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Single Cell Analysis by Using ICP-MS

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Metallomics

Abstract

Single cell analysis by using inductively coupled plasma mass spectrometry (ICP-MS) has been attracting attention for investigating a cell-to-cell variation of content of elements and biomolecules. ICP-MS has a unique feature that can be applied to a highly sensitive elemental analysis for evaluating a cell-to-cell variance or cellular uptake of elements, drugs, and nanoparticles and a multiparametric analysis for characterizing a cell population based on multiparameters, like a flow cytometry (so-called mass cytometry). In addition, subcellular localization analysis including multiparametric imaging can be performed with the coupling of a laser ablation system. In this chapter, we describe an overview of single cell analysis by using ICP-MS and its future prospects, focusing on cytometric analysis and imaging analysis.

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References

  1. Szpunar J (2004) Metallomics: a new frontier in analytical chemistry. Anal Bioanal Chem 378:54–56

    Article  CAS  PubMed  Google Scholar 

  2. Sanz-Medel A, Montes-Bayon M, Bettmer J, Fernandez-Sanchez M, Encinar J (2012) ICP-MS for absolute quantification of proteins for heteroatom-tagged, targeted proteomics. Trac Trends Anal Chem 40:52–63

    Article  CAS  Google Scholar 

  3. Sanz-Medel A, Montes-Bayon M, de la Campa M, Encinar J, Bettmer J (2008) Elemental mass spectrometry for quantitative proteomics. Anal Bioanal Chem 390:3–16

    Article  CAS  PubMed  Google Scholar 

  4. Montaser A (1998) Inductively coupled plasma mass spectrometry. Wiley-VCH, New York

    Google Scholar 

  5. Tomas R (2013) Practical guide to ICP-MS: a tutorial for beginners, 3rd edn. CRC Press, Boca Raton

    Google Scholar 

  6. Pröfrock D, Prange A (2012) Inductively coupled plasma-mass spectrometry (ICP-MS) for quantitative analysis in environmental and life sciences: a review of challenges, solutions, and trends. Appl Spectrosc 66:843–868

    Article  PubMed  Google Scholar 

  7. Engelhard C (2011) Inductively coupled plasma mass spectrometry: recent trends and developments. Anal Bioanal Chem 399:213–219

    Article  CAS  PubMed  Google Scholar 

  8. Dittrich P, Jakubowski N (2014) Current trends in single cell analysis. Anal Bioanal Chem 406:6957–6961

    Article  CAS  PubMed  Google Scholar 

  9. Mueller L, Traub H, Jakubowski N, Drescher D, Baranov VI, Kneipp J (2014) Trends in single-cell analysis by use of ICP-MS. Anal Bioanal Chem 406:6963–6977

    Article  CAS  PubMed  Google Scholar 

  10. Bendall SC, Nolan GP, Roederer M, Chattopadhyay PK (2012) A deep profiler’s guide to cytometry. Trends Immunol 33:323–332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ornatsky O, Bandura D, Baranov V, Nitz M, Winnik MA, Tanner S (2010) Highly multiparametric analysis by mass cytometry. J Immunol Methods 361:1–20

    Article  CAS  PubMed  Google Scholar 

  12. Atkuri KR, Stevens JC, Neubert H (2015) Mass cytometry: a highly multiplexed single-cell technology for advancing drug development. Drug Metab Dispos 43:227–233

    Article  PubMed  Google Scholar 

  13. Schmid A, Kortmann H, Dittrich PS, Blank LM (2010) Chemical and biological single cell analysis. Curr Opin Biotechnol 21:12–20

    Article  CAS  PubMed  Google Scholar 

  14. Trouillon R, Passarelli MK, Wang J, Kurczy ME, Ewing AG (2013) Chemical analysis of single cells. Anal Chem 85:522–542

    Article  CAS  PubMed  Google Scholar 

  15. Haselgrubler T, Haider M, Ji BZ, Juhasz K, Sonnleitner A, Balogi Z, Hesse J (2014) High-throughput, multiparameter analysis of single cells. Anal Bioanal Chem 406:3279–3296

    Article  PubMed  Google Scholar 

  16. Tanner SD, Bandura DR, Ornatsky O, Baranov VI, Nitz M, Winnik MA (2008) Flow cytometer with mass spectrometer detection for massively multiplexed single-cell biomarker assay. Pure Appl Chem 80:2627–2641

    Article  CAS  Google Scholar 

  17. Bandura DR, Baranov VI, Ornatsky OI, Antonov A, Kinach R, Lou XD, Pavlov S, Vorobiev S, Dick JE, Tanner SD (2009) Mass cytometry: technique for real time single cell multitarget immunoassay based on inductively coupled plasma time-of-flight mass spectrometry. Anal Chem 81:6813–6822

    Article  CAS  PubMed  Google Scholar 

  18. Groombridge AS, Miyashita S, Fujii S, Nagasawa K, Okahashi T, Ohata M, Umemura T, Takatsu A, Inagaki K, Chiba K (2013) High sensitive elemental analysis of single yeast cells (Saccharomyces cerevisiae) by time-resolved inductively-coupled plasma mass spectrometry using a high efficiency cell introduction system. Anal Sci 29:597–603

    Article  CAS  PubMed  Google Scholar 

  19. Miyashita S, Groombridge AS, Fujii S, Takatsu A, Chiba K, Inagaki K (2014) Time-resolved ICP-MS measurement: a new method for elemental and multiparametric analysis of single cells. Anal Sci 30:219–224

    Article  CAS  PubMed  Google Scholar 

  20. Miyashita S, Groombridge AS, Fujii S, Minoda A, Takatsu A, Hioki A, Chiba K, Inagaki K (2014) Highly efficient single-cell analysis of microbial cells by time-resolved inductively coupled plasma mass spectrometry. J Anal At Spectrom 29:1598–1606

    Article  CAS  Google Scholar 

  21. Olesik JW, Gray PJ (2012) Considerations for measurement of individual nanoparticles or microparticles by ICP-MS: determination of the number of particles and the analyte mass in each particle. J Anal At Spectrom 27:1143–1155

    Article  CAS  Google Scholar 

  22. Ho KS, Chan WT (2010) Time-resolved ICP-MS measurement for single-cell analysis and on-line cytometry. J Anal At Spectrom 25:1114–1122

    Article  CAS  Google Scholar 

  23. Wang HL, Wang B, Wang M, Zheng LN, Chen HQ, Chai ZF, Zhao YL, Feng WY (2015) Time-resolved ICP-MS analysis of mineral element contents and distribution patterns in single cells. Analyst 140:523–531

    Article  CAS  PubMed  Google Scholar 

  24. Tsang CN, Ho KS, Sun HZ, Chan WT (2011) Tracking bismuth antiulcer drug uptake in single Helicobacter pylori cells. J Am Chem Soc 133:7355–7357

    Article  CAS  PubMed  Google Scholar 

  25. Zheng LN, Wang M, Zhao LC, Sun BY, Wang B, Chen HQ, Zhao YL, Chai ZF, Feng WY (2015) Quantitative analysis of Gd@C82(OH)22 and cisplatin uptake in single cells by inductively coupled plasma mass spectrometry. Anal Bioanal Chem 407:2383–2391

    Article  CAS  PubMed  Google Scholar 

  26. Zheng LN, Wang M, Wang B, Chen HQ, Ouyang H, Zhao YL, Chai ZF, Feng WY (2013) Determination of quantum dots in single cells by inductively coupled plasma mass spectrometry. Talanta 116:782–787

    Article  CAS  PubMed  Google Scholar 

  27. Li F, Armstrong DW, Houk RS (2005) Behavior of bacteria in the inductively coupled plasma: atomization and production of atomic ions for mass spectrometry. Anal Chem 77:1407–1413

    Article  CAS  PubMed  Google Scholar 

  28. Shigeta K, Koellensperger G, Rampler E, Traub H, Rottmann L, Panne U, Okino A, Jakubowski N (2013) Sample introduction of single selenized yeast cells (Saccharomyces cerevisiae) by micro droplet generation into an ICP-sector field mass spectrometer for label-free detection of trace elements. J Anal At Spectrom 28:637–645

    Article  CAS  Google Scholar 

  29. Shigeta K, Traub H, Panne U, Okino A, Rottmann L, Jakubowski N (2013) Application of a micro-droplet generator for an ICP-sector field mass spectrometer – optimization and analytical characterization. J Anal At Spectrom 28:646–656

    Article  CAS  Google Scholar 

  30. Bendall SC, Simonds EF, Qiu P, Amir EAD, Krutzik PO, Finck R, Bruggner RV, Melamed R, Trejo A, Ornatsky OI, Balderas RS, Plevritis SK, Sachs K, Pe’er D, Tanner SD, Nolan GP (2011) Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum. Science 332:687–696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Gschwind S, Flamigni L, Koch J, Borovinskaya O, Groh S, Niemax K, Günther D (2011) Capabilities of inductively coupled plasma mass spectrometry for the detection of nanoparticles carried by monodisperse microdroplets. J Anal At Spectrom 26:1166–1174

    Article  CAS  Google Scholar 

  32. Iwai T, Shigeta K, Aida M, Ishihara Y, Miyahara H, Okino A (2015) A transient signal acquisition and processing method for micro-droplet injection system inductively coupled plasma mass spectrometry (M-DIS-ICP-MS). J Anal At Spectrom 30:1617–1622

    Article  CAS  Google Scholar 

  33. Strenge I, Engelhard C (2016) Capabilities of fast data acquisition with microsecond time resolution in inductively coupled plasma mass spectrometry and identification of signal artifacts from millisecond dwell times during detection of single gold nanoparticles. J Anal At Spectrom 31:135–144

    Article  CAS  Google Scholar 

  34. Todoli JL, Mermet JM (2006) Sample introduction systems for the analysis of liquid microsamples by ICP-AES and ICP-MS. Spectrochim Acta B 61:239–283

    Article  Google Scholar 

  35. Inagaki K, Fujii S, Takatsu A, Chiba K (2011) High performance concentric nebulizer for low-flow rate liquid sample introduction to ICP-MS. J Anal At Spectrom 26:623–630

    Article  CAS  Google Scholar 

  36. Groombridge AS, Inagaki K, Fujii S, Nagasawa K, Okahashi T, Takatsu A, Chiba K (2012) Modified high performance concentric nebulizer for inductively coupled plasma optical emission spectrometry. J Anal At Spectrom 27:1787–1793

    Article  CAS  Google Scholar 

  37. Kaburaki Y, Nomura A, Ishihara Y, Iwai T, Miyahara H, Okino A (2013) Development of injection gas heating system for introducing large droplets to inductively coupled plasma. Anal Sci 29:1147–1151

    Article  CAS  PubMed  Google Scholar 

  38. Ishihara Y, Aida M, Nomura A, Miyahara H, Hokura A, Okino A (2015) Development of desolvation system for single-cell analysis using droplet injection inductively coupled plasma atomic emission spectroscopy. Anal Sci 31:781–785

    Article  CAS  PubMed  Google Scholar 

  39. Verboket PE, Borovinskaya O, Meyer N, Günther D, Dittrich PS (2014) A new microfluidics-based droplet dispenser for ICPMS. Anal Chem 86:6012–6018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Tanner SD, Baranov VI, Ornatsky OI, Bandura DR, George TC (2013) An introduction to mass cytometry: fundamentals and applications. Cancer Immunol Immunother 62:955–965

    Article  PubMed  Google Scholar 

  41. Bjornson ZB, Nolan GP, Fantl WJ (2013) Single-cell mass cytometry for analysis of immune system functional states. Curr Opin Immunol 25:484–494

    Article  CAS  PubMed  Google Scholar 

  42. Di Palma S, Bodenmiller B (2015) Unraveling cell populations in tumors by single-cell mass cytometry. Curr Opin Biotechnol 31:122–129

    Article  PubMed  Google Scholar 

  43. Nair N, Mei HE, Chen SY, Hale M, Nolan GP, Maecker HT, Genovese M, Fathman CG, Whiting CC (2015) Mass cytometry as a platform for the discovery of cellular biomarkers to guide effective rheumatic disease therapy. Arthritis Res Ther 17:127–135

    Article  PubMed  PubMed Central  Google Scholar 

  44. Proserpio V, Lönnberg T (2016) Single-cell technologies are revolutionizing the approach to rare cells. Immunol Cell Biol 94:225–229

    Article  CAS  PubMed  Google Scholar 

  45. Qiu P, Simonds EF, Bendall SC, Gibbs KD Jr, Bruggner RV, Linderman MD, Sachs K, Nolan GP, Plevritis SK (2011) Extracting a cellular hierarchy from high-dimensional cytometry data with SPADE. Nat Biotechnol 29:886–891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Newell EW, Sigal N, Bendall SC, Nolan GP, Davis MM (2012) Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes. Immunity 36:142–152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Leipold MD, Ornatsky O, Baranov V, Whitfield C, Nitz M (2011) Development of mass cytometry methods for bacterial discrimination. Anal Biochem 419:1–8

    Article  CAS  PubMed  Google Scholar 

  48. Gibbs KD Jr, Jager A, Crespo O, Goltsev Y, Trejo A, Richard CE, Nolan GP (2012) Decoupling of tumor-initiating activity from stable immunophenotype in HoxA9-Meis1-driven AML. Cell Stem Cell 10:210–217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Bodenmiller B, Zunder ER, Finck R, Chen TJ, Savig ES, Bruggner RV, Simonds EF, Bendall SC, Sachs K, Krutzik PO, Nolan GP (2012) Multiplexed mass cytometry profiling of cellular states perturbed by small-molecule regulators. Nat Biotechnol 30:858–867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Hare D, Austin C, Doble P (2012) Quantification strategies for elemental imaging of biological samples using laser ablation-inductively coupled plasma-mass spectrometry. Analyst 137:1527–1537

    Article  CAS  PubMed  Google Scholar 

  51. Drescher D, Giesen C, Traub H, Panne U, Kneipp J, Jakubowski N (2012) Quantitative imaging of gold and silver nanoparticles in single eukaryotic cells by laser ablation ICP-MS. Anal Chem 84:9684–9688

    Article  CAS  PubMed  Google Scholar 

  52. Drescher D, Zeise I, Traub H, Guttmann P, Seifert S, Büchner T, Jakubowski N, Schneider G, Kneipp J (2014) In situ characterization of SiO2 nanoparticle biointeractions using BrightSilica. Adv Funct Mater 24:3765–3775

    Article  CAS  Google Scholar 

  53. Wang HAO, Grolimund D, Giesen C, Borca CN, Shaw-Stewart JRH, Bodenmiller B, Günther D (2013) Fast chemical imaging at high spatial resolution by laser ablation inductively coupled plasma mass spectrometry. Anal Chem 85:10107–10116

    Article  CAS  PubMed  Google Scholar 

  54. Giesen C, Wang HAO, Schapiro D, Zivanovic N, Jacobs A, Hattendorf B, Schüffler PJ, Grolimund D, Buhmann JM, Brandt S, Varga Z, Wild PJ, Günther D, Bodenmiller B (2014) Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry. Nat Methods 11:417–422

    Article  CAS  PubMed  Google Scholar 

  55. Mellors JS, Jorabchi K, Smith LM, Ramsey JM (2010) Integrated microfluidic device for automated single cell analysis using electrophoretic separation and electrospray ionization mass spectrometry. Anal Chem 82:967–973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Mao P, Wang HT, Yang P, Wang D (2011) Multinozzle emitter arrays for nanoelectrospray mass spectrometry. Anal Chem 83:6082–6089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Yin H, Marshall D (2012) Microfluidics for single cell analysis. Curr Opin Biotechnol 23:110–119

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Kazumi Inagaki .

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Miyashita, Si., Fujii, Si., Shigeta, K., Inagaki, K. (2017). Single Cell Analysis by Using ICP-MS. In: Ogra, Y., Hirata, T. (eds) Metallomics. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56463-8_5

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