Mass spectrometer system including a double ion guide interface and method of operation

Abstract

There is described an interface for delivering ions generated in an ion source into a mass analyzer in a chamber under vacuum pressure. In particular, the interface employs two consecutive ion guides operated to dissociate adduct ions formed in the ion source or high pressure regions of the interface between the ion source and the mass analyzer, thus improving the limit of detection or limit of quantitation of the mass analyzer by increasing the analyte ion current. The questions raised in reexamination request no. 90/007,724, filed Sep. 16, 2005 have been considered and the results thereof are reflected in this reissue patent which constitutes the reexamination certificate required by 35 U.S.C. 307 as provided in 37 CFR 1.570(e), for ex parte reexaminations, or the reexamination certificate required by 35 U.S.C. 316 as provided in 37 CFR 1.997(e) for inter partes reexaminations.

1. A mass spectrometer system including a mass analyzer disposed in a high vacuum chamber for analyzing sample ions formed at atmospheric pressure and directed to the analyzer through intermediate vacuum chambers in which sample ions and solvent molecules form adduct ions with a reduction of sample ion current including:
 first and second evacuated chambers directly preceding the mass analyzer chamber with the first chamber being at a higher pressure than the second chamber,  
 a first multipole ion guide in the first chamber for guiding ions into said second chamber,  
 a second multipole ion guide in the second chamber for guiding ions from the first chamber into the high vacuum chamber for mass analysis, and  
 means associated with one or both of said first and second multipole ion guides for increasing the translational kinetic energy of the adduct ions so that at the vacuum pressure of the second interface chamber adduct ions traveling into the chamber are converted into sample ions without fragmentation of sample ions whereby to increase the sample ion current and therefore the sensitivity of the mass spectrometer system.  
 
     
     
       2. A mass analyzer as in  claim 1  including ion lenses preceding each said multipole ion guide and a DC voltage is applied between a selected lens and its associated ion guide to increase the translational kinetic energy of the adduct ions entering the second interface chamber. 
     
     
       3. A method of mass analyzing sample ions produced at atmospheric pressure and introduced into a mass analyzer disposed in a vacuum chamber, and in which some sample ions and solvent molecules combine to form adduct ions with a reduction of sample ions comprising the step of dissociating the adduct ions prior to entry into the mass analyzer to form sample ions to increase the sample ion current entering into the mass analyzer. 
     
     
       4. The method of operating a mass spectrometer system including a mass analyzer which analyzes sample ions formed at atmospheric pressure, and in which some sample ions and solvent molecules combine to form adduct ions with a reduction of sample ions, said system including first and second multipole ion guides disposed in serial first and second evacuated chambers separated by an ion lens for guiding analyte ions into said mass analyzer and an ion lens defining the first evacuated chamber which comprises
 applying a DC offset voltage between a selected one or both lenses and the succeeding multipole ion guide having an amplitude so as to provide translational kinetic energy to said adduct ions to dissociate the adduct ions without dissociating sample ions at the pressure of the second chamber to increase the sample ion current and the sensitivity of the mass spectrometer system.  
 
     
     
       5. A mass spectrometer system as in  claim 4  in which the pressure in the first chamber is below 500 mTorr, and in the second chamber is below 1 mTorr, and the offset voltage applied between the interchamber lens and the second multipole ion guide is between ±10 volts and ±30 volts. 
     
     
       6. A mass spectrometer system as in  claim 5  in which the pressure in the first chamber is less than 250 mTorr, and in the second chamber is less than 0.7 mTorr. 
     
     
       7. A mass spectrometer system as in  claim 5  in which the pressure in the first chamber is less than 175 mTorr, and in the second chamber is less than 0.5 mTorr. 
     
     
       8. A mass spectrometer as in  claim 6  or  7  in which the offset voltage is ±10 volts. 
     
     
       9. The method of analyzing ions in a mass analyzer which includes a first chamber maintained at a first pressure and a second chamber maintained at a lower pressure comprising the steps of:
 forming sample ions at atmospheric pressure with some of the sample ions combining with solvent ions to form adduct ions,  
 guiding said sample ions and adduct ions through at least a first chamber maintained at a first pressure and a second chamber maintained at a lower pressure,  
 adding translational kinetic energy to said adduct ions as they travel through said chambers such that in the second chamber the adduct ions are dissociated without fragmenting the sample ions prior to entering the mass analyzer.  
 
     
     
       10. A mass spectrometer system, comprising:
   an ion source for creating sample ions at atmospheric pressure from a sample which is in association with a solvent;        a mass analyzer, disposed in a high vacuum mass analyzer chamber, for analyzing said sample ions;        two consecutive multipole ion guides disposed between said ion source and said high vacuum mass analyzer chamber for directing ions from said ion source to said high vacuum mass analyzer chamber, said multipole ion guides maintained at a pressure below atmospheric but higher than the pressure of said high vacuum mass analyzer chamber; and        at least one of said multipole ion guides having means associated therewith for defining the translational kinetic energy of ions directed therethrough, and wherein said translational kinetic energy is chosen so that solvent adduct species formed in high pressure regions of the system are converted within said multipole ion guides to sample ions by collision - induced dissociation without fragmentation of sample ions before entering said high vacuum mass analyzer chamber.     
     
     
       11. The mass spectrometer system of  claim 10  wherein said means is for increasing said translational kinetic energy. 
     
     
       12. The mass spectrometer system of  claim 10  wherein said two consecutive multipole ion guides are contained, respectively, in two consecutive evacuated chambers. 
     
     
       13. The mass spectrometer system of  claim 12  wherein the first evacuated chamber containing the first of said multipole ion guides is at a pressure greater than the pressure in the second evacuated chamber containing the second of said multipole ion guides. 
     
     
       14. The mass spectrometer system of  claim 10  wherein said mass analyzer is a tandem mass analyzer. 
     
     
       15. The mass spectrometer system of  claim 10  wherein said mass analyzer is a quadrupole ion trap mass analyzer. 
     
     
       16. A mass spectrometer system including a mass analyzer disposed in a high vacuum chamber for analyzing sample ions formed at atmospheric pressure and directed to the analyzer through intermediate vacuum chambers in which sample ions and solvent molecules form adduct ions with a reduction of sample ion current including:
   first and second evacuated chambers directly preceding the mass analyzer chamber with the first chamber being at a higher pressure than the second chamber,        a first multipole ion guide in the first chamber for guiding ions into said second chamber,        a second multipole ion guide in the second chamber for guiding ions from the first chamber into the high vacuum chamber for mass analysis, and        means associated with one or both of said first and second multipole ion guides for defining the translational kinetic energy of the adduct ions so that at the vacuum pressure of the second interface chamber adduct ions traveling into the chamber are converted into sample ions without fragmentation of the sample ions whereby to increase the sample ion current and therefore the sensitivity of the mass spectrometer system.     
     
     
       17. A mass spectrometer system including a mass analyzer disposed in a high vacuum chamber for analyzing sample ions formed at atmospheric pressure and directed to the analyzer through one or more intermediate vacuum chambers in which sample ions and solvent molecules form adduct ions with a reduction of sample ion current including:
   first and second multipole ion guides disposed consecutively in said one or more intermediate vacuum chambers, with said first multipole ion guide maintained at a higher pressure than said second multipole ion guide, for directing ions into the high vacuum chamber for mass analysis, and        means associated with one or both of said first and second multipole ion guides for defining the translational kinetic energy of the adduct ions directed therethrough so that at the pressure of said one or both ion guides adduct ions traveling therethrough are converted into sample ions without fragmentation of the sample ions whereby to increase the sample ion current and therefore the sensitivity of the mass spectrometer system.     
     
     
       18. A mass spectrometer system according to  claim 17  wherein said means is for increasing said translational kinetic energy. 
     
     
       19. A mass spectrometer system, including:
   A. an ion source for creating ions from a sample which is in association with a solvent;        B. a first chamber, a second chamber, and a tandem mass analyzer, the first chamber being disposed between the ion source and the second chamber, the second chamber being disposed between the first chamber and the tandem mass analyzer, the first chamber being evacuated to a first pressure, the second chamber being evacuated to a second pressure;        C. a first multipole ion guide disposed in the first chamber for guiding ions received in the first chamber towards the second chamber;        D. a second multipole ion guide disposed in the second chamber for guiding ions received in the second chamber towards the tandem mass analyzer, at least some of the ions in the second chamber being a solvent adduct species;        E. a lens disposed between the first and second multipole ion guides, a voltage difference between the lens and the second multipole ion guide defining a kinetic energy of ions in the second chamber, the kinetic energy being sufficient to dissociate the sample from the solvent in the solvent adduct species without causing fragmentation of the sample ions.     
     
     
       20. A mass spectrometer system according to  claim 19  wherein the kinetic energy is sufficient to dissociate the sample from the solvent in the solvent adduct species in a majority of the solvent adduct species. 
     
     
       21. A mass spectrometer system according to  claim 20  wherein the solvent adduct species includes one sample ion and one solvent molecule. 
     
     
       22. A mass spectrometer system according to  claim 20  wherein the solvent adduct species includes one sample ion and one solvent ion. 
     
     
       23. A mass spectrometer system according to  claim 20  wherein the ion source is an electrospray ion source. 
     
     
       24. A mass spectrometer system according to  claim 23  wherein the ion source is an atmospheric pressure electrospray ion source. 
     
     
       25. A mass spectrometer system according to  claim 20  wherein the ion source is an atmospheric pressure chemical ionization source. 
     
     
       26. A mass spectrometer system according to  claim 20 , the tandem mass analyzer including a Q 1  stage, a Q 2  stage, a Q 3  stage, and a detector, the Q 1  stage including a first multipole rod structure, the Q 2  stage including a second multipole rod structure, and the Q 3  stage including a third multipole rod structure. 
     
     
       27. A mass spectrometer system according to  claim 20 , the first pressure being higher than the second pressure. 
     
     
       28. A mass spectrometer system according to  claim 20 , the first ion guide being a quadrupole ion guide. 
     
     
       29. A mass spectrometer system according to  claim 20 , the second ion guide being a quadrupole ion guide. 
     
     
       30. A mass spectrometer system, including:
   A. an ion source for creating ions from a sample which is in association with a solvent;        B. a first chamber, a second chamber, and a tandem mass analyzer, the first chamber being disposed between the ion source and the second chamber, the second chamber being disposed between the first chamber and the tandem mass analyzer, the first chamber being evacuated to a first pressure, the second chamber being evacuated to a second pressure;        C. a first multipole ion guide disposed in the first chamber for guiding ions received in the first chamber towards the second chamber;        D. a second multipole ion guide disposed in the second chamber for guiding ions received in the second chamber towards the tandem mass analyzer, at least some of the ions in the second chamber being a solvent adduct species;        E. a first lens disposed between the first and second multipole ion guides, and a second lens disposed between the ion source and the first multipole ion guide, a voltage difference between the first or second lenses and the second multipole ion guide defining a kinetic energy of ions in the second chamber, the kinetic energy being sufficient to dissociate the sample from the solvent in the solvent adduct species without causing fragmentation of the sample ions.     
     
     
       31. A mass spectrometer system, including:
   A. an ion source for creating ions from a sample which is in association with a solvent;        B. a first chamber, a second chamber, and a tandem mass analyzer, the first chamber being disposed between the ion source and the second chamber, the second chamber being disposed between the first chamber and the tandem mass analyzer, the first chamber being evacuated to a first pressure, the second chamber being evacuated to a second pressure;        C. a first multipole ion guide disposed in the first chamber for guiding ions received in the first chamber towards the second chamber;        D. a second multiple ion guide disposed in the second chamber for guiding ions received in the second chamber towards the tandem mass analyzer, at least some of the ions in the second chamber being a solvent adduct species;        E. a lens disposed between the first and second multipole ion guides, a voltage difference between the lens and the second multipole ion guide increasing a kinetic energy of ions in the second chamber, the kinetic energy being sufficient to dissociate the sample from the solvent in the solvent adduct species without causing fragmentation of the sample ions.     
     
     
       32. A mass spectrometer system according to  claim 31  wherein the kinetic energy is sufficient to dissociate the sample from the solvent in the solvent adduct species in a majority of the solvent adduct species. 
     
     
       33. A mass spectrometer system according to  claim 32  wherein the solvent adduct species includes one sample ion and one solvent molecule. 
     
     
       34. A mass spectrometer system according to  claim 32  wherein the solvent adduct species includes one sample ion and one solvent ion. 
     
     
       35. A mass spectrometer system according to  claim 32  wherein the ion source is an electrospray ion source. 
     
     
       36. A mass spectrometer according to  claim 35  wherein the ion source is an atmospheric pressure electrospray ion source. 
     
     
       37. A mass spectrometer system according to  claim 32  wherein the ion source is an atmospheric pressure chemical ionization source. 
     
     
       38. A mass spectrometer system according to  claim 32 , the tandem mass analyzer including a Q 1  stage, a Q 2  stage, a Q 3  stage, and a detector, the Q 1  stage including a first multipole rod structure, the Q 2  stage including a second multipole rod structure, and the Q 3  stage including a third multipole rod structure. 
     
     
       39. A mass spectrometer system according to  claim 32 , the first pressure being higher than the second pressure. 
     
     
       40. A mass spectrometer system according to  claim 32 , the first ion guide being a quadrupole ion guide. 
     
     
       41. A mass spectrometer system according to  claim 32 , the second ion guide being a quadrupole ion guide. 
     
     
       42. A mass spectrometer system, including:
   A. an ion source for creating ions from a sample which is in association with a solvent;        B. a first chamber, a second chamber, and a tandem mass analyzer, the first chamber being disposed between the ion source and the second chamber, the second chamber being disposed between the first chamber and the tandem mass analyzer, the first chamber being evacuated to a first pressure, the second chamber being evacuated to a second pressure;        C. a first multipole ion guide disposed in the first chamber for guiding ions received in the first chamber towards the second chamber;        D. a second multipole ion guide disposed in the second chamber for guiding ions received in the second chamber towards the tandem mass analyzer, at least some of the ions in the second chamber being a solvent adduct species;        E. a first lens disposed between the first and second multipole ion guides, and a second lens disposed between the ion source and the first multipole ion guide, a voltage difference between the first or second lenses and the second multipole ion guide increasing a kinetic energy of ions in the second chamber, the kinetic energy being sufficient to dissociate the sample from the solvent in the solvent adduct species without causing fragmentation of the sample ions.