Multiplexed imaging of tissues using mass tags and secondary ion mass spectrometry
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsSean C. Bendall, Garry P. Nolan, Robert M. Angelo
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Abstract
A method of generating a high resolution two-dimensional image of a sample comprising cells and extracellular structures is provided. In certain embodiments, the method comprises: labeling a sample with at least one mass tag, thereby producing a labeled sample; scanning the sample with a secondary ion mass spectrometer (SIMS) ion beam to generate a data set that comprises spatially-addressable measurements of the abundance of the mass tag across an area of the sample; and outputting the data set. In many embodiments, the data set contains the identity and abundance of the mass tag. A system for performing the method is also provided.
Claims19
A method of generating a high resolution two-dimensional image of a tissue sample comprising cells and extracellular structures, the method comprising:
- labeling a tissue section with a plurality of distinguishable elemental isotopic mass tags, thereby producing a labeled tissue section in which biological features are bound to the elemental isotopic mass tags;
- scanning a plurality of positions across an area of the labeled tissue section with a secondary ion mass spectrometer (SIMS) ion beam to, at each position, simultaneously measure the plurality of elemental isotopic mass tags, to thereby generate a data set that comprises identity and spatially-addressable measurements of the abundance of each of the plurality of elemental isotopic mass tags at each of the plurality of positions in the tissue section;
- and
- outputting an image of the tissue section showing the biological features therein.
A system for analyzing a tissue sample comprising cells, the system comprising:
- a) a secondary ion mass spectrometry (SIMS) system comprising a holder for retaining a substrate comprising a tissue section, wherein the system is configured to (i) scan a plurality of positions across an area of the tissue section with a SIMS ion beam to, at each position, simultaneously measure a plurality of elemental isotopic mass tags that are bound to biological features in the tissue section, (ii) generate a data set that comprises the identity and spatially-addressable measurements of the abundance of each of the plurality of elemental isotopic mass tags at the plurality of positions across the area of said tissue section, and (iii) output the data set;
- and
- b) a computer comprising an image analysis module that processes said data set to produce an image of said tissue section.
Dependencies are inferred from the claim text.