Gold implantation/deposition of biological samples for laser desorption three dimensional depth profiling of tissues
First Claim
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1. An analytical instrument for the characterization and analysis of a sample comprising:
- a MALDI sampling device to desorb at least a portion of said sample, said MALDI sampling device comprising a sample stage, said sample stage capable of accommodating a sample;
a component selected from the group consisting of an inorganic cluster ion beam source, a vapor deposition system, a laser ablation deposition system, a desorption deposition source, and any combination thereof, said component being capable of adding a matrix to said sample, said component being fluidly coupled to said MALDI sampling device;
a laser coupled to said MALDI sampling device, said laser being capable of desorbing material from said sample;
an ion mobility cell having a drift tube, said mobility cell coupled to said MALDI sampling device and capable of receiving sample from said MALDI sampling device; and
,a time-of-flight mass spectrometer having a flight tube positioned orthogonally to said drift tube, said flight tube fluidly coupled to said drift tube.
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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.
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Citations
34 Claims
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1. An analytical instrument for the characterization and analysis of a sample comprising:
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a MALDI sampling device to desorb at least a portion of said sample, said MALDI sampling device comprising a sample stage, said sample stage capable of accommodating a sample; a component selected from the group consisting of an inorganic cluster ion beam source, a vapor deposition system, a laser ablation deposition system, a desorption deposition source, and any combination thereof, said component being capable of adding a matrix to said sample, said component being fluidly coupled to said MALDI sampling device; a laser coupled to said MALDI sampling device, said laser being capable of desorbing material from said sample; an ion mobility cell having a drift tube, said mobility cell coupled to said MALDI sampling device and capable of receiving sample from said MALDI sampling device; and
,a time-of-flight mass spectrometer having a flight tube positioned orthogonally to said drift tube, said flight tube fluidly coupled to said drift tube. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19)
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20. A method for the collection of mass spectrometric data from a sample, comprising the steps of:
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adding matrix to the sample with a component selected from the group consisting of an inorganic cluster ion beam, a vapor deposition system, a laser ablation deposition system, a desorption deposition source, and any combination thereof; laser desorbing chemical species from said sample; separating the desorbed chemical species in a drift tube by ion mobility; and
,further separating the chemical species in a time-of-flight mass spectrometer. - View Dependent Claims (21, 22, 23, 28, 29, 30, 31, 32, 33)
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24. The method of sentence 21, wherein the step of adding matrix to the sample comprises adding matrix to the sample with a laser ablation deposition system.
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25. The method of sentence 24, further comprising the step of rotating the sample.
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26. The method of sentence 21, wherein the step of adding matrix to the sample comprises adding matrix to the sample with a desorption source coupled to a mobility cell.
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27. The method of sentence 26, wherein the desorption source comprises a laser ablation source, an electrospray ionization source, or a combination thereof.
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34. The method of sentence 33, further comprising the step of rotating the sample.
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