Charge-stripping of multiply-charged ions

Patent metadata

Field	Value
Publication number	US-9905406-B2
Application number	US-201415031015-A
Country	US
Kind code	B2
Filing date	Oct 23, 2014
Priority date	Oct 23, 2013
Publication date	Feb 27, 2018
Grant date	Feb 27, 2018

Abstract

A method of mass spectrometry or ion mobility spectrometry is disclosed wherein a sample is ionized by an electrified sprayer so as to produce multiply charged analyte ions of a first polarity in gas-phase. A reaction region is provided downstream of the electrified sprayer, wherein the reaction region is maintained substantially at atmospheric pressure and is maintained substantially free of electric-fields. A gas flow is provided from said electrified sprayer to said reaction region such that the gas flow carries the analyte ions from the electrified sprayer into the reaction region. Free electrons or reagent ions of a second polarity are generated in the reaction region, wherein the second polarity is opposite to said first polarity. The free electrons or reagent ions are then reacted with the analyte ions in the reaction region so as to reduce the charge state of the multiply charged analyte ions and thereby produce charge-reduced analyte ions.

First claim

The invention claimed is:

1. A method of mass spectrometry or ion mobility spectrometry comprising:
ionising a sample using an electrified sprayer so as to produce multiply charged analyte ions of a first polarity in gas-phase;
providing a reaction region downstream of the electrified sprayer, wherein the reaction region is maintained substantially at atmospheric pressure, is maintained at a temperature of ≦80° C., and is maintained substantially free of electric-fields;
providing a gas flow from said electrified sprayer to said reaction region such that the gas flow carries said analyte ions from the electrified sprayer into the reaction region;
generating free electrons or generating reagent ions of a second polarity within the reaction region, wherein said second polarity is opposite to said first polarity;
reacting the free electrons or reagent ions with the analyte ions in the reaction region so as to reduce the charge state of the multiply charged analyte ions and thereby produce charge-reduced analyte ions; and
analysing the charge-reduced analyte ions.

2. The method of claim 1 , comprising maintaining the temperature of the reaction region at a temperature selected from the group consisting of: ≦70° C.; ≦60° C.; ≦50° C.; ≦40° C.; ≦30° C.; ≦20° C.; ≦10° C.; or substantially at room temperature.

3. The method of claim 1 , wherein substantially no fragmentation or dissociation of the analyte ions is caused by reacting the reagent ions with the analyte ions.

4. The method of claim 1 , wherein said step of reacting the free electrons or reagent ions causes the analyte ions to reduce in charge state whilst maintaining the same polarity.

5. The method of claim 1 , wherein the reaction region remains substantially free of electric fields whilst a voltage is applied to the electrified sprayer and/or whilst the sprayer is ionising the sample.

6. The method of claim 1 , comprising generating the free electrons and/or reagent ions within the reaction region by photoionising molecules in the reaction region.

7. The method of claim 6 , comprising introducing dopant molecules into the reaction region and photoionising the dopant molecules.

8. The method of claim 7 , comprising introducing the dopant molecules into the gas flow from the electrified sprayer to the reaction region and photoionising the dopant molecules in the reaction region.

9. The method of claim 7 , comprising varying the concentration of dopant in the reaction region with time so as to control the rate at which the free electrons and/or reagent ions are generated and hence control the rate at which the charge states of the analyte ions are reduced.

10. The method of claim 1 , wherein the reagent ions are formed by providing free photoelectrons and neutral molecules in the reaction region such that the neutral molecules are ionised by the photoelectrons to form said reagent ions.

11. The method of claim 10 , wherein the neutral molecules are oxygen molecules which react with the photoelectrons to form superoxide anions.

12. The method of claim 10 , wherein the neutral molecules have a higher electron affinity than oxygen and are present in a concentration such that the neutral molecules react with the photoelectrons to form said reagent ions.

13. The method of claim 10 , further comprising varying the concentration of said neutral molecules within said reaction region so as to vary the concentration of reagent ions generated and hence vary the level of charge state reduction of the analyte ions.

14. The method of claim 1 , wherein the reaction region is arranged and configured such that electric fields generated by the electrified sprayer substantially do not enter the reaction region.

15. The method of claim 14 , wherein a gas flow conduit is provided between the electrified sprayer and the reaction region for carrying said gas flow from the sprayer to the reaction region, and wherein a wire mesh is arranged in the conduit between the electrified sprayer and the reaction region so as to substantially prevent electric fields from the electrified sprayer from entering the reaction region.

16. The method of claim 14 , wherein a gas flow conduit is provided between the electrified sprayer and the reaction region for carrying said gas flow from the sprayer to the reaction region, and wherein the conduit comprises one or more bends between the electrified sprayer and the reaction region so as to substantially prevent electric fields from the electrified sprayer from entering the reaction region.

17. The method of claim 14 , wherein a gas flow conduit is provided between the electrified sprayer and the reaction region for carrying said gas flow from the sprayer to the reaction region, and wherein the diameter and length of the conduit between the electrified sprayer and the reaction region are such that electric fields from the electrified sprayer are substantially prevented from entering the reaction region.

18. The method of claim 1 , wherein the reaction region is maintained substantially free of electric-fields for a first time period and an electric field is applied in said reaction region for a second time period.

19. The method of claim 18 , wherein the electric field applied during the second time period is used to control the reaction rate at which the reagent ions are generated and/or to control the reaction rate between analyte ions and either the free electrons or reagent ions.

20. The method of claim 1 , wherein the charge states of the analyte ions are reduced via proton transfer reactions.

21. The method of claim 1 , wherein the analyte is a polyethylene glycol (PEG) or comprises at least one covalently bonded polyethylene glycol.

22. A mass spectrometer or ion mobility spectrometer comprising:
an electrified sprayer configured to ionise a sample so as to produce multiply charged analyte ions of a first polarity in gas-phase;
a reaction region arranged downstream of the electrified sprayer, wherein the reaction region is configured to be maintained substantially at atmospheric pressure, maintained at a temperature of ≦80° C., and maintained substantially free of electric fields;
means for providing a gas flow from said electrified sprayer to said reaction region such that, in use, the gas flow carries said analyte ions from the electrified sprayer into the reaction region;
means for generating free electrons or for generating reagent ions of a second polarity within the reaction region, wherein said second polarity is opposite to said first polarity, such that the free electrons or reagent ions react with the analyte ions in the reaction region to reduce the charge state of the multiply charged analyte ions and thereby produce charge-reduced analyte ions; and
means for analysing the charge-reduced analyte ions.

23. The method of claim 1 , wherein analysing the charge-reduced analyte ions comprises determining structural information for the charge-reduced analyte ions.

Assignees

• Micromass Ltd
• Univ British Columbia

Inventors

• Brown Jeffery Mark
• Robb Damon

Classifications

• H01J49/00

  Particle spectrometers or separator tubes · CPC title

• H01J49/0077 Primary

  specific reactions other than fragmentation · CPC title

• H01J49/165

  Electrospray ionisation · CPC title