Leland Stanford Junior University

Robert M Angelo

Garry P Nolan

Sean Bendall

Sean C Bendall

A method of analyzing a population of cells is disclosed. In certain embodiments, the method includes i) obtaining an array of cells on a substrate, wherein the cells are labeled with one or more mass tags and are separated from one another, ii) measuring, using secondary ion mass spectrometry (SIMS), the abundance of the one or more mass tags at a plurality of locations occupied by the cells, thereby generating, for each individual cell measured, a set of data, and iii) outputting the set of data for each of the cells analyzed. Also provided herein are systems that find use in performing the subject method. In some embodiments, the system is an automated system for analyzing a population of cells using SIMS.

Single cell analysis using secondary ion mass spectrometry

Disclosed herein is a method of generating a high resolution image of a cellular sample, the method including i) labeling a cellular sample with at least one mass tag, thereby producing a labeled sample in which a biological feature of interest is associated with the at least one mass tag, ii) scanning the sample with a continuous or near-continuous primary ion beam to generate sputtered secondary ions and sputtered neutral species, iii) photoionizing the sputtered neutrals to generate ionized neutral species, wherein the sputtered neutrals are photoionized at a site that is proximal to their source on the sample, iv) detecting the ionized neutral species by mass spectrometry, thereby obtaining spatially addressed measurements of the abundance of the at least one mass tag across an area of the sample, and v) producing an image of the sample using the measurements. A system for performing the method is also provided.

Method for multiplexed sample analysis by photoionizing secondary sputtered neutrals

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.

Multiplexed imaging of tissues using mass tags and secondary ion mass spectrometry

A mass spectrometer system having: a primary ion source capable of irradiating a segment on a planar sample with a beam of primary ions, an orthogonal ion mass-to-charge ratio, the analyzer being configured to separate secondary elemental atomic ions according to their mass-to-charge ratio by time of flight; an ion detector for detecting secondary elemental atomic ions and producing mass spectra measurements; and a synchronizer. In the system, the beam of primary ions scans across the planar sample in two dimensions and the synchronizer associates the mass spectra measurements with positions on the planar sample.

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Oakland, CA, United States of America

Robert M Angelo