Technology information

Description
Isotopically Encoded Nanotags for Multiplexed Ion Beam Imaging. 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.

Comment
Mass spectrometry‐based method is one of the highly multiplex techniques to capture the protein spatial intensity. Multiplexed ion beam imaging (MIBI), using secondary ion mass spectrometry to image labelled antibodies, is able to analyse one hundred markers of the same tissue. This technology yields precise quantification of immune cell subpopulation and their spatial patterns inside the tumour. However, this Method dependent on the performance of antibodies and are relatively costly. It is still challenging to increase the current throughput to proteome‐wide. Bias may also exist when designing the panel of markers rather than discovering functional proteins from the proteomics data. [PMID: 35040595]

Keywords
Reproducibility Of Results, Immunohistochemistry, Erbb-2, Receptor, Secondary Ion, Sensitivity And Specificity, Biomarkers, Antibodies, Chemistry, Spectrometry, Diagnostic Imaging, Spatial Analysis, Tumor Microenvironment, Mass, Neoplasms, Cytology, Systems Biology, Pathology, Female, Proteomics, Tumor, Imaging, Immunology, Breast Neoplasms

Targets
Protein

Spatial resolution
Subcellular