JP6362161B2 - Mass spectrometer - Google Patents

Description

In the present invention, the components eluted from a plurality of separation columns are introduced into the mass spectrometer simultaneously and continuously, and from the measurement results in which signals derived from the plurality of separation columns obtained by the mass spectrometer are mixed. The present invention relates to a method for arbitrarily extracting only signals derived from a specific separation column.

In recent years, a method combining a separation analysis method and a mass spectrometry method has been used in various fields. It is effective to perform this analysis in parallel to increase the analysis efficiency, but it is difficult to prepare many expensive mass spectrometers. Therefore, it is desired to develop a method for combining one mass spectrometer and a plurality of separation analyzers. As a conventional method, in order to introduce sample components eluted from a plurality of separation columns in parallel into one mass spectrometer, the separation column used for introduction into the mass spectrometer is switched every time using a flow path switching valve. There is a method. (Non-Patent Document 1).

In the above conventional method, the system of the sample solution introduced into the mass spectrometer is sequentially changed by the flow path switching valve. That is, focusing on a certain moment, only one system sample is introduced into the mass spectrometer, and simultaneous analysis of a plurality of systems is not performed. In this method, handling of sample solutions other than the system introduced into the mass spectrometer can be broadly divided into two methods: a method of discarding the sample solution without stopping it and a method of stopping the solution flow.

When there are n systems and the analysis system is switched, what is actually measured in each system is 1 / n of the total analysis time. In the method of discarding the sample solution without stopping it, in other systems other than the one system, the sample solution while being not measured is discarded and lost, so the analysis efficiency is lowered. On the other hand, in the method in which the solution flow is stopped, the separation process is also stopped when mass spectrometry is not performed. Therefore, even if parallel introduction is performed, the measurement time is to perform each analysis multiple times in succession. It is not possible to shorten the time, and high efficiency of analysis cannot be achieved. As described above, the method using the flow path switching valve is a pseudo parallel introduction method, and true parallel separation analysis-mass spectrometry is not performed.

“Evaluation of a Four-Channel Multiplexed Electrospray Triple Quadrupole Mass Spectrometer for the Simultaneous Validation of LC / MS / MS Methods in Four Different Preclinical Matrixes”, Liyu Yang, Thierry D. Mann, David Little, Ning Wu, Robert P. Clement, and Patrick J. Rudewicz, Anal. Chem., 2001, 73 (8), pp 1740-1747 (DOI: 10.1021 / ac0012694).

In view of the above problems, the object of the present invention is to introduce a sample solution eluted from each separation column into a mass spectrometer in parallel and continuously to perform measurement, and from mass spectrometry data obtained as a mixed signal. It is to provide a mass spectrometer having a function of extracting data derived from a specific separation column.

In order to perform simultaneous mass spectrometry in which a separation column is specified for a sample solution eluted in parallel from a plurality of separation columns, the inventors introduce a sample into the mass spectrometer for each separation column. The idea was to change the frequency periodically and change the frequency of the fluctuation. That is, the following mass spectrometer is provided.

[1] and a plurality of ionizer capable of a plurality of analytes introducing said plurality of analytes in parallel and continuously in the mass spectrometer ionizes, the plurality of analytical samples, said specific An identification signal providing unit having a function of providing an identification signal having a different frequency for extracting a signal derived from each ionization unit, and the plurality of ionized analysis samples are introduced in parallel and continuously, and mixed extracted with the mass spectrometer for performing mass spectrometry of the plurality of analysis samples, from the identification signal observed the mass analyzer mass spectrometer measurements of the mixed signal, the mass spectrometry results for each of the identification signal an identification signal extraction unit for mass spectrometer having.

It is the schematic which shows the structure which has the interruption | blocking board which rotates in order to provide an identification signal to the front-end | tip part of the spray needle for electro play ionization in 1st Embodiment of this invention. The figure which shows the time change of the signal intensity | strength obtained by using the apparatus shown in FIG. 1 of 1st Embodiment of this invention by the mass spectrometer in which two systems of signals shielded at different frequencies are mixed. is there. It is a figure which shows the result obtained by Fourier-transforming the data of FIG. 2 of 1st Embodiment of this invention. It is a figure which shows the result obtained by carrying out an inverse Fourier transform only about the component of frequency 0.07 Hz or less among the data of FIG. 3 of 1st Embodiment of this invention. It is a figure which shows the result obtained by performing an inverse Fourier transform only about the component of frequency 0.07-0.20 Hz among the data of FIG. 3 of 1st Embodiment of this invention. It is a figure which shows the result obtained by performing an inverse Fourier transform only about the component of frequency 0.38-0.47 Hz among the data of FIG. 3 of 1st Embodiment of this invention.

Hereinafter, embodiments of the present invention will be described with reference to the drawings. The present invention is not limited to the following embodiments, and changes, modifications, and improvements can be added without departing from the scope of the invention.

(First embodiment)
The mass spectrometer of the present invention includes a plurality of ionization units capable of ionizing an analysis sample and introducing the analysis sample in parallel and continuously to the mass spectrometer, and a mass spectrometry measurement result observed as a mixed signal. Mass analysis of an analysis sample in which an identification signal providing unit having a function of providing an identification signal for extracting a signal derived from a specific ionization unit by information processing and an ionized analysis sample are introduced in parallel and continuously And an identification signal extraction unit that extracts a signal derived from a specific ionization source using the given identification signal from a mass spectrometry measurement result observed as a mixed signal. A device having a motor-rotating blocking plate for periodically blocking the introduction of ionized sample components into a mass spectrometer at the tip of an electroplating ionization spray needle for ionizing an analysis sample It was shown in 1. By using the apparatus shown in FIG. 1, it is possible to periodically block a sample that is continuously supplied to a mass spectrometer in a normal electroplating ionization method. This cutoff frequency can be used as an identification signal for extracting a signal from the mixed signal. The cutoff frequency can be arbitrarily set according to the number of rotations of the motor and the numerical aperture of the shielding plate.

A device capable of introducing samples into a single mass spectrometer in parallel and continuously was prepared by using two electroplate ion parts having a periodic shielding part (identification signal applying part) shown in FIG. . It should be noted that sample introduction from each electroplate ionization section to the mass spectrometer can be blocked at different periods. FIG. 2 shows the time variation of the signal intensity obtained by mass spectrometry in which two systems of signals shielded at different frequencies obtained by using the electroplating ionization section having the periodic shielding section shown in FIG. 1 are mixed. showed that. One signal is blocked at 0.133 Hz, and the other signal is blocked at 0.417 Hz, so that an identification signal for signal processing is given. FIG. 3 shows the result of Fourier transform processing on the mixed signal shown in FIG. In addition to the low frequency component of 0.07 Hz or less, it can be confirmed that signals derived from the identification signals 0.133 Hz and 0.417 Hz are included. Next, from the results of the Fourier transform shown in FIG. 3, only the signals of 0-0.07 Hz, 0.07-0.20 Hz, and 0.38-0.47 Hz are extracted and subjected to inverse Fourier transform, respectively, as shown in FIGS. It is shown in FIG. In FIGS. 5 and 6, since the result of the inverse Fourier transform takes a negative value, processing is performed so that all the values become positive values by taking absolute values.

FIG. 4 shows that the result of removing the shielding signal for identification is obtained by performing inverse Fourier transform on only the low frequency component. However, in FIG. 4, the result of mixing the signals of the two systems is obtained. On the other hand, in FIG. 5, it can be seen that a component corresponding to 0.133 Hz is extracted from the signal shown in FIG. In FIG. 6, a component corresponding to 0.417 Hz is extracted. That is, only signals related to a specific identification signal can be extracted from the mixed signal based on the identification signal given by periodic interruption. In principle, it is possible to perform parallel analysis of samples eluted from two or more columns by appropriately setting a multiple of the frequency that becomes the identification signal so that it does not overlap with the frequency of other identification signals. it can.

(Other embodiments)
In the above-described embodiment, signal extraction is performed by Fourier transform and inverse Fourier transform, but this can be replaced by other frequency analysis methods (for example, wavelet transform or the like). In addition, a rotating shielding plate is used to give an identification signal, but other methods, for example, placing an electrode near the ionization section, applying a voltage to this electrode, and It can be substituted by a method of blocking the flow.

The present invention can be used for a mass spectrometer.

Claims (1)

A plurality of ionization portion capable of introducing said plurality of analytes in parallel and continuously a plurality of analytes into the mass analyzer is ionized, the plurality of analytical samples, each of the ionization part of the specific The identification signal applying unit having a function of applying an identification signal having a different frequency for extracting a signal derived from the above and the plurality of ionized analysis samples introduced in parallel and continuously and mixed and the mass analyzer for performing mass spectrometry analysis sample, from said mixed signal observed the mass analyzer mass spectrometer measurements as the identification signal, the identification signal for extracting the mass spectrometry results for each of the identification signal mass spectrometer having an extraction unit, a.