journal article·2020-07Open access

Isotopically Encoded Nanotags for Multiplexed Ion Beam Imaging

Stefan Harmsen, Ahmet F. Coskun, Shambavi Ganesh, Garry P. Nolan, Sanjiv S. Gambhir

Advanced Materials Technologies· Volume 5· Issue 7

Abstract

Abstract High‐dimensional profiling of markers and analytes using approaches, such as barcoded fluorescent imaging with repeated labeling and mass cytometry has allowed visualization of biological processes at the single‐cell level. To address limitations of sensitivity and mass‐channel capacity, a nanobarcoding platform is developed for multiplexed ion beam imaging (MIBI) using secondary ion beam spectrometry that utilizes fabricated isotopically encoded nanotags. Use of combinatorial isotope distributions in 100 nm sized nanotags expands the labeling palette to overcome the spectral bounds of mass channels. As a proof‐of‐principle, a four‐digit (i.e., 0001–1111) barcoding scheme is demonstrated to detect 16 variants of 2H, 19F, 79/81Br, and 127I elemental barcode sets that are encoded in silica nanoparticle matrices. A computational debarcoding method and an automated machine learning analysis approach are developed to extract barcodes for accurate quantification of spatial nanotag distributions in large ion beam imaging areas up to 0.6 mm2. Isotopically encoded nanotags should boost the performance of mass imaging platforms, such as MIBI and other elemental‐based bioimaging approaches.
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Research context

OpenAlex topics: Advanced biosensing and bioanalysis techniques · Ion-surface interactions and analysis · Molecular Biology Techniques and Applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Radiology Stanford University School of Medicine Stanford CA 94305 USA

Molecular Imaging Program at Stanford University (MIPS) Stanford University School of Medicine Stanford CA 94305 USA

Department of Microbiology and Immunology Stanford University School of Medicine Stanford CA 94305 USA

Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University Atlanta GA 30332 USA

School of Electrical and Computer Engineering Georgia Institute of Technology Atlanta GA 30332 USA

Department of Bioengineering Stanford University Schools of Medicine and of Engineering Stanford CA 94305 USA

Department of Materials Science & Engineering At Stanford University School of Medicine Stanford CA 94305 USA

Funding

Canary Foundation · National Science Foundation · Burroughs Wellcome Fund · Georgia Institute of Technology · Department of Chemistry, Vanderbilt University · National Institutes of Health

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