ports, the cooling gas is likely to stagnate, particularly around the extraction electrode located near the ejection-side ion passage port. Therefore, some of the positive ions ejected from the ion-capturing space collide with the molecules of the cooling gas stagnating near the extraction electrode. Consequently, some ions are prevented from entering the flight space in the TOFMS, while some other ions enter the flight space yet deviate from the intended flight path. Since those ions cannot reach the detector, the detection sensitivity will be lower. By comparison, in the IT-TOFMS 1 according to the present embodiment, the cooling gas in the ion trap holder 60 can be discharged through the cooling-gas discharge ports 64 of the ion trap holder 60. The amount of cooling gas reaching an area near the extraction electrode 34 is thereby reduced, so that a higher level of detection sensitivity can be achieved.
(2-2) Operation of TOFMS 4
The positive ions P introduced into the TOFMS 4 pass through the TOF ion inlet 401 and enter the flight space 40. In the flight space 40, due to the loop-flight electric field created within the flight space 40, the positive ions P fly in an orbit 403 in which the ions fly along the substantially elliptical loop orbit a plurality of times, with the loop orbit gradually changing its orientation counterclockwise as viewed from the positive side of the Y direction for each turn of the ions (see
The MT-TOF type of TOFMS 4 used in the present embodiment makes positive ions P fly in the loop orbit a plurality of times. Therefore, a longer flight distance can be obtained than in the case of making ions fly in a linear path. This advantageously leads to a higher level of time-of-flight resolving power, and consequently, a higher level of m/z resolving power. However, the MT-TOF type of TOFMS 4 has a drawback: if the positive ion P in the ion-capturing space 315 of the ion trap 3 has a high amount of kinetic energy at the moment of ejection, the positive ion P may possibly deviate from the intended loop orbit within the flight space 40 in the TOFMS 4 depending on the direction of its initial velocity, with the result that the ion fails to be detected by the ion detector 43, causing the detection intensity to be lower. By comparison, in the IT-TOFMS 1 according to the present embodiment, since the cooling gas supplied into the ion-capturing space 315 of the ion trap 3 is discharged to the outside of the ion trap holder 60 through the cooling-gas discharge ports 64 in the ion trap holder 60, a sufficient amount of cooling gas can be supplied without causing the molecules of the cooling gas to interfere with the flight of the positive ion P in the vicinity of the extraction electrode 34. Thus, the kinetic energy of the positive ion P within the ion-capturing space 315 can be sufficiently lowered, so that the positive ion P will be prevented from deviating from the intended loop orbit within the flight space 40 of the TOFMS 4 depending on the direction of its initial velocity. Consequently, the detection intensity in the ion detector 43 will be improved.
The present invention is not limited to the previously described embodiment; it can be modified in various forms. The modified examples described hereinafter are some of those various modified examples. There are also other possible variations.
In the previously described embodiment, the ion trap 3 (including the main electrode 31, ion introduction-side end electrode 32 and ion non-introduction-side end electrode 33) is fixed to the wall 61 made of an insulator. As another possibility, the wall of the ion trap holder may be made of a non-insulator (e.g., metal), and a holding part made of an insulator may be provided between the ion trap and the wall. This configuration can create electric insulation between the ion trap and the wall or other external elements while holding the ion trap with the ion trap holder.
In the previously described embodiment, a parallel-plate linear ion trap formed by a combination of plate electrodes is used as the ion trap 3. A linear ion trap formed by a combination of rod electrodes in place of the plate electrodes may also be used. Other commonly known types of ion traps used in IT-TOFMSs can also be used in the present invention.
In the previously described embodiment, a MT-TOFMS is used as the TOFMS 4, in place of which any commonly known type of TOFMS used in IT-TOFMSs may be used, such as a TOFMS with a linear flight space or a TOFMS which makes ions fly in a roughly round-trip path within the flight space by repelling the ions with a reflector.
The aforementioned modified examples of the ion trap 3 and those of the TOFMS 4 may be appropriately combined.
[Modes] A person skilled in the art can understand that the previously described illustrative embodiment is a specific example of the following modes of the present invention.
(Clause 1)
A mass spectrometer according to Clause 1 includes:
In the mass spectrometer according to Clause 1, the cooling gas introduced from the gas introduction tube into the ion-capturing space in the ion trap flows through the gap between the plurality of electrodes forming the ion-capturing space, as well as through the cooling-gas discharge port in the ion trap holder, into the space which is outside the ion trap holder yet inside the first chamber, from which the cooling gas is further discharged to the outside of the first chamber due to the evacuation of the inner space of the first chamber. This configuration reduces the amount of cooling gas flowing to the ion ejection port, so that the decrease in the detection intensity of the ions is reduced.
The wall may be made of an insulator or a non-insulator (e.g., metal). In the case of using the wall made of a non-insulator, it is preferable to create electric insulation between the ion trap and the wall (and other elements external to the ion trap holder) by providing a holding part made of an insulator between the ion trap and the wall.
(Clause 2)
In the mass spectrometer according to Clause 2, which is a specific form of the mass spectrometer according to Clause 1, the time-of-flight mass spectrometer is a multiturn time-of-flight mass spectrometer.
A multiturn time-of-flight mass spectrometer is a type of time-of-flight mass spectrometer which includes a set of electrodes configured to create an electric field within a flight space so as to make ions fly in a substantially identical loop orbit a plurality of times within the flight space, and an ion detector located at a position at which the ions arrive after flying in the loop orbit a plurality of times within the flight space.
Multiturn time-of-flight mass spectrometers are characterized in that a longer flight distance can be obtained than in the case of making ions fly in a linear path, so that a higher level of time-of-flight resolving power, and consequently, a higher level of m/z resolving power can be achieved. However, multiturn time-of-flight mass spectrometers generally have the problem that ions may deviate from the intended loop orbit depending on the direction of the initial velocity of the ions at the moment of ejection into the flight space, with the result that the ions fail to be detected by the ion detector, causing the detection intensity to be lower. By comparison, in the mass spectrometer according to Clause 2, since the cooling gas supplied into the ion-capturing space of the ion trap is discharged through the cooling-gas discharge ports and other areas to the outside of the first chamber, suppressing the amount of cooling gas flowing into the ion ejection port. Therefore, a sufficient amount of cooling gas can be supplied so as to sufficiently lower the kinetic energy of the ions within the ion-capturing space. Consequently, the initial velocity of the ions at the moment of ejection into the flight space in the multiturn time-of-flight mass spectrometer will be sufficiently lowered, so that the deviation of the ions from the intended loop orbit depending on the direction of their initial velocity will be prevented, and the detection intensity in the ion detector will be improved.
(Clause 3)
The mass spectrometer according to Clause 3 is a specific form of the mass spectrometer according to Clause 1 or 2 and further includes a differential pumping system configured to evacuate the vacuum container so that the degree of vacuum in the second chamber becomes higher than the degree of vacuum in the first chamber.
In the mass spectrometer according to Clause 3, the vacuum container is evacuated in a differential manner so that the degree of vacuum in the second chamber becomes higher than the degree of vacuum in the first chamber. Therefore, even if a portion of the cooling gas flows into an area near the ion ejection port, that cooling gas is quickly discharged to the outside of the vacuum container through the second chamber which has a higher degree of vacuum. Thus, the cooling gas is prevented from interfering with the ejection of the ions into the time-of-flight mass spectrometer.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2021-100229 | Jun 2021 | JP | national |
| Number | Name | Date | Kind |
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| 20040195502 | Hashimoto et al. | Oct 2004 | A1 |
| 20060289746 | Raznikov | Dec 2006 | A1 |
| 20210013022 | Tateishi | Jan 2021 | A1 |
| Number | Date | Country |
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| 2009-146905 | Jul 2009 | JP |
| 2021-015688 | Feb 2021 | JP |
| 2013057505 | Apr 2013 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 20220406588 A1 | Dec 2022 | US |
