Quantitative characterization of nanoparticle agglomeration within biological media

Nicole Hondow, Rik Brydson, Peiyi Wang, Mark D. Holton, M. Rowan Brown, Paul Rees, Huw D. Summers, Andy Brown

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


Quantitative analysis of nanoparticle dispersion state within biological media is essential to understanding cellular uptake and the roles of diffusion, sedimentation, and endocytosis in determining nanoparticle dose. The dispersion of polymer-coated CdTe/ZnS quantum dots in water and cell growth medium with and without fetal bovine serum was analyzed by transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques. Characterization by TEM of samples prepared by plunge freezing the blotted solutions into liquid ethane was sensitive to the dispersion state of the quantum dots and enabled measurement of agglomerate size distributions even in the presence of serum proteins where DLS failed. In addition, TEM showed a reduced packing fraction of quantum dots per agglomerate when dispersed in biological media and serum compared to just water, highlighting the effect of interactions between the media, serum proteins, and the quantum dots. The identification of a heterogeneous distribution of quantum dots and quantum dot agglomerates in cell growth medium and serum by TEM will enable correlation with the previously reported optical metrology of in vitro cellular uptake of this quantum dot dispersion. In this paper, we present a comparative study of TEM and DLS and show that plunge-freeze TEM provides a robust assessment of nanoparticle agglomeration state.

Original languageEnglish (US)
Article number977
JournalJournal of Nanoparticle Research
Issue number7
StatePublished - Jul 2012


  • Dispersion
  • Environmental and health effects
  • Image analysis
  • Nanomedicine
  • Nanoparticle
  • Plunge freeze
  • Transmission electron microscopy

ASJC Scopus subject areas

  • Atomic and Molecular Physics, and Optics
  • Condensed Matter Physics
  • Modeling and Simulation
  • Chemistry(all)
  • Materials Science(all)
  • Bioengineering


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