MALDI-IM-ortho-TOF mass spectrometry with simultaneous positive and negative mode detection

• US 7,170,052 B2
• Filed: 12/29/2004
• Issued: 01/30/2007
• Est. Priority Date: 12/31/2003
• Status: Expired due to Fees

• Current Assignee: Ionwerks, Inc., Regents of the University of California (University of California)
• Original Assignee: Ionwerks, Inc., Regents of the University of California (University of California)
• Inventors: Schultz, J. Albert, Ugarov, Michael V., Furutani, Hiroshi, Prather, Kimberly
• Primary Examiner(s): Wells; Nikita
• Assistant Examiner(s): Souw; Bernard
• Application Number:
  US11/025,640
• Publication Number:
  US 20050230615A1
• Time in Patent Office: 762 Days
• Field of Search: 250/281
• US Class Current: 250/287
• CPC Class Codes: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: G01N 27/622 Ion mobility spectrometry
• CPC Class Codes: H01J 49/0095 Particular arrangements for generating, introducing or analyzing both positive and negative analyte ions ion/ion reactions H01J49/0072
• CPC Class Codes: H01J 49/0445 with means for introducing as a spray, a jet or an aerosol electrospray ion sources H01J49/165
• CPC Class Codes: H01J 49/164 Laser desorption/ionisation, e.g. matrix-assisted laser desorption/ionisation [MALDI] sample holders H01J49/0418
• CPC Class Codes: H01J 49/40 Time-of-flight spectrometers H01J49/36 takes precedence
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

An ion mobility/mass spectrometry method and instrument using aerosolized samples and dual positive and negative mode detection is described. Sample preparation methods are also described.

Claims

1. A method of preparing an aerosolized sample for analysis by laser desorption mass spectrometry, comprising the steps of:

combining the sample with a matrix comprising a native or derivatized fullerene; and

,

producing aerosol particles from the combined sample and matrix.

2. The method of claim 1, wherein the native or derivatized fullerene is selected from the group consisting of C₆₀, C₇₀, C₇₆, C₈₄, and combinations thereof.

3. The method of claim 1, wherein the sample comprises peptides or proteins, or combinations thereof.

4. The method of claim 3, wherein the peptides or protein may be antibodies, enzymes or combinations thereof.

5. The method of claim 1, wherein the sample comprises a nucleic acid, a nucleic acid base, a nucleotide, a nucleoside, or combinations thereof.

6. The method of claim 1, wherein the sample comprises lipids, lipoproteins, or combinations thereof.

7. The method of claim 1, wherein the sample comprises phospholipids, ceramides, derivatives thereof, or combinations thereof.

8. The method of claim 1, wherein the sample comprises glycosylated proteins, glycosylated lipids, lipopolysaccharides, glycans, or combinations thereof.

9. The method of claim 1, wherein the sample comprises natural or synthetic organic polymers, natural or synthetic inorganic polymers, or combinations thereof.

10. The method of claim 1, wherein the sample comprises small organic molecules, organometallic molecules, or combinations thereof.

11. A method of preparing an aerosolized sample for analysis by laser desorption mass spectrometry, comprising the steps of:

combining the sample with a matrix comprising a native or derivatized nanotube; and

,

producing aerosol particles from the combined sample and matrix.

12. The method of claim 11, wherein the nanotube is a derivatized nanotube.

13. The method of claim 11, wherein the native or derivatized nanotube is a native or derivatized single wall nanotube.

14. The method of claim 11, wherein the sample comprises peptides, proteins, antibodies, enzymes, or combinations thereof.

15. The method of claim 11, wherein the sample comprises a nucleic acid, a nucleic acid base, a nucleotide, a nucleoside, or combinations thereof.

16. The method of claim 11, wherein the sample comprises a lipoprotein.

17. The method of claim 11, wherein the sample comprises phospholipids, ceramides, derivatives thereof, or combinations thereof.

18. The method of claim 11, wherein the sample comprises glycosylated proteins, glycosylated lipids, lipopolysaccharides, glycans, or combinations thereof.

19. The method of claim 11, wherein the sample comprises natural or synthetic organic polymers, natural or synthetic inorganic polymers, or combinations thereof.

20. The method of claim 11, wherein the sample comprises small organic molecules, organometallic molecules, or combinations thereof.

21. A method of preparing an aerosolized sample for analysis by laser desorption mass spectrometry, comprising the steps of:

combining the sample with a matrix comprising a surface derivatized inorganic particle; and

,

producing aerosol particles from the combined sample and matrix.

22. The method of claim 21, wherein the surface derivatized inorganic particle used as said matrix is selected from the group consisting of titanium nitride, aluminum nitride, boron nitride, carbonitride, carbon boron nitride, gold, molybdenum, copper, copper lithium alloy, platinum, silver, and combinations thereof.

23. A method of preparing an aerosolized sample for analysis by laser desorption mass spectrometry, comprising the steps of:

combining the sample with a matrix comprising nanoparticulates; and

,

producing aerosol particles from the combined sample and matrix.

24. A method for the analysis of samples using ion mobility resolved mass spectrometric data comprising the steps of:

introducing a sample comprising a liquid droplet or aerosol into a desorption source;

ionizing and desorbing gaseous analyte species from said liquid droplet or aerosol;

separating said analyte species from one another in an ion mobility cell; and

,

resolving said analyte species in an orthogonal time-of-flight mass spectrometer.

25. The method of claim 24, further comprising the step of forming said liquid droplet or aerosol with a vibrating orifice aerosol generator.

26. The method of claim 25, wherein said vibrating orifice aerosol generator generates droplets at the rate of up to 10 MHz.

27. The method of claim 24, wherein said step of ionizing and desorbing comprises ionizing and desorbing with coaxial laser irradiation.

28. The method of claim 24, wherein said sample is an aerosolized sample of a previously airborne pathogen.

29. The method of claim 28, wherein said pathogen is a bacteria, virus, prion, or cell.

30. The method of claim 24, wherein said sample is an aerosolized sample from a distribution of whole cells or whole cell lysate.

31. The method of claim 24 further comprising the step of correlating said ion mobility resolved mass spectrometric data with fluorescence data.

32. The method of claim 24, wherein said step of ionizing and desorbing comprises multiply impinging said sample with an energy source.

33. The method of claim 32, wherein said energy source is selected from the group consisting of a laser, a pulsed X-ray source, a chopped continuous infrared source, and a pulsed electron beam source.

34. An instrument for the collection of ion mobility resolved mass spectrometric data comprising:

an aerosol formation apparatus to form an aerosol;

a desorption ionization source coupled to said apparatus and capable of desorbing and ionizing species comprising the aerosol;

two ion mobility cells fluidly coupled to said aerosol formation apparatus, each mobility cell comprising a drift tube having a separation axis configured 180°

to the separation axis of the drift tube of the other mobility cell; and

,

at least one time-of-flight mass spectrometer fluidly coupled to said mobility cell and having a flight tube orthogonal to the axis of the drift tube of the mobility cell.

35. The instrument of claim 34, wherein one of the mobility cells operates in positive mode and the other mobility cell operates in negative mode.

36. The instrument of claim 34, wherein the desorption ionization source comprises a laser.

37. The instrument of claim 36, wherein said laser emits a radiation beam which is coaxial to the path of a particle or droplet of said aerosol.

38. The instrument of claim 36, wherein said laser emits a radiation beam which is coaxial to a particle or droplet train of said aerosol.

39. The instrument of claim 36, wherein said aerosol comprises a sample in a fullerene-based matrix.

40. The instrument of claim 36, wherein said aerosol comprises a sample in a nanotube-based matrix.

41. The instrument of claim 40, wherein the nanotubes are single wall nanotubes.

42. The instrument of claim 34, wherein aerosolized matrix particles formed from said aerosol are fluidly coupled to said mobility cell using a single particle injection apparatus.

43. The instrument of claim 42, wherein said single particle injection apparatus is a converging nozzle aerosol interface.

44. The instrument of claim 43, further comprising a differentially pumped vacuum stage.

45. The instrument of claim 34, wherein said aerosol formation apparatus is a vibrating orifice aerosol generator.

46. The instrument of claim 45, wherein said vibrating orifice aerosol generator couples said mobility cells and said time-of-flight mass spectrometer to a liquid chromatograph.

47. The instrument of claim 45, wherein said vibrating orifice aerosol generator is directly interfaced to said mobility cell.

48. The instrument of claim 45, wherein the desorption ionization source comprises a laser.

49. The instrument of claim 48, wherein said laser emits a radiation beam which is coaxial to the path of a particle or droplet train of said aerosol.

50. The instrument of claim 48, wherein said laser emits a radiation beam which is coaxial to a particle or droplet train of said aerosol.

51. The instrument of claim 45, wherein said mobility cell further comprises multiapertures and periodic focusing fields.

52. The instrument of claim 34, further comprising a pathogen detection device which correlates the ion mobility resolved mass spectrometric data with fluorescence data.

53. The instrument of claim 34, further comprising a heated substrate fluidly coupled to or located within at least one of said ion mobility cells.

54. The instrument of claim 53, wherein said heated substrate comprises molybdenum or tantalum.

55. An apparatus for generating matrix particles for implantation into a sample for desorption/ionization comprising:

a nanoparticle source;

a charging device fluidly coupled to and receiving nanoparticles from said nanoparticle source and forming charged nanoparticles;

a focusing lens fluidly coupled to the charging device to focus said charged nanoparticles,

a particle accelerator fluidly coupled to said focusing lens; and

,

a sample stage to position a sample and receive charged nanoparticles from said particle accelerator.