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Isotopically Encoded Nanotags for Multiplexed Ion Beam Imaging
Author(s) -
Harmsen Stefan,
Coskun Ahmet F.,
Ganesh Shambavi,
Nolan Garry P.,
Gambhir Sanjiv S.
Publication year - 2020
Publication title -
advanced materials technologies
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.184
H-Index - 42
ISSN - 2365-709X
DOI - 10.1002/admt.202000098
Subject(s) - barcode , materials science , ion beam , mass spectrometry , mass spectrometry imaging , analyte , multiplexing , nanotechnology , analytical chemistry (journal) , biological system , beam (structure) , computer science , chemistry , optics , environmental chemistry , chromatography , physics , biology , telecommunications , operating system
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 2 H, 19 F, 79/81 Br, and 127 I 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 mm 2 . Isotopically encoded nanotags should boost the performance of mass imaging platforms, such as MIBI and other elemental‐based bioimaging approaches.