An introduction to mass cytometry: fundamentals and applications

Mass cytometry addresses the analytical challenges of polychromatic flow cytometry by using metal atoms as tags rather than fluorophores and atomic mass spectrometry as the detector rather than photon optics. The many available enriched stable isotopes of the transition elements can provide up to 100 distinguishable reporting tags, which can be measured simultaneously because of the essential independence of detection provided by the mass spectrometer. We discuss the adaptation of traditional inductively coupled plasma mass spectrometry to cytometry applications. We focus on the generation of cytometry-compatible data and on approaches to unsupervised multivariate clustering analysis. Finally, we provide a high-level review of some recent benchmark reports that highlight the potential for massively multi-parameter mass cytometry.

[1]  Raphael Gottardo,et al.  flowClust: a Bioconductor package for automated gating of flow cytometry data , 2009, BMC Bioinformatics.

[2]  Dmitry Bandura,et al.  Highly multiparametric analysis by mass cytometry. , 2010, Journal of immunological methods.

[3]  Sean C. Bendall,et al.  Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes. , 2012, Immunity.

[4]  Guohua Zhang,et al.  Polymer-based elemental tags for sensitive bioassays. , 2007, Angewandte Chemie.

[5]  M. Roederer,et al.  Data analysis in flow cytometry: The future just started , 2010, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[6]  Jian Huang,et al.  Regularized gene selection in cancer microarray meta-analysis , 2009, BMC Bioinformatics.

[7]  S. Tanner.  Space charge in ICP-MS: calculation and implications , 1992 .

[8]  O. Ornatsky,et al.  Mass cytometry: technique for real time single cell multitarget immunoassay based on inductively coupled plasma time-of-flight mass spectrometry. , 2009, Analytical chemistry.

[9]  Alan L. Gray,et al.  Inductively coupled argon plasma as an ion source for mass spectrometric determination of trace elements , 1980 .

[10]  Arvind Gupta,et al.  Data reduction for spectral clustering to analyze high throughput flow cytometry data , 2010, BMC Bioinformatics.

[11]  H. Hoos,et al.  RchyOptimyx: Cellular hierarchy optimization for flow cytometry , 2012, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[12]  Sean C. Bendall,et al.  Extracting a Cellular Hierarchy from High-dimensional Cytometry Data with SPADE , 2011, Nature Biotechnology.

[13]  O. Ornatsky,et al.  Study of cell antigens and intracellular DNA by identification of element-containing labels and metallointercalators using inductively coupled plasma mass spectrometry. , 2008, Analytical chemistry.

[14]  Mohsen Soleimani,et al.  Synthesis of a functional metal-chelating polymer and steps toward quantitative mass cytometry bioassays. , 2010, Analytical chemistry.

[15]  Erin F. Simonds,et al.  A platinum‐based covalent viability reagent for single‐cell mass cytometry , 2012, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[16]  Maurice H. T. Ling,et al.  BIOADI: a machine learning approach to identifying abbreviations and definitions in biological literature , 2009, BMC Bioinformatics.

[17]  J. Olesik,et al.  Considerations for measurement of individual nanoparticles or microparticles by ICP-MS: determination of the number of particles and the analyte mass in each particle , 2012 .

[18]  Sean C. Bendall,et al.  Single-Cell Mass Cytometry of Differential Immune and Drug Responses Across a Human Hematopoietic Continuum , 2011, Science.

[19]  D. J. Douglas,et al.  Nonspectroscopic interelement interferences in inductively coupled plasma mass spectrometry , 1988 .

[20]  H. W. Balfoort,et al.  Automatic identification of algae: neural network analysis of flow cytometric data , 1992 .

[21]  Jill P. Mesirov,et al.  Automated High-Dimensional Flow Cytometric Data Analysis , 2010, RECOMB.

[22]  Karen Sachs,et al.  Multiplexed mass cytometry profiling of cellular states perturbed by small-molecule regulators , 2012, Nature Biotechnology.