Field-release mass spectrometry

• US 5,952,654 A
• Filed: 10/29/1997
• Issued: 09/14/1999
• Est. Priority Date: 10/29/1997
• Status: Expired due to Fees

• Current Assignee: Northeastern University
• Original Assignee: Northeastern University
• Inventors: Giese, Roger
• Primary Examiner(s): Berman, Jack I.
• Application Number:
  US08/960,305
• Time in Patent Office: 685 Days
• Field of Search: 250/288, 436/155, 436/173, 435/6
• US Class Current: 250/288
• CPC Class Codes: H01J 49/0409 Sample holders or containers containers for retaining a material to be analyzed, B01L3/50, for DNA, C12Q1/6834, for biological materials, G01N33/543
• CPC Class Codes: H01J 49/0418 for laser desorption, e.g. matrix-assisted laser desorption/ionisation [MALDI] plates or surface enhanced laser desorption/ionisation [SELDI] plates
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

Methods of releasing and analyzing substrates such as DNA, comprising: a) covalently or ligandly binding substrate to a first electrode via a release group, which release group is cleavable in response to applied energy; b) introducing an electrical field so as to establish a charge potential between the first electrode and a second electrode separated by a vacuum or gas phase from the first electrode, the strength of such field sufficient to bristle said covalently-bound or ligandly-bound substrate; and c) applying sufficient energy directly to the release group to cleave the release group and release the substrate into a vacuum or gas phased

Claims

1. A method of releasing a substrate into a vacuum or gas phase, comprising

a) covalently or ligandly binding said substrate to the tip of a first electrode via a release group, which release group is cleavable in response to applied energy;

b) introducing an electrical field so as to establish a charge potential between said first electrode and a second electrode separated from said first electrode via a vacuum or gas phase, the strength of such field sufficient to bristle said covalently-bound or ligandly-bound substrate; and

c) applying sufficient energy to said release group to cleave said release group and thereby release said substrate into a vacuum or gas phase.

2. The method of claim 1 wherein said substrate is covalently-bound to said first electrode.

3. The method of claim 1 wherein 10% or more of the total amount of said substrate released from said first electrode is nonobstructively exposed before release via the vacuum or gas phase to said second electrode.

4. The method of claim 1 wherein 50% or more of the total amount of said substrate that is released from said first electrode is nonobstructively exposed before release via the vacuum or gas phase to said second electrode.

5. The method of claim 1 wherein 90% or more of the total amount of said substrate that is released from said first electrode is nonobstructively exposed before release via the vacuum or gas phase to said second electrode.

6. The method of claim 1 wherein said first electrode comprises a metal selected from the group consisting of gold;

silver;

cobalt;

tin;

copper;

gallium;

arsenic, and mixtures thereof.

7. The method of claim 1 wherein said first electrode comprises a tip having a width or radius of ≦

100μ

in the part where substrate is covalently or ligandly bound.

8. The method of claim 1 wherein said first electrode comprises a tip having a width or radius of ≦

10μ

in the part where substrate is covalently or ligandly bound.

9. The method of claim 1 wherein said first electrode further comprises a coating on its surface and said substrate is covalently or ligandly bound to this coating.

10. The method of claim 1 wherein the strength of said electrical field is ≧

10⁵ V/cm.

11. The method of claim 1 wherein the strength of said electrical field is ≧

10⁶ V/cm.

12. The method of claim 1 wherein the strength of said electrical field is between 10⁷ V/cm and 10⁸ V/cm.

13. The method of claim 1 wherein said substrate is selected from the group consisting of nucleic acids;

proteins;

lipids;

polysaccharides;

microorganisms; and

microscopic organic or inorganic particles.

14. The method of claim 1 wherein said substrate in said vacuum or gas phase is detected by a mass spectrometric detector.

15. The method of claim 1 wherein said applied energy is selected from the group consisting of photolytic energy;

thermal energy;

electrical energy; and

fast atoms or ions.

16. The method of claim 1 wherein said applied energy is photolytic energy applied directly to said release group.

17. A method of releasing into a vacuum or gas phase a substrate covalently or ligandly bound to a first electrode via a release group, which release group is cleavable in response to applied energy, comprising the steps of

a) introducing an electrical field so as to establish a charge potential between said first electrode and a second electrode separated by a vacuum or gas phase from said first electrode, the strength of such field sufficient to bristle said covalently-bound or ligandly-bound substrate;

and

b) applying sufficient energy to said release group to cleave said release group and thereby release said substrate into a vacuum or gas phase.

18. The method of claim 17 wherein said substrate is covalently-bound to said first electrode.

19. The method of claim 17 wherein 10% or more of the total amount of said substrate released from said first electrode is nonobstructively exposed before release via the vacuum or gas phase to said second electrode.

20. The method of claim 17 wherein 50% or more of the total amount of said substrate that is released from said first electrode is nonobstructively exposed before release via the vacuum or gas phase to said second electrode.

21. The method of claim 17 wherein 90% or more of the total amount of said substrate that is released from said first electrode is nonobstructively exposed before release via the vacuum or gas phase to said second electrode.

22. The method of claim 17 wherein said first electrode comprises a metal selected from the group consisting of gold;

silver;

cobalt;

tin;

copper;

gallium;

arsenic, and mixtures thereof.

23. The method of claim 17 wherein said first electrode comprises a tip having a width or radius of ≦

100μ

in the part where substrate is covalently or ligandly bound.

24. The method of claim 17 wherein said first electrode comprises a tip having a width or radius of ≦

10μ

in the part where substrate is covalently or ligandly bound.

25. The method of claim 17 wherein said first electrode further comprises a coating on its surface and said substrate is covalently or ligandly bound to this coating.

26. The method of claim 17 wherein the strength of said electrical field is ≧

10⁵ V/cm.

27. The method of claim 17 wherein the strength of said electrical field is ≧

10⁶ V/cm.

28. The method of claim 17 wherein the strength of said electrical field is between 10⁷ V/cm and 10⁸ V/cm.

29. The method of claim 17 wherein said substrate is selected from the group consisting of nucleic acids;

proteins;

lipids;

polysaccharides;

microorganisms; and

microscopic organic or inorganic particles.

30. The method of claim 17 wherein said substrate in said vacuum or gas phase is detected by a mass spectrometric detector.

31. The method of claim 17 wherein said applied energy is selected from the group consisting of photolytic energy;

thermal energy;

electrical energy; and

fast atoms or ions.

32. The method of claim 17 wherein said applied energy is photolytic energy applied directly to said release group.

33. A method of bristling a substrate covalently or ligandly bound to the tip of a first electrode, comprising

a) exposing the bound substrate to a vacuum or gas phase;

and

b) introducing an electrical field so as to establish a bristling charge potential between said first electrode and a second electrode separated by a vacuum or gas phase from said first electrode.

34. The method of claim 33 wherein said substrate is covalently-bound to said first electrode.

35. The method of claim 33 wherein said first electrode comprises a metal selected from the group consisting of gold;

silver;

cobalt;

tin;

copper;

gallium;

arsenic, and mixtures thereof.

36. The method of claim 33 wherein said first electrode comprises a tip having a width or radius of ≦

100μ

in the part where substrate is covalently or ligandly bound.

37. The method of claim 33 wherein said first electrode comprises a tip having a width or radius of ≦

10μ

in the part where substrate is covalently or ligandly bound.

38. The method of claim 33 wherein said first electrode further comprises a coating on its surface and said substrate is covalently or ligandly bound to this coating.

39. The method of claim 33 wherein the strength of said electrical field is ≧

10⁵ V/cm.

40. The method of claim 33 wherein the strength of said electrical field is ≧

10⁶ V/cm.

41. The method of claim 33 wherein the strength of said electrical field is between 10⁷ V/cm and 10⁸ V/cm.