JP4994119B2 - Tandem time-of-flight mass spectrometer - Google Patents

Description

  The present invention relates to a tandem time-of-flight mass spectrometer capable of switching between a single MS mode and a tandem MS / MS mode with a simple configuration.

  A time-of-flight mass spectrometer applies a certain amount of kinetic energy to a group of ions having various mass-to-charge ratios, and when the ions fly toward a detector separated by a predetermined distance, This is a device that measures the mass-to-charge ratio of ions by performing mass separation using the fact that smaller ions reach the detector faster (hereinafter referred to as MS measurement). Since the principle is simple, a low-cost device can be made with a simple configuration.

  In a time-of-flight mass spectrometer, since a higher-resolution mass spectrum can be obtained as the flight distance is longer, a device for extending only the flight distance without increasing the outer shape of the apparatus has been devised. A spiral orbit time-of-flight mass spectrometer recently developed is one example (Patent Document 1).

  In addition, after selecting desired ions (referred to as precursor ions) with the first time-of-flight mass spectrometer, the precursor ions are cleaved using an ion cleaving means such as a collision chamber filled with a low-pressure inert gas. A tandem time-of-flight mass spectrometer (hereinafter referred to as MS / MS measurement) that performs molecular structure analysis by analyzing a generated ion group using a second time-of-flight mass spectrometer is also known. A tandem time-of-flight mass spectrometer that significantly increases the selectivity of precursor ions has been developed by adopting the aforementioned spiral orbit time-of-flight mass spectrometer as the first time-of-flight mass spectrometer.

  FIG. 1 is a diagram showing an example of a tandem time-of-flight mass spectrometer that significantly increases the selectivity of precursor ions by adopting a spiral orbit time-of-flight mass spectrometer. (A) is the figure which looked at the apparatus to the Y direction, (b) is the figure seen from the arrow direction of (a) figure.

  In the figure, 19 is a matrix-assisted laser ionization (MALDI) ion source, 19a is a deflector, 15a is a first ion detector that detects ions (hereinafter referred to as ion detector 1), and 52 is passed through the ion detector 1. The ion gate that selects the precursor ions upon receipt of the generated ions, 53 is a collision chamber that cleaves the ions, 54 is a reflection field in which the cleaved ions are incident, and 15 is a first ion that detects the ions reflected by the reflection field 54. 2 detectors (hereinafter referred to as ion detectors 2). The ion detector 1 can move as shown in FIG. The operation of the apparatus configured as described above will be described as follows.

  The sample is ionized by the MALDI ion source 19, and kinetic energy is given to the ions by a pulse voltage to accelerate the sample. Ions emitted from the MALDI ion source 19 are adjusted in flight angle by a deflector 19a and are incident on a laminated sector electric field 17 made of a Mazda plate. The ions sequentially pass through the laminated sector electric fields 1 to 4 and make one round flight in an 8-shaped form. When returning to the original laminated sector electric field 1 after completing one turn, the position in the Y direction is shifted by one pitch in the Y direction compared to before the turn, so the ion trajectory moves in the Y direction each time the turn is repeated. Go.

  In the case of MS measurement, ions are detected using the ion detector 1 arranged on the orbit. In the case of MS / MS measurement, the ion detector 1 is removed from the ion trajectory, and the ions are caused to travel straight toward the ion gate 52. Ions can pass through the ion gate 52 when the ion gate voltage is off, and cannot pass when the ion gate voltage is on.

  The ion gate 52 is turned off only during the time when the precursor ion to be selected among the ions that have finished the last round passes, and a specific isotope peak of the precursor ion is selected. The selected precursor ions enter the collision chamber 53 and are cleaved by collision with a low-pressure inert gas filled inside. Precursor ions that have not been cleaved and product ions that have been cleaved pass through the reflected field 54 and are detected by the ion detector 2.

  Since the time for folding the reflection field 54 varies depending on the mass and kinetic energy of the ions, the precursor ions and the product ions of each cleavage path can be mass-separated. In this example, by selecting a specific isotope peak in advance (for example, a monoisotopic ion), it is possible to avoid complications due to isotopes, simplifying the interpretation of the mass spectrum, and mass spectrometry. Accuracy can be improved.

  The monoisotopic ion is an ion formed only with an isotope having the smallest mass of the contained element in a compound having a certain composition formula. Since the peak of monoisotopic ions on the mass spectrum contains only a single mass component, it is often used for database searches and the like.

  FIG. 2 is a diagram showing another example of a tandem time-of-flight mass spectrometer that significantly increases the selectivity of precursor ions by adopting a spiral orbit time-of-flight mass spectrometer. The same components as those in FIG. 1 are denoted by the same reference numerals as those in FIG. (A) is the figure which looked at the apparatus to the Y direction, (b) is the figure seen from the arrow direction of (a) figure.

  In the figure, 57 is a continuous ion source, 58 is an ion transport part constituted by an ion guide, 59 is a vertical acceleration part, and 60 is a deflector. Other configurations are the same as those in FIG. The operation of the apparatus configured as described above will be described as follows.

  The sample is ionized by the ion source 57, and the ions are transported to the vertical acceleration unit 59 by the ion transport unit 58. The ions emitted from the vertical accelerating unit 59 are adjusted in flight angle by the deflector 60 and are incident on the laminated sector electric field 17 made of a Mazda plate. The ions sequentially pass through the laminated sector electric fields 1 to 4 and make one round flight in an 8-shaped form. When returning to the original laminated sector electric field 1 after completing one turn, the position in the Y direction is shifted by one pitch in the Y direction compared to before the turn, so the ion trajectory moves in the Y direction each time the turn is repeated. Go.

  In the case of MS measurement, ions are detected using the ion detector 1 arranged on the orbit. In the case of MS / MS measurement, the ion detector 1 is removed from the ion trajectory, and the ions are caused to travel straight toward the ion gate 52. Ions can pass through the ion gate 52 when the ion gate voltage is off, and cannot pass when the ion gate voltage is on.

  The ion gate 52 is turned off only during the time when the precursor ion to be selected among the ions that have finished the last round passes, and a specific isotope peak of the precursor ion is selected. The selected precursor ions enter the collision chamber 53 and are cleaved by collision with a low-pressure inert gas filled inside. Precursor ions that have not been cleaved and product ions that have been cleaved pass through the reflected field 54 and are detected by the ion detector 2.

  Since the time for folding the reflection field 54 varies depending on the mass and kinetic energy of the ions, the precursor ions and the product ions of each cleavage path can be mass-separated. In this example, by selecting a specific isotope peak in advance (for example, a monoisotopic ion), it is possible to avoid complications due to isotopes, simplifying the interpretation of the mass spectrum, and mass spectrometry. Accuracy can be improved.

International Publication No. 2005/114702 Pamphlet, FIG. 14, FIG.

  By the way, when switching from actual MS measurement to MS / MS measurement, ion detection installed between the spiral orbit time-of-flight mass spectrometer (first MS) and the reflective time-of-flight mass spectrometer (second MS). Since the device 1 was moved from the flight trajectory of the ions out of the flight trajectory to enable the flight of ions from the first MS to the second MS, there was a problem that it took time to switch and the analysis time was long.

  Then, when the mass peaks are close, if switching takes time, the MS time axis may be shifted due to a change in the voltage over time, and the possibility of erroneously analyzing the adjacent ions may occur. In addition, in the case of liquid chromatograph mass spectrometry (LC / MS) and the like, ions that are eluted in a short time continuously take a long time to switch. It can be wasted.

  In view of the above points, an object of the present invention is to eliminate time and sample waste generated when switching between the single MS mode and the tandem MS / MS mode with a simple configuration.

In order to achieve this object, a tandem time-of-flight mass spectrometer according to the present invention includes:
In the tandem time-of-flight mass spectrometer that uses the spiral orbit type time -of- flight mass spectrometer as the first mass spectrometer and introduces ions from the first mass spectrometer into the second mass spectrometer to perform mass analysis,
An ion flight path within or ion detector disposed in the ion flight path near the ion pre SL ion detector disposed within the spiral track of the first mass spectrometer to deflect towards the deflector Prepared ,
The ions flying in the first mass spectrometer are sequentially detected by an ion detector in the ion flight trajectory, or ions are deflected toward the ion detector in the vicinity of the ion flight trajectory by the deflector and sequentially detected. A first mode;
Only the desired ions separated by the first mass spectrometer are subjected to mass analysis by the second mass spectrometer placed at the subsequent stage of the first mass spectrometer, and other ions are deflected by the deflector to be deflected. It is characterized in that it can be switched between a second mode in which detection is sequentially performed by the placed ion detector.

  Further, a cleaving means for cleaving ions is provided between the first mass spectrometer and the second mass spectrometer, and after cleaving desired ions separated by the first mass spectrometer, the second mass spectrometry is performed. It is characterized by mass spectrometry using an apparatus.

In addition, in the tandem time-of-flight mass spectrometer that uses the spiral orbital time -of- flight mass spectrometer as the first mass spectrometer and introduces ions from the first mass spectrometer into the second mass spectrometer to perform mass analysis,
And arranged deflectors in a spiral track of the first mass spectrometer to deflect the flight path of ions, located in the deflection destination, setting a cleavage means cleaves the deflected ions,
A normal measurement mode for sequentially detecting ions flying in the first mass spectrometer;
Only desired ions separated by the first mass spectrometer are deflected by the deflector, cleaved by the cleaving means, and switched to a tandem measurement mode in which mass analysis is performed by the second mass spectrometer at the subsequent stage. It is characterized by that.

  Further, the desired ion is a monoisotopic ion.

According to the tandem time-of-flight mass spectrometer of the present invention,
In the tandem time-of-flight mass spectrometer that uses the spiral orbit type time -of- flight mass spectrometer as the first mass spectrometer and introduces ions from the first mass spectrometer into the second mass spectrometer to perform mass analysis,
An ion flight path within or ion detector disposed in the ion flight path near the ion pre SL ion detector disposed within the spiral track of the first mass spectrometer to deflect towards the deflector Prepared ,
The ions flying in the first mass spectrometer are sequentially detected by an ion detector in the ion flight trajectory, or ions are deflected toward the ion detector in the vicinity of the ion flight trajectory by the deflector and sequentially detected. A first mode;
Only the desired ions separated by the first mass spectrometer are subjected to mass analysis by the second mass spectrometer placed at the subsequent stage of the first mass spectrometer, and other ions are deflected by the deflector to be deflected. Since the second mode of sequentially detecting with the placed ion detector is provided to be switchable,
With a simple configuration, it has become possible to eliminate time and sample waste that occur when switching between the single MS mode and the tandem MS / MS mode.

In addition, in the tandem time-of-flight mass spectrometer that uses the spiral orbital time -of- flight mass spectrometer as the first mass spectrometer and introduces ions from the first mass spectrometer into the second mass spectrometer to perform mass analysis,
And arranged deflectors in a spiral track of the first mass spectrometer to deflect the flight path of ions, located in the deflection destination, setting a cleavage means cleaves the deflected ions,
A normal measurement mode for sequentially detecting ions flying in the first mass spectrometer;
Only desired ions separated by the first mass spectrometer are deflected by the deflector, cleaved by the cleaving means, and switched to a tandem measurement mode in which mass analysis is performed by the second mass spectrometer at the subsequent stage. So
With a simple configuration, it has become possible to eliminate time and sample waste that occur when switching between the single MS mode and the tandem MS / MS mode.

  Embodiments of the present invention will be described below with reference to the drawings.

  FIG. 3 is a diagram showing an embodiment of a time-of-flight mass spectrometer according to the present invention. (A) is the figure which looked at the apparatus to the Y direction, (b) is the figure seen from the arrow direction of (a) figure.

  In the figure, 19 is a MALDI ion source, 19a is a first deflector, 100 is a second deflector that slightly deflects ions other than the desired precursor ions, and 15a is placed in front of the final orbit to detect ions. A first ion detector (hereinafter referred to as ion detector 1), 53 is a collision chamber for cleaving ions, 54 is a reflected field where the cleaved ions are incident, and 15 is detected by ions reflected from the reflected field 54 Detector (hereinafter referred to as ion detector 2). The ion detector 1 can move as shown in FIG. The operation of the apparatus configured as described above will be described as follows.

  The sample is ionized by the MALDI ion source 19, and kinetic energy is given to the ions by a pulse voltage to accelerate the sample. Ions emitted from the MALDI ion source 19 are adjusted in flight angle by a deflector 19a and are incident on a laminated sector electric field 17 made of a Mazda plate. The ions sequentially pass through the laminated sector electric fields 1 to 4 and make one round flight in an 8-shaped form. When returning to the original laminated sector electric field 1 after completing one turn, the position in the Y direction is shifted by one pitch in the Y direction compared to before the turn, so the ion trajectory moves in the Y direction each time the turn is repeated. Go.

  In the case of MS measurement, ions are detected by using the ion detector 1 disposed one round before the last round stage. In the case of MS / MS measurement, as shown in FIG. 4, the ion detector 1 is slightly shifted from the ion trajectory (a half pitch of one turn stage) in the Y direction, and a pulse voltage is applied to the second deflector 100. Then, ions other than the desired precursor ions are slightly deflected in the Y direction. As a result, ions other than the desired precursor ions fly in the final orbit slightly deviating in the Y direction, and sequentially enter the ion detector 1 that has been waiting in advance by moving about half a pitch in the Y direction.

  On the other hand, only desired precursor ions, to which no pulse voltage is applied by the second deflector 100, fly in the center of the final orbit, enter the collision chamber 53, and fill with the low-pressure inert gas. Cleavage on collision. Some precursor ions that have not been cleaved and product ions that have been cleaved pass through the reflected field 54 and are detected by the ion detector 2.

  Since the time for folding the reflection field 54 varies depending on the mass and kinetic energy of the ions, the precursor ions and the product ions of each cleavage path can be mass-separated. In this example, by selecting a specific isotope peak in advance (for example, a monoisotopic ion), it is possible to avoid complications due to isotopes, simplifying the interpretation of the mass spectrum, and mass spectrometry. Accuracy can be improved.

  In addition, since ions other than the desired precursor ions are also detected by the ion detector 1, all the ions can be observed simultaneously even in the tandem MS / MS mode. The waste that existed when switching between the mode and the tandem MS / MS mode can be eliminated.

  In this embodiment, the spiral orbit time-of-flight mass spectrometer is used as the first mass spectrometer. However, the first mass spectrometer can be any high-resolution time-of-flight mass spectrometer capable of separating isotope peaks. Well, not limited to spiral orbital ones.

  In the present embodiment, the ion detector 1 is moved. However, the ion detector 1 is fixed to the ion deflection destination, and not only in the tandem MS / MS mode but also in the single MS mode. The ions may be detected by being deflected toward the ion detector 1 by the second deflector 100.

  FIG. 5 is a diagram showing another embodiment of the time-of-flight mass spectrometer according to the present invention. The same components as those in FIG. 1 are denoted by the same reference numerals as those in FIG. (A) is the figure which looked at the apparatus to the Y direction, (b) is the figure seen from the arrow direction of (a) figure.

  In the figure, 57 is a continuous ion source, 58 is an ion transport part constituted by an ion guide, 59 is a vertical acceleration part, and 60 is a deflector. Other configurations are the same as those in FIG. The operation of the apparatus configured as described above will be described as follows.

  The sample is ionized by the ion source 57, and the ions are transported to the vertical acceleration unit 59 by the ion transport unit 58. The ions emitted from the vertical accelerating unit 59 are adjusted in flight angle by the deflector 60 and are incident on the laminated sector electric field 17 made of a Mazda plate. The ions sequentially pass through the laminated sector electric fields 1 to 4 and make one round flight in an 8-shaped form. When returning to the original laminated sector electric field 1 after completing one turn, the position in the Y direction is shifted by one pitch in the Y direction compared to before the turn, so the ion trajectory moves in the Y direction each time the turn is repeated. Go.

  In the case of MS measurement, ions are detected by using the ion detector 1 disposed one round before the last round stage. In the case of MS / MS measurement, as shown in FIG. 4, the ion detector 1 is slightly shifted from the ion trajectory (a half pitch of one turn stage) in the Y direction, and a pulse voltage is applied to the second deflector 100. Then, ions other than the desired precursor ions are slightly deflected in the Y direction. As a result, ions other than the desired precursor ions fly in the final orbit slightly deviating in the Y direction, and sequentially enter the ion detector 1 that has been waiting in advance by moving about half a pitch in the Y direction.

  On the other hand, only desired precursor ions, to which no pulse voltage is applied by the second deflector 100, fly in the center of the final orbit, enter the collision chamber 53, and fill with the low-pressure inert gas. Cleavage on collision. Some precursor ions that have not been cleaved and product ions that have been cleaved pass through the reflected field 54 and are detected by the ion detector 2.

  Since the time for folding the reflection field 54 varies depending on the mass and kinetic energy of the ions, the precursor ions and the product ions of each cleavage path can be mass-separated. In this example, by selecting a specific isotope peak in advance (for example, a monoisotopic ion), it is possible to avoid complications due to isotopes, simplifying the interpretation of the mass spectrum, and mass spectrometry. Accuracy can be improved.

  In addition, since ions other than the desired precursor ions are also detected by the ion detector 1, all the ions can be observed simultaneously even in the tandem MS / MS mode. The waste that existed when switching between the mode and the tandem MS / MS mode can be eliminated.

  In this embodiment, the spiral orbit time-of-flight mass spectrometer is used as the first mass spectrometer. However, the first mass spectrometer can be any high-resolution time-of-flight mass spectrometer capable of separating isotope peaks. Well, not limited to spiral orbital ones.

  In the present embodiment, the ion detector 1 is moved. However, the ion detector 1 is fixed to the ion deflection destination, and not only in the tandem MS / MS mode but also in the single MS mode. The ions may be detected by being deflected toward the ion detector 1 by the second deflector 100.

  Various modifications can be made to the present invention. For example, in the previous embodiment, ions other than the desired ions are deflected by the deflector 100, but conversely, only desired ions are deflected by the deflector 100 as shown in FIG. A configuration may be adopted in which ions are cleaved by a cleaving means such as the collision chamber 53 and MS / MS measurement is performed by a second mass spectrometer (not shown) in the subsequent stage. In this case, the ion group that has not been deflected by the deflector 100 is subjected to normal measurement, and is directly detected as an MS spectrum by the ion detector of the first mass spectrometer.

  Various modifications can also be made to the first mass spectrometer. For example, the first MS spectroscopic part constituting the spiral trajectory does not necessarily need to be constituted by a Mazda plate. A Mazda plate and other configuration examples are described in Patent Document 1.

  In addition, the first MS spectroscopic part constituting the spiral trajectory does not necessarily need to be an 8-shaped. You may make it circulate circularly or elliptically.

  In addition, the second deflector does not necessarily have to be placed just before one turn of the ion detector 1. It may be before 1/2 turn or before 1/4 turn.

  Further, the moving direction of the ion detector 1 is not necessarily the Y direction. For example, the reverse Y direction may be used.

  Further, the ion detector 1 does not move, but a hole is formed in the center, and ions other than the desired precursor ion are detected in a portion around the hole by the deflection by the second deflector. Anyway.

  Further, the second time-of-flight mass spectrometer that analyzes cleavage ions does not necessarily have to have a reflection field.

  In addition to the collision chamber using a low-pressure inert gas, laser beam irradiation or the like can be used as the ion cleavage means.

  In addition to the MALDI ion source and the vertical acceleration ion source, a pulse ion source that discharges ions in a pulse form from an ion trap can be used as the ion generation source (ion source).

  It can be widely used for mass spectrometry measurement.

It is a figure which shows an example of the conventional tandem time-of-flight mass spectrometer. It is a figure which shows another example of the conventional tandem time-of-flight mass spectrometer. It is a figure which shows one Example of the tandem time-of-flight mass spectrometer concerning this invention. It is an enlarged view which shows the principal part of this invention. It is a figure which shows another Example of the tandem time-of-flight mass spectrometer concerning this invention.

Explanation of symbols

15: Second ion detector, 15a: First ion detector, 17: Stacked sector electric field, 19: MALDI ion source, 19a: Deflector, 52: Ion gate, 53: Collision chamber, 54: Reflection field, 57 : Continuous ion source, 58: ion transport unit, 59: vertical acceleration unit, 60: deflector, 100: second deflector

Claims (4)

In the tandem time-of-flight mass spectrometer that uses the spiral orbit type time -of- flight mass spectrometer as the first mass spectrometer and introduces ions from the first mass spectrometer into the second mass spectrometer to perform mass analysis,
An ion flight path within or ion detector disposed in the ion flight path near the ion pre SL ion detector disposed within the spiral track of the first mass spectrometer to deflect towards the deflector Prepared ,
The ions flying in the first mass spectrometer are sequentially detected by an ion detector in the ion flight trajectory, or ions are deflected toward the ion detector in the vicinity of the ion flight trajectory by the deflector and sequentially detected. A first mode;
Only the desired ions separated by the first mass spectrometer are subjected to mass analysis by the second mass spectrometer placed at the subsequent stage of the first mass spectrometer, and other ions are deflected by the deflector to be deflected. A tandem time-of-flight mass spectrometer characterized in that it can be switched between a second mode in which detection is sequentially performed by the ion detector placed. A cleaving means for cleaving ions is provided between the first mass spectrometer and the second mass spectrometer, and after cleaving desired ions separated by the first mass spectrometer, the second mass spectrometer The tandem time-of-flight mass spectrometer according to claim 1, wherein mass spectrometry is performed. In the tandem time-of-flight mass spectrometer that uses the spiral orbit type time -of- flight mass spectrometer as the first mass spectrometer and introduces ions from the first mass spectrometer into the second mass spectrometer to perform mass analysis,
And arranged deflectors in a spiral track of the first mass spectrometer to deflect the flight path of ions, located in the deflection destination, setting a cleavage means cleaves the deflected ions,
A normal measurement mode for sequentially detecting ions flying in the first mass spectrometer;
Only desired ions separated by the first mass spectrometer are deflected by the deflector, cleaved by the cleaving means, and switched to a tandem measurement mode in which mass analysis is performed by the second mass spectrometer at the subsequent stage. A tandem time-of-flight mass spectrometer. 4. The tandem time-of-flight mass spectrometer according to claim 1, wherein the desired ion is a monoisotopic ion.

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