Tantalum Oxide Nanoparticle-Based Mass Tag for Mass Cytometry

Zhang, Yefeng; Zabinyakov, Nick; Majonis, Daniel; Bouzekri, Alexandre; Ornatsky, Olga; Baranov, Vladimir; Winnik, Mitchell A.

doi:10.1021/acs.analchem.9b04970

Cited by 22 publications

(33 citation statements)

References 43 publications

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“…All the stable isotopes of exogenous cellular elements across the mass range from 75 to 209 Da can be applied as reporters for CyTOF, which shows minimal spectral overlap and requires no compensation between detection channels. [ 5 ] To date, various metal isotopes, including yttrium (Y), [ 6 ] silver (Ag), [ 7 ] cadmium (Cd), [ 8 ] indium (In), [ 9 ] lanthanide elements (Ln, from La to Lu, except Pm), [ 10 ] tantalum (Ta), [ 11 ] and bismuth (Bi) [ 12 ] have been investigated for protein analysis (identity, function, modification, expression level), while tellurium (Te), [ 13 ] ruthenium (Ru), [ 14,15 ] rhodium (Rh), [ 16 ] iridium (Ir), [ 16 ] palladium (Pd), [ 17 ] osmium (Os), [ 15 ] iodine (I), [ 18 ] platinum (Pt) [ 19 ] have been tested for cell identification (nucleus, viability, cell cycle, cell barcode). In order to site‐specifically attach metal cations to an antibody for biomarker detection, elemental labeling strategies based on polymer and nanoparticles (NPs) have been developed.…”

Section: Introductionmentioning

confidence: 99%

New Structure Mass Tag based on Zr‐NMOF for Multiparameter and Sensitive Single‐Cell Interrogating in Mass Cytometry

Dang

Zhang

et al. 2021

Advanced Materials

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Mass cytometry, also called cytometry by time‐of‐flight (CyTOF), is an emerging powerful proteomic analysis technique that utilizes metal chelated polymer (MCP) as mass tags for interrogating high‐dimensional biomarkers simultaneously on millions of individual cells. However, under the typical polymer‐based mass tag system, the sensitivity and multiplexing detection ability has been highly restricted. Herein, a new structure mass tag based on a nanometal organic framework (NMOF) is reported for multiparameter and sensitive single‐cell biomarker interrogating in CyTOF. A uniform‐sized Zr‐NMOF (33 nm) carrying 105 metal ions is synthesized under modulator/reaction time coregulation, which is monodispersed and colloidally stable in water for over one‐year storage. On functionalization with an antibody, the Zr mass tag exhibits specific molecular recognition properties and minimal cross‐reaction toward nontargeted cells. In addition, the Zr‐mass tag is compatible with MCP mass tags in a multiparameter assay for mouse spleen cells staining, which exploits four additional channels, m/z = 90, 91, 92, 94, for single‐cell immunoassays in CyTOF. Compared to the MCP mass tag, the Zr‐mass tag provides an additional fivefold signal amplification. This work provides the fundamental technical capability for exploiting NMOF‐based mass tags for CyTOF application, which opens up possibility of high‐dimensional single‐cell immune profiling, low abundant antigen detection, and development of new barcoding systems.

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Section: Introductionmentioning

confidence: 99%

New Structure Mass Tag based on Zr‐NMOF for Multiparameter and Sensitive Single‐Cell Interrogating in Mass Cytometry

Dang

Zhang

et al. 2021

Advanced Materials

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“…Most commercial Qdots used for conventional flow cytometry contain isotopes of cadmium ( 106-116 Cd) with either selenium ( 72-82 Se) or tellurium ( 120-130 Te), which are readily available as antibody conjugates ( 36 , 37 ). More recent options for antibody labels include streptavidin-coated gold or silver nanoparticles ( 38 , 39 ) and tantalum oxide nanoparticles ( 40 ).…”

Section: Experimental Designmentioning

confidence: 99%

CyTOF® for the Masses

2022

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Mass cytometry has revolutionized immunophenotyping, particularly in exploratory settings where simultaneous breadth and depth of characterization of immune populations is needed with limited samples such as in preclinical and clinical tumor immunotherapy. Mass cytometry is also a powerful tool for single-cell immunological assays, especially for complex and simultaneous characterization of diverse intratumoral immune subsets or immunotherapeutic cell populations. Through the elimination of spectral overlap seen in optical flow cytometry by replacement of fluorescent labels with metal isotopes, mass cytometry allows, on average, robust analysis of 60 individual parameters simultaneously. This is, however, associated with significantly increased complexity in the design, execution, and interpretation of mass cytometry experiments. To address the key pitfalls associated with the fragmentation, complexity, and analysis of data in mass cytometry for immunologists who are novices to these techniques, we have developed a comprehensive resource guide. Included in this review are experiment and panel design, antibody conjugations, sample staining, sample acquisition, and data pre-processing and analysis. Where feasible multiple resources for the same process are compared, allowing researchers experienced in flow cytometry but with minimal mass cytometry expertise to develop a data-driven and streamlined project workflow. It is our hope that this manuscript will prove a useful resource for both beginning and advanced users of mass cytometry.

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“…Introducing new metal-chelating agents, such as deferoxamine (DFO), seems to be essential to expand the arsenal of metal isotopes of interest for MCPs and to fully exploit the multiparametric properties of mass cytometry. In fact, the last generation mass cytometer (Helios, Fluidigm) can detect over 135 metal isotopes simultaneously . Likewise, lanthanide antennas usually used in photoluminescence represent an interesting option to form strong and stable complexes with lanthanides and transition metals.…”

Section: Mass-tag Reagentsmentioning

confidence: 99%

“…Currently, MCPs are able to bind 20–50 metal atoms per polymer, bearing approximately 100–250 metal atoms per antibody. − In general, this number is enough to detect and quantify highly abundant biomarkers (10 4 –10 7 per cell) . However, many mass cytometry applications are focused on low-abundance biomarkers, so the development of MCPs bearing a higher number of metal atoms is required.…”

Section: Mass-tag Reagentsmentioning

confidence: 99%

Mass Cytometry Tags: Where Chemistry Meets Single-Cell Analysis

Delgado-González

Sánchez‐Martín

2020

Anal. Chem.

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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.

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Tantalum Oxide Nanoparticle-Based Mass Tag for Mass Cytometry

Cited by 22 publications

References 43 publications

New Structure Mass Tag based on Zr‐NMOF for Multiparameter and Sensitive Single‐Cell Interrogating in Mass Cytometry

New Structure Mass Tag based on Zr‐NMOF for Multiparameter and Sensitive Single‐Cell Interrogating in Mass Cytometry

CyTOF® for the Masses

Mass Cytometry Tags: Where Chemistry Meets Single-Cell Analysis

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