Gold implantation/deposition of biological samples for laser desorption two and three dimensional depth profiling of biological tissues

• US 20060138317A1
• Filed: 09/21/2005
• Published: 06/29/2006
• Est. Priority Date: 06/06/2003
• Status: Active Grant

• Current Assignee: Ionwerks, Inc.
• Original Assignee: Ionwerks, Inc.
• Inventors: Le bayec, Yvon, Schultz, J. Albert, Egan, Thomas F., Tempez, Agnes, Ugarov, Michael V., Negra, Serge D.
• Granted Patent: US 7,629,576 B2
• Time in Patent Office: Days
• US Class Current: 250/287
• CPC Class Codes: H01J 49/0031 Step by step routines describing the use of the apparatus H01J49/0081 takes precedence
• 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: H01J 49/164 Laser desorption/ionisation, e.g. matrix-assisted laser desorption/ionisation [MALDI] sample holders H01J49/0418

Abstract

The present invention enhances the laser desorption of biological molecular ions from surfaces by creating a surface localized MALDI particle matrix by ion implantation of low energy ionized clusters (gold, aluminum, etc.) or chemically derivatized clusters into the near surface region of the sample. MALDI analysis of the intact biomolecules on the surface or within a narrow subsurface region defined by the implantation range of the ions can then be performed by laser desorption into a mass spectrometer or, in a preferred embodiment, into a combined ion mobility orthogonal time of flight mass spectrometer.

Claims

1-33. -33. (canceled)

34. A method for creating and analyzing secondary ions from a sample comprising the steps of:

impinging incident ions onto said sample to form secondary ions;

cooling said secondary ions, said step of cooling comprising contacting said secondary ions with one ore more gases; and

,

transporting said secondary ions into a mass spectrometer.

35. The method of claim 34, wherein said step of impinging incident ions comprises forming said incident ions from a component selected from the group consisting of a cluster ion beam source, a vapor deposition system, a laser ablation deposition system, an electrospray ionization source, an ionized aerosol generator, and any combination thereof.

36. The method of claim 35, wherein said component operates at pressure up to and including atmospheric pressure.

37. The method of claim 35, wherein said cluster ion beam source is an inorganic cluster ion beam source.

38. The method of claim 37, wherein the inorganic cluster ion beam is a metal ion cluster beam.

39. The method of claim 38, wherein said metal ion cluster ion beam source is a gold ion cluster source.

40. The method of claim 38, wherein said metal ion cluster beam is selected from the group consisting of an aluminum ion cluster beam source, an indium ion cluster beam source, a gallium ion cluster beam source, and a metal ion cluster beam source wherein the metal is any combination of the foregoing metals.

41. The method of claim 34, further comprising the step of transporting said incident ions through an ion mobility cell prior to said step of impinging.

42. The method of claim 41, wherein said ion mobility cell is at a pressure less than or equal to atmospheric pressure.

43. The method of claim 34, further comprising the step of varying the energy of said incident ions.

44. The method of claim 34, further comprising the step of varying the pressure around said sample.

45. The method of claim 34, wherein said incident ions form an ion beam which is microfocussed onto a spot on said sample.

46. The method of claim 34, wherein said step of impinging comprises impinging in one or more pulses of ions.

47. The method of claim 46, wherein said pulses are of a duration of about 1-10 microseconds.

48. The method of claim 34, wherein the step of transporting comprises transporting said ion through an ion mobility cell followed by introduction into said mass spectrometer.

49. The method of claim 34, wherein said mass spectrometer is a time-of-flight mass spectrometer.

50. The method of claim 34, further comprising the step of depositing material to the surface or near-surface region of said sample.

51. The method of claim 50, wherein said step of depositing material is performed prior to said step of impinging incident ions onto said sample to form secondary ions.

52. The method of claim 50, wherein said step of impinging incident ions onto said sample to add material and said step of impinging incident ions onto said sample to form secondary ions are performed simultaneously.

53. The method of claim 50, wherein said material is selected from the group consisting of alkali metals, alkali metal salts, and alkali metal compounds.

54. The method of claim 34, further comprising the step of moving the sample in either or both of the X and Y directions.

55. The method of claim 54, further comprising the step of rotating the sample.

56. The method of claim 55, wherein said steps of impinging, cooling, transporting, moving the sample in either or both of the X and Y directions, and rotating the sample are performed repetitively.

57. A method for the mobility resolution of secondary ions desorbed from a sample, comprising the steps of:

impinging incident ions onto said sample to form secondary ions;

cooling said secondary ions, said step of cooling comprising contacting said secondary ions with one ore more gases; and

,

separating said secondary ions in a drift tube by ion mobility.

58. The method of claim 57, wherein said step of impinging incident ions comprises forming said incident ions from a component selected from the group consisting of a cluster ion beam source, a vapor deposition system, a laser ablation deposition system, an electrospray ionization source, an ionized aerosol generator, and any combination thereof.

59. The method of claim 58, wherein said component operates at pressure up to and including atmospheric pressure.

60. The method of claim 58, wherein said cluster ion beam source is an inorganic cluster ion beam source.

61. The method of claim 60, wherein the inorganic cluster ion beam is a metal ion cluster beam.

62. The method of claim 61, wherein said metal ion cluster ion beam source is a gold ion cluster source.

63. The method of claim 61, wherein said metal ion cluster beam is selected from the group consisting of an aluminum ion cluster beam source, an indium ion cluster beam source, a gallium ion cluster beam source, and a metal ion cluster beam source wherein the metal is any combination of the foregoing metals.

64. The method of claim 57, further comprising the step of transporting said incident ions through an ion mobility cell prior to said step of impinging.

65. The method of claim 64, wherein said ion mobility cell is at a pressure less than or equal to atmospheric pressure.

66. The method of claim 57, further comprising the step of varying the energy of said incident ions.

67. The method of claim 57, further comprising the step of varying the pressure around said sample.

68. The method of claim 57, wherein said incident ions form an ion beam which is microfocussed onto a spot on said sample.

69. The method of claim 57, wherein said step of impinging comprises impinging in one or more pulses of ions.

70. The method of claim 69, wherein said pulses are of a duration of about 1-10 microseconds.

71. The method of claim 57, further comprising the step of introducing said ions into a mass spectrometer after said step of separating.

72. The method of claim 57, wherein said mass spectrometer is a time-of-flight mass spectrometer.

73. The method of claim 57, further comprising the step of depositing material to the surface or near-surface region of said sample.

74. The method of claim 73, wherein said step of depositing material is performed prior to said step of impinging incident ions onto said sample to form secondary ions.

75. The method of claim 73, wherein said step of impinging incident ions onto said sample to add material and said step of impinging incident ions onto said sample to form secondary ions are performed simultaneously.

76. The method of claim 73, wherein said material is selected from the group consisting of alkali metals, alkali metal salts, and alkali metal compounds.

77. The method of claim 57, further comprising the step of moving the sample in either or both of the X and Y directions.

78. The method of claim 77, further comprising the step of rotating the sample.

79. The method of claim 78, wherein said steps of impinging, cooling, transporting, moving the sample in either or both of the X and Y directions, and rotating the sample are performed repetitively.

80. An apparatus for the analysis of a sample, said apparatus comprising:

a first component selected from the group consisting of a cluster ion beam source, a vapor deposition system, a laser ablation deposition system, an electrospray ionization source, an ionized aerosol generator, and any combination thereof;

a first ion mobility drift cell fluidly coupled to said component;

said ion mobility drift cell configured such that its output is directed to said sample; and

,

a mass spectrometer fluidly coupled to said sample such that material emitted by said sample is introduced into said mass spectrometer.

81. The apparatus of claim 80, wherein said first component is an electrospray ionization source.

82. The apparatus of claim 80, wherein said first component is an ionized aerosol generator.

83. The apparatus of claim 80, wherein said first component is a cluster ion beam source.

84. The apparatus of claim 80, wherein said first component operates at a pressure at or below atmospheric pressure.

85. The apparatus of claim 80, wherein said first ion mobility drift cell operates at a pressure at or below atmospheric pressure.

86. The apparatus of claim 80, wherein said mass spectrometer is a time-of-flight mass spectrometer.

87. The apparatus of claim 80, further comprising a second ion mobility drift cell fluidly coupled to said sample to said sample such that material emitted by said sample is introduced into said second ion mobility drift cell and wherein said mass spectrometer is fluidly coupled to, and received the output of, said second ion mobility cell.

88. An apparatus for the analysis of a sample, said apparatus comprising:

a first component selected from the group consisting of a cluster ion beam source, a vapor deposition system, a laser ablation deposition system, an electrospray ionization source, an ionized aerosol generator, and any combination thereof;

a first ion mobility drift cell fluidly coupled to said component;

said ion mobility drift cell configured such that its output is directed to said sample; and

,

a second ion mobility drift cell fluidly coupled to said sample such that material emitted by said sample is introduced into said second ion mobility drift cell.

89. The apparatus of claim 88, wherein said first component is an electrospray ionization source.

90. The apparatus of claim 88, wherein said first component is an ionized aerosol generator.

91. The apparatus of claim 88, wherein said first component is a cluster ion beam source.

92. The apparatus of claim 88, wherein said first component operates at a pressure at or below atmospheric pressure.

93. The apparatus of claim 88, wherein said first ion mobility drift cell operates at a pressure at or below atmospheric pressure.

94. The apparatus of claim 88, further comprising a mass spectrometer fluidly coupled to said second ion mobility drift cell to receive the output of said second ion mobility drift cell.

95. The apparatus of claim 94, wherein said mass spectrometer is a time-of-flight mass spectrometer.