Methods and systems for quantitative mass analysis

Patent metadata

Field	Value
Publication number	US-10347477-B2
Application number	US-201815911304-A
Country	US
Kind code	B2
Filing date	Mar 5, 2018
Priority date	Mar 24, 2017
Publication date	Jul 9, 2019
Grant date	Jul 9, 2019

Abstract

A method of quantitative mass analysis of precursor ion species of different mass-to-charge (m/z) ratios from the same or common ion injection event is disclosed. A plurality of precursor ion species with different respective m/z ratios are introduced into an ion trap mass analyzer at the same time. The precursor ion species are isolated. A first subset of the isolated precursor ions, which are multiply charged and have a first m/z ratio range, is fragmented and scanned by dividing the scan into at least two separate scan windows. A first mass spectrum is generated for the fragment ions of the first subset of precursor ions. A second subset of the isolated precursor ions having a second m/z ratio is fragmented and scanned, and a second mass spectrum is generated for the fragment ions of the second subset of precursor ions.

First claim

What is claimed is:

1. A method of operating an ion trap mass analyzer for quantification of analytes in a sample, comprising:
a. introducing sample ions into the ion trap mass analyzer in a single injection event, the sample ions including first precursor ions having a first mass-to-charge ratio (m/z) range and second precursor having a second m/z range, the first precursor ions being multiply charged;
b. concurrently isolating the first precursor ions and the second precursor ions;
c. fragmenting the first precursor ions, but not the second precursor ions, to generate first product ions;
d. performing a first scan at a first value of a resonance ejection q to mass-selectively eject to a detector first product ions having m/z's lower than the second precursor ion m/z range, and performing a second scan at a second value of the resonance ejection q, lower than the first value, to mass-selectively eject to the detector first product ions having m/z's greater than the second precursor ion m/z range, wherein the second precursor ions are retained in the ion trap mass analyzer during the first and second resonance ejection scans;
e. fragmenting the second precursor ions to generate second product ions; and
f. performing a third scan to mass-selectively eject to the detector second product ions.

2. The method of claim 1 wherein the first precursor ions are one of analyte precursor ions and internal standard precursor ions, and the second precursor ions are the other of analyte precursor ions and internal standard precursor ions.

3. The method of claim 2 further comprising determining an amount of the analyte using a relationship between intensities of the first and second product ions measured in steps (d) and (f).

4. The method of claim 1 further comprising applying a notched waveform to concurrently isolate the first precursor ions and the second precursor ions from any background ions.

5. The method of claim 1 wherein the fragmenting is carried out using ion trap collision-induced dissociation (CID).

6. The method of claim 1 wherein the resonance ejection q values in step (d) range from about 0.05 to about 0.90.

7. The method of claim 6 wherein the first resonance ejection q value is approximately 0.78 and the second resonance ejection q value is approximately 0.30.

8. A method of operating an ion trap mass analyzer for quantification of analytes in a sample, comprising:
a. introducing sample ions into the ion trap mass analyzer in a single injection event, the sample ions including first precursor ions having a first mass-to-charge ratio (m/z) range and second precursor ions having a second m/z range, the first precursor ions being multiply charged;
b. concurrently isolating the first precursor ions and the second precursor ions;
c. fragmenting the first precursor ions, but not the second precursor ions, to generate first product ions of m/z above and below the second m/z;
d. performing a first scan divided into at least two separate scan windows to mass-selectively eject and detect the first product ions and acquire a first mass spectrum of the first product ions, while retaining in the ion trap the second precursor ions, by performing resonance ejections at different q-values in each scan window, while the low-mass cut-off (LMCO) is kept below the m/z of the second precursor ions;
e. fragmenting the second precursor ions to generate second product ions; and
f. performing a second scan to mass-selectively eject and detect the second product ions and acquire a second mass spectrum of the second product ions.

9. The method of claim 8 wherein the first precursor ions are one of analyte precursor ions and internal standard precursor ions, and the second precursor ions are the other of analyte precursor ions and internal standard precursor ions.

10. The method of claim 9 further comprising determining an amount of the analyte in the sample using a relationship between intensities of the product ions in the first mass spectrum and the second mass spectrum.

11. The method of claim 8 further comprising applying a notched waveform to concurrently isolate the first precursor ions and the second precursor ions from any background ions.

12. The method of claim 8 wherein the fragmenting is carried out using ion trap collision-induced dissociation (CID).

13. The method of claim 8 wherein the ejection q-values range from about 0.05 to about 0.90.

14. The method of claim 13 wherein the first resonance ejection q-value is approximately 0.78 and the second resonance ejection q-value is approximately 0.30.

15. The method of claim 8 wherein the RF amplitude is scanned from low mass value product ions to high mass value product ions.

16. The method of claim 8 wherein performing the second scan comprises dividing the second scan into at least two separate scan windows to mass-selectively eject and detect the second product ions and acquire the second mass spectrum of the second product ions.

17. An ion trap mass spectrometer system for quantification of analytes in a sample, comprising:
a. an ion source configured to generate sample ions, the sample ions including first precursor ions having a first mass-to-charge ratio (m/z) range and second precursor ions having a second m/z, the first precursor ions being multiply charged;
b. an ion trap mass analyzer positioned to receive the sample ions, the ion trap mass analyzer having a controller being programmed with an algorithm comprising instructions to the ion trap mass analyzer to cause the ion trap mass analyzer to performs steps of: (a) concurrently isolating the first precursor ions and the second precursor ions; (b) to fragment the first precursor ions, but not the second precursor ions, to generate first product ions of m/z above and below the second m/z; (c) performing a first scan divided into at least two separate scan windows to mass-selectively eject and detect the first product ions and acquire a first mass spectrum of the first product ions, while retaining in the ion trap the second precursor ions, by performing resonance ejections at different q-values in each scan window, while the low-mass cut-off (LMCO) is kept below the m/z of the second precursor ions; (d) fragmenting the second precursor ions to generate second product ions; and (e) performing a second scan to mass-selectively eject and detect the second product ions and acquire a second mass spectrum of the second product ions.

18. The system of claim 17 wherein the first precursor ions are one of analyte precursor ions and internal standard precursor ions, and the second precursor ions are the other of analyte precursor ions and internal standard precursor ions.

19. The system of claim 18 wherein an amount of the analyte in the sample is determined using a relationship between intensities of the product ions in the first mass spectrum and the second mass spectrum.

20. The system of claim 17 wherein the ejection q-values range from about 0.05 to about 0.90.

21. The system of claim 17 wherein performing the second scan comprises dividing the second scan into at least two separate scan windows to mass-selectively eject and detect the second product ions and acquire the second mass spectrum of the second product ions.

Assignees

• Thermo Finnigan Llc

Inventors

• Li Linfan
• Schwartz Jae C

Classifications

• H01J49/0031 Primary

  Step by step routines describing the use of the apparatus (H01J49/0081 takes precedence) · CPC title

• H01J49/0081

  Tandem in time, i.e. using a single spectrometer · CPC title

• G01N27/62 Primary

  by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode · CPC title

• H01J49/0009

  Calibration of the apparatus · CPC title

• H01J49/429

  Scanning an electric parameter, e.g. voltage amplitude or frequency · CPC title