Ionization probe assemblies

• US 8,158,936 B2
• Filed: 02/12/2010
• Issued: 04/17/2012
• Est. Priority Date: 02/12/2009
• Status: Active Grant

• Current Assignee: Ibis Biosciences Incorporated
• Original Assignee: Ibis Biosciences Incorporated
• Inventors: Hofstadler, Steven A., Gutierrez, Jose R., Hannis, James C., Drader, Jared J., Bare, Rex O., Smith, Jeffrey C., Gleason, Paul J., Nathanson, Jared
• Primary Examiner(s): Wells, Nikita
• Application Number:
  US12/705,352
• Publication Number:
  US 20100219336A1
• Time in Patent Office: 795 Days
• Field of Search: 250/288, 250/281, 250/282, 250/425, 239/692
• US Class Current: 250/288
• CPC Class Codes: C12Q 1/6872 involving mass spectrometry
• CPC Class Codes: G01N 23/00 Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups G01N3/00 – G01N17/00, G01N21/00 or G01N22/00
• CPC Class Codes: G01R 31/2812 Checking for open circuits or shorts, e.g. solder bridges; Testing conductivity, resistivity or impedance of connections G01R31/66
• CPC Class Codes: G01R 31/2848 using simulation
• CPC Class Codes: G01R 31/2853 Electrical testing of internal connections or -isolation, e.g. latch-up or chip-to-lead connections G01R31/31717 takes precedence; test of chip-to-PCB or lead-to-PCB connections G01R31/66
• CPC Class Codes: H01J 27/02 Ion sources; Ion guns for examination or processing discharge tubes H01J37/08; ion sources, ion guns for particle spectrometer or separator tubes H01J49/10; ion propulsion F03H1/00
• CPC Class Codes: H01J 49/0422 for gaseous samples interfaces to gas chromatographs G01N30/7206
• CPC Class Codes: H01J 49/0431 for liquid samples interfaces to liquid chromatographs G01N30/7233
• CPC Class Codes: H01J 49/0468 with means for heating or cooling the sample
• CPC Class Codes: H01J 49/165 Electrospray ionisation

Abstract

The invention relates generally to sample ionization, and provides ionization probe assemblies, systems, computer program products, and methods useful for this purpose.

Claims

1. An ionization probe assembly, comprising:

at least one probe mounting structure;

at least one probe that is movably coupled to the probe mounting structure, which probe is configured to discontinuously introduce sample aliquots into an ion source housing;

at least one probe conveyance mechanism operably connected to the probe, which probe conveyance mechanism is configured to convey the probe between at least a first position and at least a second position, wherein the first position is substantially electrically isolated from the second position; and

wherein said probe conveyance mechanism is configured to selectively convey the probe support structure such that the probe slides between a spray position and a rinse position.

2. The ionization probe assembly of claim 1, wherein the probe mounting structure comprises at least one view port.

3. The ionization probe assembly of claim 1, comprising at least one cover operably connected to the probe mounting structure.

4. An electrospray ion source housing comprising the ionization probe assembly of claim 1.

5. A mass spectrometer comprising the electrospray ion source housing of claim 4.

6. The ionization probe assembly of claim 1, wherein the probe mounting structure comprises an ion source housing back plate that is configured to operably connect to an ion source housing.

7. The ionization probe assembly of claim 6, wherein the ion source housing back plate comprises at least one alignment feature that is structured to align the ion source housing back plate relative to the ion source housing when the ion source housing back plate operably connects to the ion source housing.

8. The ionization probe assembly of claim 1, wherein at least one channel is disposed through a length of the probe.

9. The ionization probe assembly of claim 8, wherein the probe comprises at least one sprayer needle that fluidly communicates with the channel.

10. The ionization probe assembly of claim 8, wherein at least one nebulizer gas source and/or nebulizer gas sheath fluidly communicates with the channel.

11. The ionization probe assembly of claim 1, comprising at least one thermal modulator operably connected to the probe, which thermal modulator is configured to modulate a temperature of the probe.

12. The ionization probe assembly of claim 11, wherein the thermal modulator comprises a nebulizer gas heater.

13. The ionization probe assembly of claim 11, comprising at least one controller circuit board operably connected to the thermal modulator.

14. The ionization probe assembly of claim 1, comprising at least a first mounting component operably connected to the probe mounting structure, which first mounting component is configured to engage at least a second mounting component that is operably connected to an ion source housing when the probe mounting structure is mounted on the ion source housing.

15. The ionization probe assembly of claim 14, wherein the first and second mounting components comprise hinge and/or latch components.

16. The ionization probe assembly of claim 1, comprising at least one cavity disposed in or proximal to the probe mounting structure, which cavity comprises the second position.

17. The ionization probe assembly of claim 16, wherein the cavity fluidly communicates with at least one outlet.

18. The ionization probe assembly of claim 1, comprising at least two probes that are each movably coupled to the probe mounting structure.

19. The ionization probe assembly of claim 18, wherein the probes are independently movably coupled to the probe mounting structure.

20. The ionization probe assembly of claim 1, wherein the probe mounting structure comprises an ion source housing.

21. The ionization probe assembly of claim 20, wherein the ion source housing comprises at least one view port.

22. The ionization probe assembly of claim 1, comprising at least two probes independently movably coupled to the probe mounting structure.

23. The ionization probe assembly of claim 22, wherein each probe is movably coupled to the probe mounting structure via a pivot mechanism.

24. The ionization probe assembly of claim 23, wherein the probe conveyance mechanism comprises at least one motor operably connected to at least one of the pivot mechanisms via a pulley and belt drive assembly.

25. The ionization probe assembly of claim 22, wherein each probe is configured to move between a spray position and a rinse position, wherein the spray position is substantially electrically isolated from the rinse position.

26. The ionization probe assembly of claim 25, comprising at least one cavity disposed in or proximal to the probe mounting structure, which cavity comprises at least one of the rinse positions.

27. The ionization probe assembly of claim 26, wherein the cavity fluidly communicates with at least one outlet.

28. The ionization probe assembly of claim 1, wherein the probe is movably coupled to the probe mounting structure via a slide mechanism.

29. The ionization probe assembly of claim 28, wherein the slide mechanism comprises at least two probes.

30. The ionization probe assembly of claim 29, wherein the probes are substantially fixedly coupled to the slide mechanism.

31. The ionization probe assembly of claim 29, wherein the first position comprises a spray position and wherein the second position comprises at least first and second rinse positions that are each substantially electrically isolated from the spray position.

32. The ionization probe assembly of claim 31, wherein when a first probe is in the spray position, a second probe is in the second rinse position, and when the second probe is in the spray position, the first probe is in the first rinse position.

33. The ionization probe assembly of claim 28, wherein the slide mechanism comprises a probe support plate coupled to the probe mounting structure via a linear slide, and wherein the probe is mounted on the probe support plate.

34. The ionization probe assembly of claim 33, wherein the probe conveyance mechanism comprises a dual acting pneumatic cylinder operably connected to the probe mounting structure and to the probe support plate.

35. The ionization probe assembly of claim 1, wherein said at least one probe comprises at least one wide-bore probe.

36. The ionization probe assembly of claim 1, wherein said probe mounting structure comprises a removable cartridge.

37. The ionization probe assembly of claim 36, wherein said removable cartridge is spring-loaded.

38. The ionization probe assembly of claim 36, wherein said probe mounting structure is configured to accept removable cartridges from a variety of commercial instruments.

39. The ionization probe assembly of claim 1, further comprising one or more nebulizer gas lines configured to deliver gas from a nebulizer gas source to said at least one probe.

40. The ionization probe assembly of claim 39, wherein said one or more nebulizer gas lines comprise a thermal modulator to heat gas within said one or more nebulizer gas lines.

41. An ionization probe assembly, comprising:

at least one ion source housing back plate that comprises one or more surfaces that define at least one spray orifice, which ion source housing back plate is configured to operably connect to an ion source housing;

at least one rinse cavity that is at least partially disposed within the ion source housing back plate, wherein the rinse cavity communicates with the spray orifice via at least one opening;

at least one probe support structure coupled to the ion source housing back plate via at least one linear slide;

at least one probe substantially fixedly mounted on the probe support structure; and

,

at least one probe conveyance mechanism operably connected to the probe support structure, which probe conveyance mechanism is configured to selectively convey the probe support structure such that the probe slides between the spray orifice and the rinse cavity through the opening.

42. The ionization probe assembly of claim 41, wherein the rinse cavity fluidly communicates with at least one outlet.

43. An ionization probe assembly, comprising:

at least one ion source housing back plate that comprises one or more surfaces that define at least one spray orifice, which ion source housing back plate is configured to operably connect to an ion source housing;

at least one rinse cavity that is at least partially disposed within the ion source housing back plate, wherein the rinse cavity communicates with the spray orifice via at least one opening;

at least one probe movably coupled to the ion source housing back plate via at least one pivot mechanism; and

,

at least one probe conveyance mechanism that comprises at least one motor operably connected to the pivot mechanism via a pulley and belt drive assembly, which probe conveyance mechanism is configured to selectively convey the probe between the spray orifice and the rinse cavity through the opening.

44. A molecular mass measurement system, comprising:

at least one mass spectrometer that comprises at least one ion source housing;

at least one ionization probe assembly operably connected to the ion source housing, which ionization probe assembly comprises;

at least one probe mounting structure;

at least one probe that comprises at least one inlet and at least one outlet, wherein the inlet fluidly communicates with the outlet, wherein the probe is movably coupled to the probe mounting structure, which probe is configured to discontinuously introduce sample aliquots into the ion source housing; and

at least one probe conveyance mechanism operably connected to the probe, which probe conveyance mechanism is configured to convey the probe between a spray position and a rinse position, wherein the spray position is substantially electrically isolated from the rinse position;

at least one sample source in fluid communication with the inlet of the probe;

at least one rinse fluid source in fluid communication with the inlet of the probe; and

,

at least one controller operably connected at least to the ionization probe assembly, which controller is configured to selectively direct the ionization probe assembly to;

(a) convey the probe from the rinse position to the spray position;

(b) spray at least one sample aliquot into the ion source housing from the sample source when the probe is in the spray position;

(c) convey the probe from the spray position to the rinse position; and

(d) rinse the probe with rinse fluid from the rinse fluid source when the probe is in the rinse position.

45. The system of claim 44, comprising at least one additional system component selected from the group consisting of:

at least one nucleic acid amplification component;

at least one sample preparation component;

at least one microplate handling component;

at least one mixing station;

at least one material transfer component;

at least one sample processing component; and

at least one database.

46. A computer program product, comprising a computer readable medium having one or more logic instructions for directing an ionization probe assembly of a molecular mass measurement system to:

(a) convey a first probe from a first rinse position to a first spray position of the molecular mass measurement system, wherein the first rinse position and the first spray position are substantially electrically isolated from one another;

(b) convey a second probe from a second spray position to a second rinse position of the molecular mass measurement system, wherein the second spray position and the second rinse position are substantially electrically isolated from one another;

(c) spray at least a first sample aliquot into an ion source housing of the molecular mass measurement system via the first probe when the first probe is in the first spray position;

(d) rinse the second probe when the second probe is in the second rinse position;

(e) convey the first probe from the first spray position to the first rinse position;

(f) convey the second probe from the second rinse position to the second spray position;

(g) spray at least a second sample aliquot into the ion source housing of the molecular mass measurement system via the second probe when the second probe is in the second spray position; and

,

(h) rinse the first probe when the first probe is in the first rinse position.

47. The computer program product of claim 46, comprising at least one logic instruction for directing the ionization probe assembly of the molecular mass measurement system to modulate a temperature of the first probe and/or second probe using at least one thermal modulator operably connected to the first probe and/or second probe.

48. The computer program product of claim 46, wherein the logic instructions are configured to direct the ionization probe assembly to execute (a) substantially simultaneously with (b), (c) substantially simultaneously with (d), (e) substantially simultaneously with (f), and/or (g) substantially simultaneously with (h).

49. The computer program product of claim 46, wherein a controller of the molecular mass measurement system comprises the logic instructions.

50. A method of spraying sample aliquots into an ion source housing of a molecular mass measurement system, the method comprising:

(a) conveying a first probe from a first rinse position to a first spray position of the molecular mass measurement system, wherein the first rinse position and the first spray position are substantially electrically isolated from one another and wherein the first spray position is in fluid communication with the ion source housing;

(b) conveying a second probe from a second spray position to a second rinse position of the molecular mass measurement system, wherein the second spray position and the second rinse position are substantially electrically isolated from one another;

(c) spraying at least a first sample aliquot into the ion source housing via the first probe when the first probe is in the first spray position;

(d) rinsing the second probe when the second probe is in the second rinse position;

(e) conveying the first probe from the first spray position to the first rinse position;

(f) conveying the second probe from the second rinse position to the second spray position, wherein the second spray position is in fluid communication with the ion source housing;

(g) spraying at least a second sample aliquot into the ion source housing of the molecular mass measurement system via the second probe when the second probe is in the second spray position; and

,

(h) rinsing the first probe when the first probe is in the first rinse position, thereby spraying the sample aliquots into the ion source housing of the molecular mass measurement system.

51. The method of claim 50, comprising performing (a) substantially simultaneously with (b), (c) substantially simultaneously with (d), (e) substantially simultaneously with (f), and/or (g) substantially simultaneously with (h).

52. The method of claim 50, comprising modulating a temperature of the first probe and/or second probe using at least one thermal modulator operably connected to the first probe and/or second probe.

53. The method of claim 50, comprising ionizing the first sample aliquot and the second sample aliquot when the first sample aliquot and the second sample aliquot are sprayed into the ion source housing.

54. The method of claim 50, comprising measuring a molecular mass of at least one component of the first sample aliquot and/or the second sample aliquot using the molecular mass measurement system.

55. The method of claim 50, wherein the component of the first sample aliquot and/or the second sample aliquot comprises at least one nucleic acid molecule and wherein the method comprises determining a base composition of the nucleic acid molecule from the molecular mass of the nucleic acid molecule.

56. The method of claim 50, comprising correlating the base composition of the nucleic acid molecule with an identity or property of the nucleic acid molecule.