Chemical noise reduction for mass spectrometry

• US 8,030,610 B2
• Filed: 03/25/2009
• Issued: 10/04/2011
• Est. Priority Date: 02/07/2006
• Status: Active Grant

• Current Assignee: DH Technologies Development Pte. Ltd. (Danaher Corporation)
• Original Assignee: DH Technologies Development Pte. Ltd. (Danaher Corporation)
• Inventors: Covey, Tom, Guo, Xinghua, Bruins, Andries P.
• Primary Examiner(s): NGUYEN, KIET TUAN
• Application Number:
  US12/411,140
• Publication Number:
  US 20090256073A1
• Time in Patent Office: 923 Days
• Field of Search: 250/281, 250/286, 250/287, 250/290, 250/292
• US Class Current: 250/281
• CPC Class Codes: G01N 33/6848 Methods of protein analysis involving mass spectrometry
• CPC Class Codes: H01J 49/0077 specific reactions other than fragmentation
• CPC Class Codes: H01J 49/421 Mass filters, i.e. deviating unwanted ions without trapping

Abstract

In various aspects, the present teachings provide systems and methods for reducing chemical noise in a mass spectrometry instrument that use a neutral chemical reagent and one or more mass filters to reduce interfering chemical background ion signals that are generated by ionization sources of mass spectrometers. In various embodiments, the neutral chemical reagent belongs to the class of organic chemical species containing a disulfide functionality.

Claims

1. A mass spectrometer comprising:

a) an ion source that generates ions of an analyte of interest and one or more background ions;

b) a mass separator that receives ions generated by the ion source, the mass separator substantially separating ions in a first range of mass-to-charge ratio values and transmitting at least a portion of the ions in the first range of mass-to-charge ratio values through an exit;

c) a reaction region containing a neutral organic chemical species, the reaction region receiving the ions transmitted through the exit of the mass separator and causing collisions of at least a portion of the transmitted ions with the neutral organic chemical species that reacts with the one or more background ions to change the m/z value of one or more background ions, but that does not substantially react with the ions of the analyte of interest, thereby allowing only ions with mass-to-charge ratio values in a second mass-to-charge ratio range to be extracted from an exit of the reaction region; and

d) an ion detector that detects ions extracted from the reaction region, the ion detector detecting the ions of the analyte of interest with a level of noise that is reduced by the collisions in the reactive region, wherein a mass-to-charge ratio of the ions of the analyte of interest can be determined from the ion detection.

2. The mass spectrometer of claim 1 wherein the mass separator comprises a quadrupole mass spectrometer.

3. The mass spectrometer of claim 1 wherein the first range of mass-to-charge ratio values is a range of mass-to-charge ratio values that is below a selected mass-to-charge ratio value.

4. The mass spectrometer of claim 1 wherein the neutral organic chemical species comprises a disulfide.

5. The mass spectrometer of claim 1 further comprising a second mass separator that receives ions extracted from the exit of the reaction region, the second mass separator substantially separating ions in a third mass-to-charge ratio range and transmitting at least a portion of the ions in the third mass-to-charge ratio range through an exit to the ion detector.

6. The mass spectrometer of claim 1 further comprising an ion mobility spectrometer that receives ions extracted from the reaction region, the ion mobility spectrometer substantially separating ions in a range of ion mobility values that corresponds to a third mass-to-charge ratio range and transmitting the separated ions through an exit to the ion detector.

7. The mass spectrometer of claim 1 further comprising a bandpass mass filter positioned proximate to the exit of the reaction region, the bandpass mass filter passing only ions with mass-to-charge ratios that are within a predetermined mass-to-charge ratio range to the ion detector.

8. The mass spectrometer of claim 7 wherein the bandpass mass filter comprises at least one high-field asymmetric waveform ion mobility spectrometry.

9. The mass spectrometer of claim 1 further comprising a high-pass mass filter positioned proximate to the exit of the mass separator before the reaction region, the high-pass mass filter passing only ions with mass-to-charge ratios that have masses greater than a predetermined mass-to-charge ratio value to the reaction region.

10. The mass spectrometer of claim 1 further comprising a gas flow controller that adjusts the partial pressure of the neutral organic chemical species to change an efficiency of ion-molecule reactions in the reaction region.

11. A mass spectrometer comprising:

a) an ion source that generates ions of an analyte of interest and one or more background ions;

b) an ion mobility spectrometer that receives ions generated by the ion source, the ion mobility spectrometer substantially separating ions in a range of ion mobility values and transmitting at least a portion of the ions in the range of ion mobility values through an exit;

c) a reaction region containing a neutral organic chemical species, the reaction region receiving the ions transmitted through the exit of the ion mobility spectrometer and causing collisions of at least a portion of the transmitted ions with the neutral organic chemical species that reacts with the one or more background ions to change the m/z value of one or more background ions, but that does not substantially react with the ions of the analyte of interest, thereby allowing only ions with mass-to-charge ratio values in a first selected mass-to-charge ratio range to be extracted from an exit of the reaction region; and

d) an ion detector that detects ions extracted from the reaction region with a level of noise that is reduced by the collisions in the reactive region, wherein a mass-to-charge ratio of the ions of the analyte of interest can be determined from the ion detection.

12. The mass spectrometer of claim 11 wherein the ion mobility spectrometer separates ions in the first range of ion mobility values by both steady-state ion mobility and by differential ion mobility.

13. The mass spectrometer of claim 11 wherein the range of ion mobility values is a range of ion mobility values that correspond to a range of mass-to-charge ratios that is below a selected range of mass-to-charge ratio values.

14. The mass spectrometer of claim 11 wherein the neutral organic chemical species comprises a disulfide.

15. The mass spectrometer of claim 11 further comprising a second mass ion mobility spectrometer that receives ions extracted from the exit of the reaction region, the second mass ion mobility spectrometer substantially separating ions in a second range of ion mobility values and transmitting at least a portion of the ions in the second range of ion mobility values through an exit to the ion detector.

16. The mass spectrometer of claim 11 further comprising a mass separator that receives ions extracted from the exit of the reaction region, the mass separator substantially separating ions in a second range of mass-to-charge ratio range and transmitting at least a portion of the ions in the second mass-to-charge ratio range through an exit to the ion detector.

17. The mass spectrometer of claim 11 further comprising a bandpass mass filter positioned proximate to the exit of the reaction region, the bandpass mass filter passing only ions with mass-to-charge ratios that are within a predetermined mass-to-charge ratio range.

18. The mass spectrometer of claim 17 wherein the bandpass mass filter comprises at least one high-field asymmetric waveform ion mobility spectrometry.

19. The mass spectrometer of claim 11 further comprising a high-pass mass filter positioned proximate to the exit of the ion mobility spectrometer before the reaction region, the high-pass mass filter passing only ions with mass-to-charge ratios that have masses greater than a predetermined mass-to-charge ratio value to the reaction region.

20. The mass spectrometer of claim 11 further comprising a gas flow controller that adjusts the partial pressure of the neutral organic chemical species to change an efficiency of ion-molecule reactions in the reaction region.

21. A mass spectrometer comprising:

a) an ion source that generates ions of an analyte of interest and one or more background ions;

b) a first mass separator that receives ions generated by the ion source, the first mass separator substantially separating ions below a selected mass-to-charge ratio value and transmitting at least a portion of the ions with mass-to-charge ratio values above the selected mass-to-charge ratio through an exit;

c) a reaction region containing a neutral organic chemical species, the reaction region receiving the ions transmitted through the exit of the mass separator and causing collisions of at least a portion of the transmitted ions with the neutral organic chemical species that reacts with the one or more background ions to change the m/z value of one or more background ions, but that does not substantially react with the ions of the analyte of interest, thereby allowing only ions with mass-to-charge ratio values in a first selected mass-to-charge ratio range to be extracted from an exit of the reaction region;

d) a second mass separator that receives ions exiting the reaction region, the second mass separator substantially separating ions in a second selected mass-to-charge ratio range and transmitting at least a portion of the ions in the second selected mass-to-charge ratio range through an exit; and

e) an ion detector that detects ions extracted from the second mass separator, the ion detector detecting the ions of the analyte of interest with a level of noise that is reduced by the collisions in the reactive region, wherein a mass-to-charge ratio of the ions of the analyte of interest can be determined from the ion detection.

22. The mass spectrometer of claim 21 wherein at least one of the first and the second mass separators comprise a quadrupole mass spectrometer.

23. A mass spectrometer comprising:

a) a means for generating ions of an analyte of interest and one or more background ions;

b) a means for separating ions generated by the means for generating ions that have mass-to-charge ratio values in a first selected range;

c) a means for reacting ions in the first selected range of mass-to-charge ratio values to causes collisions of at least a portion of the selected ions with a neutral organic chemical species that reacts with the one or more background ions to change the m/z value of one or more background ions, but that does not substantially react with the ions of the analyte of interest, thereby allowing only ions with mass-to-charge ratio values in a second selected mass-to-charge ratio range to be extracted from an exit of the means for reacting ions; and

d) a means for detecting ions of the analyte of interest with a level of noise that is reduced by the collisions in the means for reacting ions, wherein a mass-to-charge ratio of the ions of the analyte of interest can be determined from the ion detection.