Multi-dimensional survey scans for improved data dependent acquisitions

Patent metadata

Field	Value
Publication number	US-9576777-B2
Application number	US-201314386355-A
Country	US
Kind code	B2
Filing date	Mar 11, 2013
Priority date	Mar 22, 2012
Publication date	Feb 21, 2017
Grant date	Feb 21, 2017

Abstract

A method of analyzing ions is disclosed comprising performing an initial multi-dimensional survey scan comprising separating parent ions according to a first physico-chemical property (e.g. ion mobility) and then separating the parent ions according to a second physico-chemical property (e.g. mass to charge ratio). A plurality of parent ions of interest are then determined from the initial multi-dimensional survey scan. Once parent ions of interest have been determined, the plurality of parent ions of interest are sequentially selected based upon the first and second physico-chemical properties during a single cycle of separation. The parent ions of interest may then be fragmented and corresponding fragment ions may then be mass analyzed.

First claim

The invention claimed is:

1. A method of analysing ions in a Data Dependent Acquisition (DDA) experiment comprising:
performing an initial multi-dimensional survey scan comprising separating parent ions according to a first physico-chemical property and separating said parent ions according to a second physico-chemical property;
determining a plurality of parent ions of interest to be selected for the DDA experiment from said initial multi-dimensional survey scan; and then
sequentially selecting and transmitting said plurality of parent ions of interest based upon said first physico-chemical property and said second physico-chemical property during a single acquisition or cycle of separation; and
analysing either: (i) one or more of said plurality of parent ions of interest; or (ii) one or more fragment, product or other ions derived from one or more of said plurality of parent ions of interest.

2. A method as claimed in claim 1 , wherein said first physico-chemical property comprises ion mobility or differential ion mobility.

3. A method as claimed in claim 1 , wherein said first physico-chemical property comprises mass, mass to charge ratio or time of flight.

4. A method as claimed in claim 1 , wherein said second physico-chemical property comprises ion mobility or differential ion mobility.

5. A method as claimed in claim 1 , wherein said second physico-chemical property comprises mass, mass to charge ratio or time of flight.

6. A method as claimed in claim 1 , wherein the step of separating ions according to said first physico-chemical property comprises separating ions temporally.

7. A method as claimed in claim 1 , wherein the step of separating ions according to said second physico-chemical property comprises separating ions temporally.

8. A method as claimed in claim 1 , wherein the step of separating ions according to said first physico-chemical property comprises separating ions spatially.

9. A method as claimed in claim 1 , wherein the step of separating ions according to said second physico-chemical property comprises separating ions spatially.

10. A method as claimed in claim 1 , wherein the step of selecting said plurality of parent ions of interest comprises separating or filtering said parent ions according to said first physico-chemical property and filtering said parent ions according to said second physico-chemical property.

11. A method as claimed in claim 10 , wherein the step of selecting said plurality of parent ions of interest comprises separating or filtering said parent ions according to said first physico-chemical property which comprises ion mobility or differential ion mobility.

12. A method as claimed in claim 11 , further comprising using an ion mobility or differential ion mobility separator to separate said parent ions according to their ion mobility or differential ion mobility.

13. A method as claimed in claim 11 , wherein the step of selecting said plurality of parent ions of interest comprises filtering said parent ions according to said second physico-chemical property which comprises mass, mass to charge ratio or time of flight.

14. A method as claimed in claim 13 , further comprising using a quadrupole rod set mass filter to filter said parent ions according to their mass, mass to charge ratio or time of flight.

15. A method as claimed in claim 1 , wherein the step of selecting said plurality of parent ions of interest based upon said first physico-chemical property and said second physico-chemical property during a single acquisition or cycle of separation comprises using a quadrupole rod set mass filter to filter ions according to said second physico-chemical property which comprises mass, mass to charge ratio or time of flight.

16. A method as claimed in claim 15 , wherein said method further comprises applying a broadband excitation voltage to said mass filter in order to attenuate or reject ions having a range of masses or mass to charge ratios and wherein said broadband excitation voltage includes one or more frequency notches so that ions having specific desired masses or mass to charge ratios are not substantially attenuated or rejected by said mass filter.

17. A method as claimed in claim 1 , further comprising attenuating ions in a time dependent manner in order to prevent saturation of an ion detector.

18. A method as claimed in claim 1 , further comprising after the step of selecting one or more parent ions of interest causing said one or more parent ions of interest to fragment or react so as to form fragment or product ions.

19. A method as claimed in claim 1 , wherein said first physico-chemical property and said second physico-chemical property are the same or are substantially correlated.

20. A method as claimed in claim 1 , wherein said first physico-chemical property and said second physico-chemical property are substantially different or are substantially uncorrelated.

21. A method as claimed in claim 1 , further comprising increasing the spatial distribution of one or more of said plurality of parent ions of interest or one or more fragment, product or other ions derived from one or more of said plurality of parent ions of interest after one or more of said plurality of parent ions have been sequentially selected and transmitted and prior to the step of analysing either: (i) one or more of said plurality of parent ions of interest; or (ii) one or more fragment, product or other ions derived from one or more of said plurality of parent ions of interest.

22. A method of mass spectrometry, comprising a method as claimed in claim 1 .

23. An analytical instrument for analysing ions in a Data Dependent Acquisition (DDA) experiment comprising:
a first separator or filter for separating or filtering ions according to a first physico-chemical property;
a second separator or filter for separating or filtering ions according to a second physico-chemical property;
an analyser; and
a control system arranged and adapted:
(i) to perform an initial multi-dimensional survey scan comprising separating parent ions according to said first physico-chemical property using said first separator and separating said parent ions according to said second physico-chemical property using said second separator;
(ii) to determine a plurality of parent ions of interest to be selected for the DDA experiment from said initial multi-dimensional survey scan; and then
(iii) to sequentially select and transmit said plurality of parent ions of interest based upon said first physico-chemical property and said second physico-chemical property during a single acquisition or cycle of separation; and
(iv) to cause said analyser to analyse either: (i) one or more of said plurality of parent ions of interest; or (ii) one or more fragment, product or other ions derived from one or more of said plurality of parent ions of interest.

24. A mass spectrometer comprising an analytical instrument as claimed in claim 23 .

25. A method of analysing ions in a Data Dependent Acquisition (DDA) experiment comprising:
performing an initial multi-dimensional survey scan comprising separating parent ions according to a first physico-chemical property and separating said parent ions according to a second physico-chemical property;
determining a plurality of parent ions of interest to be selected for the DDA experiment from said initial multi-dimensional survey scan; and then fragmenting said parent ions to generate a

Assignees

• Micromass Ltd

Inventors

• Giles Kevin
• Wildgoose Jason Lee

Classifications

• H01J49/004 Primary

  Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn · CPC title

• H01J49/04

  Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components · CPC title

• H01J49/0031 Primary

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

• G01N27/624

  Differential mobility spectrometry [DMS]; Field asymmetric-waveform ion mobility spectrometry [FAIMS] · CPC title

• H01J49/40

  Time-of-flight spectrometers (H01J49/36 takes precedence) · CPC title