# US 9,520,277 B2 · Substance identification method and mass spectrometry system used for the same method

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- Number: US 9,520,277 B2
- Document ID: US9520277B2
- Status: Granted
- Kind: B2
- Application number: 13/848,324
- Filed: 2013-03-21
- Published: 2013-09-26
- Granted: 2016-12-13
- Earliest claimed: 2012-03-22
- Assignees: Shimadzu Corporation
- Applicants: Shimadzu Corporation
- Inventors: Yoshihiro Yamada
- Web page: https://patentgrep.com/patent/US9520277B2

## CPC

- H01J 49/0036: {Step by step routines describing the handling of the data generated during a measurement}
- G16C 20/20: Identification of molecular entities, parts thereof or of chemical compositions
- G16C 99/00: Subject matter not provided for in other groups of this subclass
- H01J 49/004: {Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn}
- H01J: ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS (spark-gaps H01T; electric arc lamps H05B31/00; particle accelerators H05H)
- G16C: COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE

## Abstract

An identification probability estimation model, which shows the relationship between the S/N ratios of MS1 peaks and the cumulative number of the peaks in the case where MS2 measurements and identifications is performed in descending order of S/N ratio, is created beforehand from the S/N ratios of MS1 peaks as well as the results of MS1 or MS2 measurements and identifications (success or failure) performed for a number of fractionated samples obtained from a predetermined sample. Based on an evaluated value of the identification probability and that of the identification probability increment, an order of priority of MS2 measurements for a plurality of MS1 peaks is determined, and an MS2 measurement sequence which gives the maximal expectation value of the number of substances to be identified under a limitation on the number of MS2 measurements or other factors is determined.

## Claims

### Claim 1

A substance identification method for identifying a substance contained in each of a plurality of fractionated samples obtained by separating various substances contained in a sample according to a predetermined separation parameter comprising:
a) an identification probability estimation model creation step, in which an identification probability estimation model is created by using peak information values showing information on MSn-1 peaks found by MSn-1 measurements (where n is an integer equal to or greater than two) for a plurality of fractionated samples obtained from a predetermined sample and results of substance identification based on results of MSn measurements using each of the MSn-1 peaks as a precursor ion, the model showing a relationship between peak information values of a plurality of MSn-1 peaks originating from a same kind of sample and a cumulative number of peaks successfully identified through a series of MSn measurements and identifications in which the MSn-1 peaks are sequentially selected as a precursor ion in order of the s peak information values thereof, and identification probability estimation model information representing the identification probability estimation model is stored;
b) a peak information value acquisition step, in which, after an MSn-1 measurement for at least one fractionated sample obtained from a target sample to be identified has been completed, peak information value is obtained for each of a plurality of MSn-1 peaks selected as candidates of the precursor ion from among the MSn-1 peaks found by the MSn-1 measurement;
c) an identification probability estimation step, in which an estimated value of the identification probability of each of the MSn-1 peaks is calculated from the peak information values of the MSn-1 peaks obtained in the peak information value acquisition step, with reference to the identification probability estimation model derived from the identification probability estimation model information;
d) an identification probability increment estimation step, in which an estimated increment of the identification probability, which shows a degree of increase in the identification probability achieved by performing an MSn measurement for a same MSn-1 peak a plurality of times and accumulating the results of the measurement, is calculated from the estimated value of the identification probability calculated for each of a plurality of MSn-1 peaks selected as the candidates of the precursor ion in the identification probability estimation step;
e) an MSn measurement order determination step, in which, for each of a plurality of MSn-1 peaks selected as the candidates of the precursor ion, an order of priority of the MSn measurements for a plurality of MSn-1 peaks under the condition that a plurality of MSn measurements are allowed for the same MSn-1 peak is determined based on the estimated value of the identification probability of each MSn-1 peak calculated in the identification probability estimation step and the increment of the identification probability estimated in the identification probability increment estimation step;
f) an MSn spectrum acquisition step, in which MSn spectra are obtained by performing an MSn measurement for each of a plurality of fractionated samples obtained by separating the target sample to be identified according to the predetermined separation parameter and fractionating the sample, using the order of priority determined in the MSn measurement order determination step; and
g) a substance identification step, in which a substance contained in each of the plurality of fractionated samples is identified based on the MSn spectra obtained in the MSn spectrum acquisition step.

### Claim 2 (depends on 1)

The substance identification method according to claim 1, further comprising:
an MSn measurement sequence determination step, in which a measurement sequence for performing MSn measurements for a plurality of MSn-1 peaks is determined, based on the order of priority determined in the MSn measurement order determination step and the peak information value of each MSn-1 peak, under an upper limit of the number of times of the MSn measurements to be performed for one fractionated sample.

### Claim 3 (depends on 1)

The substance identification method according to claim 1, wherein:
a measurement for a predetermined sample is performed before the measurement for the target sample, and based on a result of the former measurement, the identification probability estimation model is created in the identification probability estimation model creation step.

### Claim 4 (depends on 1)

The substance identification method according to claim 1, wherein:
a measurement sequence of the MSn measurement for a fractionated sample is determined by a sequential process of the peak information value acquisition step, the identification probability estimation step, the MSn measurement order determination step and the MSn measurement sequence determination step before the MSn measurement for that fractionated sample is actually performed.

### Claim 5 (depends on 4)

The substance identification method according to claim 4, wherein:
a measurement sequence of the MSn measurement for a fractionated sample is determined by a sequential process of the peak information value acquisition step, the identification probability estimation step, the MSn measurement order determination step and the MSn measurement sequence determination step before the MSn measurement for that fractionated sample is performed; and
after the MSn measurement according to the measurement sequence is initiated, the measurement sequence is modified by using an identification result obtained in a course of the MSn measurement.

### Claim 6 (depends on 1)

The substance identification method according to claim 1, wherein:
the peak information values showing the information on MSn-1 peaks are signal-to-noise ratios.

### Claim 7

A mass spectrometry system used for identifying a substance or substances contained in each of a plurality of fractionated samples obtained by separating various substances contained in a sample according to a predetermined separation parameter, comprising:
a) an identification probability estimation model information memory for storing identification probability estimation model information representing an identification probability estimation model which shows a relationship between peak information values of a plurality of MSn-1 peaks originating from a same kind of sample and a cumulative number of MSn peaks successfully identified through a series of MSn measurements and identifications in which the MSn-1 peaks are sequentially selected as a precursor ion in order of the peak information values thereof, the identification probability estimation model being created by using the peak information values showing information on MSn-1 peaks found by MSn-1 measurements (where n is an integer equal to or greater than two) for a plurality of fractionated samples obtained from a predetermined sample and results of substance identification based on results of MSn measurements using each of the MSn-1 peaks as a precursor ion;
b) a peak information value obtainer, which, after an MSn-1 measurement for at least one fractionated sample obtained from a target sample to be identified has been completed, obtains a peak information value for each of a plurality of MSn-1 peaks selected as candidates of the precursor ion from among the MSn-1 peaks found by the MSn-1 measurement;
c) an identification probability estimator for calculating an estimated value of the identification probability of each of the MSn-1 peaks from the peak information values of the MSn-1 peaks obtained by the peak information value obtainer, with reference to the identification probability estimation model derived from the identification probability estimation model information;
d) an identification probability increment estimator, in which an estimated increment of the identification probability, which shows a degree of increase in the identification probability achieved by performing an MSn measurement for a same MSn-1 peak a plurality of times and accumulating the results of the measurement, is calculated from the estimated value of the identification probability calculated for each of a plurality of MSn-1 peaks selected as the candidates of the precursor ion by the identification probability estimator;
e) an MSn measurement order determiner for determining an order of priority of the MSn measurements of the plurality of MSn-1 peaks as the candidates of the precursor ion, under the condition that a plurality of MSn measurements are allowed for the same MSn-1 peak, based on the estimated value of the identification probability of each MSn-1 peak calculated by the identification probability estimator and the increment of the identification probability estimated by the identification probability increment estimator;
f) an MSn spectrum obtainer for obtaining MSn spectra by performing an MSn measurement for each of a plurality of fractionated samples obtained by separating the target sample to be identified according to the predetermined separation parameter and fractionating the sample, using the order of priority determined in the MSn measurement order determiner; and
g) a substance identifier for identifying a substance contained in each of the plurality of fractionated samples based on the MSn spectra obtained in the MSn spectrum obtainer.

### Claim 8 (depends on 7)

The mass spectrometry system according to claim 7, further comprising:
an MSn measurement sequence determiner, in which a measurement sequence for performing MSn measurements for a plurality of MSn-1 peaks is determined, based on the order of priority determined by the MSn measurement order determiner and the peak information value of each MSn-1 peak, under an upper limit of the number of times of the MSn measurements to be performed for one fractionated sample.

### Claim 9 (depends on 7)

The mass spectrometry system according to claim 7, wherein:
a measurement for a predetermined sample is performed before the measurement for the target sample, and based on a result of the former measurement, the identification probability estimation model is created by the identification probability estimation model creator.

### Claim 10 (depends on 7)

The mass spectrometry system according to claim 7, wherein:
a measurement sequence of the MSn measurement for a fractionated sample is determined by a sequential process performed by the peak information value obtainer, the identification probability estimator, the MSn measurement order determiner and the MSn measurement sequence determiner before the MSn measurement for that fractionated sample is actually performed.

### Claim 11 (depends on 10)

The mass spectrometry system according to claim 10, wherein:
a measurement sequence of the MSn measurement for a fractionated sample is determined by a sequential process performed by the peak information value obtainer, the identification probability estimator, the MSn measurement order determiner and the MSn measurement sequence determiner before the MSn measurement for that fractionated sample is performed; and
after the MSn measurement according to the measurement sequence is initiated, the measurement sequence is modified by using an identification result obtained in a course of the MSn measurement.

### Claim 12 (depends on 7)

The mass spectrometry system to claim 7, wherein:
the peak information values showing the information on MSn-1 peaks are signal-to-noise ratios.