Skip to main content

Assessing nanoparticle colloidal stability with single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS)

Abstract

Biological interactions, toxicity, and environmental fate of engineered nanoparticles are affected by colloidal stability and aggregation. To assess nanoparticle aggregation, analytical methods are needed that allow quantification of individual nanoparticle aggregates. However, most techniques used for nanoparticle aggregation analysis are limited to ensemble measurements or require harsh sample preparation that may introduce artifacts. An ideal method would analyze aggregate size in situ with single-nanoparticle resolution. Here, we established and validated single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS) as an unbiased high-throughput analytical technique to quantify nanoparticle size distributions and aggregation in situ. We induced nanoparticle aggregation by exposure to physiologically relevant saline conditions and applied SP-ICP-MS to quantify aggregate size and aggregation kinetics at the individual aggregate level. In situ SP-ICP-MS analysis revealed rational surface engineering principles for the preparation of colloidally stable nanoparticles. Our quantitative SP-ICP-MS technique is a platform technology to evaluate aggregation characteristics of various types of surface-engineered nanoparticles under physiologically relevant conditions. Potential widespread applications of this method may include the study of nanoparticle aggregation in environmental samples and the preparation of colloidally stable nanoparticle formulations for bioanalytical assays and nanomedicine.

Graphical abstract

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Pelaz B, Alexiou C, Alvarez-Puebla RA, et al. Diverse applications of nanomedicine. ACS Nano. 2017;11:2313–81. https://doi.org/10.1021/acsnano.6b06040.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. Wilhelm S. Perspectives for upconverting nanoparticles. ACS Nano. 2017;11:10644–53.

    CAS  Article  Google Scholar 

  3. Narum SM, Le T, Le DP, et al. Passive targeting in nanomedicine: fundamental concepts, body interactions, and clinical potential. In: Nanoparticles for Biomedical Applications: Elsevier; 2020. p. 37–53.

  4. Albanese A, Walkey CD, Olsen JB, et al. Secreted biomolecules alter the biological identity and cellular interactions of nanoparticles. ACS Nano. 2014;8:5515–26. https://doi.org/10.1021/nn4061012.

    CAS  Article  PubMed  Google Scholar 

  5. Wilhelm S, Tavares AJ, Dai Q, et al. Analysis of nanoparticle delivery to tumours. Nat Rev Mater. 2016;1:1–12.

    Google Scholar 

  6. Poon W, Zhang YN, Ouyang B, et al. Elimination pathways of nanoparticles. ACS Nano. 2019;13:5785–98. https://doi.org/10.1021/acsnano.9b01383.

    CAS  Article  PubMed  Google Scholar 

  7. Donahue ND, Acar H, Wilhelm S. Concepts of nanoparticle cellular uptake, intracellular trafficking, and kinetics in nanomedicine. Adv Drug Deliv Rev. 2019;143. https://doi.org/10.1016/j.addr.2019.04.008.

  8. Modena MM, Rühle B, Burg TP, Wuttke S. Nanoparticle characterization: what to measure? Adv Mater. 2019;31:1901556. https://doi.org/10.1002/adma.201901556.

    CAS  Article  Google Scholar 

  9. Marquis BJ, Love SA, Braun KL, Haynes CL. Analytical methods to assess nanoparticle toxicity. Analyst. 2009;134:425–39.

    CAS  Article  Google Scholar 

  10. Hoo CM, Starostin N, West P, Mecartney ML. A comparison of atomic force microscopy (AFM) and dynamic light scattering (DLS) methods to characterize nanoparticle size distributions. J Nanopart Res. 2008;10:89–96. https://doi.org/10.1007/s11051-008-9435-7.

    CAS  Article  Google Scholar 

  11. Olson J, Dominguez-Medina S, Hoggard A, et al. Optical characterization of single plasmonic nanoparticles. Chem Soc Rev. 2015;44:40–57.

    CAS  Article  Google Scholar 

  12. Montaño MD, Lowry GV, Blue J. Current status and future direction for examining engineered nanoparticles in natural systems. 2010. https://doi.org/10.1071/EN14037.

  13. Brar SK, Verma M. Measurement of nanoparticles by light-scattering techniques. TrAC - Trends Anal Chem. 2011;30:4–17.

    CAS  Article  Google Scholar 

  14. Dastanpour R, Boone JM, Rogak SN. Automated primary particle sizing of nanoparticle aggregates by TEM image analysis. Powder Technol. 2016;295:218–24. https://doi.org/10.1016/j.powtec.2016.03.027.

    CAS  Article  Google Scholar 

  15. Filipe V, Hawe A, Jiskoot W. Critical evaluation of nanoparticle tracking analysis (NTA) by NanoSight for the measurement of nanoparticles and protein aggregates. Pharm Res. 2010;27:796–810. https://doi.org/10.1007/s11095-010-0073-2.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. Montaño MD, Olesik JW, Barber AG, et al. Single particle ICP-MS: advances toward routine analysis of nanomaterials. Anal Bioanal Chem. 2016;408:5053–74. https://doi.org/10.1007/s00216-016-9676-8.

    CAS  Article  PubMed  Google Scholar 

  17. Mozhayeva D, Engelhard C. A critical review of single particle inductively coupled plasma mass spectrometry – a step towards an ideal method for nanomaterial characterization. J Anal At Spectrom. 2020. https://doi.org/10.1039/c9ja00206e.

  18. Corte Rodríguez M, Álvarez-Fernández García R, Blanco E, et al. Quantitative evaluation of cisplatin uptake in sensitive and resistant individual cells by single-cell ICP-MS (SC-ICP-MS). Anal Chem. 2017;89:11491–7. https://doi.org/10.1021/acs.analchem.7b02746.

    CAS  Article  PubMed  Google Scholar 

  19. Wilhelm S, Bensen RC, Kothapali NR, et al (2018) Quantification of gold nanoparticle uptake into cancer cells using single cell ICP-MS. PerkinElmer Appl Note.

  20. Lee JC, Donahue ND, Mao AS, et al. Exploring maleimide-based nanoparticle surface engineering to control cellular interactions. ACS Appl Nano Mater. 2020;3:2421–9. https://doi.org/10.1021/acsanm.9b02541.

    CAS  Article  Google Scholar 

  21. Albanese A, Tang PS, Chan WCW. The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu Rev Biomed Eng. 2012;14:1–16. https://doi.org/10.1146/annurev-bioeng-071811-150124.

    CAS  Article  PubMed  Google Scholar 

  22. Wilhelm S, Kaiser M, Würth C, et al. Water dispersible upconverting nanoparticles: effects of surface modification on their luminescence and colloidal stability. Nanoscale. 2015;7:1403–10. https://doi.org/10.1039/c4nr05954a.

    CAS  Article  PubMed  Google Scholar 

  23. Muhr V, Wilhelm S, Hirsch T, Wolfbeis OS. Upconversion nanoparticles: from hydrophobic to hydrophilic surfaces. Acc Chem Res. 2014;47:3481–93. https://doi.org/10.1021/ar500253g.

    CAS  Article  PubMed  Google Scholar 

  24. Hassellöv M, Readman JW, Ranville JF, Tiede K. Nanoparticle analysis and characterization methodologies in environmental risk assessment of engineered nanoparticles. Ecotoxicology. 2008;17:344–61.

    Article  Google Scholar 

  25. Love SA, Maurer-Jones MA, Thompson JW, et al. Assessing nanoparticle toxicity. Annu Rev Anal Chem. 2012;5:181–205. https://doi.org/10.1146/annurev-anchem-062011-143134.

    CAS  Article  Google Scholar 

  26. Buchman JT, Hudson-Smith NV, Landy KM, Haynes CL. Understanding nanoparticle toxicity mechanisms to inform redesign strategies to reduce environmental impact. Acc Chem Res. 2019;52:1632–42. https://doi.org/10.1021/acs.accounts.9b00053.

    CAS  Article  PubMed  Google Scholar 

  27. Albanese A, Chan WCW. Effect of gold nanoparticle aggregation on cell uptake and toxicity. ACS Nano. 2011;5:5478–89. https://doi.org/10.1021/nn2007496.

    CAS  Article  PubMed  Google Scholar 

  28. Maurer-Jones MA, Lin YS, Haynes CL. Functional assessment of metal oxide nanoparticle toxicity in immune cells. ACS Nano. 2010;4:3363–73. https://doi.org/10.1021/nn9018834.

    CAS  Article  PubMed  Google Scholar 

  29. Maurer-Jones MA, Gunsolus IL, Murphy CJ, Haynes CL. Toxicity of engineered nanoparticles in the environment. Anal Chem. 2013;85:3036–49. https://doi.org/10.1021/ac303636s.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. Kim HA, Lee BT, Na SY, et al. Characterization of silver nanoparticle aggregates using single particle-inductively coupled plasma-mass spectrometry (spICP-MS). Chemosphere. 2017;171:468–75. https://doi.org/10.1016/j.chemosphere.2016.12.063.

    CAS  Article  PubMed  Google Scholar 

  31. Perrault SD, Warren CWC. Synthesis and surface modification of highly monodispersed, spherical gold nanoparticles of 50−200 nm. J Am Chem Soc. 2009;131:17042–3. https://doi.org/10.1021/ja907069u.

    CAS  Article  PubMed  Google Scholar 

  32. Vigderman L, Zubarev ER. High-yield synthesis of gold nanorods with longitudinal SPR peak greater than 1200 nm using hydroquinone as a reducing agent. Chem Mater. 2013;25:1450–7. https://doi.org/10.1021/cm303661d.

    CAS  Article  Google Scholar 

  33. Zhou S, Huo D, Goines S, et al. Enabling complete ligand exchange on the surface of gold nanocrystals through the deposition and then etching of silver. J Am Chem Soc. 2018;140:11898–901. https://doi.org/10.1021/jacs.8b06464.

    CAS  Article  PubMed  Google Scholar 

  34. Merrifield RC, Stephan C, Lead JR. Quantification of Au nanoparticle biouptake and distribution to freshwater algae using single cell - ICP-MS. Environ Sci Technol. 2018;52:2271–7. https://doi.org/10.1021/acs.est.7b04968.

    CAS  Article  PubMed  Google Scholar 

  35. Corte-Rodríguez M, Blanco-González E, Bettmer J, Montes-Bayón M. Quantitative analysis of transferrin receptor 1 (TfR1) in individual breast cancer cells by means of labeled antibodies and elemental (ICP-MS) detection. Anal Chem. 2019;91:15532–8. https://doi.org/10.1021/acs.analchem.9b03438.

    CAS  Article  PubMed  Google Scholar 

  36. Mavrakis E, Mavroudakis L, Lydakis-Simantiris N, Pergantis SA. Investigating the uptake of arsenate by Chlamydomonas reinhardtii cells and its effect on their lipid profile using single cell ICP-MS and easy ambient sonic-spray ionization-MS. Anal Chem. 2019;91:9590–8. https://doi.org/10.1021/acs.analchem.9b00917.

    CAS  Article  PubMed  Google Scholar 

  37. Cuello-Nuñez S, Abad-Álvaro I, Bartczak D, et al. The accurate determination of number concentration of inorganic nanoparticles using spICP-MS with the dynamic mass flow approach. J Anal At Spectrom. 2020. https://doi.org/10.1039/c9ja00415g.

  38. Pace HE, Rogers NJ, Jarolimek C, et al. Determining transport efficiency for the purpose of counting and sizing nanoparticles via single particle inductively coupled plasma mass spectrometry. Anal Chem. 2011;83:9361–9. https://doi.org/10.1021/ac201952t.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. Pace HE, Rogers NJ, Jarolimek C, et al. Single particle inductively coupled plasma-mass spectrometry: a performance evaluation and method comparison in the determination of nanoparticle size. Environ Sci Technol. 2012;46:12272–80. https://doi.org/10.1021/es301787d.

    CAS  Article  PubMed  Google Scholar 

  40. Kang H, Buchman JT, Rodriguez RS, et al. Stabilization of silver and gold nanoparticles: preservation and improvement of plasmonic functionalities. Chem Rev. 2019;119:664–99.

    CAS  Article  Google Scholar 

  41. Muhammad Syed A, Sindhwani S, Wilhelm S, et al. Three-dimensional imaging of transparent tissues via metal nanoparticle labeling. J Am Chem Soc. 2017;139:9961–71. https://doi.org/10.1021/jacs.7b04022.

    CAS  Article  Google Scholar 

  42. Haiss W, Thanh NTK, Aveyard J, Fernig DG. Determination of size and concentration of gold nanoparticles from UV-Vis spectra. Anal Chem. 2007;79:4215–21. https://doi.org/10.1021/ac0702084.

    CAS  Article  PubMed  Google Scholar 

  43. Hineman A, Stephan C. Effect of dwell time on single particle inductively coupled plasma mass spectrometry data acquisition quality. J Anal At Spectrom. 2014;29:1252–7. https://doi.org/10.1039/c4ja00097h.

    CAS  Article  Google Scholar 

  44. Lee S, Bi X, Reed RB, et al. Nanoparticle size detection limits by single particle ICP-MS for 40 elements. Environ Sci Technol. 2014;48:10291–300. https://doi.org/10.1021/es502422v.

    CAS  Article  PubMed  Google Scholar 

  45. Tan J, Yang Y, El Hadri H, et al. Fast quantification of nanorod geometry by DMA-spICP-MS. Analyst. 2019;144:2275–83. https://doi.org/10.1039/c8an02250j.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  46. Kálomista I, Kéri A, Ungor D, et al. Dimensional characterization of gold nanorods by combining millisecond and microsecond temporal resolution single particle ICP-MS measurements. J Anal At Spectrom. 2017;32:2455–62. https://doi.org/10.1039/c7ja00306d.

    CAS  Article  Google Scholar 

  47. Christau S, Moeller T, Genzer J, et al. Salt-induced aggregation of negatively charged gold nanoparticles confined in a polymer brush matrix. Macromolecules. 2017;50:7333–43. https://doi.org/10.1021/acs.macromol.7b00866.

    CAS  Article  Google Scholar 

  48. Pamies R, Cifre JGH, Espín VF, et al. Aggregation behaviour of gold nanoparticles in saline aqueous media. J Nanopart Res. 2014;16. https://doi.org/10.1007/s11051-014-2376-4.

  49. Kim T, Lee CH, Joo SW, Lee K. Kinetics of gold nanoparticle aggregation: experiments and modeling. J Colloid Interface Sci. 2008;318:238–43. https://doi.org/10.1016/j.jcis.2007.10.029.

    CAS  Article  PubMed  Google Scholar 

  50. Suk JS, Xu Q, Kim N, et al. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev. 2016;99:28–51.

    CAS  Article  Google Scholar 

  51. Jokerst JV, Lobovkina T, Zare RN, Gambhir SS. Nanoparticle PEGylation for imaging and therapy. Nanomedicine. 2011;6:715–28.

    CAS  Article  Google Scholar 

  52. Manson J, Kumar D, Meenan BJ, Dixon D. Polyethylene glycol functionalized gold nanoparticles: the influence of capping density on stability in various media. Gold Bull. 2011;44:99–105. https://doi.org/10.1007/s13404-011-0015-8.

    CAS  Article  Google Scholar 

  53. Zhang XD, Wu D, Shen X, et al. Size-dependent in vivo toxicity of PEG-coated gold nanoparticles. Int J Nanomedicine. 2011;6:2071–81. https://doi.org/10.2147/ijn.s21657.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  54. Walkey CD, Olsen JB, Guo H, et al. Nanoparticle size and surface chemistry determine serum protein adsorption and macrophage uptake. J Am Chem Soc. 2012;134:2139–47. https://doi.org/10.1021/ja2084338.

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors acknowledge assistance and fruitful discussions by Drs. S. Foster, R. Merrifield, C. Stephan, A. Madden P. Larson, R. Forester, H. Kirit, and PerkinElmer.

Funding

This work was supported in part by an NSF MRI grant (Award # 1828234), the IBEST/OUHSC Seed Grant for Interdisciplinary Research, and the Oklahoma Tobacco Settlement Endowment Trust awarded to the University of Oklahoma - Stephenson Cancer Center.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stefan Wilhelm.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Disclaimer

The content is solely the responsibility of the authors and does not necessarily represent the official views of the Oklahoma Tobacco Settlement Endowment Trust.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

ABC Highlights: authored by Rising Stars and Top Experts.

Electronic supplementary material

ESM 1

(PDF 895 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Donahue, N.D., Francek, E.R., Kiyotake, E. et al. Assessing nanoparticle colloidal stability with single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS). Anal Bioanal Chem 412, 5205–5216 (2020). https://doi.org/10.1007/s00216-020-02783-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-020-02783-6

Keywords

  • Nanoparticle
  • Single-particle ICP-MS
  • Elemental analysis
  • Aggregation
  • Colloidal stability
  • Surface chemistry