CA2512290A1 - Method and apparatus for desorption and ionization of analytes - Google Patents
Method and apparatus for desorption and ionization of analytes Download PDFInfo
- Publication number
- CA2512290A1 CA2512290A1 CA002512290A CA2512290A CA2512290A1 CA 2512290 A1 CA2512290 A1 CA 2512290A1 CA 002512290 A CA002512290 A CA 002512290A CA 2512290 A CA2512290 A CA 2512290A CA 2512290 A1 CA2512290 A1 CA 2512290A1
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- CA
- Canada
- Prior art keywords
- probe
- energy absorbing
- absorbing molecules
- analyte
- sample presenting
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/02—Details
- H01J49/04—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
- H01J49/0409—Sample holders or containers
- H01J49/0418—Sample holders or containers for laser desorption, e.g. matrix-assisted laser desorption/ionisation [MALDI] plates or surface enhanced laser desorption/ionisation [SELDI] plates
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/40—Concentrating samples
- G01N1/405—Concentrating samples by adsorption or absorption
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
- G01N33/6848—Methods of protein analysis involving mass spectrometry
- G01N33/6851—Methods of protein analysis involving laser desorption ionisation mass spectrometry
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/24—Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
- Y10T436/25375—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
- Y10T436/255—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.] including use of a solid sorbent, semipermeable membrane, or liquid extraction
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- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Bioinformatics & Computational Biology (AREA)
- Analytical Chemistry (AREA)
- Optics & Photonics (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Urology & Nephrology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Food Science & Technology (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
- Electron Tubes For Measurement (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Photoreceptors In Electrophotography (AREA)
Abstract
A probe that is removably insertable into a mass spectrometer, the probe having a sample presenting surface for presenting an analyte to an energy source that emits energy capable of desorbing/ionizing the analyte from the probe for analyte detection, wherein said surface is derivatised with a non-crystalline layer of energy absorbing molecules which are capable of absorbing said energy to facilitate the desorption of an analyte presented thereon.
Claims (82)
1. A mass spectrometry probe comprising:
(a) a sample presenting surface;
(b) energy absorbing molecules associated with the sample presenting surface; and (c) an analyte which is not dispersed in a matrix crystalline structure, but is presented within, on or above the energy absorbing molecules, wherein the probe promotes desorption of substantially intact analyte molecules when the probe is exposed to laser energy.
(a) a sample presenting surface;
(b) energy absorbing molecules associated with the sample presenting surface; and (c) an analyte which is not dispersed in a matrix crystalline structure, but is presented within, on or above the energy absorbing molecules, wherein the probe promotes desorption of substantially intact analyte molecules when the probe is exposed to laser energy.
2. The probe of claim 1, wherein the sample presenting surface is derivatized with the energy absorbing molecules.
3. The probe of claim 1, wherein the energy absorbing molecules are covalently bound to the sample presenting surface.
4. The probe of claim 1, wherein the sample presenting surface is adhered to the probe magnetically.
5. The probe of claim 1, wherein the sample presenting surface comprises metal, metal coated with a synthetic polymer, glass, ceramic, a synthetic polymer or a mixture thereof.
6. The probe of claim 1, wherein the sample presenting surface comprises a synthetic polymer.
7. The probe of claim 6, wherein the energy absorbing molecules are comprised within the synthetic polymer.
8. The probe of claim 1, wherein the energy absorbing molecules are arranged in a predetermined array.
9. The probe of claim 1, wherein the analyte comprises a protein.
10. The probe of claim 1, wherein the analyte comprises a carbohydrate.
11. The probe of claim 1, wherein the analyte comprises a nucleic acid.
12. The probe of claim 11, wherein the nucleic acid is DNA.
13. The probe of any of claims 1-12, wherein the energy absorbing molecules are selected from the group consisting of dimethoxy hydroxycinnamic acid, cinnamamide, cinnamyl bromide, dihydroxybenzoic acid, and cyanohydroxycinnamic acid.
14. The probe of any of claims 1-12, wherein the sample presenting surface is a surface of the probe.
15. The probe of any of claims 1-12, wherein the sample presenting surface is a bead associated with the probe surface.
16. A method for promoting desorption of analytes in substantially intact form into the gas phase comprising:
(a) depositing an analyte on a sample presenting surface of a probe, wherein energy absorbing molecules are associated with the sample presenting surface and the analyte is not dispersed in a matrix crystalline structure, but is presented within, on or above the energy absorbing molecules wherein the probe promotes desorption of substantially intact analyte molecules when the probe is exposed to an energy source; and (b) exposing the probe to laser energy.
(a) depositing an analyte on a sample presenting surface of a probe, wherein energy absorbing molecules are associated with the sample presenting surface and the analyte is not dispersed in a matrix crystalline structure, but is presented within, on or above the energy absorbing molecules wherein the probe promotes desorption of substantially intact analyte molecules when the probe is exposed to an energy source; and (b) exposing the probe to laser energy.
17. The method of claim 16, wherein the sample presenting surface is derivatized with the energy absorbing molecules.
18. The method of claim 16, wherein the energy absorbing molecules are covalently bound to the sample presenting surface.
19. The method of claim 16, wherein the sample presenting surface is adhered to the probe magnetically.
20. The method of claim 16, wherein the sample presenting surface comprises metal, metal coated with a synthetic polymer, glass, ceramic, a synthetic polymer or a mixture thereof.
21. The method of claim 16, wherein the sample presenting surface comprises a synthetic polymer.
22. The method of claim 21, wherein the energy absorbing molecules are comprised within the synthetic polymer.
23. The method of claim 16, wherein the energy absorbing molecules are arranged in a predetermined array.
24. The method of claim 16, wherein the analyte is from a biological sample.
25. The method of claim 24, wherein the biological sample is selected from the group consisting of blood, tears, urine, saliva, gastrointestinal fluids, spinal fluid, amniotic fluid, bone marrow, bacteria, viruses, cells in culture, biopsy tissue, plant tissue or fluids and insect tissue or fluids.
26. The method of claim 16, wherein the analyte comprises a protein.
27. The method of claim 16, wherein the analyte comprises a carbohydrate.
28. The method of claim 16, wherein the analyte comprises a nucleic acid.
29. The method of claim 28, wherein the nucleic acid is DNA.
30. The method of any of claims 16-29, wherein the energy absorbing molecules are selected from the group consisting of dimethoxy hydroxycinnamic acid, cinnamamide, cinnamyl bromide, dihydroxybenzoic acid, and cyanohydroxycinnamic acid.
31. The method of any of claims 16-29, wherein the sample presenting surface is a surface of the probe.
32. The method of any of claims 16-29, wherein the sample presenting surface is a bead associated with the probe surface.
33. A mass spectrometry apparatus for promoting desorption of analytes in substantially intact form into the gas phase comprising:
(a) a probe for promoting desorption of analytes in substantially intact form into the gas phase comprising:
i. a sample presenting surface;
ii. energy absorbing molecules associated with the sample presenting surface; and iii. an analyte which is not dispersed in a matrix crystalline structure, but is presented within, on or above the energy absorbing molecules; wherein the probe promotes desorption of substantially intact analyte molecules when the probe is exposed to an energy source;
(b) an energy source that directs laser energy to the sample presenting surface for desorbing and ionizing the analyte; and (c) a detector that detects the desorbed, ionized analyte.
(a) a probe for promoting desorption of analytes in substantially intact form into the gas phase comprising:
i. a sample presenting surface;
ii. energy absorbing molecules associated with the sample presenting surface; and iii. an analyte which is not dispersed in a matrix crystalline structure, but is presented within, on or above the energy absorbing molecules; wherein the probe promotes desorption of substantially intact analyte molecules when the probe is exposed to an energy source;
(b) an energy source that directs laser energy to the sample presenting surface for desorbing and ionizing the analyte; and (c) a detector that detects the desorbed, ionized analyte.
34. The apparatus of claim 33, further comprising:
(d) a spectrometer tube into which ionized analyte is accelerated; and (e) means for applying an accelerating electrical potential to the desorbed, ionized analyte; wherein the mass spectrometer is a time-of-flight mass spectrometer.
(d) a spectrometer tube into which ionized analyte is accelerated; and (e) means for applying an accelerating electrical potential to the desorbed, ionized analyte; wherein the mass spectrometer is a time-of-flight mass spectrometer.
35. The apparatus of claim 34, further comprising:
(f) vacuum means for applying a vacuum to the interior of the tube.
(f) vacuum means for applying a vacuum to the interior of the tube.
36. The apparatus of claim 33, wherein the detector comprises an electron multiplier.
37. The apparatus of claim 33, wherein the sample presenting surface is derivatized with the energy absorbing molecules.
38. The apparatus of claim 33, wherein the energy absorbing molecules are covalently bound to the sample presenting surface.
39. The apparatus of claim 33, wherein the sample presenting surface is adhered to the probe magnetically.
40. The apparatus of claim 33, wherein the sample presenting surface comprises metal, metal coated with a synthetic polymer, glass, ceramic, a synthetic polymer or a mixture thereof.
41. The apparatus of claim 33, wherein the sample presenting surface comprises a synthetic polymer.
42. The apparatus of claim 41, wherein the energy absorbing molecules are comprised within the synthetic polymer.
43. The apparatus of claim 33, wherein the energy source is energy from a nitrogen laser.
44. The apparatus of claim 33, wherein the energy source is energy from an Nd-YAG laser.
45. The apparatus of claim 33, wherein the energy absorbing molecules axe arranged in a predetermined array.
46. The apparatus of claim 33, wherein the analyte comprises a protein.
47. The apparatus of claim 33, wherein the analyte comprises a carbohydrate.
48. The apparatus of claim 33, wherein the analyte comprises a nucleic acid.
49. The apparatus of claim 48, wherein the nucleic acid is DNA.
50. The apparatus of any of claims 33-49, wherein the energy absorbing molecules are selected from the group consisting of dimethoxy hydroxycinnamic acid, cinnamamide, cinnamyl bromide, dihydroxybenzoic acid, and cyanohydroxycinnamic acid.
51. The apparatus of any of claims 33-49, wherein the sample presenting surface is a surface of the probe.
52. The apparatus of any of claims 33-49, wherein the sample presenting surface is a bead associated with the probe surface.
53. A probe that is removably insertable into a mass spectrometer, the probe having a surface that is derivitized with a layer of energy absorbing molecules, wherein the energy absorbing molecules absorb energy from a laser energy source thereby enabling desorption of analyte molecules from the probe.
54. The probe of claim 53 wherein the energy absorbing molecules are noncovalently bound to the surface.
55. The probe of claim 53 wherein the energy absorbing molecules are covalently bound to the surface.
56. The probe of claim 54 or 55 wherein the energy absorbing molecules are selected from the group consisting of dimethoxy hydroxycinnamic acid, cinnamamide, cinnamyl bromide, dihydroxybenzoic acid and cyanohydroxycinnamic acid.
57. The probe of claim 54 or 55 wherein the probe is free of the analyte.
58. The probe of claim 54 or 55 further comprising the analyte deposited on the probe for presentation to the high energy source.
59. The probe of claim 54 or 55 wherein the layer comprises a plurality of different energy absorbing molecules.
60. The probe of claim 54 or 55 comprising a plurality of layers of different energy absorbing molecules.
61. The probe of claim 54 or 55 herein the surface is adhered to the probe magnetically.
62. The probe of claim 54 or 55 wherein the surface comprises metal, metal coated with a synthetic polymer, glass, ceramic, a synthetic polymer or a mixture thereof.
63. The probe of claim 54 or 55 wherein the surface is coated with a synthetic polymer.
64. The probe of claim 54 or 55 wherein the energy absorbing molecules are comprised in spots arranged in a predetermined array.
65. The probe of claim 62 wherein the energy absorbing molecules are comprised within the synthetic polymer.
66. The probe of claim 63 wherein the energy absorbing molecules are comprised within the synthetic polymer.
67. The probe of claim 64 wherein the array comprises an array of spots from 0.005 to 0.080 inches in diameter.
68. A mass spectrometry apparatus comprising:
(a) a probe comprising:
i. a sample presenting surface; and ii. a layer of energy absorbing molecules derivitized to the sample presenting surface; and (b) an energy source that directs laser energy to the sample presenting surface for desorbing and ionizing the analyte; and (c) a detector that detects the desorbed, ionized analyte.
(a) a probe comprising:
i. a sample presenting surface; and ii. a layer of energy absorbing molecules derivitized to the sample presenting surface; and (b) an energy source that directs laser energy to the sample presenting surface for desorbing and ionizing the analyte; and (c) a detector that detects the desorbed, ionized analyte.
69. The apparatus of claim 68, further comprising:
(d) a spectrometer tube into which ionized analyte is accelerated; and (e) means for applying an accelerating electrical potential to the desorbed, ionized analyte; wherein the mass spectrometer is a time-of-flight mass spectrometer.
(d) a spectrometer tube into which ionized analyte is accelerated; and (e) means for applying an accelerating electrical potential to the desorbed, ionized analyte; wherein the mass spectrometer is a time-of-flight mass spectrometer.
70. The apparatus of claim 69, further comprising:
(f) vacuum means for applying a vacuum to the interior of the tube.
(f) vacuum means for applying a vacuum to the interior of the tube.
71. The apparatus of claim 68, wherein the detector comprises an electron multiplier.
72. The apparatus of claim 68, wherein the energy absorbing molecules are covalently bound to the sample presenting surface.
73. The apparatus of claim 68, wherein the sample presenting surface is adhered to the probe magnetically.
74. The apparatus of claim 68, wherein the sample presenting surface comprises metal, metal coated with a synthetic polymer, glass, ceramic, a synthetic polymer or a mixture thereof.
75. The apparatus of claim 68, wherein the sample presenting surface comprises a synthetic polymer.
76. The apparatus of claim 75, wherein the energy absorbing molecules are comprised within the synthetic polymer.
77. The apparatus of claim 68, wherein the energy source is energy from a nitrogen laser.
78. The apparatus of claim 68, wherein the energy source is energy from an Nd-YAG laser.
79. The apparatus of claim 68, wherein the energy absorbing molecules are arranged in a predetermined array.
80. The apparatus of any of claims 68-79, wherein the energy absorbing molecules are selected from the group consisting of dimethoxy hydroxycinnamic acid, cinnamamide, cinnamyl bromide, dihydroxybenzoic acid, and cyanohydroxycinnamic acid.
81. The apparatus of any of claims 68-79, wherein the sample presenting surface is a surface of the probe.
82. The apparatus of any of claims 68-79, wherein the sample presenting surface is a bead associated with the probe surface.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6889693A | 1993-05-28 | 1993-05-28 | |
| US08/068,896 | 1993-05-28 | ||
| CA002163426A CA2163426C (en) | 1993-05-28 | 1994-05-27 | Method and apparatus for desorption and ionization of analytes |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002163426A Division CA2163426C (en) | 1993-05-28 | 1994-05-27 | Method and apparatus for desorption and ionization of analytes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2512290A1 true CA2512290A1 (en) | 1994-12-08 |
| CA2512290C CA2512290C (en) | 2010-02-02 |
Family
ID=22085400
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002163426A Expired - Lifetime CA2163426C (en) | 1993-05-28 | 1994-05-27 | Method and apparatus for desorption and ionization of analytes |
| CA002512290A Expired - Lifetime CA2512290C (en) | 1993-05-28 | 1994-05-27 | Method and apparatus for desorption and ionization of analytes |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002163426A Expired - Lifetime CA2163426C (en) | 1993-05-28 | 1994-05-27 | Method and apparatus for desorption and ionization of analytes |
Country Status (12)
| Country | Link |
|---|---|
| US (9) | US5719060A (en) |
| EP (2) | EP0700521B1 (en) |
| JP (3) | JP3639594B2 (en) |
| AT (1) | ATE242485T1 (en) |
| AU (1) | AU676582B2 (en) |
| CA (2) | CA2163426C (en) |
| DE (1) | DE69432791T2 (en) |
| DK (1) | DK0700521T3 (en) |
| ES (1) | ES2201077T3 (en) |
| NZ (1) | NZ267842A (en) |
| PT (1) | PT700521E (en) |
| WO (1) | WO1994028418A1 (en) |
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- 1994-05-27 PT PT94919287T patent/PT700521E/en unknown
- 1994-05-27 WO PCT/US1994/006064 patent/WO1994028418A1/en active IP Right Grant
- 1994-05-27 DK DK94919287T patent/DK0700521T3/en active
- 1994-05-27 ES ES94919287T patent/ES2201077T3/en not_active Expired - Lifetime
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