JP3409936B2 - Mass spectrometer - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a mass spectrometer, and more particularly, to capillary electrophoresis / mass for highly sensitive separation analysis of a substance such as a biological substance, an environment-related substance or a complex thereof obtained in a trace amount. Analyzer coupling device (CE / M
S), Liquid chromatograph / mass spectrometer coupling device (LC
/ MS), gas chromatography / mass spectrometer coupling device
(GC / MS).

[0002]

[Prior Art] Journal of Chromatography
559 (1991) 515-528 (Journa
l of Chromatography 559 (1991) pp515-
528) describes a capillary electrophoresis / mass spectrometer combination device (CE / MS) in which a capillary electrophoresis device (CE) and a quadrupole mass spectrometer are combined. In CE,
A sample solution having a volume of about nanoliter is introduced into one end of a quartz capillary, and a high voltage of about 30 kV is applied to both ends of the capillary to separate the mixed solution.

The separated component separated by CE is detected as a CE pattern by absorption of ultraviolet rays by a separated component detecting section installed at the other end of the quartz capillary, and then converted into gaseous ions by the ionizing section of the mass spectrometer. To be converted. Ions generated in the atmosphere are introduced into a vacuum through a mass spectrometer sampling orifice (pore) and are mass separated.

The mass analysis unit periodically performs a mass scan, and the data processing unit records all the obtained mass spectra. After that, by correlating the CE pattern with the mass spectrum, the correspondence relationship between the separation component detected on the CE pattern and the mass spectrum is obtained, and the separated substance is identified.

Further, JP-A-60-207051 and JP-A-61-1166
In Japanese Patent Publication No. 54, a control system for setting the cycle of mass scan is provided according to the time width (band width) of the peak of the separated component
There is a description of a mass spectrometer that makes the number of mass scans almost the same for any of the peaks. When a capillary column is used as the sample separation unit, the band width of the later-detected component tends to become wider than the band width of the separated component detected first. Therefore, when using a mass spectrometer such as a magnetic field type or a quadrupole type that requires mass scanning, when performing mass analysis at a mass scan cycle corresponding to the bandwidth of the first detected separation component, data processing The storage capacity stored in the unit becomes unnecessarily large. Therefore, the number of mass scans for a single separated component is set to an integer such as 5 to 10, and the mass scan cycle is sequentially lengthened according to each bandwidth to minimize the amount of stored data. To do.

[0006]

The time width (bandwidth) of one peak corresponding to one separated component (peak) in the LC or GC pattern is narrow and is about 10 seconds. on the other hand,
A mass scan of a quadrupole mass spectrometer or a double-focusing mass spectrometer usually requires about several seconds. Therefore, in the above-mentioned conventional technique, mass analysis can be reliably performed by repeating the mass scan of the mass spectrometric unit. However, CE has a higher separation capacity and has a short bandwidth of about 1 second. In this case, there arises a problem that ions of sample molecules in the solution separated by CE may not be detected on the mass spectrum.

Further, in CE, there is no guarantee that the first detected separated component has the shortest bandwidth, and it is difficult to predict the relationship between the order of the detected separated components and the bandwidth. Therefore, if the scan cycle of the mass spectrometric unit is set according to the bandwidth of the separation component that is detected first and the scan cycle is sequentially extended for the subsequent separation components, the ions derived from the separation component that are detected later will be generated. On the other hand, there is a possibility that mass spectrometry may not be possible.

Further, in the prior art, when the sample concentration introduced is extremely low, even if the band width of the separated component is longer than the cycle of the mass scan performed in the mass spectrometric section, the ions mass separated in the mass spectrometric section. There is a problem in sensitivity that the output (signal level) of the ion detector derived from is not detected because it is too small compared to the noise level.

An object of the present invention is to provide CE / MS, LC / MS or GC / MS which can reliably analyze a dilute mixed sample with high separation and high sensitivity.

[0010]

In order to perform high-sensitivity separation analysis, calculation is performed corresponding to the time when ions generated from one separation component separated by the separation component detection unit are introduced into the mass analysis unit. The output from the unit is output, and based on that, the ion accumulation in the ion accumulation unit is started and stopped, and the mass analysis of the mass analysis unit is executed.

[0011]

[Function] The time (bandwidth) at which one separation component separated by the sample separation unit (capillary electrophoresis, liquid chromatography, or gas chromatography) is detected by the separation component detection unit is the separation component (peak) in the ionization unit.
It is almost the same as the time during which the ions generated by the above are continuously introduced into the mass spectrometric section. Ions generated from each of the separated components separated in the sample separation unit are made to match the time to start reaching the ion accumulation unit and the time to start accumulation of the ions in the ion accumulation unit, and By matching the time when the generated ions reach the ion storage unit with the time when the ion storage in the ion storage unit ends, and by executing the mass analysis in the mass analysis unit at the same time or immediately after the above time, the mass analysis is performed. When the analysis time in a part is less than or equal to the bandwidth of one separation component, mass spectrometry is reliably performed.

Further, in a time-of-flight mass spectrometer and a magnetic field mass spectrometer provided with an array type ion detector, mass analysis takes a sufficiently short time (1 ms or less) as compared with the bandwidth.
Will be realized in. Therefore, all the ions generated from one separated component separated in the sample separation unit are temporarily stored in the ion storage unit such as a quadrupole trap, and the concentrated ions are collected, and the concentrated ions are analyzed by a time-of-flight mass spectrometer or array type. When momentarily moving to a mass spectrometer such as a magnetic field mass spectrometer equipped with an ion detector and performing mass spectrometry at once, when integrating the mass spectra obtained by mass spectrometry in multiple times, In comparison, a spectrum having a significantly high S / N ratio can be obtained. This corresponds to a significant improvement in the sensitivity of the device, and enables separation and analysis of extremely dilute mixed samples. In addition, with the Penning trap, not only ion accumulation but also ion mass analysis can be realized at the same time.

[0013]

1 is a block diagram of a mass spectrometer according to an embodiment of the present invention. The separated components separated by the sample separation unit 1 are detected by the separated component detection unit 2, converted into gaseous ions in the ionization unit 3, accumulated in the ion accumulation unit 4, and then mass analyzed in the mass analysis unit 5. And is detected by the ion detector 6. The output of the solution detector 2 is introduced into the calculator 7. The output of the ion detector 6 is also introduced to the data processor 8. The calculation unit 7 controls the ion storage unit 4, the mass analysis unit 5, the ion detection unit 6, or the data processing unit 8 based on the output of the solution detection unit 2.

FIG. 2 shows a temporal correspondence diagram between the output of the separated component detection unit 2 and the output of the calculation unit 7 based on the output of the separated component detection unit in the mass spectrometer according to the embodiment of the present invention. In the separated component detection unit 2, the separated component is detected by a detecting means such as a change in the electric conductivity of the liquid, and a separation pattern is obtained from the temporal output. That is, a single peak signal (band) corresponds to one separated component. Based on the output of the separated component detection unit 2, the calculation unit 7 sends the output corresponding to the start time and the end time when the ions generated from one separated component are introduced into the ion storage unit 4. From this, the mass spectrometric unit 5, the ion detection unit 6, or the data processing unit 8 is controlled.

FIG. 3 shows a block diagram of a mass spectrometer according to the second embodiment of the present invention. In this example, the ion storage unit 4 is a Penning trap that stores ions using an electrostatic field and a static magnetic field. Mass spectrometry and ion detection are performed by measuring the induced current due to the movement of ions as a function of time using the electrodes of the ion storage unit 4. Therefore, the ion storage unit 4 also serves as a mass analysis unit. The separated component separated by the sample separation unit 1 is detected by the separated component detection unit 2, and the output thereof is introduced into the calculation unit 7. As shown in FIG. 2, the calculation unit 7 recognizes each separated component, and the ions generated from one separated component are introduced and accumulated in the ion accumulation unit 4.

FIG. 4 shows a block diagram of a mass spectrometer according to the third embodiment of the present invention. The mass spectrometer 5 is composed of a time-of-flight mass spectrometer. The output of the separated component detection unit 2 is introduced into the calculation unit 7. While the ions generated from one separation solution are introduced into the ion accumulation unit 4 from the output of the calculation unit 7, the ions are accumulated in the ion accumulation unit 4 and when the introduction of the ions generated from one separation component is completed, The ions accumulated in the ion accumulator 4 are instantaneously released from the ion accumulator 4 by a pulsed electric field after a fixed time, and the acceleration electrode 9
The ions are accelerated by the ions, and after the ion orbit is converged by the electrostatic lens 10, the ions are deflected by the deflection electrode 11 and the ions pass through the reflector electrode 12, and the ions are detected.
Reach The data processing unit 8 is synchronized with the timing when ions are ejected from the ion storage unit 4. The mass of the ions is determined by the flight time of the ions reaching the ion detector 6. A quadrupole trap or a Penning trap can be used for the ion storage unit 4, but the same effect can be obtained even if another device capable of storing ions is used. When the amount of introduced ions is sufficiently large, it is not necessary to store ions in the ion storage section 4. In this case, the ions pass through the ion storage unit 4, and the ions introduced into the mass analysis unit 5 are pulse-accelerated by the acceleration electrode 9 and directly introduced into the time-of-flight mass spectrometer for analysis. Is possible.

FIG. 5 shows a block diagram of a mass spectrometer according to the fourth embodiment of the present invention. The mass spectrometer 5 is composed of a magnetic field type mass spectrometer. The ion detector 6 is an array type. While the ions generated from one separated component from the output of the calculation unit 7 are introduced into the ion storage unit 4, the ion storage unit 4
Then, the ions are accumulated, and when the introduction of the ions generated from the one separated component is completed, the ions accumulated in the ion accumulator 4 are instantaneously released from the ion accumulator 4 by the pulsed electric field. The ions are accelerated by the accelerating electrode 9, and after the ion orbit is converged by the electrostatic lens 10, the electrode 1
Energy is converged by the electric field generated by 3 and mass-separated in the magnetic field generated by the electromagnet 14. The mass of the ions is determined by the detection position in the array type ion detector 6. In the data processing unit 7, the output from the ion detection unit 6 is read in synchronization with the timing when the pulse electric field is applied.

[0018]

According to the present invention, the calculation section recognizes the time when the ions generated from the respective separated components separated in the solution separation section are introduced into the ion storage section. Therefore, by synchronizing the introduction of ions into the ion storage unit and the control of the ion storage unit and the mass analysis unit, it is possible to reliably analyze the ions even when the separation component has a short bandwidth.

Further, an ion trap or the like is used in the ion accumulating portion, and ion accumulation (concentration) is performed in the ion accumulating portion while the ions derived from the single separated component are introduced, and the accumulated ions are collected at a time. If you do mass spectrometry,
High-sensitivity analysis is reliably performed even when the ion introduction time to the mass spectrometric section is short, such as about 1 second.

Further, when the mass spectrometric section is composed of a time-of-flight mass spectrometer, there is no upper limit to the mass of the ion that can be mass-analyzed, and high-sensitivity analysis is surely performed.

Further, when the mass spectrometric section is composed of a magnetic field type mass spectrometer using an array type detector and mass spectrometry is performed by the magnetic field type mass spectrometer, high resolution and high sensitivity analysis is surely performed.

[Brief description of drawings]

FIG. 1 is a block diagram of a mass spectrometer according to an embodiment of the present invention.

FIG. 2 is a timing chart of the output of the solution detection unit and the output of the calculation unit in the mass spectrometer according to the embodiment of the present invention.

FIG. 3 is a block diagram of a mass spectrometer according to a second embodiment of the present invention.

FIG. 4 is a block diagram of a mass spectrometer according to a third embodiment of the present invention.

FIG. 5 is a block diagram of a mass spectrometer according to a fourth embodiment of the present invention.

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 ... Sample separation part, 2 ... Separation component detection part, 3 ... Ionization part, 4 ... Ion accumulation part, 5 ... Mass analysis part, 6 ... Ion detection part, 7 ... Calculation part, 8 ... Data processing part.

─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Hideaki Koizumi 1-280 Higashi Koikekubo, Kokubunji City, Tokyo Inside Central Research Laboratory, Hitachi, Ltd. (56) Reference JP 1-97350 (JP, A) JP 2 -176459 (JP, A) JP-A-64-43963 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) G01N 30/72 G01N 27/447 G01N 27/62 H01J 49/26

Claims (14)

(57) [Claims] 1. A sample separation unit for separating a mixed sample, a separated component detection unit for detecting the separated sample, an ionization unit for converting the sample into gaseous ions, and an ion storage unit capable of accumulating ions. , A mass spectrometric unit for mass-separating ions,
Has an ion detector for detecting the mass separated ions, and a data processing unit for the output of the ion detector is introduced, and a calculator for output from the separating component detection unit is introduced, the separated components Introducing a temporal output from the detection unit Based on the output from the calculation unit, the start and end of ion accumulation in the ion accumulation unit and the execution of mass spectrometry in the mass analysis unit are performed in the temporal manner. Not done in sync with the output
Mass spectrometer characterized in that it is. 2. The mass spectrometer according to claim 1, wherein each separation component separated by the sample separation unit can be recognized by the calculation unit based on the output from the separation component detection unit. 3. The mass spectrometer according to claim 2, wherein the calculation unit recognizes the start of the arrival of the ions generated by the separated components separated by the sample separation unit to the ion storage unit. 4. The mass spectrometer according to claim 3, wherein the calculation unit recognizes that the ions generated from the respective separated components separated by the sample separation unit have reached the ion accumulation unit. 5. The method according to claim 2 or 4, which corresponds to the time when the ions generated from the respective separated components separated by the sample separating unit reach the ion accumulating unit.
A mass spectrometer in which mass analysis of ions is performed in the mass analysis unit, or ion detection is performed in the ion detection unit, or output processing from the ion detection unit is performed in the data processing unit. 6. The mass spectrometer according to claim 1, wherein the calculation unit recognizes that the only component detected by the separated component detection unit is a solvent. 7. The mass spectrometer according to claim 6, wherein when the component detected by the separated component detection unit is only a solvent, the ions generated corresponding to the solution are not accumulated in the ion accumulation unit. Total. 8. The ion accumulation in the ion accumulation section according to claim 1, while the ions generated corresponding to each separation solution separated in the sample separation section reach the ion accumulation section. Mass spectrometer. 9. The output of the calculation unit according to claim 8, corresponding to the time when the ions generated corresponding to each of the separated components separated by the sample separation unit start to reach the ion storage unit. A mass spectrometer in which ion accumulation is started in the ion accumulation unit based on the above. 10. The calculation unit according to claim 8, wherein the ions generated corresponding to each of the separated components separated by the sample separation unit reach the ion accumulation unit at a time corresponding to the time when the ions are generated. A mass spectrometer in which ion accumulation is stopped in the ion accumulation unit based on the output. 11. The mass spectrometer according to claim 9, wherein when the ion accumulation in the ion accumulating section is stopped, mass spectrometry of ions is executed. 12. The mass spectrometer according to claim 11, wherein the mass spectrometer comprises a time-of-flight mass spectrometer, and mass spectrometry of ions is performed by the time-of-flight mass spectrometer. 13. The mass spectrometer according to claim 11, wherein the mass spectrometer comprises a double-focusing mass spectrometer, and the double-focusing mass spectrometer performs mass analysis of ions. 14. Claims 1, 2, 3, 4, 5, 6, 7,
8. A mass spectrometer according to 8, 9, 10, 11, 12 or 13, wherein the sample separation section is a capillary electrophoresis device or liquid chromatography or gas chromatography.