# US 2014/0197308 A1 · Function Switching With Fast Asynchronous Acquisition

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- Number: US 2014/0197308 A1
- Document ID: US20140197308A1
- Status: Published application
- Kind: A1
- Application number: 14/113,160
- Filed: 2012-04-20
- Published: 2014-07-17
- Earliest claimed: 2011-04-20
- Assignees: Micromass UK Limited
- Inventors: Martin Raymond Green
- Web page: https://patentgrep.com/patent/US20140197308A1

## CPC

- H01J 49/0031: {Step by step routines describing the use of the apparatus (H01J49/0081 takes precedence)}
- H01J 49/0036: {Step by step routines describing the handling of the data generated during a measurement}
- H01J 49/401: {characterised by orthogonal acceleration, e.g. focusing or selecting the ions, pusher electrode}
- H01J: ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS (spark-gaps H01T; electric arc lamps H05B31/00; particle accelerators H05H)

## Abstract

A method of analysing a sample is disclosed comprising transmitting a first population of ions through a mass spectrometer and switching a state or mode of the mass spectrometer to produce a second population of ions. A sequential stream of mass spectra is acquired asynchronously with respect to switching the state or mode of the mass spectrometer. The stream of mass spectral data is then post-processed to produce mass spectra corresponding predominantly to the first and second population of ions.

## Claims

### Claim 1

A method of analysing a sample comprising:
operating a mass spectrometer in a state or mode wherein first ions are analysed;
switching a state or mode of said mass spectrometer so that second ions are analysed;
acquiring a stream of mass spectral data wherein the acquisition of said mass spectral data is substantially asynchronous with and/or is not synchronised with the switching of said mass spectrometer between states or modes; and
post-processing said stream of mass spectral data to produce: (i) mass spectral data relating to said first ions; and/or (ii) mass spectral data relating to said second ions.

### Claim 2 (depends on 1)

A method as claimed in claim 1, wherein said method further comprises repeatedly switching said mass spectrometer between different states or modes.

### Claim 3 (depends on 1, 2)

A method as claimed in claim 1 or 2, wherein said step of switching a state or mode of said mass spectrometer comprises switching a state or mode or said mass spectrometer substantially abruptly and/or without pausing for a delay period during which delay period said mass spectrometer would otherwise be allowed to equilibrate.

### Claim 4 (depends on 1, 2, 3)

A method as claimed in claim 1, 2 or 3, wherein said step of switching a state or mode of said mass spectrometer comprises changing, switching, altering or varying the composition and/or intensity of a population of ions.

### Claim 5

A method as claimed in any preceding claim, wherein said step of switching a state or mode of said mass spectrometer comprises switching the polarity of an ion source.

### Claim 6

A method as claimed in any preceding claim, wherein said step of switching a state or mode of said mass spectrometer comprises fragmenting or reacting parent ions to produce fragment or product ions.

### Claim 7

A method as claimed in any preceding claim, wherein said step of switching a state or mode of said mass spectrometer comprises switching the transmission characteristics of a mass, mass to charge ratio, ion mobility or differential ion mobility filter or separator.

### Claim 8

A method as claimed in any preceding claim, wherein said step of switching a state or mode of said mass spectrometer comprises selecting a different species of parent or precursor ion.

### Claim 9

A method as claimed in any preceding claim, wherein said step of switching a state or mode of said mass spectrometer comprises selecting a different Collision Induced Dissociation collision energy.

### Claim 10

A method as claimed in any preceding claim, wherein said step of switching a state or mode of said mass spectrometer comprises selecting a different fragmentation or reaction state of said mass spectrometer so that different ions are fragmented or reacted and/or ions are fragmented or reacted to different degrees.

### Claim 11

A method as claimed in any preceding claim, wherein said step of switching a state or mode of said mass spectrometer comprises switching or altering an operational parameter of said mass spectrometer.

### Claim 12

A method as claimed in any preceding claim, wherein said stream of mass spectral data which is acquired is substantially continuous.

### Claim 13

A method as claimed in any preceding claim, wherein said step of acquiring a stream of mass spectral data comprises continuously acquiring a stream of mass spectral data.

### Claim 14

A method as claimed in any preceding claim, wherein said step of acquiring a stream of mass spectral data comprises substantially continuously acquiring mass spectral data without dividing a mass spectral data acquisition period into a plurality of mass spectral data acquisition windows separated from each other by an equilibration delay time period during which time period: (i) no mass spectral data is acquired; and/or (ii) said mass spectrometer is allowed to equilibrate; and/or (iii) said mass spectrometer is switched between states or modes.

### Claim 15

A method as claimed in any preceding claim, wherein said step of acquiring a stream of mass spectral data comprises substantially continuously acquiring mass spectral data without pausing the acquisition of said mass spectral data immediately before and/or during and/or immediately after a state or mode of said mass spectrometer has been switched.

### Claim 16

A method as claimed in any preceding claim, further comprising:
repeatedly switching said mass spectrometer between a first state or mode and a second state or mode, wherein said mass spectrometer is in said first state or mode for a time T1 and is in said second state or mode for a time T2;
wherein said stream of mass spectral data is continuously acquired over a time period>T1 and >T2.

### Claim 17

A method as claimed in any preceding claim, further comprising:
operating said mass spectrometer in a first state or mode wherein said first ions are analysed during a first time period t1-t2;
switching said state or mode of said mass spectrometer to a second state or mode wherein said second ions are analysed during a second time period t2-t3 immediately following said first time period;
operating said mass spectrometer in said second state or mode during a third time period t3-t4 immediately following said second time period; and
continuously acquiring mass spectral data during said first, second and third time periods t1-t4.

### Claim 18

A method as claimed in any preceding claim, further comprising mass analysing said first ions and/or said second ions.

### Claim 19 (depends on 18)

A method as claimed in claim 18, further comprising mass analysing said first ions and/or said second ions using an orthogonal acceleration Time of Flight mass analyser, a quadrupole mass analyser or a Fourier Transform mass analyser.

### Claim 20

A method as claimed in any preceding claim, wherein during a single mass spectral data acquisition period a state or mode of said mass spectrometer is switched a plurality of times.

### Claim 21

A method as claimed in any preceding claim, wherein a state or mode of said mass spectrometer is repeatedly switched with a frequency f1 and wherein mass spectral data is acquired during acquisition periods with a frequency f2, wherein f2<f1.

### Claim 22

A method as claimed in any preceding claim, wherein said stream of mass spectral data is acquired substantially independently of any switching of a state or mode of said mass spectrometer.

### Claim 23

A method as claimed in any preceding claim, wherein:
said stream of mass spectral data is acquired during a mass spectral data acquisition period; and
said acquisition period is substantially asynchronous with and/or is not synchronised with the switching of said mass spectrometer between states or modes.

### Claim 24 (depends on 23)

A method as claimed in claim 23, wherein the start and/or end time of said acquisition period is substantially asynchronous with and/or is not synchronised with the switching of said mass spectrometer between states or modes.

### Claim 25

A method as claimed in any previous claim, wherein:
said stream of mass spectral data is acquired during a mass spectral data acquisition period;
said acquisition period comprises a plurality of sample periods; and
said sample periods are substantially asynchronous with and/or are not synchronised with the switching of said mass spectrometer between states or modes.

### Claim 26 (depends on 25)

A method as claimed in claim 25, wherein the start and/or end times of said sample periods are substantially asynchronous with and/or are not synchronised with the switching of said mass spectrometer between states or modes.

### Claim 27 (depends on 25, 26)

A method as claimed in claim 25 or 26, wherein a state or mode of said mass spectrometer is repeatedly switched with a frequency f1 and wherein said sample periods have a frequency f3, wherein f3>f1.

### Claim 28

A method as claimed in any previous claim, wherein said step of post-processing said stream of mass spectral data comprises detecting ion peaks in said stream of mass spectral data and determining a plurality of ion peak times and a plurality of ion peak intensities associated with said stream of mass spectral data.

### Claim 29

A method as claimed in any previous claim, wherein said step of post-processing said stream of mass spectral data comprises determining which portions or sample periods of said stream of mass spectral data relate to said first ions or to said second ions.

### Claim 30

A method as claimed in any preceding claim, wherein said step of post-processing said stream of mass spectral data comprises determining which portions or sample periods of said stream of mass spectral data relate to both said first ions and to said second ions, and rejecting those portions or sample periods.

### Claim 31

A method as claimed in any preceding claim, wherein said step of post-processing said stream of mass spectral data comprises producing a mass spectrum for (i) said first ions and/or (ii) said second ions by combining portions or sample periods of said stream of mass spectral data determined to relate to said first ions and/or by combining portions or sample periods of said stream of mass spectral data determined to relate to said second ions.

### Claim 32

A method as claimed in any previous claim, wherein said step of post-processing said stream of mass spectral data comprises producing reconstructed mass chromatograms for ion peaks appearing in said stream of mass spectral data.

### Claim 33 (depends on 32)

A method as claimed in claim 32, further comprising deconvoluting each of said mass chromatograms and determining one or more deconvoluted chromatogram peaks associated with each of said mass chromatograms.

### Claim 34 (depends on 33)

A method as claimed in claim 33, wherein said step of deconvoluting each of said mass chromatograms comprises determining or approximating a point spread function characteristic of chromatogram peaks in said mass chromatograms.

### Claim 35 (depends on 33, 34)

A method as claimed in claim 33 or 34, further comprising determining which of said deconvoluted chromatogram peaks relate to said first ions and/or determining which of said deconvoluted chromatogram peaks relate to said second ions.

### Claim 36 (depends on 35)

A method as claimed in claim 35, further comprising producing a mass spectrum for (i) said first ions and/or (ii) said second ions by combining said deconvoluted chromatogram peaks determined to relate to said first ions and/or by combining said deconvoluted chromatogram peaks determined to relate to said second ions.

### Claim 37

A mass spectrometer comprising:
a control system arranged and adapted:
(i) to operate a mass spectrometer in a state or mode wherein first ions are analysed;
(ii) to switch a state or mode of said mass spectrometer so that second ions are analysed;
(iii) to acquire a stream of mass spectral data wherein the acquisition of said mass spectral data is substantially asynchronous with and/or is not synchronised with the switching of said mass spectrometer between states or modes; and
(iv) to post-process said stream of mass spectral data to produce: (a) mass spectral data relating to said first ions; and/or (b) mass spectral data relating to said second ions.
