US 8,941,057 B2Granted

Probe and method for obtaining three-dimensional compositional maps of a biological sample

AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Services

InventorSriram Subramaniam

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Abstract

The invention provides a probe and a method of obtaining a three-dimensional compositional map of one or more targets in a biological sample, or a portion thereof, comprising: (a) milling a surface layer of a biological sample with a focused ion beam, thereby creating a newly exposed surface layer of the biological sample; (b) imaging the newly exposed surface layer of the biological sample; (c) identifying the chemical composition of the newly exposed surface layer of the biological sample, or a portion thereof, with a mass spectrometer; and (d) repeating (a) to (c) until a three-dimensional compositional map of one or more targets in the biological sample, or portion thereof, is obtained. Uses of the three-dimensional map obtained from the inventive method are further provided.

Claims1

Dependent claims

A method of obtaining a three-dimensional compositional map of one or more targets in a biological sample comprising one or more cells, or a portion thereof, comprising:

(a) milling a surface layer of a biological sample with a focused ion beam thereby creating a newly exposed surface layer of the biological sample;
(b) imaging the newly exposed surface layer of the biological sample;
(c) positioning a probe over the newly exposed surface layer, the probe comprising:
(i) a base;
and
(ii) at least one cylindrical extension spatially associated with at least one other cylindrical extension, wherein the cylindrical extensions are attached to the base at one end of the long axis of each of the cylindrical extensions;
wherein the spatial association of the cylindrical extensions provides for micron and/or submicron resolution of the sample, or portion thereof, on the three-dimensional compositional map;
(d) contacting the probe with the newly exposed surface layer, thereby lifting off components of the surface layer onto the probe;
(e) optionally transferring the components of the surface layer from the probe into a receiving unit;
(f) identifying the chemical composition of the components on the probe or in the receiving unit with the mass spectrometer;
and
(g) repeating (a) to (f) until a three-dimensional compositional map of one or more targets in the biological sample, or portion thereof, is obtained.

9 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/676,861Filed 4 Sep 2008 · us provisional application
Priority: 5 Sep 2007
Published: US 2011/0011190 A120 Jan 2011
Granted: 27 Jan 2015
Term ends: Not estimatedThe source records don’t support an estimate.

Classification13 codes

G01N 33/6848
General methods of protein analysis not limited to specific proteins or families of proteins: methods of protein analysis involving mass spectrometry
G01N 33/5082
For testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics: supracellular entities, e.g. tissue, organisms
H01J 37/28
Electron or ion microscopes; Electron or ion diffraction tubes: with scanning beams
H01J 37/3053
For casting, melting, evaporating, or etching: for evaporating or etching