JP5533255B2 - Mass spectrometry method and apparatus - Google Patents

Description

  The present invention is a multi-round time-of-flight mass spectrometer that separates and detects ions according to a mass-to-charge ratio (m / z value) by repeatedly flying a sample-derived ion along a closed orbit. And a mass spectrometric method using a multi-turn time-of-flight mass spectrometer.

  In general, in a time-of-flight mass spectrometer (hereinafter referred to as “TOFMS”), ions accelerated by applying a certain energy have a flight speed corresponding to the mass-to-charge ratio. Based on this, the time required for such ions to fly a certain distance is measured, and mass analysis is performed by converting the time of flight into a mass-to-charge ratio. Therefore, in order to improve the mass resolution, the flight distance may be increased. However, in order to extend the linear flight distance, it is necessary to enlarge the apparatus. Therefore, in order to achieve both the extension of the flight distance and the miniaturization of the device, multiple laps in which ions are repeatedly caused to fly along a closed orbit in various forms such as a substantially circular shape, a substantially elliptical shape, and a substantially 8-shaped shape. A time-of-flight mass spectrometer (Multi Turn TOFMS, hereinafter abbreviated as “MT-TOFMS”) has been developed (see, for example, Patent Documents 1 and 2).

  In addition, for the same purpose, a multiple reflection time-of-flight mass spectrometer has been developed that extends the flight distance by using a reciprocating orbit that reflects ions multiple times by a reflected electric field instead of the orbit as described above. Yes. Although the ion optical system is different between the multi-round time-of-flight type and the multiple reflection time-of-flight type, the basic principle for improving the mass resolution is the same. Therefore, in this specification, the “multiple orbit flight time type” includes the “multiple reflection flight time type”.

  As described above, although MT-TOFMS can achieve a high mass resolution, there is a drawback due to the closed flight path of ions. That is, as the number of laps increases, ions with a high speed at a low mass to charge ratio catch up with ions with a low speed at a high mass to charge ratio and overtake. When overtaking of ions with different mass-to-charge ratios occurs in this way, on the acquired time-of-flight spectrum, the number of laps of ions corresponding to each peak is different for each observed peak, that is, the flight distance is different. A situation occurs. In this case, since the mass-to-charge ratio of ions and the flight distance cannot be uniquely determined, the time-of-flight spectrum cannot be directly converted into a mass spectrum.

  Due to the above drawbacks, in the conventional MT-TOFMS, ions limited to the mass range where the overtaking does not occur are selected from the ions derived from the sample generated by the ion source, and the selected ions are put into the orbit. In general, the control is performed such that the detection is performed after flying a predetermined number of laps. With such a technique, a mass spectrum with high mass resolution can be obtained, but the mass range of the mass spectrum is considerably limited. This is contrary to the advantage of TOFMS that a mass spectrum in a relatively wide mass range can be obtained by one analysis.

  In order to convert the time of flight into the mass-to-charge ratio, various methods for estimating the number of rounds of a peak appearing on the time-of-flight spectrum have been proposed. For example, Patent Document 3 proposes a method for estimating the number of rounds of a peak appearing on a time-of-flight spectrum by comparing the results obtained by executing a plurality of mass analyzes with different conditions on the same sample. Has been. Although such a technique is effective, it is inevitable that data processing becomes complicated. In addition, it is difficult to estimate the number of laps, particularly when the number of components included in the sample is large.

In Patent Document 4, a plurality of time-of-flight spectra obtained by changing the timing at which ions orbiting a circular orbit are emitted from the orbit and directed to the detector (that is, the number of laps of the same type of ions is different) is acquired. A method of reconstructing a time-of-flight spectrum of a single turn by calculating a multiple correlation function of these time-of-flight spectra has been proposed. In this method, the following equation (1) is used to obtain the signal intensity G (T) of an ion whose flight time on a circular orbit is T for a plurality of flight time spectrum data.
Here, Fj (j = 1, 2,..., R) is the signal intensity of the ion having the number of laps Nj found from the measurement data, y is the deviation of the flight time, yl is the lower limit value of this deviation time, and yu is the deviation time. The upper limit value, H, is a function determined by the value of the variable Fj. Specific examples of the function H include arithmetic mean, minimum value, geometric mean, harmonic mean, etc. In order to eliminate false peaks where Fj accidentally has a large value, Therefore, it is desirable to define the function H so that a small value rather than a large value is reflected in H.

  According to the above-mentioned Patent Document 4, it is pointed out that an ineffective period in which a part of ions flying on the circular orbit is not detected occurs depending on the extraction timing of ions from the circular orbit. However, no countermeasure has been proposed for that purpose. This invalid period is such that the gate electrode for emitting ions from the orbit has a finite length, and the ions passing through the gate electrode at the time of trying to emit the circulating ions are in an appropriate direction. This occurs because the light is not emitted in a direction that can be detected by the detector. As described above, when processing according to H defined with emphasis on small values of Fj rather than large values is performed, specifically when the geometric mean or harmonic mean is adopted, the peak intensity Fj If one of them has zero intensity, the peak is not included in the reconstructed time-of-flight spectrum. That is, for ions that have not been observed in a plurality of mass spectrometry with different number of laps due to the ineffective period as described above, the peak does not appear in the reconstructed spectrum. For this reason, detection of ions may be overlooked, which may cause an erroneous determination that the soot component contained in the sample is not included.

JP 2006-228435 A JP 2008-27683 A JP-A-2005-116343 JP-A-2005-79049 International Publication No. 2010/052756 Pamphlet

  The inventor of the present application has proposed a new mass spectrometry method in Patent Document 5 for the above-described problems of the prior art. This method distributes the ion intensity value detected on the multi-round time-of-flight spectrum to each mass-to-charge ratio with corrected number of laps using the time-of-flight spectrum measured in non-round mode without ion overtaking. By doing so, it is reconstructed as a mass spectrum. In this method, a plurality of reconstructed mass spectra each obtained from multiple orbital flight time spectra with different timings of ion extraction from the orbit are obtained, and these can be displayed simultaneously. Therefore, there is a great advantage that the analyst can confirm the existence of ions that are not normally detected due to the emission timing from the circular orbit by comparing the plurality of reconstructed mass spectra.

  When the number of flying ions is relatively small, the above-described new method is excellent. However, when the number of ions increases, a problem may occur. As will be described in detail later, according to the study of the present inventor, when there are many types of ions and peaks derived from a plurality of ions overlap on the multi-round flight time spectrum, the distribution of the ion intensity values of the overlapped peaks is It has been found that the accuracy of the reconstructed mass spectrum may be reduced if not performed properly.

  The present invention has been made in order to solve the above-mentioned problems, and the purpose of the present invention is to correct normalization due to the emission timing from the orbit when reconstructing a plurality of time-of-flight spectra obtained by multiple laps. By making it possible to confirm the presence of ions that have not been detected, it is possible to prevent components from being overlooked and overlooked. Especially for complex time-of-flight spectra in which various ions exist, peak intensity It is an object of the present invention to provide a multi-round time-of-flight mass spectrometer and a mass spectrometry method that can accurately obtain a high-accuracy mass spectrum.

In order to solve the above problems, the first invention is to introduce various ions starting from an ion source repeatedly into a detector along a circular orbit, and then introduce the mass spectrum on the basis of the detection signal. A mass spectrometry method using a multi-round time-of-flight mass spectrometer to obtain,
a) In the first measurement mode in which ions are allowed to fly with a number of laps that is guaranteed not to catch up or overtake different types of ions without making multiple laps along the orbit, or even when making multiple laps. A first measurement mode execution step of performing mass analysis on the measurement sample and obtaining a non-overtaking time-of-flight spectrum based on a detection signal obtained by the detector;
b) Mass spectrometry for the sample to be measured in the second measurement mode in which ions are released from the orbit and are introduced into the detector after a predetermined time after multiple orbits so that overtaking of ions occurs on the orbit. Performing a second measurement mode for obtaining an overtaking time-of-flight spectrum based on a detection signal obtained by the detector;
c) multiplying a matrix having elements of the intensity of each peak on the overtaking time-of-flight spectrum obtained by execution of the second measurement mode and a matrix having elements of the intensity of each peak on the target mass spectrum; An arithmetic processing step for obtaining a coefficient matrix equal to a matrix having the intensity of each peak on the overtaking time-of-flight spectrum as an element, and calculating an inverse matrix of the coefficient matrix to obtain the target mass spectrum;
And the computing step uses a regularized general inverse matrix of the inverse matrix to minimize the square error between the estimated target mass spectrum and the true mass spectrum approximated by the non-passing time-of-flight spectrum. It is characterized by obtaining a general inverse matrix.

In the mass spectrometry method according to the first invention, specifically, when a coefficient matrix of m rows and n columns is A, a regularized general inverse matrix represented by the following equation is used, and the regularization parameter λ in the equation is expressed as λ = Σ (standard deviation of noise), and the penalty matrix P is P = (X ₀ X ₀ ^T ) ⁻¹ (where X ₀ is a mass spectrum obtained from the non-passing time- of -flight spectrum). The mean square error between the mass spectrum and the mass spectrum obtained from the non-passing time-of-flight spectrum can be minimized.
When m ≦ n, A ⁺ = A ^T (AA ^T + λ ² P) ⁻¹
Where P is m rows and m columns
When m> n
A ⁺ = ( A ^T A + λ ² P) ⁻¹ A ^T
Where P is n rows and n columns

Further, the second invention made to solve the above problems is to introduce various ions starting from an ion source repeatedly into a detector along a circular orbit and then introduce them into a detector, and based on the detection signal, a mass spectrum. A mass spectrometry method using a multi-round time-of-flight mass spectrometer that acquires
a) Mass spectrometry based on a measurement mode in which ions are released from the orbit and introduced into the detector after a predetermined time after multiple orbits so that overtaking of ions occurs on the orbit is performed from the orbit. A measurement execution step of performing two or more times on the sample to be measured while changing the timing of the separation of and acquiring two or more overtaking time-of-flight spectra based on a detection signal obtained by the detector;
b) The point of giving a spread in time of flight to the matrix whose element is the intensity of each peak on the target mass spectrum and the relationship between one of the two or more overtaken time-of-flight spectra acquired and the target mass spectrum. Multiply by a coefficient matrix that introduces a spread function to organize a relationship that obtains a matrix having the intensity of each peak on the overtaking time-of-flight spectrum as an element, and simultaneously establish the relationship with respect to the two or more obtained overtaking time-of-flight spectra. An arithmetic processing step of calculating an inverse matrix of the coefficient matrix using a regularized general inverse matrix in order to obtain a target coefficient spectrum,
It is characterized by having.

In the multi-orbit time-of-flight mass spectrometer, once the extraction time of ions from the orbit is determined, a one-to-many relationship between the time of flight and the mass-to-charge ratio is theoretically obtained. That is, since it is known what mass-to-charge ratio ions may appear corresponding to a certain flight time (however, the number of laps varies depending on the mass-to-charge ratio), a certain flight time on the flight time spectrum The peak intensity at can be expressed by a linear combination of peak intensities at a plurality of mass-to-charge ratios on the mass spectrum. For this reason, the matrix Y having the peak intensity at each time of flight on the overtaking time spectrum as the element and the matrix X having the peak intensity at each mass-to-charge ratio on the target mass spectrum as the elements are Y with the coefficient matrix being A. = AX, where A is a sparse matrix containing several elements with a value of 1. Since obtaining the mass spectrum means obtaining the elements of the matrix X, if the inverse matrix A ⁻¹ of the coefficient matrix A is obtained, the mass spectrum can be obtained from the observed time-of-flight spectrum.

  Although it is effective to use a regularized general inverse matrix to obtain the inverse matrix as described above, in the first invention, in particular, a constraint based on the non-overtaking time-of-flight spectrum is attached to the penalty matrix of the regularized general inverse matrix . Specifically, a generalized inverse matrix is used to minimize the square error between the estimated target mass spectrum and the true mass spectrum approximated by the non-passing time-of-flight mass spectrum. Ask for. Thereby, the target mass spectrum can be estimated accurately.

  On the other hand, an ion having a certain mass-to-charge ratio spreads in time with flight and is observed at a plurality of times of flight. Therefore, in the second invention, the point spread function that gives the spread is introduced into the coefficient matrix. Then, two or more multiple orbital flight time spectra having different numbers of laps are used as simultaneous determinants, and by solving this, a generalized inverse matrix is obtained to calculate a mass spectrum. This makes it possible to obtain consistent mass spectral peaks for multiple time-of-flight spectral peaks measured under the same conditions for ions of the same type (with the same mass charge). Calculation is possible. However, since the coefficient matrix of the simultaneous determinant is usually a huge matrix, it is often difficult to calculate a generalized inverse matrix due to hardware limitations. Therefore, a Bayesian successive approximation method can be used as an alternative solution.

That is, in the third invention made to solve the above-mentioned problem, various ions starting from the ion source are repeatedly caused to fly along the circular trajectory and then introduced into the detector, and the mass is determined based on the detection signal. A mass spectrometry method using a multi-round time-of-flight mass spectrometer that acquires a spectrum,
a) Mass spectrometry based on a measurement mode in which ions are released from the orbit and introduced into the detector after a predetermined time after multiple orbits so that overtaking of ions occurs on the orbit is performed from the orbit. A measurement execution step of performing two or more times on the sample to be measured while changing the timing of the separation of and acquiring two or more overtaking time-of-flight spectra based on a detection signal obtained by the detector;
b) The point of giving a spread in time of flight to the matrix whose element is the intensity of each peak on the target mass spectrum and the relationship between one of the two or more overtaken time-of-flight spectra acquired and the target mass spectrum. Multiply by a coefficient matrix that introduces a spread function to organize a relationship that obtains a matrix having the intensity of each peak on the overtaking time-of-flight spectrum as an element, and simultaneously establish the relationship with respect to the two or more obtained overtaking time-of-flight spectra. A coefficient matrix, and based on each element of the coefficient matrix and the intensity of each peak on the overtaking time-of-flight spectrum, a Bayesian iterative solution to the point spread function is used for each mass-to-charge ratio on the target mass spectrum. An arithmetic processing step for calculating a peak intensity;
It is characterized by having.

The Bayesian successive approximation method for the point spread function is a method generally used for image processing or the like, and the peak intensity at each mass-to-charge ratio on the target mass spectrum can be calculated using this method. Specifically, the probability that a true peak occurs at m / z = i on the mass spectrum is f (i), and the point spread at which the peak at m / z = i is observed at time tof = k on the time-of-flight spectrum. When the function is h (k | i), the following recurrence formula is obtained.
f ^{r + 1} (i) = ^fr (i) Σ _k {h (k | i) f (i) · h (k) / {Σ _j f ^r (j) · h (k | j)}
if converges when r → ∞ to ^{f r (i) → f (} i), the equation in r → calculated as ∞ f ^r (i) is determined f (i), i.e. at the target mass-to-charge ratio Peak intensity. Of course, it is not necessary to make r → ∞ practically, and approximation can be terminated at the stage where r is set to an appropriate value.

A fourth invention made to solve the above problems is an apparatus for carrying out the mass spectrometry method according to the first invention, wherein various ions starting from an ion source are repeatedly flew a plurality of times along a circular orbit. In a multi-turn time-of-flight mass spectrometer that is introduced into a detector and acquires a mass spectrum based on the detection signal,
a) In the first measurement mode in which ions are allowed to fly with a number of laps that is guaranteed not to catch up or overtake different types of ions without making multiple laps along the orbit, or even when making multiple laps. First measurement mode execution means for performing mass spectrometry on the measurement sample and obtaining a non-overtaking time-of-flight spectrum based on a detection signal obtained by the detector;
b) Mass spectrometry for the sample to be measured in the second measurement mode in which ions are released from the orbit and are introduced into the detector after a predetermined time after multiple orbits so that overtaking of ions occurs on the orbit. And a second measurement mode executing means for acquiring a passing time-of-flight spectrum based on a detection signal obtained by the detector;
c) multiplying a matrix having elements of the intensity of each peak on the overtaking time-of-flight spectrum obtained by execution of the second measurement mode and a matrix having elements of the intensity of each peak on the target mass spectrum; A means for obtaining a coefficient matrix equal to a matrix having the intensity of each peak on the overtaking time-of-flight spectrum as an element, and calculating an inverse matrix of the coefficient matrix to obtain the target mass spectrum, Arithmetic processing means for obtaining a general inverse matrix so as to minimize a square error between a target mass spectrum to be estimated and a true mass spectrum approximated by the non-passing time-of-flight spectrum using a regularized general inverse matrix;
It is characterized by having.

A fifth invention made to solve the above problems is an apparatus for carrying out the mass spectrometry method according to the second invention, wherein various ions starting from an ion source are repeatedly flew a plurality of times along a circular orbit. In a multi-turn time-of-flight mass spectrometer that is introduced into a detector and acquires a mass spectrum based on the detection signal,
a) Mass spectrometry based on a measurement mode in which ions are released from the orbit and introduced into the detector after a predetermined time after multiple orbits so that overtaking of ions occurs on the orbit is performed from the orbit. Measurement execution means for changing the timing of separation of the sample to be measured twice or more with respect to the sample to be measured, and obtaining two or more overtaking time-of-flight spectra based on a detection signal obtained by the detector;
b) The point of giving a spread in time of flight to the matrix whose element is the intensity of each peak on the target mass spectrum and the relationship between one of the two or more overtaken time-of-flight spectra acquired and the target mass spectrum. Multiply by a coefficient matrix that introduces a spread function to organize a relationship that obtains a matrix having the intensity of each peak on the overtaking time-of-flight spectrum as an element, and simultaneously establish the relationship with respect to the two or more obtained overtaking time-of-flight spectra. An arithmetic processing means for calculating an inverse matrix of the coefficient matrix using a regularized general inverse matrix in order to obtain a target coefficient matrix,
It is characterized by having.

A sixth invention made to solve the above problems is an apparatus for carrying out the mass spectrometry method according to the third invention, and various ions starting from an ion source are repeatedly flew a plurality of times along a circular orbit. In a multi-turn time-of-flight mass spectrometer that is introduced into a detector and acquires a mass spectrum based on the detection signal,
a) Mass spectrometry based on a measurement mode in which ions are released from the orbit and introduced into the detector after a predetermined time after multiple orbits so that overtaking of ions occurs on the orbit is performed from the orbit. Measurement execution means for changing the timing of separation of the sample to be measured twice or more with respect to the sample to be measured, and obtaining two or more overtaking time-of-flight spectra based on a detection signal obtained by the detector;
b) The point of giving a spread in time of flight to the matrix whose element is the intensity of each peak on the target mass spectrum and the relationship between one of the two or more overtaken time-of-flight spectra acquired and the target mass spectrum. Multiply by a coefficient matrix that introduces a spread function to organize a relationship that obtains a matrix having the intensity of each peak on the overtaking time-of-flight spectrum as an element, and simultaneously establish the relationship with respect to the two or more obtained overtaking time-of-flight spectra. A coefficient matrix, and based on each element of the coefficient matrix and the intensity of each peak on the overtaking time-of-flight spectrum, a Bayesian iterative solution to the point spread function is used for each mass-to-charge ratio on the target mass spectrum. Arithmetic processing means for calculating peak intensity;
It is characterized by having.

  According to the mass spectrometry method according to the first to third inventions and the mass spectrometry apparatus according to the fourth to sixth inventions, it is possible to obtain a long flight distance by repeatedly flying ions along a circular orbit. Based on the time-of-flight spectrum, a mass spectrum with high mass resolution and mass accuracy and accurate peak intensity can be obtained. Even when the number of components contained in the sample to be measured is large or when the number of acquired multi-round flight time spectra is small, an accurate and high mass resolution mass spectrum can be obtained.

The schematic block diagram of MT-TOFMS by one Example of this invention. The flowchart which shows the analysis procedure in MT-TOFMS of a present Example. The conceptual diagram of the structure of a coefficient matrix. The figure which shows the mass spectrum estimated by the square error minimum method. The conceptual diagram of the structure of a coefficient matrix at the time of introducing a point spread function. The figure which shows the mass spectrum estimated by the Bayesian iterative approximation method. The figure which shows the result of having simulated the flight time spectrum of the frequency | count of 1 round. The figure which shows the mass spectrum produced by converting the horizontal axis of the time-of-flight spectrum of FIG. 7 into m / z. The enlarged view (a) near the maximum peak in the time-of-flight spectrum shown in FIG. 7 and the enlarged view (b) near the maximum peak in the mass spectrum shown in FIG. The figure which shows the time-of-flight spectrum which simulated the case where an ion which is m / z150 radiates | emits from a circular orbit at the timing after 100 laps. The figure which shows the relationship between m / z and the frequency | count of a rotation in the conditions shown in FIG. The figure which shows the relationship between m / z and tof value on the conditions shown in FIG. The figure which shows a mass spectrum when conversion is performed appropriately. FIG. 14 is an enlarged view near the maximum peak in the mass spectrum shown in FIG. 13. The figure which shows the mass spectrum obtained by reconstructing the time-of-flight spectrum shown in FIG. 10 using one of the conventional methods. The figure which shows intensity distribution of the peak of the tof value in which the peak of 2 types of ions of m / z179 and m / z138 overlapped.

  An embodiment of a mass spectrometer to which the mass spectrometry method according to the present invention is applied will be described with reference to the accompanying drawings. FIG. 1 is a schematic configuration diagram of the MT-TOFMS of this embodiment.

  In the ion source 1, sample molecules are ionized, and the generated various ions are given predetermined energy to start flying. The ion source 1 temporarily holds various externally generated ions, such as a three-dimensional quadrupole ion trap, and applies energy to these ions at a predetermined timing for flight. It can be started.

  Ions that have started flying from the ion source 1 are introduced into the orbit 5 via the deflection electric field formed by the gate electrode 2. The orbit 5 is formed by the action of an electric field generated by each of the plurality of toroidal sector electrodes 4. Note that the shape of the circular track 5 is not limited to this, and various shapes such as an 8-shaped shape can be realized. Further, it may be a linear or curved reciprocating orbit, a spiral orbit whose position gradually shifts, etc., instead of a completely closed orbit.

  The ions are released (exited) from the circular orbit 5 via the deflection electric field formed by the gate electrode 2 after making one or more rounds in the circular orbit 5 and reach the detector 8 provided outside to be detected. The In this example, the gate electrode 2 for entering the circular orbit 5 and the gate electrode 2 for emitting from the circular orbit 5 are common, but this may be different, or a part of the sector electrode 4 may be a gate electrode. It can also be set as the structure used instead of 2.

  The detection signal from the detector 8 is input to the data processing unit 9, where the flight time from when the ions exit the ion source 1 until finally reaching the detector 8 is measured, and a flight time spectrum is created. Is done. Further, a mass spectrum is created from the time-of-flight spectrum by executing data analysis processing as will be described later. The incoming / outgoing voltage generator 11 applies a deflection voltage for injecting ions to the circular orbit 5 and a deflection voltage for emitting ions from the circular orbit 5 to the gate electrode 2 at a predetermined timing. The orbital flight voltage generator 12 forms a sector electric field by applying a predetermined voltage to each of the plurality of sector electrodes 4. These voltage generators 11 and 12 and the ion source 1 all operate under the control of the control unit 10. The control unit 10 is connected to an input unit 13 for inputting various parameters for analysis by a user and a display unit 14 for displaying analysis results such as a mass spectrum.

In Figure 1, incident track 6 is ion flight path to the entrance point of the orbit 5 from the ion source 1, the distance is L _in. The exit trajectory 7 is a flight path of ions from the ion exit point from the orbit 5 to the detector 8, and the distance is L _out . Further, the flight distance of one turn of the orbit 5, that is, the _turn length is L _turn .

  In the MT-TOFMS of this embodiment, various ions emitted from the ion source 1 pass through the incident orbit 6 and are introduced into the orbit 5 via the gate electrode 2 controlled by the incident / exit voltage generator 11. The orbit 5 flies around the orbit 5 one or more times in accordance with the electric sector formed by the sector electrode 4 controlled by the flight voltage generator 12. The emission of various ions from the ion source 1 is almost simultaneous, but the ions having a smaller mass-to-charge ratio have a faster flight speed. Therefore, as ions circulate along the orbit 5, the intervals between ions having different mass-to-charge ratios. Will open. When the voltage applied to the gate electrode 2 from the input / output voltage generator 11 is switched to the ion emission voltage in a state where the ions are circulating on the circular orbit 5, the ions are in the circular orbit 5 in the order of arrival at the gate electrode 2. , And reaches the detector 8 through the exit track 7.

  Since the orbit 5 is closed, when ions continue to circulate along the orbit 5, the low mass-to-charge ratio ions having the fastest flight speed among the introduced ions are Catch up and overtake the slowest mass to charge ratio ions. Up to that point, by switching the voltage applied to the gate electrode 2 to the extraction voltage between the time when the ion with the lowest velocity passes through the gate electrode 2 and the time when the ion with the highest velocity reaches the gate electrode 2, the mass charge The circular orbits 5 can be separated from the ions having a small ratio in order and reach the detector 8. The measurement mode in which this is guaranteed is the first measurement mode, and the time-of-flight spectrum obtained under the first measurement mode is referred to as a non-overtaking time-of-flight spectrum. In this case, the number of circulations of ions corresponding to all peaks appearing on the time-of-flight spectrum is the same.

  On the other hand, when overtaking occurs even with one kind of ion on the circular orbit 5, the order of ions reaching the detector 8 is not in the order of decreasing mass-to-charge ratio after that point. This measurement mode is called the second measurement mode, and the time-of-flight spectrum obtained under the second measurement mode is called the overtaking time-of-flight spectrum. In this case, the number of circulations of the ions corresponding to the peak appearing on the time-of-flight spectrum is not the same, and the number of circulations of the ions that are delayed is relatively small. However, since the mass resolution depends on the flight distance, that is, the number of laps, the mass resolution increases as the number of laps increases. Therefore, in order to calculate an accurate mass-to-charge ratio, it is necessary to obtain a mass spectrum from an overtaking time-of-flight spectrum rather than a non-overtaking time-of-flight spectrum. Therefore, the MT-TOFMS of this embodiment performs characteristic measurement and data processing for that purpose. This will be described with reference to FIGS.

Before describing the mass spectrometry method according to the present invention, a case where the accuracy of the derived mass spectrum is reduced in the mass spectrometry method proposed in Patent Document 5 described above will be described.
The relationship between the flight time tof and the mass to charge ratio m / z in MT-TOFMS can be expressed by the following formula (2) or (3). At this time, the number of turns n _turn can be calculated by equation (4).
Here, u is the atomic mass [kg], e is the elementary charge [C], V ₀ is the ion acceleration voltage [V], L _in , L _out , and L _turn are the distances [m] and T in FIG. _g represents a time [sec] for opening the gate electrode 2 in order to release ions on the orbit 5.

FIG. 7 shows the result of simulating the time-of-flight spectrum at the number of laps 1 with n _turn = 1 in the above equation (2). FIG. 8 is a mass spectrum created by converting the horizontal axis of the time-of-flight spectrum of FIG. 7 into m / z. In the time-of-flight spectrum shown in FIG. 7, there is no ion overtaking. Therefore, although the peak intensity of the mass spectrum shown in FIG. 8 is accurate, the mass resolution is low. 9A is an enlarged view in the vicinity of tof = 30.6989 [μsec], which is the maximum peak in the time-of-flight spectrum shown in FIG. 7, and FIG. 9B is m / which is the maximum peak in the mass spectrum shown in FIG. It is an enlarged view near z200. FIG. 9B shows that the half-value width of the peak is widened and the mass resolution is low.

  FIG. 10 shows a time-of-flight spectrum that simulates the case where the gate electrode 2 is opened and ions are emitted from the circular orbit 5 at the timing after the ion of m / z 150 has made 100 laps. The vertical axis of this time-of-flight spectrum has the same relative intensity as that in FIG. 7, and there is a peak whose intensity exceeds 100 although 100 is originally the maximum. From this, it can be inferred that in this time-of-flight spectrum, peaks derived from a plurality of ions having different m / z are observed overlapping (simultaneously).

  At this time, when the number of times of ion circulation is calculated using the above equation (4), it can be seen that ions in the mass range of m / z 100 to 200 rotate 86 times to 126 times as shown in FIG. Further, when the relationship between the mass-to-charge ratio m / z and the flight time tof is obtained by the above equations (2) and (3), it is as shown in FIG. That is, it can be seen that while the tof value is determined according to the m / z value, a plurality of discrete m / z values correspond to one tof value. As shown in FIG. 11, if ions with overlapping peaks can be separated from the time-of-flight spectrum in which peaks derived from ions with different m / z overlap, the number of laps can be determined appropriately, respectively. A mass spectrum as shown is obtained. FIGS. 14A and 14B are enlarged views near the maximum peak in FIGS. As shown in FIG. 14B, it can be seen that in this case, the half width of the peak in the mass spectrum is very narrow, and the mass resolution is high.

  FIG. 15 shows a mass spectrum obtained by reconstructing the multi-round flight time spectrum shown in FIG. 10 using the method proposed in Patent Document 5. As can be seen by comparing this mass spectrum with the mass spectrum shown in FIG. 13, the peak intensity is not correctly estimated although there is no peak disappearing. This is because the peak intensity where ions of different m / z overlap in the time-of-flight spectrum may be mistakenly distributed to other ions in the mass spectrum. It is. As an example, FIG. 16 shows an intensity distribution of a peak having a tof value = 1049.0 [μsec] in which peaks of two kinds of ions m / z 179 and m / z 138 overlap. Int. In FIG. 16 is the intensity distributed as a result of processing. As can be seen in this figure, the intensity of this peak should originally be assigned only to m / z 179 and m / z 138, but in fact, there are other m / z 148.9712, m / z 191.0519, etc. It has also been assigned to ions with a mass-to-charge ratio. As the number of ions contained in the sample to be measured increases, the possibility of such inappropriate intensity distribution increases, and as a result, the accuracy of the intensity of the mass spectrum decreases.

  In contrast, in the data processing employed in the mass spectrometry method according to the present invention, the relative intensity of the peak can be estimated with high accuracy even when there are many types of ions contained in the sample to be measured. FIG. 2 is a flowchart showing a characteristic analysis procedure in MT-TOFMS of this embodiment.

  When performing measurement on an unknown sample to be measured, the sample to be measured is controlled under the control of the control unit 10 under the first measurement mode, that is, under conditions in which it is guaranteed that no overtaking of different types of ions occurs. Is subjected to mass spectrometry, and a non-overtaking time-of-flight spectrum is acquired (step S1). In the non-overtaking time-of-flight spectrum, no catch-up or overtaking of different types of ions occurs, so that the ion peaks are arranged in descending order of flight speed, that is, in descending order of mass to charge ratio.

  When the component contained in the sample to be measured is completely unknown, various ions starting from the ion source 1 may be introduced into the detector 8 without being circulated at all along the circular orbit 5. In the configuration of FIG. 1, it is only necessary to pass the circular orbit 5 by passing various ions straight as they are without applying a deflection voltage to the gate electrode 2 and directly guiding the incident orbit 6 to the exit orbit 7. In addition, when the component contained in the sample to be measured can be estimated, and when it is certain that various ions are put on a circular orbit and circulated 1 to a small number of times, it is sure that no ion catch-up or overtaking occurs. Such laps may be allowed.

  Next, with respect to the same sample to be measured, a second measurement mode, that is, a voltage applied to the gate electrode 2 so that various ions orbit around the orbit 5 is directed to the detector 8 via the gate electrode 2 is applied. Control and execute mass analysis to acquire the overtaking time-of-flight spectrum (step S2). In this overtaking time-of-flight spectrum, since different types of ions are overtaking, the peaks are not arranged in ascending order of mass to charge ratio, and the number of rounds of each peak is not the same.

Now, let us consider the case where the overtaking time-of-flight spectrum is obtained as shown in FIG. As described above, the number of laps of ions having m / z 100 to 200 on this time-of-flight spectrum is 86 to 122, and the relationship between the mass-to-charge ratio m / z and the number of laps n _turn is shown in FIG. 11 as shown. Therefore, it can be considered that each peak on the time-of-flight spectrum observed as shown in FIG. 10 is obtained by adding peaks derived from ions having different numbers of laps. Taking an example based on the relationship between the tof value and the m / z value shown in FIG. 12, the ion intensity y (1049.0) of tof = 1049.0 [μsec] is expressed as x (m / z ) Is expressed by the following equation (5).
y (1049.0) = x (179.0000) + x (138.0001) + x (148.9712) + x (191.0519) + ... (5)
Similarly, the peak intensity y (vector of length m: m is the number of sample points in the tof value) at all tof values is the peak intensity x (vector of length n: n is a sample at m / z). Represented by several additions of points). Therefore, the determinant by the following equation (6) is established. Here, X is a matrix having x (m / z) as an element, and Y is a matrix having y (tof) as an element.
Y = AX (6)
A is a coefficient matrix, which is a sparse matrix including several elements having a value of 1. FIG. 3 conceptually shows the structure of the coefficient matrix A. The number of rows of the coefficient matrix A is the number of measured tof samples, the number of columns is the number of m / z samples on the mass spectrum after conversion, and the filled portion in FIG. Yes. The data processing unit 9 calculates the coefficient matrix A based on the spectrum data constituting the overtaking flight time spectrum (step S3).

If equation (6) is modified, the following equation (7) is obtained. That is, if the peak intensity y (tof) observed on the time-of-flight spectrum is multiplied by the inverse matrix A ⁻¹ of the coefficient matrix A having m rows and n columns, the peak intensity x at the target mass-to-charge ratio m / z. (m / z) can be obtained.
X = A ⁻¹ Y (7)
Therefore, the operation of obtaining the mass spectrum from the time-of-flight spectrum is reduced to the operation of calculating the inverse matrix A ⁻¹ from the coefficient matrix A. In general, there are several methods for finding a certain inverse matrix.
Specifically, the Moore-Penrose general inverse matrix (pseudo inverse matrix) A ⁺ shown in the following equation (8) is used to obtain the inverse matrix A ⁻¹ in the above equation (7). Then, there is a method of calculating a minimum norm solution with a constraint that minimizes the norm of X.
A ⁺ = A ^T (AA ^T ) ⁻¹ (8)
More generally, by using a regularized general inverse matrix shown in the following equation (9), a least square constraint can be added simultaneously with a minimum norm constraint. Here, λ is a regularization parameter, and P is a penalty matrix.
When m ≦ n, A ⁺ = A ^T (AA ^T + λ ² P) ⁻¹ (9)
Where P is m rows and m columns
When m> n
A ⁺ = ( A ^T A + λ ² P) ⁻¹ A ^T (9)
Here, P is n rows and n columns. The evaluation function at this time is expressed by the following equation (10).
S (x) = | y- Ax | 2 + λ 2 x T Px ... (10)
The above equation (8) is a unique case where λ = 0 in equation (9).

In this embodiment, a regularized general inverse matrix is calculated by an algorithm of the mean square error minimization method. That is, in Equations (9) and (10), assuming that λ = σ (standard deviation of noise) and P = <x ₀ x ₀ ^T > ⁻¹ (= R _xx ⁻¹ ), the estimated mass spectrum x The mean square error with the true mass spectrum x ₀ can be minimized. The inverse matrix and evaluation function at this time are as follows.
When m ≦ n, A ⁺ = A ^T (AA ^T + σ ² R _xx ⁻¹ ) ⁻¹ (11)
When m> n
A ⁺ = (R _xx A ^T A + σ ² I) ⁻¹ R _xx A ^T (11)
S (x) = <(x ₀ −x) ^T (x ₀ −x)> (12)
R _xx, that is, the true mass spectrum x ₀ is originally unknown, but the mass spectrum obtained from the non-overtaking time-of-flight spectrum as shown in FIG. 8 has a low mass resolution, but the relative intensity of each peak is almost the true mass spectrum. Can be considered to be reflected. Therefore, here, the true mass spectrum x ₀ is approximated by the mass spectrum obtained from the non-overtaking time-of-flight spectrum obtained in step S1. Thereby, the inverse matrix of the coefficient matrix A obtained in step S3 can be obtained based on the equations (11) and (12) (step S4).

  In the data processing unit 9, when the inverse matrix is obtained, the peak intensity at each mass to charge ratio is calculated based on the equation (7) (step S5), and a mass spectrum is created and displayed on the display unit 14 (step S5). S6).

FIG. 4 shows the result of estimating the mass spectrum based on the equation (11) for the overtaking time-of-flight spectrum shown in FIG. However, in this example, since R _xx could not be calculated due to the limitation of the computer memory for arithmetic processing, peaks are picked from the time-of-flight spectrum shown in FIG. The peak of was estimated. It can be seen that although the peaks on the mass spectrum shown in FIG. 4 are all uniformly smaller in intensity than the correct estimated mass spectrum shown in FIG. 13, the relative intensity is obtained correctly. When actually displaying a mass spectrum, the vertical axis is generally displayed as a relative intensity, so the above point is not a problem in practice.
As described above, according to the data processing using the mean square error minimization method, it has the same peak intensity as the mass spectrum obtained from the non-passing time-of-flight spectrum, and the high time resolution achieved with the overtaking time-of-flight spectrum. Can be used to create a mass spectrum with high mass resolution.

Next, a mass spectrometry method based on another embodiment of the present invention will be described. In this method, instead of acquiring the non-overtaking time-of-flight spectrum in the first measurement mode, the ion extraction timing (time for opening the gate electrode 2) from the circular orbit 5 is changed so that the number of circulations of the same type of ions is different. Two or more overtaking time-of-flight spectra are acquired. In this case, a coefficient matrix is calculated from data constituting two or more overtaking time-of-flight spectra, and a point spread function is introduced at that time.
That is, a certain m / z ion spreads in flight and is observed at several tof values. This ion spread follows a point spread function. Here, the point spread function is regarded as a Gaussian function expressing the standard deviation in mass resolution. In this case, the peak intensity y (tof) at a certain tof value on the time-of-flight spectrum is a result of overlapping spreads from nearby points. Therefore, the above formula (5) is transformed into the following formula (13), where h (u) is the point spread function.
y (1049.0) = Σh (u) × (179.0000−u) + Σh (u) × (138.0001−u) + Σh (u) × (148.9712−u) + Σh (u) × (191.0519−u) + (13) )
Therefore, the elements of the coefficient matrix A into which the point spread function is introduced include not only 1 but also a probability density value in which the sum of h (u) is 1. The concept of the structure of the coefficient matrix A in this case is shown in FIG. Here, the shading in FIG. 5 represents the magnitude of the element value.

Since the number of expressions representing the relationship between one overtaking time-of-flight spectrum and one (only) mass spectrum can be the same as the number of overtaking time-of-flight spectra, they are considered as simultaneous equations. For example, if there are two passing time-of-flight spectra obtained by measurement and these are Y ₁ and Y ₂ and the coefficient matrices are A ₁ and A ₂ , respectively, the number of laps can be calculated by determinant (14). The corrected mass spectrum X can be obtained.
From the above, the problem of obtaining the mass spectrum by correcting the difference in flight distance caused by the difference in the number of laps from the overtaking time-of-flight spectrum measured by multiple laps of ions is obtained from Y to X (or y ( tof) to x (m / z)). This is the same as the relationship of equation (6). In this case, since the coefficient matrix is not a square matrix, it is common to use the regularized general inverse matrix shown in Equation (9), and a mass spectrum can be obtained if it can be calculated. However, in general, it is difficult to obtain a regularized general inverse matrix from a large matrix with complex elements as shown in FIG. 5 due to hardware limitations. For example, when the coefficient matrix A when the time-of-flight spectrum shown in FIG. 10 is Y is calculated, it becomes a huge matrix of 238263 rows and 194014 columns, and a general-purpose computer cannot calculate an inverse matrix due to memory restrictions.

Therefore, here, in order to calculate an inverse matrix for the coefficient matrix into which the point spread function is introduced, a Bayesian successive approximation method for the point spread function is used. That is, the probability that a true peak occurs at m / z = i is f (i), the probability that a peak generated at m / z = i is observed at tof = k is h (k | i), and tof = k. When the conditional probability that the observed peak actually occurs when m / z = i is F (i | k), Equation (15) is established from the well-known Bayes' theorem.
F (i | k) = f (i) · h (k | i) / {Σ _j f (j) · h (k | j)} (15)
The original peak f (i) is
f (i) = Σ _k F (i | k) · h (k) (16)
It is. Substituting equation (15) into equation (16),
f (i) = Σ _k {h (k | i) f (i) · h (k) / {Σ _j f (j) · h (k | j)} (17)
It becomes. When f (i) on the right side of the equation (17) is f ^r (i) and f (i) on the left side is f ^{r + 1} (i), the following recurrence equation (18) is obtained.
f ^{r + 1} (i) = ^fr (i) Σ _k {h (k | i ) · h (k) / {Σ _j ^fr (j) · h (k | j)} (18)

If f ^r (i) is r → ∞ and converges to f ^r (i) → f (i), f ^r (i) obtained as r → ∞ in equation (18) becomes f (i). Can be considered. However, when r = 0 as an initial value, f ⁰ (i) = 1. Here, h (k | i) in equation (17) is a point spread function (Gaussian function) where the peak of m / z = i is observed at tof = k, and h (k) is observed at tof = k. As the peak intensity, the peak intensity f (i) at m / z = i is converged while increasing r in order. In practice, sufficient accuracy can be ensured even if the calculation for m / z = i is terminated when the number of r, that is, the number of repeated calculations reaches a predetermined value.

  FIG. 6 shows a mass spectrum that is a result of performing the frequency correction of the time-of-flight spectrum shown in FIGS. 7 and 10 by the Bayesian successive approximation method described above. Since the peak intensity on the mass spectrum in FIG. 6 is obtained as a peak area, it is different from the mass spectrum shown in FIG. 13, but there is no practical problem because the relative intensity is obtained correctly.

  Unlike the mean square error minimization method described above, this Bayesian successive approximation method does not require a non-overtaking time-of-flight spectrum with a low mass resolution, and obtains a mass spectrum from only the overtaking time-of-flight spectrum with a relatively high mass resolution. be able to. For this reason, even when the number of time-of-flight spectra used for processing is small, for example, as in the above example, a mass spectrum with high mass resolution can be obtained.

  It should be noted that the above embodiment is an example of the present invention, and it is obvious that any modification, correction, or addition as appropriate within the scope of the present invention is included in the scope of the claims of the present application.

DESCRIPTION OF SYMBOLS 1 ... Ion source 2 ... Gate electrode 4 ... Toroidal fan-shaped electrode 5 ... Circumference track | orbit 6 ... Incidence track | orbit 7 ... Output track 8 ... Detector 9 ... Data processing part 10 ... Control part 11 ... Incoming / outgoing voltage generator 12 ... Circulation flight voltage Generating unit 13 ... input unit 14 ... display unit

Claims (7)

Mass using a multi-round time-of-flight mass spectrometer that introduces various ions starting from the ion source to the detector after repeatedly flying along the orbit, and acquires a mass spectrum based on the detection signal. An analysis method,
a) In the first measurement mode in which ions are allowed to fly with a number of laps that is guaranteed not to catch up or overtake different types of ions without making multiple laps along the orbit, or even when making multiple laps. A first measurement mode execution step of performing mass analysis on the measurement sample and obtaining a non-overtaking time-of-flight spectrum based on a detection signal obtained by the detector;
b) Mass spectrometry for the sample to be measured in the second measurement mode in which ions are released from the orbit and are introduced into the detector after a predetermined time after multiple orbits so that overtaking of ions occurs on the orbit. Performing a second measurement mode for obtaining an overtaking time-of-flight spectrum based on a detection signal obtained by the detector;
c) multiplying a matrix having elements of the intensity of each peak on the overtaking time-of-flight spectrum obtained by execution of the second measurement mode and a matrix having elements of the intensity of each peak on the target mass spectrum; An arithmetic processing step for obtaining a coefficient matrix equal to a matrix having the intensity of each peak on the overtaking time-of-flight spectrum as an element, and calculating an inverse matrix of the coefficient matrix to obtain the target mass spectrum;
And the computing step uses a regularized general inverse matrix of the inverse matrix to minimize the square error between the estimated target mass spectrum and the true mass spectrum approximated by the non-passing time-of-flight spectrum. A mass spectrometric method characterized in that a general inverse matrix is obtained as follows. The mass spectrometric method according to claim 1,
When a coefficient matrix of m rows and n columns is A, a regularized general inverse matrix represented by the following formula is used, a regularization parameter λ in the formula is λ = σ (standard deviation of noise), and a penalty matrix P is P = (X ₀ X ₀ ^T ) ⁻¹ (where X ₀ is the mass spectrum obtained from the non-passing flight time spectrum), and the average of the estimated target mass spectrum and the mass spectrum obtained from the non-passing flight time spectrum A mass spectrometry method characterized by minimizing the square error.
When m ≦ n, A ⁺ = A ^T (AA ^T + λ ² P) ⁻¹
Where P is m rows and m columns
When m> n
A ⁺ = ( A ^T A + λ ² P) ⁻¹ A ^T
Where P is n rows and n columns
Mass using a multi-round time-of-flight mass spectrometer that introduces various ions starting from the ion source to the detector after repeatedly flying along the orbit, and acquires a mass spectrum based on the detection signal. An analysis method,
a) Mass spectrometry based on a measurement mode in which ions are released from the orbit and introduced into the detector after a predetermined time after multiple orbits so that overtaking of ions occurs on the orbit is performed from the orbit. A measurement execution step of performing two or more times on the sample to be measured while changing the timing of the separation of and acquiring two or more overtaking time-of-flight spectra based on a detection signal obtained by the detector;
b) The point of giving a spread in time of flight to the matrix whose element is the intensity of each peak on the target mass spectrum and the relationship between one of the two or more overtaken time-of-flight spectra acquired and the target mass spectrum. Multiply by a coefficient matrix that introduces a spread function to organize a relationship that obtains a matrix having the intensity of each peak on the overtaking time-of-flight spectrum as an element, and simultaneously establish the relationship with respect to the two or more obtained overtaking time-of-flight spectra. An arithmetic processing step of calculating an inverse matrix of the coefficient matrix using a regularized general inverse matrix in order to obtain a target coefficient spectrum,
A mass spectrometric method characterized by comprising: Mass using a multi-round time-of-flight mass spectrometer that introduces various ions starting from the ion source to the detector after repeatedly flying along the orbit, and acquires a mass spectrum based on the detection signal. An analysis method,
a) Mass spectrometry based on a measurement mode in which ions are released from the orbit and introduced into the detector after a predetermined time after multiple orbits so that overtaking of ions occurs on the orbit is performed from the orbit. A measurement execution step of performing two or more times on the sample to be measured while changing the timing of the separation of and acquiring two or more overtaking time-of-flight spectra based on a detection signal obtained by the detector;
b) The point of giving a spread in time of flight to the matrix whose element is the intensity of each peak on the target mass spectrum and the relationship between one of the two or more overtaken time-of-flight spectra acquired and the target mass spectrum. Multiply by a coefficient matrix that introduces a spread function to organize a relationship that obtains a matrix having the intensity of each peak on the overtaking time-of-flight spectrum as an element, and simultaneously establish the relationship with respect to the two or more obtained overtaking time-of-flight spectra. A coefficient matrix, and based on each element of the coefficient matrix and the intensity of each peak on the overtaking time-of-flight spectrum, a Bayesian iterative solution to the point spread function is used for each mass-to-charge ratio on the target mass spectrum. An arithmetic processing step for calculating a peak intensity;
A mass spectrometric method characterized by comprising: In a multi-round time-of-flight time-type mass spectrometer that introduces various ions starting from an ion source to a detector after repeatedly flying a plurality of times along a circular orbit, and acquires a mass spectrum based on the detection signal,
a) In the first measurement mode in which ions are allowed to fly with a number of laps that is guaranteed not to catch up or overtake different types of ions without making multiple laps along the orbit, or even when making multiple laps. First measurement mode execution means for performing mass spectrometry on the measurement sample and obtaining a non-overtaking time-of-flight spectrum based on a detection signal obtained by the detector;
b) Mass spectrometry for the sample to be measured in the second measurement mode in which ions are released from the orbit and are introduced into the detector after a predetermined time after multiple orbits so that overtaking of ions occurs on the orbit. And a second measurement mode executing means for acquiring a passing time-of-flight spectrum based on a detection signal obtained by the detector;
c) multiplying a matrix having elements of the intensity of each peak on the overtaking time-of-flight spectrum obtained by execution of the second measurement mode and a matrix having elements of the intensity of each peak on the target mass spectrum; A means for obtaining a coefficient matrix equal to a matrix having the intensity of each peak on the overtaking time-of-flight spectrum as an element, and calculating an inverse matrix of the coefficient matrix to obtain the target mass spectrum, Arithmetic processing means for obtaining a general inverse matrix so as to minimize a square error between a target mass spectrum to be estimated and a true mass spectrum approximated by the non-passing time-of-flight spectrum using a regularized general inverse matrix;
A mass spectrometer comprising: In a multi-round time-of-flight time-type mass spectrometer that introduces various ions starting from an ion source to a detector after repeatedly flying a plurality of times along a circular orbit, and acquires a mass spectrum based on the detection signal,
a) Mass spectrometry based on a measurement mode in which ions are released from the orbit and introduced into the detector after a predetermined time after multiple orbits so that overtaking of ions occurs on the orbit is performed from the orbit. Measurement execution means for changing the timing of separation of the sample to be measured twice or more with respect to the sample to be measured, and obtaining two or more overtaking time-of-flight spectra based on a detection signal obtained by the detector;
b) The point of giving a spread in time of flight to the matrix whose element is the intensity of each peak on the target mass spectrum and the relationship between one of the two or more overtaken time-of-flight spectra acquired and the target mass spectrum. Multiply by a coefficient matrix that introduces a spread function to organize a relationship that obtains a matrix having the intensity of each peak on the overtaking time-of-flight spectrum as an element, and simultaneously establish the relationship with respect to the two or more obtained overtaking time-of-flight spectra. An arithmetic processing means for calculating an inverse matrix of the coefficient matrix using a regularized general inverse matrix in order to obtain a target coefficient matrix,
A mass spectrometer comprising: In a multi-round time-of-flight time-type mass spectrometer that introduces various ions starting from an ion source to a detector after repeatedly flying a plurality of times along a circular orbit, and acquires a mass spectrum based on the detection signal,
a) Mass spectrometry based on a measurement mode in which ions are released from the orbit and introduced into the detector after a predetermined time after multiple orbits so that overtaking of ions occurs on the orbit is performed from the orbit. Measurement execution means for changing the timing of separation of the sample to be measured twice or more with respect to the sample to be measured, and obtaining two or more overtaking time-of-flight spectra based on a detection signal obtained by the detector;
b) The point of giving a spread in time of flight to the matrix whose element is the intensity of each peak on the target mass spectrum and the relationship between one of the two or more overtaken time-of-flight spectra acquired and the target mass spectrum. Multiply by a coefficient matrix that introduces a spread function to organize a relationship that obtains a matrix having the intensity of each peak on the overtaking time-of-flight spectrum as an element, and simultaneously establish the relationship with respect to the two or more obtained overtaking time-of-flight spectra. A coefficient matrix, and based on each element of the coefficient matrix and the intensity of each peak on the overtaking time-of-flight spectrum, a Bayesian iterative solution to the point spread function is used for each mass-to-charge ratio on the target mass spectrum. Arithmetic processing means for calculating peak intensity;
A mass spectrometer comprising: