Methods and apparatuses for analyzing biological samples by mass spectrometry

• US 20050029444A1
• Filed: 06/29/2004
• Published: 02/10/2005
• Est. Priority Date: 10/15/2001
• Status: Active Grant

• Current Assignee: Vanderbilt University
• Original Assignee: Vanderbilt University
• Inventors: Caprioli, Richard
• Granted Patent: US 8,778,695 B2
• Time in Patent Office: Days
• US Class Current: 250/282
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/6848 Methods of protein analysis involving mass spectrometry
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

Methods and apparatuses for analyzing proteins and other biological materials and xenobiotics within a sample. A specimen is generated, which may include an energy absorbent matrix. The specimen is struck with laser beams such that the specimen releases proteins. The atomic mass of the released proteins over a range of atomic masses is measured. An atomic mass window of interest within the range of atomic masses is analyzed to determine the spatial arrangement of specific proteins within the sample, and those specific proteins are identified as a function of the spatial arrangement. By analyzing the proteins, one may monitor and classify disease within a sample.

Claims

1-62. -62. (Canceled).

63. A method of analyzing proteins, comprising:

(a) generating a specimen;

(b) irradiating the specimen to release sample proteins;

(c) measuring atomic masses of the sample proteins;

(d) comparing specific sample protein data with similar data representing a normal sample; and

(e) assessing a state of disease associated with the specimen or monitoring development associated with the specimen by way of the comparing step.

64. The method of claim 63, where specific proteins are identified or compared as a function of spatial arrangement.

65. The method of claim 64, where the spatial arrangement is determined by graphically depicting atomic masses within an atomic mass window of interest.

66. The method of claim 63, where assessing a state or monitoring development comprises disease diagnosis.

67. The method of claim 63, where assessing a state or monitoring development comprises disease prognosis.

68. The method of claim 63, where assessing a state or monitoring development comprises assessing disease progression.

69. The method of claim 63, where assessing a state or monitoring development comprises classifying or identifying a disease.

70. The method of claim 63, where assessing a state or monitoring development comprises monitoring for onset of a disease.

71. The method of claim 70, where monitoring for onset of a disease comprises monitoring prior to appearance of the disease.

72. The method of claim 63, where assessing a state or monitoring development comprises monitoring a disease location.

73. The method of claim 63, where assessing a state or monitoring development comprises assessing an effectiveness of medical treatment.

74. The method of claim 73, where assessing an effectiveness of medical treatment comprises assessment over a course of the treatment.

75. The method of claim 63, where the specimen comprises tissue.

76. The method of claim 75, where the tissue comprises a tumor-bearing tissue.

77. The method of claim 63, where the specimen is isolated from blood.

78. The method of claim 63, where the specimen is isolated from plasma.

79. The method of claim 63, where the specimen is isolated from a biopsy specimen.

80. A method of monitoring a sample over time, comprising:

(a) generating a specimen at a first time;

(b) irradiating the specimen to release sample proteins;

(c) measuring atomic masses of the sample proteins;

(d) comparing specific sample protein data identified at the first time with specific protein data identified at a second time to monitor the sample over time.

81. The method of claim 80, where specific proteins are identified as a function of spatial arrangement.

82. The method of claim 80, where the specimen comprises tissue.

83. The method of claim 82, where the tissue comprises a tumor-bearing tissue.

84. The method of claim 80, where the specimen is isolated from blood.

85. The method of claim 80, where the specimen is isolated from plasma.

86. The method of claim 80, where the specimen is isolated from a biopsy specimen.

87. The method of claim 80, where the comparing step is used to monitor disease progression of the sample over time.

88. The method of claim 80, where the comparing step is used to monitor development of the sample over time.

89. A system for analyzing proteins, comprising:

(a) a source configured to irradiate a specimen to release sample proteins;

(b) a mass analyzer configured to measure atomic masses of the sample proteins; and

(c) a computer configured to compare specific protein data with similar data representing a normal sample to assess a disease state or monitor a sample.

90. The system of claim 89, the computer further configured to determine a spatial arrangement of specific proteins.

91. The system of claim 89, where disease assessment or monitoring of a sample comprises disease diagnosis, disease prognosis, assessing disease progression, or assessing an effectiveness of medical treatment.

92. A computer readable medium comprising computer-executable instructions, the instructions comprising:

(a) identifying specific protein data associated with a specimen that has been irradiated; and

(b) comparing the specific protein data with similar data representing a normal sample to assess a disease state or monitor a sample.

93. The medium of claim 92, the instructions further comprising comparing specific proteins as a function of spatial arrangement.

94. The medium of claim 92, where disease assessment or monitoring of a sample comprises disease diagnosis, disease prognosis, assessing disease progression, or assessing an effectiveness of medical treatment.