Methods for tandem collision-induced dissociation cells

Patent metadata

Field	Value
Publication number	US-9842730-B2
Application number	US-201514963123-A
Country	US
Kind code	B2
Filing date	Dec 8, 2015
Priority date	Dec 8, 2015
Publication date	Dec 12, 2017
Grant date	Dec 12, 2017

Abstract

A method for operating a mass spectrometer so as to detect or quantify analytes, comprises: (a) identifying a selected-reaction-monitoring (SRM) transition to be used for each respective analyte; (b) determining a time duration required for a fragmentation reaction corresponding to each identified transition to proceed to a threshold percentage of completion; and (c) for each analyte, performing the steps of (i) isolating ions corresponding to a precursor-ion mass-to-charge (m/z) ratio of the respective transition; (ii) fragmenting the respective isolated ions in one of two fragmentation cells or fragmentation cell portions; and (ii) mass analyzing for fragment ions corresponding to a product-ion m/z ratio of the respective transition, wherein, for each analyte, the fragmentation cell or fragmentation cell portion that is used for fragmenting the isolated ions is determined from the time duration determined for the respective analyte.

First claim

What is claimed is:

1. A method for operating a mass spectrometer so as to detect a presence of or a quantity of each of one or more analytes of a sample, each analyte associated with a respective pre-determined selected-reaction-monitoring (SRM) transition, the method comprising:
(a) for each of the one or more pre-determined SRM transitions, determining a time duration required for a fragmentation reaction corresponding to the respective SRM transition to proceed to a certain threshold percentage of completion;
(b) ionizing the sample in an ionization source of the mass spectrometer so as to produce one or more populations of first-generation ions; and
(c) for each of the one or more pre-determined SRM transitions, performing the steps of:
(c1) isolating a sub-population of a one of the one or more populations of first-generation ions corresponding to a precursor-ion mass-to-charge (m/z) ratio associated with the respective SRM transition;
(c2) fragmenting the respective isolated sub-population of ions in a one of two fragmentation cells of the mass spectrometer so as to produce a respective population of fragment ions; and
(c3) analyzing, with a mass analyzer of the mass spectrometer, for the presence or quantity, among the respective fragment ions, of ions corresponding to a product-ion in/z ratio associated with the respective SRM transition,

wherein, for each pre-determined SRM transition, the fragmentation cell that is used for fragmenting the isolated sub-population of ions corresponding to the respective precursor-ion in/z ratio is determined from the time duration determined for the respective pre-determined SRM transition.

2. A method as recited in claim 1 , wherein, for each of a subset of the pre-determined SRM transitions for which the determined time duration is less than or equal to a threshold time duration, the step (c2) of fragmenting the respective isolated sub-population of ions in a one of two fragmentation cells includes transferring said respective isolated sub-population of ions through the other one of the two fragmentation cells.

3. A method as recited in claim 2 , wherein the threshold time duration is 10 milliseconds.

4. A method as recited in claim 2 , wherein the threshold time duration is 100 microseconds.

5. A method as recited in claim 1 , wherein, for a subset of the pre-determined SRM transitions for which the determined time duration is greater than a threshold time duration, the analyzing step (c3) includes transferring the respective fragment ions through a one of the two fragmentation cells other than the fragmentation cell within which the respective fragment ions were produced in the fragmenting step (c2).

6. A method as recited in claim 5 , wherein the threshold time duration is 10 milliseconds.

7. A method as recited in claim 5 , wherein the threshold time duration is 100 microseconds.

8. A method as recited in claim 1 , wherein for each of a subset of the pre-determined SRM transitions for which the determined time duration is less than or equal to a threshold time duration, the step (c2) of fragmenting the respective isolated sub-population of ions in a one of two fragmentation cells comprises fragmenting the respective isolated sub-population of ions in a one of the two fragmentation cells comprising a length that is shorter than a length of the other fragmentation cell.

9. A method as recited in claim 1 , wherein, for a subset of the pre-determined SRM transitions for which the determined time duration is greater than a threshold time duration, the step (c2) of fragmenting the respective isolated sub-population of ions in a one of two fragmentation cells comprises fragmenting the respective isolated sub-population of ions in a one of the two fragmentation cells comprising a length that is greater than a length of the other fragmentation cell.

10. A method for operating a mass spectrometer so as to detect a presence of or a quantity of each of one or more analytes of a sample, each analyte associated with a respective pre-determined selected-reaction-monitoring (SRM) transition, the method comprising:
(a) for each of the one or more pre-determined SRM transitions, determining a time duration required for a fragmentation step corresponding to the pre-determined SRM transition to proceed to a certain threshold percentage of completion;
(b) ionizing the sample in an ionization source of the mass spectrometer so as to produce one or more populations of first-generation ions; and
(c) for each of the one or more pre-determined SRM transitions, performing the steps of:
(c1) isolating a sub-population of the one or more populations of first-generation ions corresponding to a precursor-ion mass-to-charge (m/z) ratio associated with the respective SRM transition;
(c2) fragmenting the respective isolated sub-population of ions in a one of two portions of a partitioned fragmentation cell of the mass spectrometer so as to produce a respective population of fragment ions; and
(c3) analyzing, with a mass analyzer of the mass spectrometer, for the presence or quantity, among the respective fragment ions, of ions corresponding to a product-ion ink ratio associated with the respective SRM transition,

wherein, for each pre-determined SRM transition, the portion of the partitioned fragmentation cell that is used for fragmenting the isolated sub-population of ions corresponding to the respective precursor-ion in/z ratio is determined from the time duration determined for the respective pre-determined SRM transition.

11. A method as recited in claim 10 , wherein, for each of a subset of the pre-determined SRM transitions for which the determined time duration is less than or equal to a threshold time duration, the step (c2), of fragmenting the respective isolated sub-population of ions in a one of the two portions of the partitioned fragmentation cell includes transferring said respective isolated sub-population of ions through the other portion of the partitioned fragmentation cell.

12. A method as recited in claim 11 , wherein the threshold time duration is 10 milliseconds.

13. A method as recited in claim 11 , wherein the threshold time duration is 100 microseconds.

14. A method as recited in claim 10 , wherein, for a subset of the pre-determined SRM transitions for which the determined time duration is greater than a threshold time duration, the analyzing step (c3) includes transferring the respective fragment ions through a one of the two portions of the partitioned fragmentation cell other than the portion of the partitioned fragmentation cell within which the respective fragment ions were produced.

15. A method as recited in claim 14 , wherein the threshold time duration is 10 milliseconds.

16. A method as recited in claim 11 , wherein the threshold time duration is 100 microseconds.

17. A method as recited in claim 10 , wherein a pressure of a collision gas within a first one of the two portions of the partitioned fragmentation cell and a pressure of the collision gas within a second one of the two portions of the partitioned fragmentation cell are controlled independently of one another.

18. A method as recited in claim 1 , wherein the step (c2) of fragmenting the respective isolated sub-population of ions in a one of two fragmentation cells so as to produce a respective population of fragment ions includes applying an axial field along an axis of the one of the two fragmentation cells.

19. A method as recited in claim 10 , wherein the step (c2) of fragmenting the respective isolated sub-population o

Assignees

• Thermo Finnigan Llc

Inventors

• Schoen Alan E
• Oser Harald

Classifications

• H01J49/005 Primary

  by collision with gas, e.g. by introducing gas or by accelerating ions with an electric field · CPC title

• H01J49/0031

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

• H01J49/421

  Mass filters, i.e. deviating unwanted ions without trapping · CPC title