JP5303286B2 - Mass spectrometer - Google Patents

Description

  The present invention relates to a mass spectrometer having high ion dissociation performance.

  When using a mass spectrometer for applications such as proteome analysis, MS / MS analysis that performs mass analysis in multiple stages is important. MS / MS analysis is effective for identifying molecular species because the structure information of precursor ions can be obtained from the pattern of fragment ions obtained by dissociating precursor ions.

  The apparatus configuration described in Non-Patent Document 1 enables electron capture dissociation (ECD) by efficiently trapping ions and electrons in a strong magnetic field of several Tesla or more. ECD is a method in which precursor ions are dissociated by reaction between precursor ions and electrons. In ECD, a specific site in the amino acid main chain sequence is selectively dissociated without depending on the structure of the precursor ion. Therefore, even in the case of a biomolecule having a modified side chain, since the side chain can be retained without dissociation, important information as to which amino acid portion the side chain was bound to can be obtained.

  The apparatus configuration described in Patent Document 1 enables ECD in the RF ion trap by applying a weak magnetic field of several hundred mTesla or less in the axial direction of a small RF ion trap.

  In the apparatus configuration described in Non-Patent Document 2, neutral gas is introduced into the ECD reaction section in a pulsed manner to excite ions to increase the internal energy of the ions and improve the ion dissociation efficiency.

  The apparatus configuration described in Patent Document 2 enables ECD in an ion trap capable of axial excitation of ions. In addition, ECD and collision-induced dissociation (CID) can be used in combination. CID is a method in which ions are excited and dissociated by applying energy to precursor ions and colliding with a neutral gas. For this reason, CID dissociates at a portion where the molecule is easily cut, so that a portion that is not dissociated by ECD can also be cleaved. By using ECD and CID together, complementary fragment ion information can be obtained, and a more detailed structure can be identified.

In the apparatus configuration described in Non-Patent Document 3, electron transfer dissociation (ETD) is performed in a state where ions are excited to improve dissociation efficiency. ETD generates unstable negative ions and reacts with negative ions and precursor ions to cause dissociation similar to ECD, but this method is completely different from ECD.
In the apparatus configuration described in Patent Document 3, since the introduced ions and electrons move in the opposite direction at a certain point, the efficiency of ECD is improved by utilizing the overlap region of the ion and electron folding point. .

JP2005-235412 JP2007-207689 US Patent 6919562

Analytical Chemistry, 1999, vol.71, p4431-4436 Analytical Chemistry, 2000, vol.72, p4778-4784 Analytical Chemistry, 2007, vol.79, p477-485

  The apparatus configuration described in Non-Patent Document 1 is expensive and large because a strong magnetic field of several Tesla or more is required.

  Although the apparatus configuration described in Patent Document 1 enables ECD in a small RF ion trap, dissociation efficiency cannot be improved by exciting and exciting ions.

  In the apparatus configuration described in Non-Patent Document 2, neutral gas is introduced into the ECD reaction section in a pulsed manner to excite ions to increase the internal energy of ions and improve ion dissociation efficiency. Ion cannot be excited.

  In the apparatus configuration described in Patent Document 2, it is possible to increase the amount of information of fragment ions by using ECD and CID together, but this is not a technique for improving the dissociation efficiency of ECD.

  In the apparatus configuration described in Non-Patent Document 3, electron transfer dissociation (ETD) is performed in a state where ions are excited in the radial direction, and dissociation efficiency is improved. If ions are dissociated in a state where the ions are excited in the radial direction and vibrated in the radial direction, fragment ions having a lower mass than the precursor ions cannot be detected.

  The device configuration described in Patent Document 3 is a technology that uses ions and electrons that are difficult to be stably trapped simultaneously in an ion trap or the like as a ECD reaction region using a minute region where the stability conditions of each other overlap. However, dissociation efficiency cannot be improved by exciting and exciting ions.

  In order to solve the above-described problems, an ion dissociation apparatus according to the present invention includes a multipole rod electrode to which a high-frequency voltage is applied, an ion trap including an electric field forming unit that forms an electric field in the axial direction of the multipole rod electrode, and an ion trap. A voltage source is applied to the electric field forming means so that the ion oscillates in the axial direction of the multipole rod electrode. And a controller that introduces particles into the ion trap.

  A mass spectrometer of the present invention includes an ion source, the above ion dissociation unit that dissociates ions generated by the ion source, and a mass analysis unit that performs mass analysis of dissociated ions generated by the ion dissociation unit. It is characterized by that.

  The mass spectrometric method of the present invention includes a step of generating ions, a step of introducing the generated ions into a linear ion trap, a step of storing the introduced ions in a linear ion trap, and a predetermined number of stored ions. A step of vibrating the first ion of m / z in the axial direction of the linear ion trap and a particle that changes the charge of the ion in a state where the first ion is vibrated in the axial direction of the linear ion trap are used as the linear ion trap. And a step of dissociating ions by a reaction between the first ions and the particles, and a step of discharging the dissociated ions from the ion trap and detecting them by mass separation.

According to the present invention, ECD and ETD can be performed with high ion energy, and ion dissociation efficiency is improved. Furthermore, the detection efficiency of low mass fragment ions is improved.

Device configuration diagram of Embodiment 1 Ion dissociation part of Example 1 Voltage application method of Example 1 Illustration of the effect of this method Explanatory diagram of problems of conventional example Voltage application method of Example 2 Voltage application method of Example 3 Voltage application method of Example 4 Ion dissociation part of Example 5 Ion dissociation part of Example 6 Voltage application method of Example 6 Configuration diagram of rod electrode of Example 6 Ion dissociation part of Example 7

  In the first embodiment, a method of performing ECD in a state where a voltage is applied to an electrode having a shape divided into two or more in the axial direction of the ion dissociation part and ions are vibrated in the axial direction of the ion dissociation part will be described.

Example 1
FIG. 1 is a configuration diagram of a mass spectrometer to which the present method is applied.

  The ions 2 generated by the ion source 1 are divided into a first differential exhaust chamber 3 held at a pressure of about 100 to 500 Pa and a second differential exhaust chamber 4 held at a pressure of about 0.1 to 3 Pa. It passes through the ion transport section 5 disposed therein and is introduced into the ion separation section 6 maintained at a pressure of 0.1 Pa or less. The ion transport part 5 uses a component having a convergence effect such as a multipole electrode in which a plurality of rod-shaped electrodes are arranged or a lens electrode in which a plurality of cylindrical electrodes are arranged in a row. In the ion separation unit 6, ions are separated in terms of time or position for each mass-to-charge ratio (m / z), such as a quadrupole filter, an ion trap, or a time-of-flight mass spectrometer. Use possible parts. The ion separator 6 separates only the precursor ions 7 to be subjected to MS / MS analysis from the ions 2 generated by the ion source 1. The precursor ions 7 are introduced into the ion dissociation part 8 and dissociated. The dissociated fragment ions 9 are introduced into the mass analyzer 10 maintained at a pressure of 0.1 Pa or less. The mass analyzer 10 is a component capable of separating ions in terms of time or position at every m / z, such as a quadrupole filter, ion trap, or time-of-flight mass spectrometer. Is used. The fragment ions 11 separated in time or position are detected by a detector 12. For the detector 12, an electron multiplier, a multi-channel plate (MCP) or the like is used.

  Next, the structure of the ion dissociation part will be described in detail with reference to FIG.

  The ion dissociation part 8 is divided into two rod electrodes 17-20 and two in the axial direction in a space 16 surrounded by a cylindrical magnet 13, an entrance electrode 14, and an exit electrode 15. An axial electric field forming electrode 21-28 is disposed, and an electron source 30 capable of irradiating electrons along the central axis 29 is disposed. A lens electrode 62 is disposed between the electron source 30 and the entrance electrode 14. As the magnet 13, a permanent magnet such as ferrite or neodymium or an electromagnet is used. A magnet 13 forms a magnetic field along the central axis 29 of the ion dissociation part 8. Since the space 16 in the ion dissociation part 8 is maintained at about 3 Pa or less with a neutral gas such as helium, argon or nitrogen, actually, a pipe for introducing a neutral gas, a magnet 13 and an inlet electrode 14 or A part for hermetically sealing with the outlet electrode 15 is necessary, but is not shown in FIG. High frequency voltages with opposite phases are alternately applied to the four rod electrodes 17-20. The high-frequency voltage has a frequency of about several hundred kHz to 1 MHz and a maximum voltage amplitude value of about several kV. The eight axial electric field forming electrodes 21-28 include a front axial electric field forming electrode 21-24 and a rear axial electric field forming electrode 25-28. The electron source 30 can be disposed on the central axis serving as an ion trajectory by using the thin filament-shaped one shown in FIG. Since the electrons irradiated from the electron source 30 are introduced along the magnetic field formed on the central axis 29, they are not easily affected by the high-frequency voltage applied to the four rod electrodes 17-20. Furthermore, a power source 35 capable of applying DC voltages 31, 32 and variable voltages 33, 34 to the front axial field forming electrode 21-24 and the rear axial field forming electrode 25-28, respectively, is provided.

  In the ion dissociation part 8 shown in FIG. 2, first, precursor ions 7 introduced from the inlet electrode 14 are caused by a radial trapping potential formed by a high-frequency voltage applied to the four rod electrodes 17-20. Accumulation is performed along the central axis 9 of the ion dissociation part 8. At this time, by applying a voltage having the same polarity as the precursor ions 7 accumulated in the entrance electrode 14 and the exit electrode 15 (a positive voltage if positive ions), the precursor ions 7 are excluded outside the ion dissociation part 8. Can be prevented. Next, the precursor ions 7 are dissociated by irradiating the precursor ions 7 with electrons generated by the electron source 30 (ECD). Finally, the fragment ions 9 generated by the dissociation are discharged from the outlet electrode 15.

  Next, a method of applying a voltage to the eight axial electric field forming electrodes when performing ion dissociation at the ion dissociation portion will be described in detail with reference to FIG.

  FIG. 3 shows a DC voltage 31 and a variable voltage 33 applied to the front axial field forming electrode 21-24 by the power source 35, and a DC voltage 32 applied to the rear axial field forming electrode 25-28. And the fluctuating voltage 34. As shown in FIG. 2, the eight axial electric field forming electrodes 21-28 are inclined with respect to the central axis 29, so that the front axial electric field forming electrodes 21-24 and the rear An electrostatic potential can be formed on the axis by applying DC voltages 31 and 32 to the axial electric field forming electrodes 25 to 28 on the side. The electrostatic potential is an axial trapping potential. The DC voltages 31 and 32 can each be applied with a voltage about 100 V higher than the offset voltage of the four rod electrodes 17-20. The DC voltages 31 and 32 correspond to the depth of the electrostatic potential. Further, opposite phase fluctuation voltages 33 and 34 are applied to the front axial field forming electrode 21-24 and the rear axial field forming electrode 25-28, respectively. As the fluctuation voltages 33 and 34 in the example of FIG. 3, a sinusoidal AC voltage having a frequency of about several hundred kHz and a maximum voltage amplitude value of about several tens of volts is used. By applying the variable voltages 33 and 34, m / z ions corresponding to the frequency vibrate in the axial direction in the electrostatic potential formed on the axis. At this time, since the electrostatic potential has a depth, ions cannot overcome the potential, so that the oscillation can be repeated in the electrostatic potential. The oscillated ions are repeatedly excited to collide with neutral gas molecules in the ion dissociation part 8, and the internal energy of the ions is increased. Dissociation efficiency is improved by performing ECD by irradiating electrons from the electron source 30 while the internal energy of ions is high.

  Next, the state of the ion trajectory when ions are vibrated in the axial direction in the ion dissociation portion according to this method will be described with reference to FIG.

  By oscillating ions in the axial direction by this method, an ion distribution 36 in the axial direction along the central axis 29 of the ion dissociation part 8 is obtained as shown in FIG. Since electrons are irradiated from the electron source 30 along the central axis 29 so as to overlap the ion distribution 36 in the axial direction, the reaction efficiency between ions and electrons is increased. This method can not only increase the internal energy of ions by excitation, but also improve the reaction efficiency between ions and electrons. Therefore, the dissociation efficiency of ECD is improved.

  Next, the state of the ion trajectory in the conventional method in which ions are vibrated in the radial direction in the ion dissociation portion will be described with reference to FIG.

  In order to vibrate ions in the radial direction, it is possible to apply an alternating voltage between the rod electrodes 17 and 19 facing each other in the radial direction or between the rod electrodes 17 and 20 in an auxiliary manner. Alternatively, it is also possible to apply an alternating voltage between the axial electric field forming electrodes opposed to each other in the radial direction among the eight axial electric field forming electrodes 21-28. By oscillating the ions in the radial direction, a radial ion distribution 37 perpendicular to the central axis 29 of the ion dissociation part 8 is obtained as shown in FIG. When ECD is performed by the conventional radial vibration method, electrons are irradiated from the electron source 30 along the central axis 29 so as to be orthogonal to the radial ion distribution 37, so that the reaction efficiency between ions and electrons is improved. Compared to FIG.

  From the comparison between FIG. 4 and FIG. 5, the method of performing ECD by irradiating electrons on the central axis in the state where the ions are vibrated in the axial direction in the ion dissociation portion according to the present invention is effective in improving the ECD dissociation efficiency There is. In addition, when ions are vibrated in the radial direction in the ion dissociation part, the ions are excited in the trap potential formed by the high-frequency voltage applied to the rod electrode 17-20, so the high-frequency voltage must be set high. The effect makes it difficult to detect low mass ions. On the other hand, when ions are vibrated in the axial direction in the ion dissociation part, the ions are excited in the axial electrostatic potential formed by the axial electric field forming electrodes 21-28, so it is necessary to set the high frequency voltage high. As a result, low mass ions can be detected.

(Example 2)
In Example 2, when performing ion dissociation at the ion dissociation part, a method in which a variable voltage is not applied to the front axial electric field forming electrode will be described in detail.

  FIG. 6 shows a DC voltage 31 and a fluctuation voltage 33 applied to the front axial field forming electrode 21-24 by the power source 35, and a DC voltage 32 applied to the rear axial field forming electrode 25-28. And the fluctuating voltage 34. DC voltage 31, 32 applied to the front axial electric field forming electrode 21-24 and the rear axial electric field forming electrode 25-28, and a variable voltage 34 applied to the rear axial electric field forming electrode 25-28. Is the same as FIG. 3, but in FIG. 6, the voltage amplitude value of the variable voltage 33 applied to the front axial electric field forming electrode 21-24 is set to zero. Even in this state, the ions vibrate in the axial direction due to the fluctuation voltage 34 of the rear axial electric field forming electrodes 25-28. By not applying the fluctuation voltage 33 applied to the front axial direction electric field forming electrode 21-24, there is an effect of suppressing disturbance of the electric field in the vicinity of the electron source 30. By suppressing the disturbance of the electric field, the efficiency of introducing electrons is improved and the dissociation efficiency of ECD is improved.

(Example 3)
In Example 3, when performing ion dissociation at the ion dissociation part, a method of applying a variable voltage of a rectangular wave to the rear axial electric field forming electrode will be described in detail.

  FIG. 7 shows a DC voltage 31 and a variable voltage 33 applied to the front axial field forming electrode 21-24 by the power source 35, and a DC voltage 32 applied to the rear axial field forming electrode 25-28. The fluctuation voltage 34 and the irradiation sequence 63 of electrons into the ion dissociation part 8 are shown. Regarding the DC voltages 31, 32 applied to the front axial field forming electrode 21-24 and the rear axial field forming electrode 25-28, and the variable voltage 33 applied to the front axial field forming electrode 25-28. As in FIG. 6, the fluctuating current voltage 34 applied to the rear axial electric field forming electrodes 25-28 is controlled by a rectangular wave having a pulse waveform. Due to the pulse-like fluctuation of the fluctuation voltage 34, ions can be vibrated in the axial direction. In the system shown in FIG. 7, the disturbance of the electric field during electron irradiation can be further suppressed by turning on the electron irradiation sequence 63 at the timing when the pulse waveform is 0V. When the electron irradiation sequence 63 is on, a negative voltage is applied to the lens electrode 62 to introduce electrons into the ion dissociation unit 8. When the electron irradiation sequence 63 is off, a positive voltage is applied to the lens electrode 62 to prevent electrons from being introduced into the ion dissociation part 8.

Example 4
In Example 4, it is applied to the axial electric field forming electrode divided into two or more in the axial direction of the ion dissociation part, and the ions are vibrated in the axial direction of the ion dissociation part, and the ions are also vibrated in the radial direction. A method for performing ECD in a state in which this is performed will be described.

  Referring to FIG. 8, a detailed description will be given of a method of applying a voltage to the eight axial electric field forming electrodes when ion dissociation is performed by vibrating ions in the axial direction and the radial direction at the ion dissociation part. FIG. 8 shows a DC voltage 31 and a variable voltage 33 applied to the front axial field forming electrode 21-24 by the power source 35, and a DC voltage 32 applied to the rear axial field forming electrode 25-28. And the fluctuating voltage 34. The DC voltages 31 and 32 and the fluctuation voltages 33 and 34 applied to the front axial field forming electrode 21-24 and the rear axial field forming electrode 25-28 are the same as those in FIG. By applying the variable voltages 33 and 34, m / z ions corresponding to the frequency vibrate in the axial direction in the electrostatic potential formed on the axis. Furthermore, a trap formed by the four rod electrodes 17-20 by applying an auxiliary AC voltage 38 between the rod electrodes 17, 19 facing each other in the radial direction of the ion dissociation part 8, or between the rod electrodes 17, 20. Ions vibrate radially in the potential. By setting the frequency of the fluctuation voltages 33 and 34 to a frequency corresponding to m / z of the precursor ion 7 to be subjected to MS / MS analysis, only the precursor ion 7 vibrates in the axial direction. By setting the frequency of the auxiliary AC voltage 38 to a frequency that does not correspond to m / z of the precursor ion 7, it is possible to prevent the precursor ion 7 from vibrating in the radial direction. Furthermore, by making the frequency of the auxiliary AC voltage 38 a composite wave having a frequency other than the frequency corresponding to the m / z of the precursor ion 7, all ions of m / z other than the precursor ion 7 are vibrated in the radial direction. You can also.

  By this method, the fragment ions 9 generated by dissociating the precursor ions 7 by ECD are different in m / z from the precursor ions 7, and thus vibrate in the radial direction without vibrating in the axial direction. As a result, the fragment ions 9 behave similarly to the radial ion distribution 37 shown in FIG. Therefore, the probability that the fragment ions 9 react with the electrons irradiated along the central axis 29 is reduced, and secondary dissociation in which the fragment ions 9 are further dissociated can be prevented.

(Example 5)
In the fifth embodiment, a method for performing ECD in a state where a voltage is applied to an electrode having a shape inclined with respect to the axial direction of the ion dissociation part and ions are vibrated in the axial direction of the ion dissociation part will be described. The inclined axial electric field forming electrode of Example 5 is not configured to be divided into two in the axial direction as shown in FIGS.

The structure of the ion dissociation part will be described in detail with reference to FIG.
The ion dissociation unit 8 includes four rod electrodes 17-20 and four axial electric field forming electrodes 25-28 in a space 16 surrounded by a cylindrical magnet 13, an entrance electrode 14, and an exit electrode 15. Further, an electron source 30 that can irradiate electrons along the central axis 29 is arranged. A lens electrode 62 is disposed between the electron source 30 and the entrance electrode 14. As the magnet 13, a permanent magnet such as ferrite or neodymium or an electromagnet is used. A magnet 13 forms a magnetic field along the central axis 29 of the ion dissociation part 8. Since the space 16 in the ion dissociation part 8 is maintained at about 3 Pa or less with a neutral gas such as helium, argon or nitrogen, actually, a pipe for introducing a neutral gas, a magnet 13 and an inlet electrode 14 or A part for hermetically sealing with the outlet electrode 15 is necessary, but is not shown in FIG. High frequency voltages with opposite phases are alternately applied to the four rod electrodes 17-20. The high-frequency voltage has a frequency of about several hundred kHz to 1 MHz and a maximum voltage amplitude value of about several kV. The electron source 30 can be disposed on the central axis serving as an ion trajectory by using the thin filament-shaped one shown in FIG. Since the electrons irradiated from the electron source 30 are introduced along the magnetic field formed on the central axis 29, they are not easily affected by the high-frequency voltage applied to the four rod electrodes 17-20. Furthermore, a power source 35 capable of applying a DC voltage 32 and a variable voltage 34 to the axial electric field forming electrodes 25-28 is provided. In the ion dissociation part 8 of FIG. 9, since there is no front axial electric field forming electrode 21-24 as shown in FIG. 2, there is an effect of suppressing disturbance of the electric field in the vicinity of the electron source 30. Further, by applying a voltage having the same polarity as the precursor ions 7 (positive voltage if positive ions) to the entrance electrode 14, it is possible to prevent the precursor ions 7 from being excluded outside the ion dissociation part 8. The entrance electrode 14 can perform the same role as that of the front-side axial electric field forming electrode 21-24 to which no fluctuating voltage is applied in the second and third embodiments.

  The method of applying a voltage to the axial electric field forming electrode when performing ion dissociation at the ion dissociation portion is a direct current applied to the front axial electric field forming electrode 21-24 in FIGS. 3, 6, 7, and 8. This is the same as that excluding the voltage 31 and the variable voltage 33.

(Example 6)
In Example 6, in an ion dissociation part having a multiple rod electrode composed of a plurality of rod electrodes, the rod electrode is composed of a plurality of rods having a resistor layer on the surface of the insulator, and voltage is applied to both ends of the rod electrode. A method of applying ECD and performing ECD in a state where ions are vibrated in the axial direction of the ion dissociation portion will be described. In the configuration of Example 6, the structure of the ion dissociation portion in Example 6 is described with reference to FIG.

  The ion dissociation part 8 has a multipole rod electrode 39 in a space 16 surrounded by a cylindrical magnet 13, an entrance electrode 14 and an exit electrode 15, and can irradiate electrons along a central axis 29. A possible electron source 30 is arranged. A lens electrode 62 is disposed between the electron source 30 and the entrance electrode 14. As the magnet 13, a permanent magnet such as ferrite or neodymium or an electromagnet is used. A magnet 13 forms a magnetic field along the central axis 29 of the ion dissociation part 8. Since the space 16 in the ion dissociation part 8 is maintained at about 3 Pa or less with a neutral gas such as helium, argon or nitrogen, actually, a pipe for introducing a neutral gas, a magnet 13 and an inlet electrode 14 or A part for hermetically sealing the outlet electrode 15 is necessary, but is not shown in FIG. The electron source 30 can be arranged on the central axis that becomes the trajectory of ions by using the thin filament-shaped one shown in FIG.

  Next, the configuration of the multipole rod electrode and the power supply unit of Example 6 and the voltage application method when performing ion dissociation at the ion dissociation unit will be described in detail with reference to FIG.

  The multipole rod electrode 39 is composed of six rod electrodes 40-45 and twelve terminal portions 46-57. The twelve terminal portions 46-57 are classified into six front terminal portions 46-51 and six rear terminal portions 52-57. The power source 35 includes a resonance coil 58, an RF amplifier 59, and the like, and can apply a high-frequency voltage having an opposite phase to the multipole rod electrode 39 alternately. The high-frequency voltage has a frequency of about several hundred kHz to 1 MHz and a maximum voltage amplitude value of about several kV. Further, the power source 35 can apply the DC voltages 31 and 32 and the fluctuation voltages 33 and 34 to the twelve terminal portions 46-57. The DC voltages 31 and 32 can each be applied with a voltage about 100 V higher than the offset voltage of the four rod electrodes 40-45.

  The detailed structure of the rod electrodes 40-45 is shown in FIG. The rod electrodes 40-45 have a resistor layer 61 on the surface of an insulating rod 60 such as ceramics. The resistor layer 61 can be formed by vapor-depositing a film such as tantalum nitride, or by applying a substance obtained by mixing a powdery conductive material with a resin material. In Example 6, a phenol resin paste mixed with carbon powder was applied to an insulating rod 60 made of alumina, and heated and cured at 150 ° C. to form a resistor layer 61. The resistor layer 61 is also formed on the end face of the insulating rod 60, and the metal terminal portions 46-57 are in contact with each other. By forming the resistor layer 61, a potential difference can be applied between the front terminal portion 46-51 and the rear terminal portion 52-57. In the configuration shown in FIG. 11, the high-frequency voltage can be applied in a state where the voltage values of the DC voltages 31 and 32 are the same as the potential difference. If the resistance value of the resistor layer 61 is small, an overcurrent flows and the burden on the power supply 35 increases. On the other hand, when the resistance value is large, the phase shift of the high-frequency voltage is large between the front side and the rear side of the rod electrodes 40-45. Therefore, in Example 6, the film thickness of the resistor layer 61 was adjusted so that the resistance value was about 1 kΩ per one between the front side and the rear side of the rod electrodes 40-45. The resistance value can be adjusted by adjusting the mixing ratio of the conductive powder as well as adjusting the film thickness. Since a potential is formed in the axial direction of the ion dissociation portion 8 due to the potential difference between the front side and the rear side, the ions can be vibrated in the axial direction by applying the variable voltages 33 and 34. The oscillated ions are repeatedly excited to collide with neutral gas molecules in the ion dissociation part 8, and the internal energy of the ions is increased. Dissociation efficiency is improved by performing ECD by irradiating electrons from the electron source 30 while the internal energy of ions is high.

  10, 11, and 12 are controlled by the control method as described in FIGS. 3, 6, 7, and 8, similarly to the device configurations shown in FIGS. 1 and 2. By doing so, the same effect can be obtained.

(Example 7)
In the seventh embodiment, a method of performing ETD in a state where a voltage is applied to an electrode having a shape divided into two or more in the axial direction of the ion dissociation part and ions are vibrated in the axial direction of the ion dissociation part will be described.

  Next, the structure of the ion dissociation part will be described in detail with reference to FIG.

  The ion dissociation part 8 is divided into two rod electrodes 17-20 and two in the axial direction in a space 16 surrounded by a cylindrical case 64, an inlet electrode 14 and an outlet electrode 15. A plurality of axial electric field forming electrodes 21-28 are arranged. The four rod electrodes 17-20 may be divided into a plurality of shapes in the axial direction so that precursor ions 7 having positive charges and negative ions having negative charges can be efficiently trapped. By disposing the negative ion source 65 and the negative ion introduction part 66, negative ions can be irradiated along the central axis 29 of the ion dissociation part 8. Since the space 16 in the ion dissociation part 8 is maintained at about 3 Pa or less with a neutral gas such as helium, argon, or nitrogen, actually, a pipe for introducing a neutral gas, the case 64 and the inlet electrode 14 or Although a part for hermetically sealing the outlet electrode 15 is necessary, FIG. 13 is not shown. High frequency voltages with opposite phases are alternately applied to the four rod electrodes 17-20. The high-frequency voltage has a frequency of about several hundred kHz to 1 MHz and a maximum voltage amplitude value of about several kV. The eight axial electric field forming electrodes 21-28 include a front axial electric field forming electrode 21-24 and a rear axial electric field forming electrode 25-28. For the negative ion introduction part 66, a multipole electrode in which a plurality of rod-shaped electrodes are arranged is used. It is also possible to use a Q deflector or the like that can deflect ions in the negative ion introduction unit 66. Furthermore, a power source 35 capable of applying DC voltages 31, 32 and variable voltages 33, 34 to the front axial field forming electrode 21-24 and the rear axial field forming electrode 25-28, respectively, is provided.

  In the apparatus configuration shown in FIG. 13, the same effect can be obtained by controlling with the control method described in FIGS. 3, 6, 7, and 8.

All of the ion dissociation parts described in Examples 1 to 7 can operate as an ion trap capable of ion separation for separating specific ions and mass spectrometry for separating fragment ions after dissociation for each m / z. is there. Therefore, the ion dissociation part can also function as ion separation and mass spectrometry. Moreover, in the ion dissociation part demonstrated in Example 1-7, not only the use which dissociates by irradiating an electron while vibrating an ion to an axial direction but can perform only dissociation (ECD) only by electron irradiation, Further, only dissociation (CID) by collision with a neutral gas due to vibration of ions can be performed. It can also be used in combination with ECD and CID (CID after ECD, ECD after CID, or repetition of these).

DESCRIPTION OF SYMBOLS 1 ... Ion source, 2 ... Ion, 3 ... 1st differential exhaust chamber, 4 ... 2nd differential exhaust chamber, 5 ... Ion transport part, 6 ... Ion separation part, 7 ... Precursor ion, 8 ... Ion dissociation part , 9 ... Fragment ion, 10 ... Mass analysis part, 11 ... Fragment ion, 12 ... Detector, 13 ... Magnet, 14 ... Inlet electrode, 15 ... Outlet electrode, 16 ... Space, 17-20 ... Rod electrode, 21-28 ... Axial electric field forming electrode, 29 ... Center axis, 30 ... Electron source, 31 ... DC voltage, 32 ... DC voltage, 33 ... Variable voltage, 34 ... Variable voltage, 35 ... Power source, 36 ... Axial ion distribution, 37 ... radial ion distribution, 38 ... auxiliary AC voltage, 39 ... multipole rod electrode, 40-45 ... rod electrode, 46-57 ... terminal part, 58 ... resonance coil, 59 ... RF amplifier, 60 ... insulating rod, 61 ... Resistor layer, 62 ... Lens electrode, 63 ... Irradiation sequence child, 64 ... case, 65 ... negative ion source, 66 ... negative ion introduction unit, 70 ... control unit

Claims (17)

An ion trap comprising a multipole rod electrode to which a high frequency voltage is applied and an electric field forming means for forming an electric field in the axial direction of the multipole rod electrode;
A power supply for applying a voltage to the electrodes constituting the ion trap;
A particle source that generates particles that change the charge of the ions;
An ion dissociation apparatus comprising: a control unit that introduces the particles into the ion trap in a state where a voltage is applied to the electric field forming unit so that ions vibrate in the axial direction. The ion dissociation apparatus according to claim 1.
The ion generator further comprises magnetic field generating means for forming a magnetic field in the axial direction, the particle source is an electron source for generating electrons, and the controller introduces electrons onto the axis of the ion trap. Dissociation device. The ion dissociation apparatus according to claim 1.
The ion dissociation apparatus, wherein the electric field forming means is an insertion electrode having a shape inserted between rod electrodes and divided into two or more in the axial direction of the rod electrode. The ion dissociation apparatus according to claim 1.
The ion dissociation apparatus, wherein the electric field forming means is an insertion electrode inserted between rod electrodes and having an inclined side facing the central axis of the ion trap. The ion dissociation apparatus according to claim 1.
The multipole rod electrode is also the electric field forming means, and the multipole rod electrode has an insulating portion having a resistor layer on a surface thereof. The ion dissociation apparatus according to claim 1.
The multipole rod electrode is also the electric field forming means, and the multipole rod electrode has a resistor. The ion dissociation apparatus according to claim 1.
The ion dissociation apparatus, wherein the particle source is a negative ion source for generating negative ions. The ion dissociation apparatus according to claim 1.
An ion dissociation apparatus, wherein the power source applies a DC voltage and an AC voltage to the electric field forming means. The ion dissociation apparatus according to claim 8.
The ion dissociation apparatus, wherein the AC voltage is a rectangular wave voltage. The ion dissociation apparatus according to claim 1.
The control unit is configured to apply a voltage to the multipole rod electrode or the electric field forming unit so that ions other than ions oscillated in the axial direction in the radial direction of the ion trap are oscillated. An ion dissociation apparatus, wherein particles are introduced into the ion trap. An ion source;
An ion dissociation part for dissociating ions generated by the ion source;
A mass spectrometer that performs mass analysis of dissociated ions generated in the ion dissociation part,
The ion dissociation unit includes an ion trap including a multipole rod electrode to which a high-frequency voltage is applied and an electric field forming unit that forms an electric field in an axial direction of the multipole rod electrode, and a power source that applies a voltage to the electric field forming unit A particle source that generates particles that change the charge of ions, and a control that introduces the particles into the ion trap in a state where a voltage is applied to the electric field forming means so that the power source vibrates in the axial direction. A mass spectrometer. The mass spectrometer according to claim 11,
And a magnetic field generating means for forming a magnetic field in the axial direction, wherein the particle source is an electron source for generating electrons, and the control unit introduces electrons on the axis of the ion trap. Analysis equipment. The mass spectrometer according to claim 11,
The mass spectrometer is characterized in that the particle source is a negative ion source for generating negative ions. A step of generating ions;
Introducing the generated ions into a linear ion trap;
Accumulating the introduced ions in the linear ion trap;
Oscillating first ions of predetermined m / z among the accumulated ions in the axial direction of the linear ion trap;
Introducing into the linear ion trap particles that change the charge of the ions while the first ions are vibrated in the axial direction;
Dissociating ions by reaction of the first ions with the particles;
A step of discharging the dissociated ions from the ion trap and separating them by mass separation. The mass spectrometric method according to claim 14,
The particle is an electron, and the electron is introduced onto the central axis of the linear ion trap in a state where a magnetic field is formed in the axial direction of the linear ion trap. The mass spectrometric method according to claim 14,
The mass spectrometric method, wherein the particles are negative ions. The mass spectrometric method according to claim 14,
Further, a particle having a step of vibrating second ions other than the first ion in the radial direction of the linear ion trap, and changing the charge of the ions in a state where the second ion is vibrated in the radial direction. Is introduced into the linear ion trap.

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