Patent Description:
Chromatography/mass spectrometry techniques are analysis methods of obtaining a mass spectrum (MS spectrum) of each sample component by separating sample components in time by chromatography, sequentially ionizing the sample components, sorting the ionized components according to mass-to-charge ratio (m/z) by a mass analyzer, and detecting the ionized components. Among these techniques, tandem mass spectrometry is an analytical method consisting of sorting ions of a certain mass-to-charge ratio (m/z) as precursor ions, cleaving the sorted ions into product ions, and obtaining a mass spectrum (MS spectrum) of the product ions.

A mass spectrometer performing an analysis as described above is equipped with a data processor for analyzing mass spectra deriving from individual sample components. Analysis of the mass spectra permits quantitative and qualitative analysis of the sample. A data processor adapted for use in tandem mass spectrometry analysis is disclosed in patent document <NUM> below.

In a tandem mass analysis, the data processor set forth in this patent document <NUM> extracts candidate compositional formulas for a compound of interest based on the mass-to-charge ratio of molecular ion peaks of the compound of interest on an MS<NUM> spectrum derived from the first stage of mass analysis and computes composition scores indicative of the degrees of coincidence with theoretical mass values. Also, the processor extracts candidate chemical structural formulas for the compound of interest, makes tentative assignments of the peaks of MS<NUM> to MS<NUM> spectra derived by the latter stage of mass spectrometry for each of the extracted candidate chemical structural formulas, and computes partial structures' scores indicative of their degrees of coincidence. Then, the processor computes total scores based on the compositional scores and partial structures' scores for all the candidate chemical structural formulas, arrays the candidate chemical structural formulas in accordance with the total scores, and displays the result on a display unit.

Patent document <NUM> provides methods, systems and algorithms for identifying high-resolution mass spectra. In some embodiments, an analyte is ionized and analyzed using high-resolution mass spectrometry (MS) at high mass accuracy (such as ≦ /<NUM> ppm or ≦ /<NUM> ppm) and the obtained mass spectra are matched with one or more prospective candidate molecules or chemical formulas. The invention provides, for example, methods and systems wherein the possible fragments that can be generated from the candidate molecules or chemical formulas are determined as well as the masses of each of these fragments. The invention provides, for example, methods and systems wherein the high-resolution mass spectra are then compared with the calculated fragment masses for each of the candidate molecules or chemical formula, and the portion of the high-resolution mass spectra that corresponds or can be explained by the calculated fragment masses is determined.

Such a mass spectrometry data processor is restricted in application to tandem mass spectrometry and is designed without taking into account the application to general mass spectrometry.

Accordingly, it is an object of the present invention to provide an apparatus and method for processing mass spectrometry data in such a way that a compositional formula for a sample component under analysis can be easily selected even in general mass spectrometry applications.

This object is achieved in accordance with the teachings of the present invention by a mass spectrometry data processor adapted to perform a qualitative analysis of a sample component based both on a first mass spectrum obtained by ionizing the sample component by a soft ionization method and on a second mass spectrum obtained by ionizing the sample component by a hard ionization method;.

The mass spectrometry data processor comprises: a molecular ion peak detector for detecting one molecular ion peak from the first mass spectrum; and a fragment ion peak detector for detecting a plurality of fragment ion peaks from the second mass spectrum; The mass spectrometry data processor is configured to obtain estimated compositional formulas for the sample component from the molecular ion peak by estimating candidate compositional formulas that can have the mass-to-charge ratio of the molecular ion peak of the first mass spectrum, the first mass spectrum containing a mass spectral signal originating from molecular ions ionized without cleaving the molecules of the sample component, and obtain estimated compositional formulas for fragments constituting the sample component from the fragment ion peaks by estimating candidate compositional formulas of fragments that can have the mass-to-charge ratio of each fragment ion peak of the second mass spectrum, the second mass spectrum containing mass spectral signals originating from multiple fragment ions which have been ionized by cleavage of the molecules of the sample component. The mass spectrometry data processor is configured to make decisions as to whether the estimated compositional formulas for the fragments of each mass-to-charge ratio can be assigned to the estimated compositional formulas for the sample component depending on whether types of elements and a number of atoms of the estimated compositional formulas for the fragments of each mass-to-charge ratio is contained within ranges of types of elements and of a number of atoms of the estimated compositional formulas for the sample component; and compute section for computing the ratio of the fragment ion peaks having the estimated compositional formulas judged to be assignable to a total number of fragment ion peaks, as the degrees of coincidence of the estimated compositional formulas for the fragments with the estimated compositional formulas for the sample component.

According to the present invention constructed as described so far, it is possible to provide an apparatus and method for processing mass spectrometry data such that a compositional formula for a sample component under analysis can be easily selected even in general mass spectrometry applications other than tandem mass spectrometry.

Embodiments of apparatus and method for processing mass spectrometry data in accordance with the present invention are hereinafter described in detail with reference to the accompanying drawings. Prior to description of the embodiments, the configuration of a mass spectrometer equipped with a mass spectrometry data processor is schematically described by referring to <FIG>. In all the embodiments, identical components are indicated by identical reference numerals; a repetition of the description thereof is omitted.

<FIG> is a schematic diagram of a mass spectrometer equipped with a mass spectrometry data processor associated with an embodiment. As shown in this figure, the mass spectrometer, generally indicated by reference numeral <NUM>, operates to sequentially mass analyze sample components separated chromatographically. The spectrometer <NUM> includes a chromatographic separator <NUM>, an ionizer <NUM>, and a mass analyzer <NUM>, as well as a mass spectrometry data processor <NUM> or <NUM>' according to an embodiment. These components of the instrument are described in detail below.

The chromatographic separator <NUM> is an instrument section for separating a sample under analysis into components. The chromatographic separator <NUM> has a column for separating a sample under analysis into components. The column is filled with a stationary phase that allows the introduced sample to pass therethrough. Various components of the sample introduced in the column are separated in time according to their speeds in passing through the stationary phase and fed into the ionizer <NUM> at their intrinsic retention times (RT).

For example, a gas chromatograph is used as the chromatographic separator <NUM>. Note that the chromatographic separator is not limited to this example. The separator may also be a liquid chromatograph or other chromatograph.

The ionizer <NUM> operates to successively ionize the sample components which are supplied to the ionizer <NUM> successively or in turn after separated by the chromatographic separator <NUM>. An ion source using a soft ionization method and an ion source using a hard ionization method can be exchangeably used as the ionizer <NUM>. These ionization methods are described hereinafter.

In the soft ionization method, the molecules of sample components can be ionized without being cleaved. Examples of such soft ionization method include chemical ionization (CI), field ionization (FI), and photoionization (PI) but the ionization method used in the present invention is not restricted to them.

On the other hand, in the hard ionization method, the molecules of sample components can be cleaved to produce ionized fragments. One example of such hard ionization method is electron ionization (EI). Of course, the hard ionization method used in the present invention is not restricted to this.

The mass analyzer <NUM> operates to separate the ionized sample components according to mass-to-charge ratio (m/z) and to detect the separated components. The mass analyzer <NUM> includes a mass separating portion and a detector.

The mass separating portion separates the ions supplied from the ionizer <NUM> according to mass-to-charge ratio (m/z) and passes only ions of a certain mass-to-charge ratio (m/z) into the detector. In the mass separating portion, the mass-to-charge ratio (m/z) of ions made to reach the detector is scanned such that the ions arrive at the detector in order of their mass-to-charge ratios (m/z). This operation is repeated at regular intervals of time. Although no restriction is imposed on the ion separation method used in the mass separating portion, a time-of-flight (TOF) type is preferably used from the point of view of accuracy at which mass-to-charge ratio (m/z) is detected.

The detector detects the signal intensity (I) of ions separated according to mass-to-charge ratio (m/z) in the mass separating portion and extracts the obtained signal intensity (I) in a corresponding manner to each scan. Consequently, there is derived a mass spectral signal representing the ion signal intensity (I) which is plotted against mass-to-charge ratio (m/z) for each scan.

Mass spectrometry data processors <NUM> and <NUM>' are instruments associated with different embodiments. Each of these data processors <NUM> and <NUM>' analyzes a sample to be analyzed on the basis of a mass spectral signal produced from the detector of the mass analyzer <NUM>.

The mass spectrometry data processors <NUM> and <NUM>' associated with different embodiments and methods for processing of mass spectrometry data implemented by these data processors <NUM> and <NUM>' are next described in detail.

The mass spectrometer <NUM> performs two mass analyses on the same sample to thereby produce mass spectral signals. Based on these mass spectral signals, the mass spectrometry data processor <NUM> according to the first embodiment performs a qualitative analysis of a certain sample component to be analyzed. The first mass analysis is performed when the ionizer <NUM> implements a soft ionization method. The second mass analysis is performed when the ionizer <NUM> implements a hard ionization method.

This mass spectrometry data processor <NUM> includes an input/output controller <NUM>, a data storage section <NUM>, a mass spectrum acquisition section <NUM>, a molecular ion peak detector 15a, a fragment ion peak detector 15b, a composition estimator <NUM>, an assignment validity decision device <NUM>, a degree of coincidence computing section <NUM>, an image data generator <NUM>, a manual control unit <NUM>, and a display unit <NUM>. The configurations of these components are as follows.

The input/output controller <NUM> controls the operational timings of the other components constituting the mass spectrometry data processor <NUM> according to a preset program and operator's input action made through the manual control unit <NUM>, thereby carrying out processing of mass spectrometry data. The input/output controller <NUM> is connected with the detector of the mass analyzer <NUM>. As the aforementioned scan is repeated, mass spectral signals are successively produced from the detector and applied to the input/output controller <NUM> according to the retention time (RT). Processing of mass spectrometry data executed by the input/output controller <NUM> is described in detail in relation to a method for processing of mass spectrometry data described hereinafter.

Whenever a mass analysis is performed, a mass spectral signal produced from the detector of the mass analyzer <NUM> is stored in the data storage section <NUM> in association with the retention time (RT) based on instructions from the input/output controller <NUM>. A mass analysis is performed twice on the same sample. For each mass analysis, resulting data is stored in the data storage section <NUM>. In the first mass analysis, a soft ionization method is implemented in the ionizer <NUM>. In the second mass analysis, a hard ionization method is practiced in the ionizer <NUM>. Accordingly, for each mass analysis, a mass spectral signal related to the retention time (RT) is stored in the data storage section <NUM> in association with a sample name and a used mass spectrometry ionization method.

The mass spectrum acquisition section <NUM> acquires the mass spectral signal detected in a certain retention time (RT) from the mass spectral signals stored in the data storage section <NUM> based on instructions from the input/output controller <NUM>. In particular, the mass spectrum acquisition section <NUM> obtains the mass spectral signal detected at the certain retention time (RT) as a mass spectrum from among mass spectral signals extracted in accordance with a normal automatic peak detection (so-called peak search) program. In this automatic peak detection, removal of noise components from a signal of intensity (I) is also carried out automatically. Typically, the noise component removal is performed by subtracting a background level (i.e., an average value of the signal intensity (I) at the tail positions on the right and left sides of a peak top of mass-to-charge ratio (m/z) appearing at each peak position on a TICC) from the signal intensity (I) at the peak top.

When a soft ionization method is implemented in the ionizer <NUM> based on instructions from the input/output controller <NUM>, the molecular ion peak detector 15a detects molecular ion peaks from a first mass spectrum acquired by the mass spectrum acquisition section <NUM>. The molecular ion peak detector 15a detects as a molecular ion peak that peak in the mass spectrum acquired by the mass spectrum acquisition section <NUM> which produces a signal intensity in excess of a preset threshold value and which has the highest mass-to-charge ratio (m/z). The molecular ion peak detector 15a may execute a program that eliminates isotope peaks. The molecular ion peak detector 15a calculates the center of gravity of the detected peak and stores the position of the calculated center of gravity as the mass-to-charge ratio (m/z) of the molecular ion peak. Alternatively, the molecular ion peak detector 15a may detect as a molecular ion peak that peak of the highest signal intensity which is contained in the mass spectrum derived by the mass spectrum acquisition section <NUM>.

When a hard ionization method is implemented in the ionizer <NUM> based on instructions from the input/output controller <NUM>, the fragment ion peak detector 15b detects a plurality of fragment ion peaks from a second mass spectrum derived by the mass spectrum acquisition section <NUM>. For example, the peak detector 15b sets a threshold value for the signal intensity of the mass spectrum obtained by the mass spectrum acquisition section <NUM> and detects peaks exceeding the threshold value as fragment ion peaks. The peak detector 15b may execute a program that eliminates isotope peaks.

For each detected fragment ion peak, the fragment ion peak detector 15b computes its center of gravity and stores the position of the computed center of gravity as the mass-to-charge ratio (m/z) of the fragment ion peak.

Based on instructions from the input/output controller <NUM>, the composition estimator <NUM> estimates a compositional formula for a molecule that can have the mass-to-charge ratio (m/z) of the molecular ion peak detected by the molecular ion peak detector 15a. Thus, an estimated compositional formula is derived. The estimated compositional formula represents the analyte. Furthermore, based on instructions from the input/output controller <NUM>, the composition estimator <NUM> estimates compositional formulas respectively for fragments that can have mass-to-charge (m/z) ratios of the fragment ion peaks detected by the fragment ion peak detector 15b, thus obtaining estimated compositional formulas for the fragments.

The processing performed by the composition estimator <NUM> may be general processing for estimating compositions. In this case, during the above-described estimation of compositional formulas, a given mass range is set for the mass-to-charge ratio (m/z) of each peak, and the compositions of ions of the peaks are estimated within the set mass range. This mass range has values determined using measurement errors of the mass-to-charge ratio (m/z) in the mass spectrometer as a reference.

A mass analysis is performed twice on the same sample. For each of these analyses, the assignment validity decision device <NUM> compares the estimated compositional formulas obtained by the composition estimator <NUM>, makes a decision as to validity of assignment between the compared estimated compositional formulas, converts the result of the decision into numerical values, and stores them in memory. The processing performed by the assignment validity decision device <NUM> will be described in further detail in relation to the method for processing of mass spectrometry data described below.

The degree of coincidence computing section <NUM> calculates the degree of coincidence of each fragment ion peak for each compositional formula for molecules estimated by the composition estimator <NUM>, based on the result of decision digitized by the assignment validity decision device <NUM>. The processing performed by the degree of coincidence computing section <NUM> will be described in further detail in relation to the method for processing of mass spectrometry data described below.

The image data generator <NUM> generates image data to be displayed on the display unit <NUM> from various data created by the mass spectrum acquisition section <NUM>, molecular ion peak detector 15a, fragment ion peak detector 15b, composition estimator <NUM>, assignment validity decision device <NUM>, and degree of coincidence computing section <NUM>. Furthermore, the image data generator <NUM> displays the details of the processing performed by the mass spectrometry data processor <NUM>. In addition, the image data generator <NUM> creates image data to be displayed on the display unit <NUM> to permit an operator to select or set images by an operator's input through the manual control unit <NUM>. The image data will be described in greater detail in relation to the method for processing of mass spectrometry data described below.

The manual control unit <NUM> permits the operator to enter various settings regarding data processing performed by the mass spectrometry data processor <NUM>. One example of the various settings regarding data processing is a setting of the retention time (RT) of the mass spectral signal derived by the mass spectrum acquisition section <NUM>. The manual control unit <NUM> may, for example, be a keyboard, a mouse, or a touch panel controller integral with the display unit <NUM>.

The display unit <NUM> operates to display the image generated by the image data generator <NUM>. The display unit <NUM> may be equipped with a touch panel controller.

<FIG> is a flowchart illustrating a method for processing of mass spectrometry data executed by the mass spectrometry data processor <NUM> according to the first embodiment. This flowchart depicts the procedure of data processing carried out in accordance with programs preset into various sections of the mass spectrometry data processor <NUM>. The method for processing of mass spectrometry data illustrated in <FIG> is a method of performing a qualitative analysis of a certain component included in a sample based on mass spectral signals respectively obtained by two mass analyses on the same sample by means of the mass spectrometer <NUM> already described in connection with <FIG>. As described previously, in the first mass analysis, a soft ionization method is implemented in the ionizer <NUM>. In the second mass analysis, a hard ionization method is practiced in the ionizer <NUM>. The method for processing of mass spectrometry data according to the first embodiment is described below by referring to the flowchart of <FIG> and also to <FIG> and other pertinent figures.

In step S100, if settings of processing conditions are entered by the operator through the manual control unit <NUM>, the input/output controller <NUM> starts a routine for data processing. One example of the entered processing conditions is a retention time (RT) intrinsic to a certain sample component under analysis (analyte), i.e., the retention time (RT) of the analyte subjected to a qualitative analysis. The input/output controller <NUM> performs a first processing subroutine (steps S101a to S104a) in the left part of <FIG> and a second processing subroutine (steps S101b to S104b) in the right part of <FIG> in parallel and separately. The subroutines are hereinafter described in turn from the first subroutine.

In step S101a, the mass spectrum acquisition section <NUM> acquires a mass spectrum of the component which has been produced by a soft ionization method and which is subjected to a qualitative analysis, based on instructions from the input/output controller <NUM>. At this time, the mass spectrum acquisition section <NUM> selects those of mass spectral signals stored in the data storage section <NUM> which arise from the sample to be analyzed and for which a soft ionization method has been implemented as a mass spectrometry ionization method. The acquisition section <NUM> then extracts the mass spectral signal which has been stored in association with the retention time (RT) entered through the manual control unit <NUM> from the selected mass spectral signals and obtains a mass spectrum consisting of the extracted mass spectral signal as a first mass spectrum.

<FIG> shows one example of mass spectrum obtained by application of a soft ionization method for illustrating the first embodiment. This mass spectrum contains a mass spectral signal originating from molecular ions ionized without cleaving the molecules of the analyte.

In step S102a, the molecular ion peak detector 15a detects a molecular ion peak from the first mass spectrum obtained at step S101a based on instructions from the input/output controller <NUM>. At this time, as described previously, the molecular ion peak detector 15a detects as a molecular ion peak the peak which has a signal intensity in excess of a preset threshold value and the highest mass-to-charge ratio (m/z), and stores the center of gravity of the detected peak as the mass-to-charge ratio (m/z) of the molecular ion peak. In the example shown in <FIG>, the highest peak in the vicinity of mass-to-charge ratio (m/z) = <NUM> is detected as a molecular ion peak. The center of gravity ((m/z) = <NUM>) of the detected highest peak is computed. The computed center of gravity is stored as the mass-to-charge ratio (m/z) of the molecular ion.

In step S103a, the composition estimator <NUM> performs a processing subroutine for estimating the composition of the molecule based on instructions from the input/output controller <NUM>. At this time, the composition estimator <NUM> estimates in a manner described above all possible compositional formulas for the molecule which can result in the mass-to-charge ratio (m/z) of the molecular ion peak detected at step S102a, thus providing estimated compositional formulas. These estimated compositional formulas are estimated compositional formulas for the analyte.

In step S104a, the image data generator <NUM> creates image data that indicate all the estimated compositional formulas obtained at step S103a as candidate compositional formulas (<NUM>) for the analyte and displays the created image data on the display unit <NUM>. At this time, the image data generator <NUM> generates image data indicating the mass-to-charge ratios (m/z) of the molecular ion peaks corresponding to the estimated compositional formulas and displays the generated image data on the display unit <NUM> together with the estimated compositional formulas of the candidate compositional formulas (<NUM>) for the analyte, for example, as shown in <FIG>.

On the other hand, at step S101b, the mass spectrum acquisition section <NUM> acquires a mass spectrum of the analyte created by a hard ionization method, based on instructions from the input/output controller <NUM>. At this time, the mass spectrum acquisition section <NUM> selects those of mass spectral signals stored in the data storage section <NUM> which arise from the sample to be analyzed and for which a mass spectrometry ionization method has been effected. Then, the acquisition section <NUM> extracts that mass spectral signal from the selected mass spectral signals which has been stored in association with the retention time (RT) entered via the manual control unit <NUM>, and obtains a mass spectrum consisting of the extracted mass spectral signal as a second mass spectrum.

<FIG> shows one example of mass spectrum obtained by application of a hard ionization method for illustrating the first embodiment. This mass spectrum contains mass spectral signals originating from multiple fragment ions which have been ionized by cleavage of the molecules of the analyte.

In step S102b, the fragment ion peak detector 15b detects a plurality of fragment ion peaks from the mass spectrum obtained at step S101b based on instructions from the input/output controller <NUM>. At this time, as described previously, the peak detector 15b eliminates isotope peaks, sets a threshold value, detects fragment ion peaks, and stores the center of gravity of each detected fragment ion peak as its mass-to-charge ratio (m/z).

In step S103b, the composition estimator <NUM> performs an operation for estimating the compositions of the fragments based on instructions from the input/output controller <NUM>. At this time, the composition estimator <NUM> obtains the estimated compositional formulas by estimating, as noted above, all compositional formulas for the fragments which can produce the mass-to-charge ratios (m/z) of the fragment ion peaks detected at step S102b. The obtained estimated compositional formulas are estimated compositional formulas for fragments resulting from cleavage of the molecules of the analyte.

In step S104b, the image data generator <NUM> generates image data such that all of the estimated compositional formulas obtained at step S103b are indicated as candidate compositional formulas (<NUM>) by the generated image data, and displays the generated image data on the display unit <NUM>. At this time, the image data generator <NUM> creates image data indicating the estimated compositional formulas of the candidate compositional formulas (<NUM>) for the fragments resulting from cleavage of the analyte as well as the mass-to-charge ratios (m/z) of the fragment ion peaks corresponding to the estimated compositional formulas, and displays the generated image data on the display unit <NUM>, for example, as shown in <FIG>. As shown in the candidate compositional formulas (<NUM>) of <FIG>, estimated compositional formulas for one or more fragments are obtained in a corresponding manner to one fragment ion peak and its mass-to-charge ratio (m/z).

In step S105, if steps S104a and S104b are both performed, the input/output controller <NUM> causes the assignment validity decision device <NUM> to make a decision as to the validity of assignment between the candidate compositional formulas (<NUM>) and (<NUM>). <FIG> shows one example of the results of decisions made as to the validity of assignment of the candidate compositional formulas (<NUM>) to the candidate compositional formulas (<NUM>) in the first embodiment. As shown in this figure, the assignment validity decision device <NUM> compares all the estimated compositional formulas of the candidate compositional formulas (<NUM>) for the molecule shown at step S104a with all the estimated compositional formulas of the candidate compositional formulas (<NUM>) shown at step S104b for all the combinations. Then, the decision device <NUM> makes a decision as to the validity of the assignment of each compared estimated compositional formula, converts the results of the decisions into numerical values, and stores them.

The decision made by the assignment validity decision device <NUM> as to the validity of assignment depends on whether the types of elements and the number of atoms of one estimated compositional formula out of the candidate compositional formulas (<NUM>) for fragments are contained within the ranges of types of elements and of the number of atoms of one estimated compositional formula out of the candidate compositional formulas (<NUM>). If they are contained without problems, it is determined that the assignments are possible. If there is any problem, it is determined that the assignments are impossible.

At this time, if it is determined that at least one of the estimated compositional formulas for the plural fragments obtained from one fragment ion peak out of the candidate compositional formulas (<NUM>) for fragments can be assigned to one estimated compositional formula out of the candidate compositional formulas (<NUM>) for the analyte, the assignment validity decision device <NUM> determines that the assignments are possible. The decision device <NUM> converts the results of the decisions made as described so far as to the validity of assignments into numerical values and stores them in memory.

In this case, if it is determined as one example that the assignments are possible as illustrated in <FIG>, "<FIG>" is attached to the combination of the estimated compositional formulas. On the other hand, if it is determined that the assignments are impossible, "<NUM>" is attached to the combination of the estimated compositional formulas.

In step S106, the image data generator <NUM> generates image data indicating the result of the decision digitized at step S105 according to instructions from the input/output controller <NUM> and displays the generated image data in the form of a matrix on the display unit <NUM>. One example of this display is shown in the above-cited <FIG>.

In step S107, for each estimated compositional formula of the candidate compositional formulas (<NUM>), the degree of coincidence computing section <NUM> computes the degrees of coincidence of fragment ion peaks based on the result of decision digitized at step S105 according to instructions from the input/output controller <NUM>. At this time, the degree of coincidence computing section <NUM> calculates the ratio of the fragment ion peaks having the estimated compositional formulas judged to be assignable at step S105 to the total number of fragment ion peaks, the ratio being defined to be the degree of coincidence of the fragment ion peaks.

With respect to the estimated compositional formula No. <NUM> of the candidate compositional formulas (<NUM>) exemplified, for example, in <FIG>, the total number of fragment peaks is <NUM>. The number of fragment ion peaks having estimated compositional formulas judged to be assignable is <NUM>. The degree of coincidence is calculated to be <NUM>/<NUM> × <NUM> = <NUM>%. In the lowermost row of <FIG>, the computed degrees of coincidence are also shown.

In step S108, the image data generator <NUM> arrays the estimated compositional formulas of the candidate compositional formulas (<NUM>) in order of their degrees of coincidence computed at step S107, generates image data also indicating the degrees of coincidence, and displays them on the display unit <NUM>, according to instructions from the input/output controller <NUM>. <FIG> shows one example of displayed image or list that represents the results of computations of the degrees of coincidence according to the first embodiment. That is, <FIG> shows the degrees of coincidence computed in accordance with the procedure described thus far. Thus, the routine for processing of mass spectrometry data is ended.

In the first embodiment described so far, the degrees of coincidence of each estimated compositional formula for the sample component to be analyzed (analyte) with the fragments originating from the analyte are computed from a mass spectrum generated by mass spectrometry utilizing a soft ionization method and from a mass spectrum generated by mass spectrometry utilizing a hard ionization method. Consequently, one appropriate estimated compositional formula can be selected easily from a plurality of estimated compositional formulas obtained regarding the analyte, by referring to the computed degrees of coincidence even in general mass spectrometry other than tandem mass spectrometry.

Because estimated compositional formulas for the analyte are arranged in order of the values of the degree of coincidence computed by the degree of coincidence computing section <NUM> and displayed together with the degrees of coincidence on the display unit <NUM> as shown also in <FIG>, if there are only small variations among the degrees of coincidence, the operator can easily select an appropriate estimated compositional formula from among a plurality of estimated compositional formulas while taking account of the degrees of coincidence and other factors.

Furthermore, as shown in <FIG>, the results of decisions made by the assignment validity decision device <NUM> are displayed in the form of a matrix on the display unit <NUM> for all the combinations of the estimated computational formulas for the analyte and the estimated compositional formulas for the fragments. This makes it possible to select an appropriate one from among a plurality of estimated compositional formulas obtained from the analyte while referring to the fragments constituting the analyte. In addition, it is possible to know the validity of assignments of the fragment ion peaks to the estimated compositional formulas and so the presence or absence of components different from the analyte can be confirmed.

The mass spectrometry data processor <NUM>' of <FIG> according to the second embodiment is similar to the mass spectrometry data processor <NUM> according to the first embodiment except for the configuration of its input/output controller, <NUM>'. The manner in which the operational timings of various other instrument components are controlled by the program in the input/output controller <NUM>' are described below in relation to the method for processing of mass spectrometry data.

<FIG> is a flowchart illustrating a procedure of processing of mass spectrometry data performed by the mass spectrometry data processor <NUM>' according to the second embodiment. The data processing is effected according to programs preset into various portions of the mass spectrometry data processor <NUM>'. The procedure of the mass spectrometry data processing (<FIG>) according to the second embodiment is similar to the procedure of the mass spectrometry data processing (<FIG>) according to the first embodiment except that steps S109 and S110 are performed after step S108. A repetition of the description of the steps S100 to S108 is omitted here; the following description centers on the steps S109 and S110.

Steps S100 to S108 are identical to the steps described in the first embodiment and carried out in the same manner as in the first embodiment.

In step S109, the input/output controller <NUM>' makes a decision as to whether or not a modification to the conditions is carried out. At this time, the input/output controller <NUM>' displays an image, for example, on the display unit <NUM> to prompt the operator to make a decision as to whether or not a modification to the data processing conditions is selected. If the operator enters an input through the manual control unit <NUM> to select a modification to the data processing conditions, the decision is YES, indicating that a modification to the conditions is carried out, and control goes to step S110. On the other hand, if the operator enters an input through the manual control unit <NUM> not to select a modification to the data processing conditions, the decision is NO, indicating that the conditions are not modified, and the processing subroutine is ended.

<FIG> show mass spectra obtained by the processing of the above steps S100 to S108 and one example of image displayed on the display unit <NUM>. The processing of the above-described steps S100 to S108 illustrate a case where it is difficult to determine compositional formulas.

<FIG> shows one example of mass spectrum obtained by application of a soft ionization method for illustrating the second embodiment. This mass spectrum is one example of the first mass spectrum derived at the aforementioned step S101a. <FIG> shows one example of displayed image indicating the candidate compositional formulas (<NUM>) for molecules of the analyte according to the second embodiment. Of these figures, <FIG> shows an estimated compositional formula for the analyte, the formula being obtained by performing the processing of steps S102a to S104a based on the mass spectrum of <FIG>.

On the other hand, <FIG> shows one example of mass spectrum obtained by application of a hard ionization method for illustrating the second embodiment. This mass spectrum is one example of the second mass spectrum derived at the above-described step S101b. <FIG> shows one example of displayed image or list indicative of the candidate compositional formulas (<NUM>) for fragments according to the second embodiment, and gives estimated compositional formulas for fragments obtained by performing the processing of steps S102b to S104b, based on the mass spectrum of <FIG>.

<FIG> shows one example of the result of a decision made as to the validity of the assignments of the candidate compositional formulas (<NUM>) to the candidate compositional formulas (<NUM>) in the second embodiment and indicates the result of step S105. <FIG> shows the result of a decision made as to the validity of the assignments of the estimated compositional formulas of the candidate compositional formulas (<NUM>) shown in <FIG> to the estimated compositional formulas of the candidate compositional formulas (<NUM>) shown in <FIG>.

<FIG> shows one example of displayed image or list indicative of the results of computations of degrees of coincidence in the second embodiment. <FIG> shows the results of computations of the degrees of coincidence obtained by performing the processing sequence of steps S107 to S108 based on the results of decisions shown in <FIG>. As can be seen from <FIG>, in the processing sequence of steps S100 to S108, the degrees of coincidence computed using the estimated compositional formulas of the candidate compositional formulas (<NUM>) are identical in value. Therefore, it is difficult to determine the compositional formula for the analyte from this result.

In this case, the operator enters an input through the manual control unit <NUM> while viewing the result of <FIG> displayed at step S108 to select a modification to the data processing conditions. Consequently, in the present step S109, the input/output controller <NUM>' determines that the conditions are modified (YES), and control proceeds to step S110.

In step S110, if the operator enters a specified component and a processing method through the manual control unit <NUM>, the input/output controller <NUM>' attaches or detaches the specified component. The entered component is a component attached or detached to or from each estimated compositional formula of the candidate compositional formulas (<NUM>) of <FIG> displayed at step S104a. This component is an appropriate component specified and entered by the operator. The processing method entered at this time consists of attaching or detaching (removing) the specified component to or from the compositional formulas of the candidate compositional formulas (<NUM>) of <FIG> displayed at step S104a. The operator selects and enters either processing step (attaching step or detaching step).

An example is now given in which the operator considers that H<NUM>O has been detached from the analyte when the component is ionized by a soft ionization method. In this case, the operator enters H<NUM>O as a specified component through the manual control unit <NUM> and enters an attaching step as a processing method.

In the present step S110, the input/output controller <NUM>' adds the specified component H<NUM>O to the estimated compositional formulas of the candidate compositional formulas (<NUM>) displayed at step S104a in response to the specified component and processing method entered via the manual control unit <NUM>, thus creating new estimated compositional formulas. Then, control returns to step S104a.

In the next step S104a, the image data generator <NUM> generates image data that represent all new estimated compositional formulas created at step S110 as new candidate compositional formulas (<NUM>) for the analyte, and displays the image data on the display unit <NUM>. <FIG> shows the new candidate compositional formulas (<NUM>) for the analyte, the new formulas being displayed on the display unit <NUM>. The candidate compositional formulas (<NUM>) displayed at this time are the estimated compositional formulas of the candidate compositional formulas (<NUM>) of <FIG> displayed at the previous step S104a to which estimated formulas the specified component H<NUM>O has been added.

As a result of the processing sequence of the following steps S105 to S106, the result of the decision as to the validity of assignments of the candidate compositional formulas (<NUM>) to the new candidate compositional formulas (<NUM>) are displayed on the display unit <NUM> as shown in <FIG>. Also, as a result of the processing sequence of the following steps S107 to S108, the computed degrees of coincidence with the new candidate compositional formulas (<NUM>) are displayed on the display unit <NUM> as shown in <FIG>.

The operator can select the single estimated compositional formula having a degree of coincidence of <NUM>% as a compositional formula for the analyte from the results of <FIG> displayed at step S108. However, if the operator determines from this result that it is still difficult to determine a compositional formula for the analyte, then a modification to the data processing conditions can be selected again by entering an input via the manual control unit <NUM>.

Another example of the implementation of the method for processing of mass spectrometry data according to the second embodiment which has been described by referring to the flowchart of <FIG> is next described. This example is another case where it is difficult to determine a compositional formula using the processing sequence of the above-described steps S100 to S108.

Steps S101 to S108 are identical to the steps described in the first embodiment and carried out in the same way as in the latter steps.

In step S109, the input/output controller <NUM>' makes a decision as to whether a modification to the conditions is carried out in the same way as in the aforementioned step S109.

<FIG> show examples of the mass spectrum obtained by the processing sequence of the above-described steps S100 to S108 and examples of the image displayed on the display unit <NUM>. Another example is herein given in which it is difficult to determine a compositional formula with the processing sequence of the steps S100 to S108.

<FIG> shows another example of the mass spectrum obtained by a soft ionization method for illustrating the second embodiment. This mass spectrum is another example of the first mass spectrum derived at the previous step S101a. <FIG> shows another example of the displayed image or list indicative of candidate compositional formulas (<NUM>) for a certain analyte according to the second embodiment. <FIG> shows an estimated compositional formula for the analyte, the formula being obtained by carrying out the processing sequence of steps S102a to S104a, based on the mass spectrum of <FIG>.

On the other hand, <FIG> shows another example of the mass spectrum obtained by application of a hard ionization method, illustrating the second embodiment. This mass spectrum is one example of the second mass spectrum derived at the previously described step S101b. <FIG> shows another example of the displayed image indicative of candidate compositional formulas (<NUM>) for fragments according to the second embodiment, and depicts estimated compositional formulas for the fragments obtained by carrying out the processing sequence of steps S102b to S104b, based on the mass spectrum of <FIG>.

<FIG> shows a further example of the result of decision as to the validity of the assignments of the candidate compositional formulas (<NUM>) to the candidate compositional formulas (<NUM>) according to the second embodiment, and depicts the results of the execution of step S105. <FIG> shows the results of the decisions of the validity of the assignments of the estimated compositional formulas of the candidate compositional formulas (<NUM>) shown in <FIG> to the estimated compositional formulas of the candidate compositional formulas (<NUM>) shown in <FIG>.

<FIG> shows a further example of the displayed image indicative of the computed degrees of coincidence according to the second embodiment. <FIG> shows the computed degrees of coincidence obtained by performing the processing sequence of steps S107 to S108 based on the results of the decisions shown in <FIG>. As can be seen from <FIG>, in the processing sequence of steps S100 to S108, the computed degrees of coincidence for the compositional formulas of the candidate compositional formulas (<NUM>) are all identically equal to <NUM>%. It is difficult to determine a compositional formula for the analyte from this result.

In this case, the operator views the result of <FIG> displayed at step S108 and makes an input through the manual control unit <NUM> to select a modification to the data processing conditions. Consequently, in the present step S109, the input/output control unit <NUM>' determines that a modification to the data processing conditions is selected (YES) and control goes to step S110.

In step S110, if the operator enters a specified component and a processing method through the manual control unit <NUM>, the input/output controller <NUM>' carries out a step of attaching or detaching the specified component in the same manner as in the step S110 already described.

As a further example, it is assumed that the operator considers that C<NUM>H<NUM> is added to the analyte when various components are ionized, for example, by a soft ionization method and that the operator enters C<NUM>H<NUM> as a specified component and enters a removing step as a processing method through the manual control unit <NUM>.

In the present step S110, the input/output controller <NUM>' creates a new estimated compositional formula from which the specified component C<NUM>H<NUM> has been detached, for each estimated compositional formula of the candidate compositional formulas (<NUM>) displayed at step S104a in response to the specified component and processing method entered through the manual control unit <NUM>. Then, control returns to step S104a.

In the next step S104a, the image data generator <NUM> generates image data indicating all new estimated compositional formulas created at step S110 as new candidate compositional formulas (<NUM>) for the analyte and displays the generated image data on the display unit <NUM>. <FIG> shows the new candidate compositional formulas (<NUM>) for the analyte, the candidates being displayed on the display unit <NUM>. The candidate compositional formulas (<NUM>) displayed at this time are the estimated compositional formulas of the candidate compositional formulas (<NUM>) of <FIG> displayed at the previous step S104a from which the specified component C<NUM>H<NUM> has been eliminated.

As a result of the processing sequence of the following steps S105 to S106, the results of decisions as to the validity of assignments of the candidate compositional formulas (<NUM>) to the new candidate compositional formulas (<NUM>) are displayed on the display unit <NUM> as shown in <FIG>. As a result of the processing sequence of the following steps S107 to S108, computed degrees of coincidence with the new candidate compositional formulas (<NUM>) are displayed on the display unit <NUM> as shown in <FIG>.

The operator can select the estimated compositional formula having a sole degree of coincidence of <NUM>% as a compositional formula for the analyte from the results of <FIG> displayed at step S108. However, if the operator judges that it is still difficult to determine a compositional formula for the analyte based on the results, the operator can again select a modification to the data processing conditions by making an input through the manual control unit <NUM>.

The second embodiment described so far can yield further advantages compared with the first embodiment because of the addition of the steps S109 and S110. In particular, if there is a possibility of attachment or detachment of other components to or from the analyte when the analyte is mass analyzed using a soft ionization method because of the results obtained by execution of the steps S100 to S108, additional data processing designed taking account of this possibility can be performed. Consequently, a compositional formula for the analyte can be derived with greater accuracy.

Claim 1:
A mass spectrometry data processor (<NUM>, <NUM>') for performing a qualitative analysis of a sample component based both on a first mass spectrum obtained by ionizing the sample component by a soft ionization method, and on a second mass spectrum obtained by ionizing the sample component by a hard ionization method, said mass spectrometry data processor (<NUM>, <NUM>') comprising:
a molecular ion peak detector (15a) for detecting one molecular ion peak from said first mass spectrum;
a fragment ion peak detector (15b) for detecting a plurality of fragment ion peaks from said second mass spectrum;
wherein the mass spectrometry data processor is configured to:
obtain estimated compositional formulas for the sample component from said molecular ion peak by estimating candidate compositional formulas that can have the mass-to-charge ratio of the molecular ion peak of the first mass spectrum, the first mass spectrum containing a mass spectral signal originating from molecular ions ionized without cleaving the molecules of the sample component;
obtain estimated compositional formulas for fragments constituting said sample component from said fragment ion peaks by estimating candidate compositional formulas of fragments that can have the mass-to-charge ratio of each fragment ion peak of the second mass spectrum, the second mass spectrum containing mass spectral signals originating from multiple fragment ions which have been ionized by cleavage of the molecules of the sample component;
make decisions as to whether the estimated compositional formulas for the fragments of each mass-to-charge ratio can be assigned to the estimated compositional formulas for the sample component depending on whether types of elements and a number of atoms of the estimated compositional formulas for the fragments of each mass-to-charge ratio is contained within ranges of types of elements and of a number of atoms of the estimated compositional formulas for the sample component; and
compute a ratio of the fragment ion peaks having the estimated compositional formulas judged to be assignable to a total number of fragment ion peaks, as degrees of coincidence of the estimated compositional formulas for the fragments with the estimated compositional formulas for the sample component.