Mass Cytometry Tags: Where Chemistry Meets Single-Cell Analysis

Abstract

Mass cytometry is a highly multiparametric proteomic technology that allows the measurement and quantification of nearly 50 markers with single-cell resolution. Mass cytometry reagents are probes tagged with metal isotopes of defined mass and act as reporters. Metals are detected using inductively coupled plasma time-offlight mass spectrometry (ICP-TOF-MS). Many different types of mass-tag reagents have been developed to afford myriad applications. We have classified these compounds into polymer-based mass-tag reagents, nonpolymer-based mass-tag reagents, and inorganic nanoparticles. Metal-chelating polymers (MCPs) are widely used to profile and quantify cellular biomarkers; however, both the range of metals that can be detected and the metal signals have to be improved. Several strategies such as the inclusion of chelating agents or highly branched polymers may overcome these issues. Biocompatible materials such as polystyrene and inorganic nanoparticles are also of profound interest in mass cytometry. While polystyrene allows the inclusion of a wide variety of metals, the high metal content of inorganic nanoparticles offers an excellent opportunity to increase the signal from the metals to detect lowabundance biomarkers. Nonpolymer-based mass-tag reagents offer multiple applications: cell detection, cell cycle property determination, biomarker detection, and mass-tag cellular barcoding (MCB). Recent developments have been achieved in live cell barcoding by targeting proteins (CD45, b2m, and CD298), by using small and nonpolar probes or by ratiometric barcoding. From this perspective, the principal applications, strengths, and shortcomings of mass-tag reagents are highlighted, summarized, and discussed, with special emphasis on mass-tag reagents for MCB. Thereafter, the future perspectives of mass-tag reagents are discussed considering the current state-of-the-art technologies.

Living in a transient world: ICP-MS reinvented via time-resolved analysis for monitoring single events

“…Again, more details of this approach, which is extremely powerful as it offers the current potential to quantify nearly 50 different markers with single-cell resolution and at high sample throughput, are provided elsewhere, 113,114 while Table 3 lists some selected applications. Please note that it is also possible to couple LA to this type of instrumentation to carry out direct high-resolution elemental mapping measurements on tissue samples using metal-tagged antibodies (the commercial name of this technology is the Hyperion Imaging System).…”

“…For reviews on mass cytometry the reader is referred elsewhere. 113,114 Due to the obvious similarities between SP-ICP-MS and SC-ICP-MS, this section attempts to stress the main differences and the most important challenges associated with the latter and will refer to more detailed reviews where appropriate.…”

Atomic spectrometry update: review of advances in atomic spectrometry and related techniques

“…They maintained that the emphasis should be on the inherent advantages of multiplexing and specificity for diagnosing conditions for which there is no current immunoassay. Delgado-Gonzalez and Sanchez-Martin 10 reviewed the use of tagging reagents in mass cytometry . They classified the different approaches using polymer-based mass-tag reagents, nonpolymer-based mass-tag reagents, and inorganic NPs.…”

“…Boron isotopes are a key proxy for palaeooceanographic pH estimation. Buisson et al 166 utilised a new micro-sublimation and direct injection uptake system with MC-ICP-MS. 10 B and 11 B ions were detected using Faraday cups equipped with 10 13 U ampliers. With this system v 11 B was determined on $1 ng with external repeatability of 0.2&, which is a similar level of precision achieved when B is isolated by ion exchange chromatography.…”

“…With this system v 11 B was determined on $1 ng with external repeatability of 0.2&, which is a similar level of precision achieved when B is isolated by ion exchange chromatography. Evans et al 167 (10), 959-968) to minimise the interference from multiply charged Ca ion species on v 11 B measurement. Their modication to this method was to utilise 10 13 U Faraday ampliers to make more precise measurement of the Ca interference by closely dening the shape of the isobaric interference.…”