Chemical Noise Reduction For Mass Spectrometry

• US 20090256073A1
• Filed: 03/25/2009
• Published: 10/15/2009
• Est. Priority Date: 02/07/2006
• Status: Active Grant

• Current Assignee: DH Technologies Development Pte. Ltd. (Danaher Corporation)
• Original Assignee: MDS Incorporated (Molecular Devices), Applera Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Covey, Tom, Guo, Xinghua, Bruins, Andries P.
• Granted Patent: US 8,030,610 B2
• Time in Patent Office: Days
• US Class Current: 250/288
• 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

1-36. -36. (canceled)

37. A mass spectrometer comprising:

a. an ion source that generates ions of an analyte of interest;

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 reactive gas, 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 reactive gas that reacts with one or more ionic species, 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.

38. The mass spectrometer of claim 37 wherein the mass separator comprises a quadrupole mass spectrometer.

39. The mass spectrometer of claim 37 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 ration value.

40. The mass spectrometer of claim 37 wherein the reactive gas comprises a neutral chemical agent.

41. The mass spectrometer of claim 40 wherein the neutral chemical agent comprises an organic chemical species containing a disulfide.

42. The mass spectrometer of claim 37 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.

43. The mass spectrometer of claim 37 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.

44. The mass spectrometer of claim 37 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.

45. The mass spectrometer of claim 44 wherein the bandpass mass filter comprises at least one high-field asymmetric waveform ion mobility spectrometry.

46. The mass spectrometer of claim 37 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.

47. The mass spectrometer of claim 37 further comprising a gas flow controller that adjusts a partial pressure of the neutral chemical reagent to change an efficiency of ion-molecule reactions in the reaction chamber.

48. A mass spectrometer comprising:

a. an ion source that generates ions of an analyte of interest;

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 reactive gas, 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 reactive gas that reacts with one or more ionic species, 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.

49. The mass spectrometer of claim 48 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.

50. The mass spectrometer of claim 48 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.

51. The mass spectrometer of claim 48 wherein the reactive gas comprises a neutral chemical agent.

52. The mass spectrometer of claim 51 wherein the neutral chemical agent comprises an organic chemical species comprising a disulfide.

53. The mass spectrometer of claim 48 further comprising a second ion mobility spectrometer that receives ions extracted from the exit of the reaction region, the second 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.

54. The mass spectrometer of claim 48 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.

55. The mass spectrometer of claim 48 further comprising a bandpass filter positioned proximate to the exit of the reaction region, the bandpass filter passing only ions with mass-to-charge ratios that are within a predetermined mass-to-charge ratio range.

56. The mass spectrometer of claim 55 wherein the bandpass filter comprises at least one high-field asymmetric waveform ion mobility spectrometer.

57. The mass spectrometer of claim 48 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 greater than a predetermined mass-to-charge ratio value to the reaction region.

58. The mass spectrometer of claim 48 further comprising a gas flow controller that adjusts a partial pressure of the neutral chemical reagent to change an efficiency of ion-molecule reactions in the reaction chamber.

59. A mass spectrometer comprising:

a. an ion source that generates ions of an analyte of interest;

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 reactive gas, 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 reactive gas that reacts with one or more ionic species, 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.

60. The mass spectrometer of claim 59 wherein at least one of the first and the second mass separator comprise a quadrupole mass spectrometer.

61. A mass spectrometer comprising:

a. a means for generating ions of an analyte of interest;

b. a means for separating ions generated by the ion source 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 reactive gas that reacts with one or more ionic species, 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 reaction region; 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 reactive region, wherein a mass-to-charge ratio of the ions of the analyte of interest can be determined from the ion detection.