JP4848657B2 - MS / MS mass spectrometer - Google Patents

Description

  The present invention relates to an MS / MS mass spectrometer.

Conventionally, an MS / MS type mass spectrometer using a quadrupole mass filter as a mass analyzer is known. FIG. 2 is a schematic configuration diagram of such an apparatus. In this mass spectrometer, three stages of quadrupoles, ie, a first stage quadrupole 2, a second stage quadrupole 3, and a third stage quadrupole 5, are provided so as to cover the second stage quadrupole 3. The collision chamber 4 is formed in the front. Various ions emitted from the ion source 1 is first introduced into the first-stage quadrupole 2, specific Weight first stage quadrupole purposes only ions are selected to have a (strictly mass-to-charge ratio m / z) 2 is passed. Passed target ions are introduced as parent ions into the second stage quadrupole 3, but collision gas such as Ar, N ₂ or the like is introduced into the collision chamber 4, and the ions are introduced into the collision chamber 4. Collides with collision gas molecules and cleaves into several daughter ions. Daughter ions produced by the dissociation is introduced into the third-stage quadrupole 5, wherein only daughter ions having a specific Mass passes is selected, is detected to reach the detector 6.

The quadrupoles 2, 3, and 5 are, for example, four substantially cylindrical rod electrodes that are rotationally symmetrically arranged so as to surround the ion optical axis. Usually, the quadrupoles 2, 3 and 5 have two electrodes facing each other across the ion optical axis, and one set of electrodes is a voltage obtained by superposing a high-frequency voltage V · cos ωt on a DC voltage U. And a voltage obtained by superimposing −V · cos ωt having a phase opposite to that of the previous high-frequency voltage on the DC voltage U is applied to the other set of electrodes. Then, it is suitably determined and the voltage U and V in accordance with the mass of ions which pass through the quadrupole 2,3,5.

  In the above configuration, when voltage sources for applying voltages to the quadrupoles 2, 3 and 5 are provided independently, even if the frequency of the high-frequency voltage is the same, the phase relationship differs each time the power is turned on. It becomes. Further, if the frequency is slightly different, the phase relationship is shifted with time. Between the adjacent quadrupoles, that is, between the first stage quadrupole 2 and the second stage quadrupole 3, or between the second stage quadrupole 3 and the third stage quadrupole 5, If the phase relationship is not appropriate, some of the ions emitted from the previous quadrupole do not enter the convergence range of the next quadrupole, which may reduce the ion transmission efficiency.

  Conventionally, for example, in the MS / MS mass spectrometer described in Patent Document 1, in order to avoid the disturbance of the frequency and phase of the high-frequency voltage between the adjacent quadrupoles as described above, it is applied to the quadrupole of each stage. The high frequency components of the voltage to be applied are set to the same frequency and the same phase. Thereby, the disturbance of the electric field between adjacent quadrupoles is eliminated and ions pass smoothly.

  However, although the ions pass smoothly between adjacent quadrupoles under the above conditions, the force that draws ions from the previous quadrupole into the next quadrupole does not necessarily work. The ion passage efficiency is not always the best.

JP-A-7-240171

  The present invention has been made to solve such problems, and the object of the present invention is to further improve the passage efficiency of ions between adjacent quadrupoles as compared with the conventional method, so that the analysis sensitivity and analysis accuracy are improved. An object of the present invention is to provide an MS / MS mass spectrometer capable of improving the efficiency.

The present invention was made in order to solve the above problems includes a first stage multipole passing select the desired ions for a specific Weight of various ions sent from the ion source, the target ions selected The second stage multipole that cleaves the target, the third stage multipole that selectively passes the target product ion of a specific mass among the product ions generated by the cleavage, and the detection that detects the selected target product ion An MS / MS mass spectrometer comprising:
a) first voltage applying means for applying a voltage in which a DC voltage and a high-frequency voltage are superimposed on the first stage multipole;
b) second voltage applying means for applying a voltage in which a DC voltage and a high-frequency voltage having the same frequency as the high-frequency voltage are superimposed on the second stage multipole;
c) third voltage applying means for applying a voltage in which a DC voltage and a high frequency voltage having the same frequency as the high frequency voltage are superimposed on the third stage multipole;
d) The phase of the high-frequency voltage having the same frequency among the voltages applied to the first to third multipoles by the first to third voltage applying means is independently determined according to the mass of ions to be passed. A means for setting, including a storage unit that holds information representing the relationship between the mass of an ion and a suitable phase of each multipole when the ion is incident on each multipole, and a preliminary measurement for a standard sample Holding the information obtained by performing in the storage unit, phase adjustment means for adjusting the phase of each multipole based on the information held in the storage unit at the time of analysis,
It is characterized by having.

In the MS / MS mass spectrometer according to the present invention, the first to third stage multipoles are configured to have four or more even-numbered electrodes such as quadrupoles, hexapoles, and octupoles. it can. In the MS / MS type mass spectrometer according to the present invention, each of a plurality of standard samples containing a component having a known mass is analyzed while changing the phase of the high-frequency voltage applied to the quadrupole of each stage. for the mass, prepared to give the phase of the high-frequency voltage such as transmission efficiency of ions is optimum or near an. Such mass and may be held in the storage unit a relationship for example by a table or by equation of the phase, the phase setting means, based on the mass at the time of analysis run is designated held in the storage unit information seeking optimal phase in each quadrupole Te adjust the phase of each quadrupole.

According to the MS / MS mass spectrometer according to the present invention, when analyzing the ions with any mass in analyte mass range, high-frequency electric field caused by the high frequency voltage applied to each quadrupole, especially A high-frequency electric field existing in the space between adjacent quadrupoles is optimal or close to passing the ions. Therefore, since the improved transmission efficiency of target ions regardless mass, as a result, also improved detection efficiency of ions in the detector. Therefore, accuracy and sensitivity of mass spectrometry are improved and reproducibility is improved.

  An MS / MS type quadrupole mass spectrometer according to an embodiment of the present invention will be described with reference to the drawings. FIG. 1 is a configuration diagram of a main part of an MS / MS type quadrupole mass spectrometer according to this embodiment.

  This apparatus includes a nozzle 10 for spraying a sample liquid, a sampling cone 11, a first ion lens 12, an octopole-type second ion lens 13, a first prerod quadrupole 15, and a first main quadrupole. A third stage consisting of a first stage quadrupole 14 comprising poles 16, a second stage quadrupole 18 disposed in the collision chamber 17, a third prerod quadrupole 21, and a third main quadrupole 22. A stage quadrupole 20, a detector 23, a first ion lens 12, a second ion lens 13, a first stage quadrupole 14, a second stage quadrupole 18, and a third stage quadrupole 20, respectively. The first to fifth voltage sources 30, 33, 36, 39, and 42 that apply a voltage obtained by superimposing the DC voltage and the high-frequency voltage, and the first to fifth voltage sources 30, 33, 36, 39, and 42 have a high frequency. A phase setting unit 32 for independently setting the phase of the voltage; 5, 38, 41, 44, and phase monitor units 31, 34, 37, 40, 43 for monitoring the phases of the high-frequency voltages applied from the first to fifth voltage sources 30, 33, 36, 39, 42, respectively. The first to fifth voltage sources 30, 33, 36, 39, 42, the DC voltage source 45 that supplies a DC voltage to the sampling cone 11, and the like, and the control unit 46 that controls the operation of each of the above units.

  Although not shown here, a path through which ions from the nozzle 10 to the detector 23 pass is arranged in a plurality of vacuum chambers, and the closer to the detector 23, the higher the degree of vacuum is set.

The basic operation of this mass spectrometer will be schematically described. A liquid chromatograph is provided in the front stage of this apparatus, and the sample liquid separated by the column of the liquid chromatograph is introduced into the nozzle 10. Various components contained in the sample are ionized in the process of vaporizing the solvent from the droplets of the sample liquid sprayed in a substantially atmospheric pressure atmosphere while being given a charge that is offset from the nozzle 10, passes through the sampling cone 11, and goes to the subsequent stage. Sent. The ions are converged when passing through the first ion lens 12 and the second ion lens 13 and are accelerated in some cases and introduced into the first stage quadrupole 14. Although ions are introduced with different mass in the first-stage quadrupole 14, the next stage of the collision purposes only ions selectively pass through the first-stage quadrupole 14 having a specific mass It is sent to the chamber 17 and other ions are diffused along the way.

A predetermined collision gas such as argon gas is introduced into the collision chamber 17 from the gas supply pipe 19, and the target ions collide gas molecules when passing through the electric field formed by the second stage quadrupole 18. When it collides with, it cleaves. In other words, the target ions become parent ions to generate daughter ions. Because aspects of cleavage will vary, mass of daughter ions generated this time is also different. These various the daughter ions are introduced into the third-stage quadrupole 20 exits from the collision chamber 17, only daughter ions having a specific mass can be selectively passed through the third-stage quadrupole 20 detector 23 The other ions are emitted along the way. Thus the ion current only daughter ions corresponding to the number reached with certain mass flow to the detector 23, is output as a detection signal.

Next, operations characteristic of the MS / MS mass spectrometer of the present embodiment will be described. In this mass spectrometer, prior to the measurement of an unknown sample, the preliminary measurement is performed by using a standard sample containing a component having a plurality of different mass in order to create a phase value table in the control unit 46.

In the preliminary measurement, the first to fifth voltage sources 30, 33, 36, 39, and 42 set the frequency of the high frequency voltage to be superimposed on the DC voltage to a specified value, and gradually change the phase of each of the detection signals. Monitor the peak value and find the phase that maximizes the peak value. Here, the phase is defined as a phase shift amount at a certain time Tr with respect to a signal of the frequency Fr of the high frequency voltage . Then, the optimum phase values in the voltage sources 30, 33, 36, 39, 42 are sequentially obtained for those in which the mass of ions passing therethrough is changed, and this is converted into a table and stored in the phase value table 47. Note that the obtained phase value may be stored in the control unit 46 in another form, for example, by formulating it instead of being tabulated. Moreover, the calculation operation of the optimum phase value as described above can be performed simultaneously with auto-tuning such as adjustment of a voltage value applied to each part and mass calibration.

When analyzing a target sample, and a mass of mass and daughter ions of the parent ions is set to the control unit 46. When the analysis is started, and sets and voltage value to the control unit 46 first to fifth voltage source 30,33,36,39,42 if etc. As a mass, from the phase value table 47 reading the phase value corresponding to the mass, as described above, setting the phase of the high frequency voltage through the phase setting section 32,35,38,41,44. If no mass data corresponding to the phase value table 47 is approximately may be calculated phase value by such interpolation processing based on the data corresponding to the mass to be close.

When performing mass scan in a predetermined mass range sequentially reads the phase value corresponding to each mass from the phase value table 47, the phase setting so that the phase of each high frequency voltage sequentially changes over time What is necessary is just to set the phase of a high frequency voltage via the part 32, 35, 38, 41, 44.

As described above, the high-frequency component of the voltage applied to the first ion lens 12, the second ion lens 13, the first stage quadrupole 14, the second stage quadrupole 18, and the third stage quadrupole 20. of the phase is set, the parent ion space between the following Te first ion lens 12 with high efficiency and the second ion lens 13, a second ion lens 13 first stage four with mass of interest The internal space of the second stage quadrupole 18 in the collision chamber 17 passing through the space between the quadrupole 14 and the space between the first stage quadrupole 14 and the second stage quadrupole 18. To be introduced. And it collides with a collision gas molecule | numerator here, and it cleaves, and produces | generates various daughter ions. Daughter ions having a mass of interest in the generated daughter ions Te than at high efficiency, the third through the second-stage quadrupole 18 the space between the third-stage quadrupole 20 is introduced into stage quadrupole 20, wherein only daughter ions having a mass of interest is selected and passed through to reach the detector 23. Thereby, the target daughter ion produced | generated by the cleavage of the target parent ion arrives at the detector 23 with high efficiency, and a highly sensitive analysis can be performed.

  In addition, although the said Example applies this invention to LC / MS, if it is MS / MS type | mold mass spectrometers, such as GC / MS, the application range will not be restricted to the said description. Also. The above embodiment is merely an example, and it is obvious that the present invention is included even if appropriate changes and modifications are made within the scope of the present invention.

The block diagram of the principal part of the MS / MS type | mold mass spectrometer by one Example of this invention. The schematic block diagram of the conventional MS / MS type | mold mass spectrometer.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 ... Nozzle 11 ... Sampling cone 12 ... 1st ion lens 13 ... 2nd ion lens 14 ... 1st stage quadrupole 15 ... 1st prerod quadrupole 16 ... 1st main quadrupole 17 ... Collision chamber 18 ... 1st Second stage quadrupole 19 ... Gas supply pipe 20 ... Third stage quadrupole 21 ... Third prerod quadrupole 22 ... Third main quadrupole 23 ... Detectors 30, 33, 36, 39, 42 ... Voltage source 31, 34, 37, 40, 43 ... phase monitor units 32, 35, 38, 41, 44 ... phase setting unit 45 ... DC voltage source 46 ... control unit 47 ... phase value table

Claims (1)

A first-stage multipole that selectively passes a target ion of a specific mass from various ions sent from an ion source, a second-stage multipole that cleaves the selected target ion, and the cleavage is generated. An MS / MS mass spectrometer comprising: a third stage multipole that selectively passes a target product ion having a specific mass in the product ions; and a detector that detects the selected target product ion.
a) first voltage applying means for applying a voltage in which a DC voltage and a high-frequency voltage are superimposed on the first stage multipole;
b) second voltage applying means for applying a voltage in which a DC voltage and a high-frequency voltage having the same frequency as the high-frequency voltage are superimposed on the second stage multipole;
c) third voltage applying means for applying a voltage in which a DC voltage and a high frequency voltage having the same frequency as the high frequency voltage are superimposed on the third stage multipole;
d) The phase of the high-frequency voltage having the same frequency among the voltages applied to the first to third multipoles by the first to third voltage applying means is independently determined according to the mass of ions to be passed. A means for setting, including a storage unit that holds information representing the relationship between the mass of an ion and a suitable phase of each multipole when the ion is incident on each multipole, and a preliminary measurement for a standard sample Holding the information obtained by performing in the storage unit, phase adjustment means for adjusting the phase of each multipole based on the information held in the storage unit at the time of analysis,
An MS / MS mass spectrometer characterized by comprising:

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